Sumaira Z. Aasi, MD

All Publications

• 5-fluorouracil 5% cream for squamous cell carcinoma in situ: Factors impacting treatment response. Journal of the American Academy of Dermatology Lin, C. P., Kibbi, N., Bandali, T., Hirotsu, K., Aasi, S. Z. 2024

  Abstract

  BACKGROUND: Complete clinical response (CCR) rates for squamous cell carcinoma in situ (SCCis) treated with 5-fluorouracil (5-FU) 5% cream range from 27-85%. Factors associated with CCR are not well-established.METHODS: Retrospective review of biopsy-proven primary SCCis diagnosed between 5/1/2019-4/30/2020 and treated with 5-FU 5% cream. Disease status at follow-up was recorded, with treatment failure defined as persistent or recurrent disease.RESULTS: The study included 149 SCCis cases, including 33.6% (50/149) arising in the context of immunosuppression. Eighteen cases failed treatment (10 persistent disease, 8 recurrent disease). By tumor size, CCR was noted in 128/144 (88.9%) tumors measuring <2 centimeters in diameter and 3/5 tumors ≥2 centimeters (60.0%, p=0.051). By treatment duration, CCR was observed in 4/7 (57.1%) tumors treated for <2 weeks, 72/83 (86.7%), tumors treated for 2 to <4 weeks, and 55/59 (93.2%) tumors treated for ≥4 weeks (p=0.019). On multivariate analysis, treatment failure was significantly associated with shorter treatment durations (OR 0.26; p=0.007) and increasing tumor size (OR 2.40; p=0.037).CONCLUSIONS: Shorter treatment duration and larger lesion size were significantly associated with failure of 5-FU in SCCis. Immunosuppression and anatomic location were not significant factors, supporting 5-FU use for SCCis in the immunosuppressed population and highlighting its versatility irrespective of anatomic location.

  View details for DOI 10.1016/j.jaad.2024.10.066

  View details for PubMedID 39521136

• Achieving Adherence With NCCN Guidelines for Nonmelanoma Skin Cancer Regarding Peripheral and Deep En Face Margin Assessment (PDEMA). Journal of the National Comprehensive Cancer Network : JNCCN Xu, Y. G., Lim, Y., Bordeaux, J. S., Aasi, S. Z., Alam, M., Chen, P., Contreras, C. M., DiMaio, D., Donigan, J. M., Farma, J. M., Grekin, R. C., Mark, L., Nehal, K. S., Nghiem, P., Olino, K., Patel, T., Scott, J., Shaha, A. R., Srivastava, D., Schmults, C. D. 2024; 22 (9)

  Abstract

  Peripheral and deep en face margin assessment (PDEMA), formerly termed by NCCN as complete circumferential peripheral and deep margin assessment (CCPDMA), has the advantages of histologic visualization of the entire marginal surface, highly accurate resection of involved tissue, and sparing of uninvolved tissue. Owing to its highest reported cure rates, PDEMA is the NCCN-preferred treatment for dermatofibrosarcoma protuberans, high-risk basal cell carcinoma, and very-high-risk cutaneous squamous cell carcinoma. In the United States, Mohs micrographic surgery (Mohs) is the most common method of PDEMA. In Germany and some other countries, non-Mohs methods of PDEMA referred to as the Tubingen torte and muffin techniques are more widely used. The Tubingen methods of PDEMA require close communication between surgeon and pathologist. This article describes the background of both Mohs and Tubingen PDEMA, reviews what constitutes PDEMA, and provides a protocol for Tubingen PDEMA detailing critical components in a stepwise fashion using illustrative photos and diagrams. We hope to broaden understanding of the NCCN Guidelines and their rationale, align practice, and optimize patient outcomes.

  View details for DOI 10.6004/jnccn.2024.7037

  View details for PubMedID 39536442

• The utility of artificial intelligence platforms for patient-generated questions in Mohs micrographic surgery: a multi-national, blinded expert panel evaluation. International journal of dermatology Lauck, K. C., Cho, S. W., DaCunha, M., Wuennenberg, J., Aasi, S., Alam, M., Arron, S. T., Bar, A., Brodland, D. G., Cerci, F. B., Cohen, J. L., Coldiron, B., Council, M. L., Harmon, C. B., Hruza, G., Läuchli, S., Moody, B. R., Wysong, A. S., Zitelli, J. A., Tolkachjov, S. N. 2024

  Abstract

  Artificial intelligence (AI) and large language models (LLMs) transform how patients inform themselves. LLMs offer potential as educational tools, but their quality depends upon the information generated. Current literature examining AI as an informational tool in dermatology has been limited in evaluating AI's multifaceted roles and diversity of opinions. Here, we evaluate LLMs as a patient-educational tool for Mohs micrographic surgery (MMS) in and out of the clinic utilizing an international expert panel.The most common patient MMS questions were extracted from Google and transposed into two LLMs and Google's search engine. 15 MMS surgeons evaluated the generated responses, examining their appropriateness as a patient-facing informational platform, sufficiency of response in a clinical environment, and accuracy of content generated. Validated scales were employed to assess the comprehensibility of each response.The majority of reviewers deemed all LLM responses appropriate. 75% of responses were rated as mostly accurate or higher. ChatGPT had the highest mean accuracy. The majority of the panel deemed 33% of responses sufficient for clinical practice. The mean comprehensibility scores for all platforms indicated a required 10th-grade reading level.LLM-generated responses were rated as appropriate patient informational sources and mostly accurate in their content. However, these platforms may not provide sufficient information to function in a clinical environment, and complex comprehensibility may represent a barrier to utilization. As the popularity of these platforms increases, it is important for dermatologists to be aware of these limitations.

  View details for DOI 10.1111/ijd.17382

  View details for PubMedID 39123288

• Mast cells orchestrate perineural invasion in aggressive epithelial cancers Srivastava, A., Bencomo, T., Mah, A., Garcia, J., Donohue, I., Tan, A., Seow, L., Nguyen, A., Jiang, T., Dwivedi, P., Rose, C. M., Brown, R., Aasi, S., Lee, C. S. ELSEVIER SCIENCE INC. 2024: S17

  View details for Web of Science ID 001276879000093

• Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study. Journal of the National Comprehensive Cancer Network : JNCCN Curtis, K. K., Fakult, N. J., Strunck, J. L., Aasi, S. Z., Ahn, C. S., Alam, M., Bar, A. A., Behshad, R., Bichakjian, C. K., Bolotin, D., Boone, S. L., Bordeaux, J. S., Brewer, J. D., Carr, D. R., Carucci, J. A., Castillo, J. R., Christensen, S. R., Clark, M. A., Collins, L. K., Demer, A. M., Eisen, D. B., Feng, H., Firoz, B. F., Grekin, R. C., Hirshburg, J. M., Holmes, T. E., Huang, C. C., Jennings, T. A., Jiang, S. I., Konda, S., Leitenberger, J. J., Lewin, J. M., Maher, I. A., Ng, E., Orengo, I. F., Samie, F. H., Saylor, D. K., Sharon, V. R., Soleymani, T., Swetter, S. M., Tate, J. A., Van Beek, M. J., Vidal, N. Y., Vij, A., Wysong, A., Xu, Y. G., Carroll, B. T., Yu, W. Y. 2024: 1-6

  Abstract

  Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials.A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale.Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2.This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

  View details for DOI 10.6004/jnccn.2024.7036

  View details for PubMedID 39079545

• Development and Validation of the Oxford Skin Cancer Treatment Scale, a Patient-Reported Outcome Measure for Health-Related Quality of Life and Treatment Satisfaction After Skin Cancer Treatment. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] Kantor, J., Aasi, S. Z., Alam, M., Paoli, J., Ratner, D. 2024

  Abstract

  Patient-reported outcome measures (PROMs) are necessary to assess the value of skin cancer treatment and to better compare therapeutic options.To develop and validate the Oxford Skin Cancer Treatment (OxSCanTr) scale, evaluating health-related quality of life and satisfaction after skin cancer treatment.After qualitative patient interviews, international expert consultation, and item reduction, 2 separate patient samples were used to assess the factor structure of the scale. Exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation was performed to establish a factor structure on Group A. Confirmatory factor analysis with a Satorra-Bentler scaled test statistic evaluating the root mean squared error of approximation (RMSEA), standardized root mean squared residual (SRMR), and comparative fit index (CFI) was conducted on Group B. Reliability as internal consistency was assessed using McDonald omega. Convergent and discriminant validity were assessed using the Pearson correlation coefficient.A total of 480 subjects returned completed surveys (completion rate 96%). A 12-item scale was developed encompassing 4 domains: aesthetic satisfaction, treatment choice satisfaction, treatment experience, and future concerns regarding recurrence/spread. Confirmatory factor analysis showed excellent goodness-of-fit characteristics, with RMSEA = 0.048, SRMR = 0.051, and CFI = 0.962 using the 4-factor model. Reliability was very good (McDonald omega 0.81-0.82), as was convergent validity with the FACE-Q skin cancer module appraisal of scars subscale (r = 0.55). Discriminant validity with a single question regarding being conservative was similarly excellent (r = -0.02).The OxSCanTr scale is a parsimonious, feasible, and valid PROM for the holistic assessment of the experience of patients who have undergone skin cancer treatment.

  View details for DOI 10.1097/DSS.0000000000004305

  View details for PubMedID 38996368

• Noninvasive virtual biopsy using micro-registered optical coherence tomography (OCT) in human subjects. Science advances Winetraub, Y., Van Vleck, A., Yuan, E., Terem, I., Zhao, J., Yu, C., Chan, W., Do, H., Shevidi, S., Mao, M., Yu, J., Hong, M., Blankenberg, E., Rieger, K. E., Chu, S., Aasi, S., Sarin, K. Y., de la Zerda, A. 2024; 10 (15): eadi5794

  Abstract

  Histological hematoxylin and eosin-stained (H&E) tissue sections are used as the gold standard for pathologic detection of cancer, tumor margin detection, and disease diagnosis. Producing H&E sections, however, is invasive and time-consuming. While deep learning has shown promise in virtual staining of unstained tissue slides, true virtual biopsy requires staining of images taken from intact tissue. In this work, we developed a micron-accuracy coregistration method [micro-registered optical coherence tomography (OCT)] that can take a two-dimensional (2D) H&E slide and find the exact corresponding section in a 3D OCT image taken from the original fresh tissue. We trained a conditional generative adversarial network using the paired dataset and showed high-fidelity conversion of noninvasive OCT images to virtually stained H&E slices in both 2D and 3D. Applying these trained neural networks to in vivo OCT images should enable physicians to readily incorporate OCT imaging into their clinical practice, reducing the number of unnecessary biopsy procedures.

  View details for DOI 10.1126/sciadv.adi5794

  View details for PubMedID 38598626

  View details for PubMedCentralID PMC11006228

• Anatomic Subtype Differences in Extramammary Paget Disease: A Meta-Analysis. JAMA dermatology Kibbi, N., Owen, J. L., Worley, B., Wang, J. X., Harikumar, V., Aasi, S. Z., Chandra, S., Choi, J. N., Fujisawa, Y., Iavazzo, C., Kim, J. Y., Lawrence, N., Leitao, M. M., MacLean, A. B., Ross, J. S., Rossi, A. M., Servaes, S., Solomon, M. J., Alam, M. 2024

  Abstract

  Importance: Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management.Objective: To compare demographic and tumor characteristics and treatment approaches for different EMPD subtypes. Recommendations for diagnosis and treatment are presented.Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Cochrane Reviews CENTRAL from December 1, 1990, to October 24, 2022.Study Selection: Articles were excluded if they were not in English, reported fewer than 3 patients, did not specify information by anatomic subtype, or contained no case-level data. Metastatic cases on presentation were also excluded.Data Extraction and Synthesis: Abstracts of 1295 eligible articles were independently reviewed by 5 coauthors, and 135 articles retained. Reporting was in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis was cunducted in August 2019 and updated in November 2022.Findings: Most vulvar EMPD cases were asymptomatic, and diagnosis was relatively delayed (mean, 25.1 months). Although most vulvar EMPD cases were intraepidermal (1247/1773 [70.3%]), radical surgeries were still performed in almost one-third of cases. Despite this aggressive surgical approach, 481 of 1423 (34%) recurred, commonly confined to the skin and mucosa (177/198 [89.4%]). By contrast, 152 of 1101 penoscrotal EMPD cases (14%) recurred, but more than one-third of these recurrences were regional or associated with distant metastases (54 of 152 [35.5%]). Perianal EMPD cases recurred in one-third of cases (74/218 [33.9%]), with one-third of these recurrences being regional or associated with distant metastasis (20 of 74 [27.0%]). Perianal EMPD also had the highest rate of invasive disease (50% of cases).Conclusions and Relevance: The diagnosis and treatment of EMPD should differ based on anatomic subtypes. Considerations for updated practice may include less morbid treatments for vulvar EMPD, which is primarily epidermal, and close surveillance for local recurrence in vulvar EMPD and metastatic recurrence in perianal EMPD. Recurrences in penoscrotal subtype were less common, and selective surveillance in this subtype may be considered. Limitations of this study include the lack of replication cohorts and the exclusion of studies that did not stratify outcomes by anatomic subtype.

  View details for DOI 10.1001/jamadermatol.2024.0001

  View details for PubMedID 38446447

• Reconstructing a Defect Involving the Medial Cheek and Upper Lip. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] Voller, L. M., Aasi, S. Z. 2024

  View details for DOI 10.1097/DSS.0000000000004131

  View details for PubMedID 38394471

• NCCN Guidelines Insights: Merkel Cell Carcinoma, Version 1.2024. Journal of the National Comprehensive Cancer Network : JNCCN Schmults, C. D., Blitzblau, R., Aasi, S. Z., Alam, M., Amini, A., Bibee, K., Bolotin, D., Bordeaux, J., Chen, P., Contreras, C. M., DiMaio, D., Donigan, J. M., Farma, J. M., Ghosh, K., Harms, K., Ho, A. L., Lukens, J. N., Manber, S., Mark, L., Medina, T., Nehal, K. S., Nghiem, P., Olino, K., Park, S., Patel, T., Puzanov, I., Rich, J., Sekulic, A., Shaha, A. R., Srivastava, D., Thomas, V., Tomblinson, C., Venkat, P., Xu, Y. G., Yu, S., Yusuf, M., McCullough, B., Espinosa, S. 2024; 22 (1D): e240002

  Abstract

  The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

  View details for DOI 10.6004/jnccn.2024.0002

  View details for PubMedID 38244274

• Noninvasive Detection of Skin Cancer by Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging. Analytical chemistry Meng, Y., Chiou, A. S., Aasi, S. Z., See, N. A., Song, X., Zare, R. N. 2023

  Abstract

  We report a technique for the noninvasive detection of skin cancer by imprint desorption electrospray ionization mass spectrometry imaging (DESI-MSI) using a transfer agent that is pressed against the tissue of interest. By noninvasively pressing a tape strip against human skin, metabolites, fatty acids, and lipids on the skin surface are transferred to the tape with little spatial distortion. Running DESI-MSI on the tape strip provides chemical images of the molecules on the skin surface, which are valuable for distinguishing cancer from healthy skin. Chemical components of the tissue imprint on the tape strip and the original basal cell carcinoma (BCC) section from the mass spectra show high consistency. By comparing MS images (about 150-μm resolution) of same molecules from the tape strip and from the BCC section, we confirm that chemical patterns are successfully transferred to the tape stripe. We also used the technique to distinguish cherry angiomas from normal human skin by comparing the molecular patterns from a tape strip. These results demonstrate the potential of the imprint DESI-MSI technique for the noninvasive detection of skin cancers as well as other skin diseases before and during clinical surgery.

  View details for DOI 10.1021/acs.analchem.3c04918

  View details for PubMedID 38155587

• Histopathologic Characterization of Incidental Lesions Encountered During Mohs Micrographic Surgery With MART-1 Immunohistochemistry. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] Hirotsu, K. E., Kibbi, N., Rieger, K. E., Aasi, S. Z. 2023

  Abstract

  As the use of melanoma antigen recognized by T cells (MART-1) immunohistochemistry (IHC) with Mohs surgery increases for the treatment of melanoma in situ and invasive melanoma, surgeons should be aware of MART-1 staining patterns of incidental lesions often encountered on frozen sections. Lack of this knowledge can lead to unnecessary additional surgery, increased health care costs, and loss of valuable laboratory staff time and resources.To characterize the histopathologic features of incidental lesions encountered during Mohs surgery for melanoma. To review key diagnostic and differentiating features on hematoxylin and eosin staining (H&E) and MART-1 IHC of these lesions.A comprehensive review of frozen-section histopathology slides from Mohs cases with MART-1 IHC at our institution was conducted from 2021 to 2023.Incidental benign and malignant lesions were identified and characterized on H&E frozen sections and MART-1 IHC. Although such entities can share MART-1 staining characteristics with melanoma in situ or melanoma, distinguishing characteristics on H&E and lack of histopathologic criteria for melanoma on MART-1 IHC can be used to distinguish these incidental lesions from melanoma.Staining of frozen sections for Mohs micrographic surgery with H&E and MART-1 IHC together can differentiate common incidental benign and malignant cutaneous lesions from melanoma.

  View details for DOI 10.1097/DSS.0000000000004048

  View details for PubMedID 38064448

• Clinical Outcomes in Sebaceous Carcinoma: A Retrospective Two-Center Cohort Study. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] Kibbi, N., Petric, U. B., El-Banna, G., Beaulieu, D. M., Rajan, N., Srivastava, D., Aasi, S. Z. 2023

  Abstract

  Sebaceous carcinoma (SC) is a rare, potentially recurrent, and life-threatening cutaneous malignancy that can be associated with Muir-Torre syndrome (MTS), a DNA mismatch repair-driven genodermatosis. Earlier studies examining factors associated with recurrence have focused on periocular tumors only.Examine outcomes of SC and identify factors associated with recurrence.Retrospective study from 2 tertiary care centers.Sixty-seven cases from 63 patients were identified, including 7 cases of MTS and 13 arising in the context of immunosuppression. Fifty-five cases (82.1%) were treated with complete circumferential peripheral and deep margin assessment (CCPDMA) methods. Five recurrences developed during the postoperative period. On univariate analysis, periocular location (odds ratio [OR] 7.6, p = .0410), and lesion size ≥2 cm (OR 9.6, p = .005) were associated with recurrence, whereas CCPDMA (OR 0.052, p = .0006) was inversely associated with recurrence. On multivariate analysis, only lesion size ≥2 cm (OR 9.6, p = .0233) and CCPDMA approaches (OR 0.052, p = .007) were significant.Non-complete circumferential peripheral and deep margin assessment methods and large lesion size were independent risk factors predicting recurrence, whereas anatomic subtype and MTS status were not. These findings can assist in identifying SC cases that may benefit from more aggressive treatment and closer surveillance.

  View details for DOI 10.1097/DSS.0000000000004016

  View details for PubMedID 37962979

• Elevated Risk of Visceral Malignant Neoplasms in Extramammary Paget Disease. JAMA dermatology Maloney, N. J., Yao, H., Aasi, S. Z., John, E. M., Linos, E., Kibbi, N. 2023

  Abstract

  This cross-sectional study evaluates the incidence and types of cancers that develop years after an extramammary Paget disease (EMPD) diagnosis.

  View details for DOI 10.1001/jamadermatol.2023.2679

  View details for PubMedID 37647047

• Association of histopathological grade with stage and survival in sebaceous carcinoma: a retrospective cohort study in the National Cancer Database. Journal of the American Academy of Dermatology Maloney, N. J., Zacher, N. C., Aasi, S. Z., Hirotsu, K. E., Zaba, L. C., Kibbi, N. 2023

  View details for DOI 10.1016/j.jaad.2023.07.1013

  View details for PubMedID 37532139

• Integrated single-cell chromatin and transcriptomic analyses of human scalp identify gene-regulatory programs and critical cell types for hair and skin diseases. Nature genetics Ober-Reynolds, B., Wang, C., Ko, J. M., Rios, E. J., Aasi, S. Z., Davis, M. M., Oro, A. E., Greenleaf, W. J. 2023

  Abstract

  Genome-wide association studies have identified many loci associated with hair and skin disease, but identification of causal variants requires deciphering of gene-regulatory networks in relevant cell types. We generated matched single-cell chromatin profiles and transcriptomes from scalp tissue from healthy controls and patients with alopecia areata, identifying diverse cell types of the hair follicle niche. By interrogating these datasets at multiple levels of cellular resolution, we infer 50-100% more enhancer-gene links than previous approaches and show that aggregate enhancer accessibility for highly regulated genes predicts expression. We use these gene-regulatory maps to prioritize cell types, genes and causal variants implicated in the pathobiology of androgenetic alopecia (AGA), eczema and other complex traits. AGA genome-wide association studies signals are enriched in dermal papilla regulatory regions, supporting the role of these cells as drivers of AGA pathogenesis. Finally, we train machine learning models to nominate single-nucleotide polymorphisms that affect gene expression through disruption of transcription factor binding, predicting candidate functional single-nucleotide polymorphism for AGA and eczema.

  View details for DOI 10.1038/s41588-023-01445-4

  View details for PubMedID 37500727

  View details for PubMedCentralID 4006068

• Advances in cutaneous squamous cell carcinoma. Nature reviews. Cancer Winge, M. C., Kellman, L. N., Guo, K., Tang, J. Y., Swetter, S. M., Aasi, S. Z., Sarin, K. Y., Chang, A. L., Khavari, P. A. 2023

  Abstract

  Human malignancies arise predominantly in tissues of epithelial origin, where the stepwise transformation from healthy epithelium to premalignant dysplasia to invasive neoplasia involves sequential dysregulation of biological networks that govern essential functions of epithelial homeostasis. Cutaneous squamous cell carcinoma (cSCC) is a prototype epithelial malignancy, often with a high tumour mutational burden. A plethora of risk genes, dominated by UV-induced sun damage, drive disease progression in conjunction with stromal interactions and local immunomodulation, enabling continuous tumour growth. Recent studies have identified subpopulations of SCC cells that specifically interact with the tumour microenvironment. These advances, along with increased knowledge of the impact of germline genetics and somatic mutations on cSCC development, have led to a greater appreciation of the complexity of skin cancer pathogenesis and have enabled progress in neoadjuvant immunotherapy, which has improved pathological complete response rates. Although measures for the prevention and therapeutic management of cSCC are associated with clinical benefit, the prognosis remains poor for advanced disease. Elucidating how the genetic mechanisms that drive cSCC interact with the tumour microenvironment is a current focus in efforts to understand, prevent and treat cSCC.

  View details for DOI 10.1038/s41568-023-00583-5

  View details for PubMedID 37286893

  View details for PubMedCentralID 4833641

• Online risk calculator and nomogram for predicting sentinel lymph node positivity in Merkel Cell Carcinoma. Journal of the American Academy of Dermatology Maloney, N. J., Aasi, S. Z., Kibbi, N., Hirotsu, K. E., Zaba, L. C. 2023

  View details for DOI 10.1016/j.jaad.2023.05.042

  View details for PubMedID 37244414

• Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche. Nature communications Haensel, D., Daniel, B., Gaddam, S., Pan, C., Fabo, T., Bjelajac, J., Jussila, A. R., Gonzalez, F., Li, N. Y., Chen, Y., Hou, J., Patel, T., Aasi, S., Satpathy, A. T., Oro, A. E. 2023; 14 (1): 2685

  Abstract

  Cancer immunotherapies have revolutionized treatment but have shown limited success as single-agent therapies highlighting the need to understand the origin, assembly, and dynamics of heterogeneous tumor immune niches. Here, we use single-cell and imaging-based spatial analysis to elucidate three microenvironmental neighborhoods surrounding the heterogeneous basal cell carcinoma tumor epithelia. Within the highly proliferative neighborhood, we find that TREM2+ skin cancer-associated macrophages (SCAMs) support the proliferation of a distinct tumor epithelial population through an immunosuppression-independent manner via oncostatin-M/JAK-STAT3 signaling. SCAMs represent a unique tumor-specific TREM2+ population defined by VCAM1 surface expression that is not found in normal homeostatic skin or during wound healing. Furthermore, SCAMs actively proliferate and self-propagate through multiple serial tumor passages, indicating long-term potential. The tumor rapidly drives SCAM differentiation, with intratumoral injections sufficient to instruct naive bone marrow-derived monocytes to polarize within days. This work provides mechanistic insights into direct tumor-immune niche dynamics independent of immunosuppression, providing the basis for potential combination tumor therapies.

  View details for DOI 10.1038/s41467-023-37993-w

  View details for PubMedID 37164949

• Comparison of clinicopathologic features, survival, and demographics in sebaceous carcinoma patients with and without Muir-Torre syndrome. Journal of the American Academy of Dermatology Maloney, N. J., Zacher, N. C., Hirotsu, K. E., Rajan, N., Aasi, S. Z., Kibbi, N. 2023

  Abstract

  Visceral malignancies in patients with Lynch syndrome behave less aggressively than in those without Lynch syndrome. The behavior of sebaceous carcinoma (SC) in Muir-Torre syndrome (MTS), a variant of Lynch syndrome, is incompletely investigated.Investigate features and survival of SC patients with and without MTS.Retrospective cohort study in the Surveillance, Epidemiology, and End Results 17 database from 2000-2019 of patients with SC. Patients were classified as MTS or non-MTS cases based on a threshold score of 2 on the Mayo MTS Risk Score.We identified 105 (2.8%) MTS cases and 3677 (97.2%) non-MTS cases. On univariate analysis, MTS patients were younger, had a higher proportion of tumors outside the head/neck, and had fewer high-grade tumors. On Kaplan-Meier analysis, MTS patients trended toward having better SC-specific survival. On multivariate Cox proportional hazards analysis adjusting for other covariates, MTS status was an independent predictor of worse overall survival. However, there was no association between MTS status and SC-specific survival.Given relatively high disease-specific survival in SC, our study may have been underpowered to detect a difference on Kaplan-Meier analysis.Our study suggests SC does not behave more aggressively in patients with MTS.

  View details for DOI 10.1016/j.jaad.2023.03.032

  View details for PubMedID 37003478

• Positive surgical margins in sebaceous carcinoma: risk factors and prognostic impact. Journal of the American Academy of Dermatology Maloney, N. J., Aasi, S. Z., Hirotsu, K. E., Zaba, L. C., Kibbi, N. 2023

  View details for DOI 10.1016/j.jaad.2023.01.049

  View details for PubMedID 36907557

• Rapid Cellular-Resolution Skin Imaging with Optical Coherence Tomography Using All-Glass Multifocal Metasurfaces. ACS nano Zhao, J., Van Vleck, A., Winetraub, Y., Du, L., Han, Y., Aasi, S., Sarin, K. Y., de la Zerda, A. 2023

  Abstract

  Cellular-resolution optical coherence tomography (OCT) is a powerful tool offering noninvasive histology-like imaging. However, like other optical microscopy tools, a high numerical aperture (N.A.) lens is required to generate a tight focus, generating a narrow depth of field, which necessitates dynamic focusing and limiting the imaging speed. To overcome this limitation, we developed a metasurface platform that generates multiple axial foci, which multiplies the volumetric OCT imaging speed by offering several focal planes. This platform offers accurate and flexible control over the number, positions, and intensities of axial foci generated. All-glass metasurface optical elements 8 mm in diameter are fabricated from fused-silica wafers and implemented into our scanning OCT system. With a constant lateral resolution of 1.1 mum over all depths, the multifocal OCT triples the volumetric acquisition speed for dermatological imaging, while still clearly revealing features of stratum corneum, epidermal cells, and dermal-epidermal junctions and offering morphological information as diagnostic criteria for basal cell carcinoma. The imaging speed can be further improved in a sparse sample, e.g., 7-fold with a seven-foci beam. In summary, this work demonstrates the concept of metasurface-based multifocal OCT for rapid virtual biopsy, further providing insights for developing rapid volumetric imaging systems with high resolution and compact volume.

  View details for DOI 10.1021/acsnano.2c09542

  View details for PubMedID 36745734

• Postoperative Complications After Interpolated Flap Repair for Mohs Defects of the Nose: A Multicenter Prospective Cohort Study. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] Perz, A. M., Lukowiak, T. M., Lee, M. P., Neal, D., Aizman, L., Miller, C. J., Golda, N., Albertini, J. G., Holmes, T., Bar, A., Leitenberger, J., Maher, I., Sobanko, J. F., Chen, D., Hollmig, T., Aasi, S., Sutton, A., Higgins, H. W., Shin, T. M., Weinberger, C., Mattox, A., Wysong, A., Etzkorn, J. R. 2023; 49 (2): 135-139

  Abstract

  BACKGROUND: Dermatologists perform most interpolated flaps after skin cancer resection. Prospective, multicenter data on complications after interpolated flap repair in this setting are limited.OBJECTIVE: To determine the rate of physician-reported complications after interpolated flap repair of the nose.METHODS: Multicenter, prospective cohort study of 169 patients undergoing 2-stage interpolated flap repair of post-Mohs nasal defects. Frequency of bleeding, infection, dehiscence, necrosis, hospitalization, and death in the 30 days after flap placement and flap takedown are reported.RESULTS: Patients experienced 23 complications after flap placement (13.61%) and 6 complications after flap takedown (3.55%) that were related to the surgical procedure. The most frequent complication after flap placement was bleeding (9, 5.33%, 95% confidence interval [CI]: 2.83%-9.82%). The most frequent complication after flap takedown was infection (5, 2.96%, 95% CI: 1.27%-6.74%). There was one hospitalization related to an adverse reaction to antibiotics. There were no deaths.CONCLUSION: Most complications after interpolated flap repair for post-Mohs defects of the nose are minor and are associated with flap placement. Interpolated flap repair for post-Mohs defects can be performed safely in the outpatient setting under local anesthesia.

  View details for DOI 10.1097/DSS.0000000000003653

  View details for PubMedID 36728063

• Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Schmults, C. D., Blitzblau, R., Aasi, S. Z., Alam, M., Amini, A., Bibee, K., Bordeaux, J., Chen, P., Contreras, C. M., DiMaio, D., Donigan, J. M., Farma, J. M., Ghosh, K., Harms, K., Ho, A. L., Lukens, J. N., Mark, L., Medina, T., Nehal, K. S., Nghiem, P., Olino, K., Park, S., Patel, T., Puzanov, I., Rich, J., Sekulic, A., Shaha, A. R., Srivastava, D., Thomas, V., Tomblinson, C., Venkat, P., Xu, Y. G., Yu, S., Yusuf, M., McCullough, B., Espinosa, S. 2023; 21 (11): 1181-1203

  Abstract

  Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

  View details for DOI 10.6004/jnccn.2023.0056

  View details for PubMedID 37935106

• Postoperative Complications After Interpolated Flap Repair for Mohs Defects of the Nose: A Multicenter Prospective Cohort Study. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] Perz, A. M., Lukowiak, T. M., Lee, M. P., Neal, D., Aizman, L., Miller, C. J., Golda, N., Albertini, J. G., Holmes, T., Bar, A., Leitenberger, J., Maher, I., Sobanko, J. F., Chen, D., Hollmig, T., Aasi, S., Sutton, A., Higgins, H. W., Shin, T. M., Weinberger, C., Mattox, A., Wysong, A., Etzkorn, J. R. 2022

  Abstract

  Dermatologists perform most interpolated flaps after skin cancer resection. Prospective, multicenter data on complications after interpolated flap repair in this setting are limited.To determine the rate of physician-reported complications after interpolated flap repair of the nose.Multicenter, prospective cohort study of 169 patients undergoing 2-stage interpolated flap repair of post-Mohs nasal defects. Frequency of bleeding, infection, dehiscence, necrosis, hospitalization, and death in the 30 days after flap placement and flap takedown are reported.Patients experienced 23 complications after flap placement (13.61%) and 6 complications after flap takedown (3.55%) that were related to the surgical procedure. The most frequent complication after flap placement was bleeding (9, 5.33%, 95% confidence interval [CI]: 2.83%-9.82%). The most frequent complication after flap takedown was infection (5, 2.96%, 95% CI: 1.27%-6.74%). There was one hospitalization related to an adverse reaction to antibiotics. There were no deaths.Most complications after interpolated flap repair for post-Mohs defects of the nose are minor and are associated with flap placement. Interpolated flap repair for post-Mohs defects can be performed safely in the outpatient setting under local anesthesia.

  View details for DOI 10.1097/DSS.0000000000003653

  View details for PubMedID 36728942

• LY6D marks pre-existing resistant basosquamous tumor subpopulations. Nature communications Haensel, D., Gaddam, S., Li, N. Y., Gonzalez, F., Patel, T., Cloutier, J. M., Sarin, K. Y., Tang, J. Y., Rieger, K. E., Aasi, S. Z., Oro, A. E. 2022; 13 (1): 7520

  Abstract

  Improved response to canonical therapies requires a mechanistic understanding of dynamic tumor heterogeneity by identifying discrete cellular populations with enhanced cellular plasticity. We have previously demonstrated distinct resistance mechanisms in skin basal cell carcinomas, but a comprehensive understanding of the cellular states and markers associated with these populations remains poorly understood. Here we identify a pre-existing resistant cellular population in naive basal cell carcinoma tumors marked by the surface marker LY6D. LY6D+ tumor cells are spatially localized and possess basal cell carcinoma and squamous cell carcinoma-like features. Using computational tools, organoids, and spatial tools, we show that LY6D+ basosquamous cells represent a persister population lying on a central node along the skin lineage-associated spectrum of epithelial states with local environmental and applied therapies determining the kinetics of accumulation. Surprisingly, LY6D+ basosquamous populations exist in many epithelial tumors, such as pancreatic adenocarcinomas, which have poor outcomes. Overall, our results identify the resistant LY6D+ basosquamous population as an important clinical target and suggest strategies for future therapeutic approaches to target them.

  View details for DOI 10.1038/s41467-022-35020-y

  View details for PubMedID 36473848

  View details for PubMedCentralID PMC9726704

• Flexible method for generating needle-shaped beams and its application in optical coherence tomography. Optica Zhao, J., Winetraub, Y., DU, L., VAN Vleck, A., Ichimura, K., Huang, C., AAsI, S. Z., Sarin, K. Y., DE LA Zerda, A. 2022; 9 (8): 859-867

  Abstract

  Needle-shaped beams (NBs) featuring a long depth-of-focus (DOF) can drastically improve the resolution of microscopy systems. However, thus far, the implementation of a specific NB has been onerous due to the lack of a common, flexible generation method. Here we develop a spatially multiplexed phase pattern that creates many axially closely spaced foci as a universal platform for customizing various NBs, allowing flexible manipulations of beam length and diameter, uniform axial intensity, and sub-diffraction-limit beams. NBs designed via this method successfully extended the DOF of our optical coherence tomography (OCT) system. It revealed clear individual epidermal cells of the entire human epidermis, fine structures of human dermal-epidermal junction in a large depth range, and a high-resolution dynamic heartbeat of alive Drosophila larvae.

  View details for DOI 10.1364/optica.456894

  View details for PubMedID 37283722

  View details for PubMedCentralID PMC10243785

• Patient-Reported Nasal Function and Appearance After Interpolation Flap Repair Following Skin Cancer Resection: A Multicenter Prospective Cohort Study. Facial plastic surgery & aesthetic medicine Veerabagu, S. A., Perz, A. M., Lukowiak, T. M., Lee, M. P., Neal, D., Aizman, L., Miller, C. J., Golda, N., Albertini, J. G., Chen, D., Bar, A., Leitenberger, J., Maher, I. A., Sobanko, J. F., Hollmig, T., Aasi, S., Sutton, A., Higgins Ii, H. W., Shin, T. M., Weinberger, C., Mattox, A., Wysong, A., Nugent, S. T., Etzkorn, J. R. 2022

  Abstract

  Objective: Among patients undergoing two-stage interpolated flap repair of nasal defects, nasal function, and appearance before surgery and at 16 weeks after flap takedown were compared using the Nasal Appearance and Function Evaluation Questionnaire (NAFEQ). Design: Multicenter prospective cohort study. Methods: Adult patients with a nasal skin cancer anticipated to require two-stage interpolation flap repair completed the NAFEQ before surgery, at 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Results: One hundred sixty-nine patients were enrolled, with 138 patients completing both presurgical and 16-week post-takedown NAFEQs. Overall NAFEQ score increased by 1.09 points (1.91% improvement, confidence interval [95% CI -0.34 to 2.53]). NAFEQ functional subscale increased by 0.72 points (2.58% increase; 95% CI [0.10-1.35]) and appearance subscale increased by 0.37 points (1.28% improvement, 95% CI [-0.65 to 1.39]). Conclusion: At 16 weeks after flap takedown, patients' perceptions of their nasal function and appearance are similar to or slightly improved when compared with their presurgical assessments.

  View details for DOI 10.1089/fpsam.2021.0271

  View details for PubMedID 35950993

• Risk factors for and prognostic impact of positive surgical margins after excision of Merkel cell carcinoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Maloney, N. J., Nguyen, K. A., So, N. A., Aasi, S. Z., Zaba, L. C. 2022; 87 (2): 444-446

  View details for Web of Science ID 000877691300006

• OCT2Hist: Non-invasive virtual biopsy using optical coherence tomography and machine learning Winetraub, Y., Aasi, S., Sarin, K. Y., de la Zerda, A. ELSEVIER SCIENCE INC. 2022: S150

  View details for Web of Science ID 000829693001418

• Tumor assembly of the spatially organized self-propagating myeloid niche Haensel, D., Daniel, B., Fabo, T., Gaddam, S., Bjelajac, J., Pan, C., Patel, T., Aasi, S., Satpathy, A., Oro, A. ELSEVIER SCIENCE INC. 2022: S15

  View details for Web of Science ID 000829693000262

• Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment. Science advances Guerrero-Juarez, C. F., Lee, G. H., Liu, Y., Wang, S., Karikomi, M., Sha, Y., Chow, R. Y., Nguyen, T. T., Iglesias, V. S., Aasi, S., Drummond, M. L., Nie, Q., Sarin, K., Atwood, S. X. 2022; 8 (23): eabm7981

  Abstract

  How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity-PAGA, cellular entropy, and regulon analysis in stromal cells reveals a cancer-specific rewiring of fibroblasts, where STAT1, TGF-beta, and inflammatory signals induce a noncanonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, whose expression we validated in situ. Last, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro vismodegib-resistant BCC cell growth, Hedgehog signaling, and in vivo tumor growth in a BCC mouse model, validating HSP70's essential role in tumor growth and reinforcing the critical nature of tumor microenvironment cross-talk in BCC progression.

  View details for DOI 10.1126/sciadv.abm7981

  View details for PubMedID 35687691

• Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease. JAMA oncology Kibbi, N., Owen, J. L., Worley, B., Wang, J. X., Harikumar, V., Downing, M. B., Aasi, S. Z., Aung, P. P., Barker, C. A., Bolotin, D., Bordeaux, J. S., Cartee, T. V., Chandra, S., Cho, N. L., Choi, J. N., Chung, K. Y., Cliby, W. A., Dorigo, O., Eisen, D. B., Fujisawa, Y., Golda, N., Halfdanarson, T. R., Iavazzo, C., Jiang, S. I., Kanitakis, J., Khan, A., Kim, J. Y., Kuzel, T. M., Lawrence, N., Leitao, M. M., MacLean, A. B., Maher, I. A., Mittal, B. B., Nehal, K. S., Ozog, D. M., Pettaway, C. A., Ross, J. S., Rossi, A. M., Servaes, S., Solomon, M. J., Thomas, V. D., Tolia, M., Voelzke, B. B., Waldman, A., Wong, M. K., Zhou, Y., Arai, N., Brackett, A., Ibrahim, S. A., Kang, B. Y., Poon, E., Alam, M. 2022

  Abstract

  Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms.To develop recommendations for the care of adults with EMPD.A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD.The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

  View details for DOI 10.1001/jamaoncol.2021.7148

  View details for PubMedID 35050310

• Flexible method for generating needle-shaped beams and its application in optical coherence tomography Optica Zhao, J., Winetraub, Y., Du, L., Vleck, A. V., Ichimura, K., Huang, C., Aasi, S. Z., Sarin, K. Y., de la Zerda, A. 2022; 9 (8): 859-867

  View details for DOI 10.1364/optica.456894

• Treatment of Cutaneous Squamous Cell Carcinoma With the Topical Histone Deacetylase Inhibitor Remetinostat. JAMA dermatology Kilgour, J. M., Shah, A., Eichstadt, S., Bailey, I., Aasi, S. Z., Sarin, K. Y. 2021

  View details for DOI 10.1001/jamadermatol.2021.4549

  View details for PubMedID 34787644

• A 10-year retrospective cohort study of ruxolitinib and association with non-melanoma skin cancer in polycythemia vera and myelofibrosis patients. Journal of the American Academy of Dermatology Lin, J. Q., Li, S. Q., Li, S., Kiamanesh, E. F., Aasi, S. Z., Kwong, B. Y., Chang, A. L. 2021

  Abstract

  BACKGROUND: Clinical trials report occurrence of non-melanoma skin cancers (NMSC) with ruxolitinib in polycythemia (PV) or myelofibrosis (MF) patients, however the level of risk and effect of covariates are not known in the real-world setting.OBJECTIVE: To systematically assess the risk of developing non-melanoma skin cancer (NMSC) after ruxolitinib exposure in PV or MF patients.METHODS: A 10-year retrospective cohort of PV or MF patients at Stanford Medical Center was identified and matched on age, gender, race, Charlson comorbidity index, disease diagnosis, and follow-up time. The main outcome measure was Hazard Ratio (HR) for NMSC (comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) after ruxolitinib exposure, adjusted for covariates.RESULTS: The study cohort consisted of 564 patients (188 exposed to ruxolitinib for at least 4 weeks, 376 unexposed). Ruxolitinib-exposed PV or MF patients had an adjusted NMSC HR of 2.69 (95% Confidence Interval (CI), 1.03-7.02). In particular, ruxolitinib exposure was associated with SCC, HR=3.24 (95% CI, 1.45-7.22), with non-JAK2 mutated patients showing even higher SCC risk, HR=7.40 (2.54-21.63).LIMITATIONS: Retrospective design.CONCLUSIONS AND RELEVANCE: Our real-world results indicate that SCC risk is increased in PV or MF patients taking ruxolitinib and supports consideration of skin cancer monitoring.

  View details for DOI 10.1016/j.jaad.2021.10.004

  View details for PubMedID 34648874

• C-FOS drives reversible basal to squamous cell carcinoma transition Kuonen, F., Li, N., Haensel, D., Patel, T., Gaddam, S., Yerly, L., Rieger, K., Aasi, S., Oro, A. ELSEVIER SCIENCE INC. 2021: S191

  View details for Web of Science ID 000706854500251

• Mutant collagen COL11A1 enhances cancerous invasion. Oncogene Lee, C. S., Siprashvili, Z., Mah, A., Bencomo, T., Elcavage, L. E., Che, Y., Shenoy, R. M., Aasi, S. Z., Khavari, P. A. 2021

  Abstract

  Collagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic function for mutant collagens is undefined. Here we identify COL11A1 mutations in 66 of 100 cutaneous squamous cell carcinomas (cSCCs), the second most common U.S. cancer, concentrated in a triple helical region known to produce trans-dominant collagens. Analysis of COL11A1 and other collagen genes found that they are mutated across common epithelial malignancies. Knockout of mutant COL11A1 impairs cSCC tumorigenesis in vivo. Compared to otherwise genetically identical COL11A1 wild-type tissue, gene-edited mutant COL11A1 skin is characterized by induction of beta1 integrin targets and accelerated neoplastic invasion. In mosaic tissue, mutant COL11A1 cells enhanced invasion by neighboring wild-type cells. These results suggest that specific collagens are commonly mutated in cancer and that mutant collagens may accelerate this process.

  View details for DOI 10.1038/s41388-021-02013-y

  View details for PubMedID 34584216

• Risk factors for and prognostic impact of positive surgical margins after excision of Merkel cell carcinoma. Journal of the American Academy of Dermatology Maloney, N. J., Nguyen, K. A., So, N. A., Aasi, S. Z., Zaba, L. C. 2021

  View details for DOI 10.1016/j.jaad.2021.09.014

  View details for PubMedID 34537251

• Patient Quality of Life After Interpolated Flap Repair of Nasal Mohs Surgery Defects: A Multicenter Prospective Cohort Study. JAMA dermatology Lukowiak, T. M., Perz, A. M., Veerabagu, S. A., Lee, M. P., Neal, D., Aizman, L., Miller, C. J., Golda, N., Albertini, J. G., Holmes, T., Bar, A., Leitenberger, J., Maher, I. A., Sobanko, J. F., Chen, D., Aasi, S., Sutton, A., Higgins, H. W., Shin, T. M., Weinberger, C., Mattox, A., Wysong, A., Etzkorn, J. R. 2021

  Abstract

  Importance: Single-center studies have shown that patients report better skin cancer-specific quality of life (QOL) after Mohs micrographic surgery (MMS), but it is unclear whether this improved QOL applies to patients after MMS and complex reconstruction in cosmetically sensitive areas.Objective: To evaluate patient QOL after MMS and interpolation flap reconstruction for patients with nasal skin cancers.Design, Setting and Participants: This multicenter prospective survey study used the Skin Cancer Index (SCI), a validated, 15-question QOL questionnaire administered at 4 time points: before MMS, 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Patients age 18 years or older with a nasal skin cancer who presented for MMS and were anticipated to undergo 2-stage interpolated flap repair by a Mohs surgeon were recruited from August 9, 2018, to February 2, 2020, at 8 outpatient MMS locations across the United States, including both academic centers and private practices.Main Outcomes and Measures: Mean difference in overall SCI score before MMS vs 16 weeks after flap takedown.Results: A total of 169 patients (92 men [54.4%]; mean [SD] age, 67.7 [11.4] years) were enrolled, with 147 patients (75 men [51.0%]; mean [SD] age, 67.8 [11.7] years) completing SCI surveys both before MMS and 16 weeks after flap takedown. Total SCI scores improved significantly 16 weeks after flap takedown compared with pre-MMS scores, increasing by a mean of 13% (increase of 7.11 points; 95% CI, 5.48-8.76; P<.001). All 3 SCI subscale scores (emotion, appearance, and social) improved significantly (emotion subscale, increase of 3.27 points; 95% CI, 2.35-4.18; P<.001; appearance subscale, increase of 1.65 points; 95% CI, 1.12-2.18; P<.001; and social subscale, increase of 2.10 points; 95% CI, 1.55-2.84; P<.001) 16 weeks after flap takedown compared with pre-MMS.Conclusions and Relevance: Removal of a nasal skin cancer and repair of the resulting defect can be distressing for patients. However, this cohort study suggests that physicians referring patients for MMS can be reassured that their patient's QOL will improve on average after surgery, even when a complex reconstruction is required.

  View details for DOI 10.1001/jamadermatol.2021.3161

  View details for PubMedID 34431977

• Phase II Open-Label, Single-Arm Trial to Investigate the Efficacy and Safety of Topical Remetinostat Gel in Patients with Basal Cell Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research Kilgour, J. M., Shah, A., Urman, N. M., Eichstadt, S., Do, H. N., Bailey, I., Mirza, A., Li, S., Oro, A. E., Aasi, S. Z., Sarin, K. Y. 2021

  Abstract

  PURPOSE: The mainstay of treatment for basal cell carcinoma (BCC) is surgical excision, which can result in significant associated morbidity, particularly for patients with recurrent tumors. We previously conducted a drug repositioning screen using molecular data from human BCCs and identified histone deacetylase (HDAC) inhibitors as a potential treatment for BCC. Here we conduct the first proof-of-principle study of a topical pan-HDAC inhibitor, remetinostat, in human BCC.PATIENTS AND METHODS: We conducted a phase II, open-label, single-arm, single-institution trial of a topical HDAC inhibitor. Participants with at least one BCC were recruited. All participants applied 1% remetinostat gel three times daily for 6 weeks, with measurements of tumor diameter conducted at baseline and week 8. Surgical excision of the remaining tumor was conducted at the end of the study and microscopic evaluation was performed.RESULTS: Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate, defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% [90% confidence interval (CI), 54%-82.5%]. On pathologic examination, 54.8% of tumors demonstrated complete resolution. Pharmacodynamic analysis demonstrated similar levels of acetylated histone H3 in skin tissue before and after treatment, however, phosphorylation was increased. No systemic adverse events were reported.CONCLUSIONS: The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing BCC disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for BCC.

  View details for DOI 10.1158/1078-0432.CCR-21-0560

  View details for PubMedID 34362809

• Systematic Review and Meta-Analysis of Local Recurrence Rates of Head and Neck Cutaneous Melanomas after Wide Local Excision, Mohs Micrographic Surgery, or Staged Excision. Journal of the American Academy of Dermatology Bittar, P. G., Bittar, J. M., Etzkorn, J. R., Brewer, J. D., Aizman, L., Shin, T. M., Sobanko, J. F., Higgins, H. W., Giordano, C. N., Cohen, J. V., Pride, R., Wan, M. T., Leitenberger, J. J., Bar, A. A., Aasi, S., Bordeaux, J. S., Miller, C. J. 2021

  Abstract

  BACKGROUND: Prospective trials have not compared local recurrence rates for different excision techniques for cutaneous melanomas on the head and neck.OBJECTIVE: To determine local recurrence rates of cutaneous head and neck melanoma after wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision.METHODS: A systematic review of PubMed, EMBASE, and Web of Science identified all English case series, cohort studies and randomized controlled trials that reported local recurrence rates after surgery of cutaneous head and neck melanoma. A meta-analysis utilizing a random effects model calculated weighted local recurrence rates and confidence intervals (CI) for each surgical technique and for subgroups of MMS and staged excision.RESULTS: Among one-hundred manuscripts with 13,998 head and neck cutaneous melanomas, 51.0% (7138) of melanomas were treated by WLE; 34.5% (4,826) by MMS; and 14.5% (2,034) by staged excision. Local recurrence rates were lowest for MMS (0.61%; 95%CI, 0.1%-1.4%); followed by staged excision (1.8%; 95%CI, 0.1%-2.9%) and WLE (7.8%; 95%CI, 6.4%-9.3%).LIMITATIONS: Definitions of local recurrence varied. Surgical techniques included varying proportions of invasive melanomas. Studies had heterogeneity.CONCLUSION: Systematic review and meta-analysis show lower local recurrence rates for cutaneous head and neck melanoma after treatment with MMS or staged excision compared to WLE.

  View details for DOI 10.1016/j.jaad.2021.04.090

  View details for PubMedID 33961921

• Is topical remetinostat gel an effective and safe treatment for basal cell carcinoma? Results of a phase 2, open label, single arm trial Kilgour, J. M., Shah, A., Urman, N. M., Eichstadt, S., Do, H., Bailey, I., Mirza, A., Li, S., Oro, A. E., Aasi, S., Sarin, K. Y. ELSEVIER SCIENCE INC. 2021: S81

  View details for Web of Science ID 000641872800467

• C-FOS drives reversible basal to squamous cell carcinoma transition Kuonen, F., Li, N., Haensel, D., Patel, T., Gaddam, S., Yerly, L., Rieger, K., Aasi, S., Oro, A. ELSEVIER SCIENCE INC. 2021: S11

  View details for Web of Science ID 000641872800065

• Association of ruxolitinib with NMSCs risk in patients with polycythemia vera and myelofibrosis Lin, J., Li, S., Li, S., Kiamanesh, E., Aasi, S., Kwong, B., Chang, A. ELSEVIER SCIENCE INC. 2021: S43

  View details for Web of Science ID 000641872800241

• Dissecting intercellular communication in adult human skin with single-cell and spatial transcriptomics Ji, A., Thrane, K., Guo, M., Rubin, A., Kim, D., Hollmig, T., Aasi, S., Lundeberg, J., Khavari, P. ELSEVIER SCIENCE INC. 2021: S17

  View details for Web of Science ID 000641872800093

• TTF-1 Expression in a Case of Cutaneous Sarcomatoid Squamous Cell Carcinoma. Journal of cutaneous pathology Nicholas, V., Say, B., Aasi, S., Rieger, K. E., Brown, R. A. 2021

  View details for DOI 10.1111/cup.13963

  View details for PubMedID 33458834

• c-FOS drives reversible basal to squamous cell carcinoma transition. Cell reports Kuonen, F., Li, N. Y., Haensel, D., Patel, T., Gaddam, S., Yerly, L., Rieger, K., Aasi, S., Oro, A. E. 2021; 37 (1): 109774

  Abstract

  While squamous transdifferentiation within subpopulations of adenocarcinomas represents an important drug resistance problem, its underlying mechanism remains poorly understood. Here, using surface markers of resistant basal cell carcinomas (BCCs) and patient single-cell and bulk transcriptomic data, we uncover the dynamic roadmap of basal to squamous cell carcinoma transition (BST). Experimentally induced BST identifies activator protein 1 (AP-1) family members in regulating tumor plasticity, and we show that c-FOS plays a central role in BST by regulating the accessibility of distinct AP-1 regulatory elements. Remarkably, despite prominent changes in cell morphology and BST marker expression, we show using inducible model systems that c-FOS-mediated BST demonstrates reversibility. Blocking EGFR pathway activation after c-FOS induction partially reverts BST in vitro and prevents BST features in both mouse models and human tumors. Thus, by identifying the molecular basis of BST, our work reveals a therapeutic opportunity targeting plasticity as a mechanism of tumor resistance.

  View details for DOI 10.1016/j.celrep.2021.109774

  View details for PubMedID 34610301

• NCCN Guidelines Insights: Squamous Cell Skin Cancer, Version 1.2022. Journal of the National Comprehensive Cancer Network : JNCCN Schmults, C. D., Blitzblau, R., Aasi, S. Z., Alam, M., Andersen, J. S., Baumann, B. C., Bordeaux, J., Chen, P., Chin, R., Contreras, C. M., DiMaio, D., Donigan, J. M., Farma, J. M., Ghosh, K., Grekin, R. C., Harms, K., Ho, A. L., Holder, A., Lukens, J. N., Medina, T., Nehal, K. S., Nghiem, P., Park, S., Patel, T., Puzanov, I., Scott, J., Sekulic, A., Shaha, A. R., Srivastava, D., Stebbins, W., Thomas, V., Xu, Y. G., McCullough, B., Dwyer, M. A., Nguyen, M. Q. 1800; 19 (12): 1382-1394

  Abstract

  The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.

  View details for DOI 10.6004/jnccn.2021.0059

  View details for PubMedID 34902824

• Perspectives on the Recommendations for Skin Cancer Management During the COVID-19 Pandemic. Journal of the American Academy of Dermatology Geskin, L. J., Trager, M. H., Aasi, S. Z., Bickers, D. R., Carvajal, R. D., Nghiem, P., Taback, B., Zeitouni, N. C., Samie, F. H. 2020

  View details for DOI 10.1016/j.jaad.2020.05.002

  View details for PubMedID 32387656

• Angular compounding for speckle reduction in optical coherence tomography using geometric image registration algorithm and digital focusing. Scientific reports Zhao, J., Winetraub, Y., Yuan, E., Chan, W. H., Aasi, S. Z., Sarin, K. Y., Zohar, O., de la Zerda, A. 2020; 10 (1): 1893

  Abstract

  Optical coherence tomography (OCT) suffers from speckle noise due to the high spatial coherence of the utilized light source, leading to significant reductions in image quality and diagnostic capabilities. In the past, angular compounding techniques have been applied to suppress speckle noise. However, existing image registration methods usually guarantee pure angular compounding only within a relatively small field of view in the focal region, but produce spatial averaging in the other regions, resulting in resolution loss and image blur. This work develops an image registration model to correctly localize the real-space location of every pixel in an OCT image, for all depths. The registered images captured at different angles are fused into a speckle-reduced composite image. Digital focusing, based on the convolution of the complex OCT images and the conjugate of the point spread function (PSF), is studied to further enhance lateral resolution and contrast. As demonstrated by experiments, angular compounding with our improved image registration techniques and digital focusing, can effectively suppress speckle noise, enhance resolution and contrast, and reveal fine structures in ex-vivo imaged tissue.

  View details for DOI 10.1038/s41598-020-58454-0

  View details for PubMedID 32024946

• Adequacy of conservative 2-3 mm surgical margins for complete excision of biopsy-proven severely dysplastic nevi: retrospective case series at a tertiary academic institution. Journal of the American Academy of Dermatology Soleymani, T. n., Swetter, S. M., Hollmig, S. T., Aasi, S. Z. 2020

  View details for DOI 10.1016/j.jaad.2019.12.077

  View details for PubMedID 31972255

• Reticulohistiocytoma (solitary epithelioid histiocytoma) with mutations in RAF1 and TSC2. Journal of cutaneous pathology Bahrani, E. n., Fernandez-Pol, S. n., Wang, J. Y., Aasi, S. Z., Brown, R. A., Novoa, R. A. 2020

  View details for DOI 10.1111/cup.13727

  View details for PubMedID 32342514

• AP-1 and TGFSS cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma. Nature communications Yao, C. D., Haensel, D., Gaddam, S., Patel, T., Atwood, S. X., Sarin, K. Y., Whitson, R. J., McKellar, S., Shankar, G., Aasi, S., Rieger, K., Oro, A. E. 2020; 11 (1): 5079

  Abstract

  Tumor heterogeneity and lack of knowledge about resistant cell states remain a barrier to targeted cancer therapies. Basal cell carcinomas (BCCs) depend on Hedgehog (Hh)/Gli signaling, but can develop mechanisms of Smoothened (SMO) inhibitor resistance. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies noncanonical Gli1 activity, but characteristics and drivers of the nMRTF cell state remain unknown. Here, we use single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlate with nMRTF and resistance to SMO inhibitors. The nMRTF cell state resembles transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFSS cooperativity driving nMRTF activation. JNK/AP-1 signaling commissions chromatin accessibility and Smad3 DNA binding leading to a transcriptional program of RhoGEFs that facilitate nMRTF activity. Importantly, small molecule AP-1 inhibitors selectively target LYPD3+/TACSTD2+/LY6D+ nMRTF human BCCs ex vivo, opening an avenue for improving combinatorial therapies.

  View details for DOI 10.1038/s41467-020-18762-5

  View details for PubMedID 33033234

• Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma. Cell Ji, A. L., Rubin, A. J., Thrane, K. n., Jiang, S. n., Reynolds, D. L., Meyers, R. M., Guo, M. G., George, B. M., Mollbrink, A. n., Bergenstråhle, J. n., Larsson, L. n., Bai, Y. n., Zhu, B. n., Bhaduri, A. n., Meyers, J. M., Rovira-Clavé, X. n., Hollmig, S. T., Aasi, S. Z., Nolan, G. P., Lundeberg, J. n., Khavari, P. A. 2020

  Abstract

  To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.

  View details for DOI 10.1016/j.cell.2020.05.039

  View details for PubMedID 32579974

• Frozen-Section Tissue Processing in Mohs Surgery. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] Aslam, A., Aasi, S. Z. 2019; 45 Suppl 2: S57–S69

  Abstract

  BACKGROUND: Mohs micrographic surgery (MMS) is the most reliable tissue-sparing technique in the management of cutaneous malignancies. Although the concept is simple, there is considerable variability in the mapping and processing techniques used by Mohs surgeons and histotechnicians.OBJECTIVE: This review article aims to examine the frozen-section tissue processing techniques. Existing variations will be discussed and pearls offered to optimize the frozen processing technique.METHODS: A PubMed search was performed for publications on methods of tissue processing in MMS.RESULTS: Our review highlights variations in debulking, embedding, processing adipose tissue, cartilage, and wedge resections. We offer pearls on how to avoid false-positive and false-negative margins and discuss advances in immunohistochemistry.CONCLUSION: Our article provides a how-to format on the different stages of tissue processing with pearls and techniques to optimize practice and improve accuracy.

  View details for DOI 10.1097/DSS.0000000000002260

  View details for PubMedID 31764292

• Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Updates on Classification and Management DERMATOLOGIC CLINICS Soleymani, T., Aasi, S. Z., Novoa, R., Hollmig, S. 2019; 37 (3): 253-+

  View details for DOI 10.1016/j.det.2019.02.001

  View details for Web of Science ID 000470954400004

• Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: Updates on Classification and Management. Dermatologic clinics Soleymani, T., Aasi, S. Z., Novoa, R., Hollmig, S. T. 2019; 37 (3): 253–59

  Abstract

  Atypical fibroxanthoma and undifferentiated pleomorphic sarcoma, or pleomorphic dermal sarcoma, are rare malignant cutaneous neoplasms existing along a clinicopathologic spectrum. Although these tumors share many similarities, recognition of distinguishing characteristics may predict differences in clinical behavior and outcomes. Salient features defining atypical fibroxanthoma include superficial tumors with minimal high-risk histologic features. Deeper tumors with high-risk histologic features are often clinically aggressive and should be appropriately designated as pleomorphic dermal sarcoma. Surgery remains gold standard in management; tumor extirpation with complete margin control is critical. In the high-risk tumor cohort, comprehensive evaluation and multidisciplinary management is paramount for optimal outcomes.

  View details for PubMedID 31084719

• Dissecting intratumoral heterogeneity and microenvironment interactions in SCC through single-cell RNA-sequencing Ji, A., Rubin, A., Reynolds, D., Guo, M., Bhaduri, A., George, B., Hollmig, S., Aasi, S., Khavari, P. ELSEVIER SCIENCE INC. 2019: S24

  View details for Web of Science ID 000465561502136

• An open-label phase 2 clinical trial of topical remetinostat gel for basal cell carcinoma Urman, N., Eichstadt, S., Do, H., Mirza, A. N., Li, S., Oro, A., Aasi, S., Sarin, K. Y. ELSEVIER SCIENCE INC. 2019: S171

  View details for Web of Science ID 000465561505130

• Dissecting the keratinocyte lineage of basal cell carcinoma using single cell RNA sequencing Lee, G., Guerrero-Juarez, C. F., Do, H., Aasi, S., Nie, Q., Sarin, K. Y., Atwood, S. ELSEVIER SCIENCE INC. 2019: S27

  View details for Web of Science ID 000465561502154

• LAP2 Proteins Chaperone GLI1 Movement between the Lamina and Chromatin to Regulate Transcription CELL Mirza, A. N., McKellar, S. A., Urman, N. M., Brown, A. S., Hollmig, T., Aasi, S. Z., Oro, A. E. 2019; 176 (1-2): 198-+

  View details for DOI 10.1016/j.cell.2018.10.054

  View details for Web of Science ID 000455410800018

• Corrigendum to 'Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis'. [Oral Oncol. 85 (2018) 60-67]. Oral oncology Chen, J. J., Harris, J. P., Kong, C. S., Sunwoo, J. B., Divi, V. n., Horst, K. C., Aasi, S. Z., Hollmig, S. T., Hara, W. Y. 2019

  View details for DOI 10.1016/j.oraloncology.2019.05.024

  View details for PubMedID 31174982

• PD-L1 Expression and Tumor-Infiltrating Lymphocytes in High-Risk and Metastatic Cutaneous Squamous Cell Carcinoma OTOLARYNGOLOGY-HEAD AND NECK SURGERY Amoils, M., Kim, J., Lee, C., Sunwoo, J. B., Colevas, A., Aasi, S. Z., Hollmig, S., Ma, Y., Divi, V. 2019; 160 (1): 93–99

  View details for DOI 10.1177/0194599818788057

  View details for Web of Science ID 000454870600012

• LAP2 Proteins Chaperone GLI1 Movement between the Lamina and Chromatin to Regulate Transcription. Cell Mirza, A. N., McKellar, S. A., Urman, N. M., Brown, A. S., Hollmig, T., Aasi, S. Z., Oro, A. E. 2018

  Abstract

  Understanding transcription factor navigation through the nucleus remains critical for developing targeted therapeutics. The GLI1 transcription factor must maintain maximal Hedgehog pathway output in basal cell carcinomas (BCCs), and we have previously shown that resistant BCCs increase GLI1 deacetylation through atypical protein kinase Ciota/lambda (aPKC) andHDAC1. Here we identify a lamina-associated polypeptide 2 (LAP2) isoform-dependent nuclear chaperoning system that regulates GLI1 movement between the nuclear lamina and nucleoplasm to achieve maximal activation. LAP2beta forms a two-site interaction with the GLI1 zinc-finger domain and acetylation site, stabilizing an acetylation-dependent reserve on the inner nuclear membrane (INM). By contrast, the nucleoplasmic LAP2alpha competes with LAP2beta for GLI1 while scaffolding HDAC1 to deacetylate the secondary binding site. aPKC functions to promote GLI1 association with LAP2alpha, promoting egress off the INM. GLI1 intranuclear trafficking by LAP2 isoforms represents a powerful signal amplifier in BCCs with implications for zinc finger-based signal transduction and therapeutics.

  View details for PubMedID 30503211

• Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis. Oral oncology Chen, J. J., Harris, J. P., Kong, C. S., Sunwoo, J. B., Divi, V., Horst, K. C., Aasi, S. Z., Hollmig, S. T., Hara, W. Y. 2018; 85: 60–67

  Abstract

  OBJECTIVES: Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes.MATERIALS AND METHODS: We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM).RESULTS: Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046).CONCLUSION: Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.

  View details for PubMedID 30220321

• Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis ORAL ONCOLOGY Chen, J., Harris, J. P., Kong, C. S., Sunwoo, J. B., Divi, V., Horst, K. C., Aasi, S. Z., Hollmig, S., Hara, W. Y. 2018; 85: 60–67

  View details for DOI 10.1016/j.oraloncology.2018.08.014

  View details for Web of Science ID 000444468900010

• Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility JCI INSIGHT Cho, H. G., Kuo, K. Y., Li, S., Bailey, I., Aasi, S., Chang, A. S., Oro, A. E., Tang, J. Y., Sarin, K. Y. 2018; 3 (15)

  Abstract

  Innate DNA repair mechanisms play a critical role in protecting skin keratinocytes from UV mutagenesis and skin cancer development. We hypothesized that individuals who develop frequent skin cancers may harbor germline defects in DNA repair genes and have increased predisposition to internal malignancies. We enrolled 61 patients with unusually frequent basal cell carcinoma (BCC) development, seen at Stanford Hospital and Clinics from January 2005 until December 2015, for germline analysis of 29 DNA repair genes. In parallel, a case-control retrospective review was performed to interrogate the association of malignancies with frequent BCC development in a large US medical insurance claims database (Truven), which included 13,264 individuals with 6 or more BCCs from 2007 to 2011. 19.7% of the frequent BCC cohort harbored pathogenic mutations in DNA repair genes: APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. Individuals with 6 or more BCCs had an increased risk of other malignancies, with a 3.5-fold increase in the frequent BCC cohort and a 3.2-fold increase in the Truven database. Individuals who developed frequent BCCs have an increased prevalence of germline mutations in DNA repair genes and increased malignancy risk. Our data implicate frequent BCC development as an external marker of inherited cancer risk.

  View details for DOI 10.1172/jci.insight.122744

  View details for Web of Science ID 000441201300022

  View details for PubMedID 30089731

• PD-L1 Expression and Tumor-Infiltrating Lymphocytes in High-Risk and Metastatic Cutaneous Squamous Cell Carcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Amoils, M., Kim, J., Lee, C., Sunwoo, J. B., Colevas, A. D., Aasi, S. Z., Hollmig, S. T., Ma, Y., Divi, A. V. 2018: 194599818788057

  Abstract

  Objective To characterize programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) positivity for locally aggressive or regionally metastatic cutaneous head and neck squamous cell carcinoma (cHNSCC). Study Design Retrospective chart review, followed by immunohistochemical staining of archived tumor specimens. Setting Tertiary academic medical center. Subjects and Methods After identification of 101 patients treated surgically for locally advanced or regionally metastatic cHNSCC, archived tissue was stained and graded for PD-L1 expression in addition to TIL presence. Cross-tabulation was performed to examine the association between either of these variables and clinicopathologic features and outcomes. Results A total of 101 patients met inclusion criteria, but archived tissue was available only for 83 (31 primaries, 52 metastases). The majority of primary tumors demonstrated grade 1 PD-L1 staining, while grade 2 staining was more likely for metastases. Neither high- nor low-grade PD-L1 expression correlated with any clinicopathologic variable for primary tumors. However, for metastases, high-grade staining was significantly associated with regional recurrence (15 of 19, P = .02). TILs were present for 65% of primary tumors and 90% of regional metastases but did not correlate with any clinicopathologic variables. Conclusion Diffuse expression of PD-L1 in this study highlights the possibility of using immunotherapy in the form of programmed death 1/PD-L1 blockade to improve treatment for this devastating disease. However, further studies are needed to clarify the significance of PD-L1 expression and TIL positivity for locally advanced or regionally metastatic cHNSCC.

  View details for PubMedID 30012051

• Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Margulis, K., Chiou, A. S., Aasi, S. Z., Tibshirani, R. J., Tang, J. Y., Zare, R. N. 2018; 115 (25): 6347–52

  View details for DOI 10.1073/pnas.1803733115

  View details for Web of Science ID 000435585200035

• Merkel Cell Carcinoma, Version 1.2018 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Bichakjian, C. K., Olencki, T., Aasi, S. Z., Alam, M., Andersen, J. S., Blitzblau, R., Bowen, G. M., Contreras, C. M., Daniels, G. A., Decker, R., Farma, J. M., Fisher, K., Gastman, B., Ghosh, K., Grekin, R. C., Grossman, K., Ho, A. L., Lewis, K. D., Loss, M., Lydiatt, D. D., Messina, J., Nehal, K. S., Nghiem, P., Puzanov, I., Schmults, C. D., Shaha, A. R., Thomas, V., Xu, Y. G., Zic, J. A., Hoffmann, K. G., Engh, A. M. 2018; 16 (6): 742–74

  Abstract

  This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

  View details for DOI 10.6004/jnccn.018.0055

  View details for Web of Science ID 000435146500010

  View details for PubMedID 29891526

• Single-cell RNA-sequencing reveals SCC intratumoral heterogeneity Ji, A., Rubin, A., Hollmig, S., Aasi, S., Khavari, P. ELSEVIER SCIENCE INC. 2018: S31

  View details for Web of Science ID 000431188500182

• MRTF inhibition displays promising therapeutic potential in human BCC patient explants Whitson, R. J., Mirza, A., Yao, C. Y., McKeller, S. A., Hollmig, S., Aasi, S., Sarin, K. Y., Tang, J., Oro, A. E. ELSEVIER SCIENCE INC. 2018: S36

  View details for Web of Science ID 000431188500211

• Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility Cho, H., Kuo, K., Li, S., Bailey-Healy, I., Aasi, S., Chang, A., Oro, A. E., Epstein, E., Tang, J., Sarin, K. Y. ELSEVIER SCIENCE INC. 2018: S28

  View details for Web of Science ID 000431188500164

• Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging. Proceedings of the National Academy of Sciences of the United States of America Margulis, K. n., Chiou, A. S., Aasi, S. Z., Tibshirani, R. J., Tang, J. Y., Zare, R. N. 2018

  Abstract

  Detection of microscopic skin lesions presents a considerable challenge in diagnosing early-stage malignancies as well as in residual tumor interrogation after surgical intervention. In this study, we established the capability of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to distinguish between micrometer-sized tumor aggregates of basal cell carcinoma (BCC), a common skin cancer, and normal human skin. We analyzed 86 human specimens collected during Mohs micrographic surgery for BCC to cross-examine spatial distributions of numerous lipids and metabolites in BCC aggregates versus adjacent skin. Statistical analysis using the least absolute shrinkage and selection operation (Lasso) was employed to categorize each 200-µm-diameter picture element (pixel) of investigated skin tissue map as BCC or normal. Lasso identified 24 molecular ion signals, which are significant for pixel classification. These ion signals included lipids observed at m/z 200-1,200 and Krebs cycle metabolites observed at m/z < 200. Based on these features, Lasso yielded an overall 94.1% diagnostic accuracy pixel by pixel of the skin map compared with histopathological evaluation. We suggest that DESI-MSI/Lasso analysis can be employed as a complementary technique for delineation of microscopic skin tumors.

  View details for PubMedID 29866838

• Modulation of the Hedgehog signaling pathway in models of basal cell carcinoma by ATP-competitive PKCi inhibitors Roffey, J., Dillon, C., Oro, A. E., Mirza, A. N., Sarin, K. Y., Aasi, S. Z., Parker, P. J., Riou, P., Barton, C., Patel, B., Turnbull, A., Stanway, E., Fowler, K., Ott, G., Ator, M. AMER ASSOC CANCER RESEARCH. 2018

  View details for DOI 10.1158/1535-7163.TARG-17-LB-B32

  View details for Web of Science ID 000590008800478

• Noncanonical hedgehog pathway activation through SRF-MKL1 promotes drug resistance in basal cell carcinomas. Nature medicine Whitson, R. J., Lee, A. n., Urman, N. M., Mirza, A. n., Yao, C. Y., Brown, A. S., Li, J. R., Shankar, G. n., Fry, M. A., Atwood, S. X., Lee, E. Y., Hollmig, S. T., Aasi, S. Z., Sarin, K. Y., Scott, M. P., Epstein, E. H., Tang, J. Y., Oro, A. E. 2018; 24 (3): 271–81

  Abstract

  Hedgehog pathway-dependent cancers can escape Smoothened (SMO) inhibition through mutations in genes encoding canonical hedgehog pathway components; however, around 50% of drug-resistant basal cell carcinomas (BCCs) lack additional variants of these genes. Here we use multidimensional genomics analysis of human and mouse drug-resistant BCCs to identify a noncanonical hedgehog activation pathway driven by the transcription factor serum response factor (SRF). Active SRF along with its coactivator megakaryoblastic leukemia 1 (MKL1) binds DNA near hedgehog target genes and forms a previously unknown protein complex with the hedgehog transcription factor glioma-associated oncogene family zinc finger-1 (GLI1), causing amplification of GLI1 transcriptional activity. We show that cytoskeletal activation through Rho and the formin family member Diaphanous (mDia) is required for SRF-MKL-driven GLI1 activation and for tumor cell viability. Remarkably, nuclear MKL1 staining served as a biomarker in tumors from mice and human subjects to predict tumor responsiveness to MKL inhibitors, highlighting the therapeutic potential of targeting this pathway. Thus, our study illuminates, for the first time, cytoskeletal-activation-driven transcription as a personalized therapeutic target for combatting drug-resistant malignancies.

  View details for PubMedID 29400712

  View details for PubMedCentralID PMC5839965

• Node-positive cutaneous squamous cell carcinoma of the head and neck: Survival, high-risk features, and adjuvant chemoradiotherapy outcomes. Head & neck Amoils, M., Lee, C. S., Sunwoo, J., Aasi, S. Z., Hara, W., Kim, J., Sirjani, D., Colevas, A. D., Chang, A. L., Divi, V. 2017

  Abstract

  Data lacks to guide treatment of regionally metastatic cutaneous head and neck squamous cell carcinoma (HNSCC).We conducted a retrospective review of 80 patients treated for regionally metastatic cutaneous HNSCC. The effect of various clinicopathologic variables on overall survival (OS) was investigated, in addition to outcomes by treatment modality.On multivariate regression, cutaneous primary >2 cm (p = .03) and extracapsular spread (ECS; p = .01) were significantly associated with decreased OS. Location of regional metastasis (neck vs parotid vs both) had no effect on OS (p = .2), nor did the presence of a cutaneous primary at the time of presentation (p = .9). The 3-year survival was 43%, 52%, and 49% for surgery alone, adjuvant radiation, and adjuvant chemoradiation, respectively. Fifty-one percent of patients had a recurrence of their disease.Regionally metastatic cutaneous HNSCC is an aggressive disease associated with high recurrence rates. Patients with tumors >2 cm and ECS have poorer OS despite adjuvant therapy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 881-885, 2017.

  View details for DOI 10.1002/hed.24692

  View details for PubMedID 28252823

• Combined inhibition of atypical PKC and histone deacetylase 1 is cooperative in basal cell carcinoma treatment. JCI insight Mirza, A. N., Fry, M. A., Urman, N. M., Atwood, S. X., Roffey, J. n., Ott, G. R., Chen, B. n., Lee, A. n., Brown, A. S., Aasi, S. Z., Hollmig, T. n., Ator, M. A., Dorsey, B. D., Ruggeri, B. R., Zificsak, C. A., Sirota, M. n., Tang, J. Y., Butte, A. n., Epstein, E. n., Sarin, K. Y., Oro, A. E. 2017; 2 (21)

  Abstract

  Advanced basal cell carcinomas (BCCs) circumvent Smoothened (SMO) inhibition by activating GLI transcription factors to sustain the high levels of Hedgehog (HH) signaling required for their survival. Unfortunately, there is a lack of efficacious therapies. We performed a gene expression-based drug repositioning screen in silico and identified the FDA-approved histone deacetylase (HDAC) inhibitor, vorinostat, as a top therapeutic candidate. We show that vorinostat only inhibits proliferation of BCC cells in vitro and BCC allografts in vivo at high dose, limiting its usefulness as a monotherapy. We leveraged this in silico approach to identify drug combinations that increase the therapeutic window of vorinostat and identified atypical PKC Ɩ/ʎ (aPKC) as a HDAC costimulator of HH signaling. We found that aPKC promotes GLI1-HDAC1 association in vitro, linking two positive feedback loops. Combination targeting of HDAC1 and aPKC robustly inhibited GLI1, lowering drug doses needed in vitro, in vivo, and ex vivo in patient-derived BCC explants. We identified a bioavailable and selective small-molecule aPKC inhibitor, bringing the pharmacological blockade of aPKC and HDAC1 into the realm of clinical possibility. Our findings provide a compelling rationale and candidate drugs for combined targeting of HDAC1 and aPKC in HH-dependent cancers.

  View details for PubMedID 29093271

• Classification of basal cell carcinoma in human skin using machine learning and quantitative features captured by polarization sensitive optical coherence tomography. Biomedical optics express Marvdashti, T., Duan, L., Aasi, S. Z., Tang, J. Y., Ellerbee Bowden, A. K. 2016; 7 (9): 3721-3735

  Abstract

  We report the first fully automated detection of basal cell carcinoma (BCC), the most commonly occurring type of skin cancer, in human skin using polarization-sensitive optical coherence tomography (PS-OCT). Our proposed automated procedure entails building a machine-learning based classifier by extracting image features from the two complementary image contrasts offered by PS-OCT, intensity and phase retardation (PR), and selecting a subset of features that yields a classifier with the highest accuracy. Our classifier achieved 95.4% sensitivity and specificity, validated by leave-one-patient-out cross validation (LOPOCV), in detecting BCC in human skin samples collected from 42 patients. Moreover, we show the superiority of our classifier over the best possible classifier based on features extracted from intensity-only data, which demonstrates the significance of PR data in detecting BCC.

  View details for PubMedID 27699133

• Classification of basal cell carcinoma in human skin using machine learning and quantitative features captured by polarization sensitive optical coherence tomography BIOMEDICAL OPTICS EXPRESS Marvdashti, T., Duan, L., Aasi, S. Z., Tang, J. Y., Bowden, A. K. 2016; 7 (9): 3721-3735

  Abstract

  We report the first fully automated detection of basal cell carcinoma (BCC), the most commonly occurring type of skin cancer, in human skin using polarization-sensitive optical coherence tomography (PS-OCT). Our proposed automated procedure entails building a machine-learning based classifier by extracting image features from the two complementary image contrasts offered by PS-OCT, intensity and phase retardation (PR), and selecting a subset of features that yields a classifier with the highest accuracy. Our classifier achieved 95.4% sensitivity and specificity, validated by leave-one-patient-out cross validation (LOPOCV), in detecting BCC in human skin samples collected from 42 patients. Moreover, we show the superiority of our classifier over the best possible classifier based on features extracted from intensity-only data, which demonstrates the significance of PR data in detecting BCC.

  View details for DOI 10.1364/BOE.7.003721

  View details for Web of Science ID 000385416500045

  View details for PubMedCentralID PMC5030045

• Update to an open-label clinical trial of vismodegib as neoadjuvant before surgery for high-risk basal cell carcinoma (BCC) JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Kwon, G. P., Ally, M., Bailey-Healy, I., Oro, A. E., Kim, J., Chang, A., Aasi, S., Tang, J. Y. 2016; 75 (1): 213–15

  View details for PubMedID 27317518

• Management of High-Risk Squamous Cell Carcinoma of the Skin. Current treatment options in oncology Fu, T., Aasi, S. Z., Hollmig, S. T. 2016; 17 (7): 34-?

  Abstract

  Non-melanoma skin cancer (NMSC) is the most common malignancy in the USA, with cutaneous squamous cell carcinomas (cSCCs) constituting approximately 20 % of all NMSC. While cSCCs typically behave in an indolent fashion and can be cured with local destructive or surgical methods, a small subset metastasizes and induces significant morbidity and mortality. Identifying and aggressively treating these "high-risk" cSCCs (HRcSCCs) is thus paramount. Recent improvements in staging cSCCs appear to offer better risk stratification than earlier staging criteria. Radiologic imaging and sentinel lymph node biopsy may be beneficial in certain cases of HRcSCC, although more studies are needed before these techniques should be uniformly incorporated into management. Surgery with complete margin control, such as that offered by the Mohs micrographic technique, represents the first-line treatment for these tumors. Radiation therapy is likely most beneficial in the adjuvant setting. Chemotherapy is typically best reserved for patients with metastatic or locally advance disease that is not controllable with surgical and/or radiation therapies. Newer targeted treatments, such as EGFR inhibitors and immunotherapies may offer greater efficacy in these settings, although further evaluation is needed.

  View details for DOI 10.1007/s11864-016-0408-2

  View details for PubMedID 27262708

• Skin Cancer Prevention and Treatment in Solid Organ Transplant Patients: A Survey of the International Transplant Skin Cancer Collaborative. Dermatologic surgery Wang, A., Chan, A., Aasi, S., Lee, C., Krathen, M. 2016; 42 (5): 682-683

  View details for DOI 10.1097/DSS.0000000000000668

  View details for PubMedID 27045747

• Basal Cell Skin Cancer, Version 1.2016 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Bichakjian, C. K., Olencki, T., Aasi, S. Z., Alam, M., Andersen, J. S., Berg, D., Bowen, G. M., Cheney, R. T., Daniels, G. A., Glass, L. F., Grekin, R. C., Grossman, K., Higgins, S. A., Ho, A. L., Lewis, K. D., Lydiatt, D. D., Nehal, K. S., Nghiem, P., Olsen, E. A., Schmults, C. D., Sekulic, A., Shaha, A. R., Thorstad, W. L., Tuli, M., Urist, M. M., Wang, T. S., Wong, S. L., Zic, J. A., Hoffmann, K. G., Engh, A. 2016; 14 (5): 574-596

  Abstract

  Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.

  View details for Web of Science ID 000375888500012

• Regionally Metastatic Cutaneous Squamous Cell Carcinoma of the Head and Neck: Survival and High-Risk Features Amoils, M., Lee, C. S., Sunwoo, J., Aasi, S. Z., Hara, W., Kim, J., Sirjani, D., Colevas, A. D., Chang, A. S., Divi, V. ELSEVIER SCIENCE INC. 2016: 954

  View details for DOI 10.1016/j.ijrobp.2015.12.304

  View details for Web of Science ID 000371581900251

• Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Christensen, S. R., McNiff, J. M., Cool, A. J., Aasi, S. Z., Hanlon, A. M., Leffell, D. J. 2016; 74 (2): 356-362

  Abstract

  Squamous cell carcinoma in situ (SCCis) has been reported to involve the hair follicle epithelium. Deep follicular invasion is often cited as a cause of treatment failure.We sought to define the frequency and the depth of hair follicle invasion by SCCis.The study included both a retrospective review of intraoperative pathology specimens from 42 SCCis cases treated with Mohs micrographic surgery and a prospective evaluation of serially sectioned SCCis tissue from 12 additional patients. Pathology specimens were analyzed for follicular invasion of SCCis.SCCis invasion of the superficial hair follicle infundibulum was observed in 61.3% to 87.5% of cases in the 2 cohorts, whereas invasion of the isthmus and lower follicle was observed in only 8.3% to 12.5% of cases. In most tumors the depth of follicular invasion was comparable with the thickness of the surrounding epidermis. The maximum observed depth of follicular invasion was 0.82 mm.The study was performed on a limited number of cases referred for surgery at a single institution.Although SCCis invasion of the upper hair follicle infundibulum is common, deep invasion below the level of the surrounding epidermis is rare. This may have implications for optimal therapy of this condition.

  View details for DOI 10.1016/j.jaad.2015.09.060

  View details for Web of Science ID 000368272600022

• Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach. Journal of the American Academy of Dermatology Christensen, S. R., McNiff, J. M., Cool, A. J., Aasi, S. Z., Hanlon, A. M., Leffell, D. J. 2016; 74 (2): 356-62

  Abstract

  Squamous cell carcinoma in situ (SCCis) has been reported to involve the hair follicle epithelium. Deep follicular invasion is often cited as a cause of treatment failure.We sought to define the frequency and the depth of hair follicle invasion by SCCis.The study included both a retrospective review of intraoperative pathology specimens from 42 SCCis cases treated with Mohs micrographic surgery and a prospective evaluation of serially sectioned SCCis tissue from 12 additional patients. Pathology specimens were analyzed for follicular invasion of SCCis.SCCis invasion of the superficial hair follicle infundibulum was observed in 61.3% to 87.5% of cases in the 2 cohorts, whereas invasion of the isthmus and lower follicle was observed in only 8.3% to 12.5% of cases. In most tumors the depth of follicular invasion was comparable with the thickness of the surrounding epidermis. The maximum observed depth of follicular invasion was 0.82 mm.The study was performed on a limited number of cases referred for surgery at a single institution.Although SCCis invasion of the upper hair follicle infundibulum is common, deep invasion below the level of the surrounding epidermis is rare. This may have implications for optimal therapy of this condition.

  View details for DOI 10.1016/j.jaad.2015.09.060

  View details for PubMedID 26670714

• Two dimensional imaging of basal cell carcinoma using desorption electrospray ionization mass spectrometry (DESI-MS) Chiou, A. S., Eberlin, L. S., Planell-Mendez, I., Ransohoff, K. J., Tang, I. Y., Aasi, S. Z., Zare, R. N. NATURE PUBLISHING GROUP. 2015: S36

  View details for Web of Science ID 000352783200210

• FIRST REPORT OF ERBIUM LASER AS THE PREFERRED TREATMENT IN A COMPARISON OF FIVE MODALITIES FOR STEATOCYSTOMA MULTIPLEX Crispin, M., Ally, M., Hollmig, T., Aasi, S., Rahman, Z. WILEY-BLACKWELL. 2015: 51

  View details for Web of Science ID 000352099900152

• Towards automated detection of basal cell carcinoma from polarization sensitive optical coherence tomography images of human skin Marvdashti, T., Duan, L., Ransohoff, K. J., Aasi, S. Z., Tang, J. Y., Ellerbee, A. K., IEEE IEEE. 2015

  View details for Web of Science ID 000370627102178

• An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Ally, M. S., Aasi, S., Wysong, A., Teng, C., Anderson, E., Bailey-Healy, I., Oro, A., Kim, J., Chang, A. L., Tang, J. Y. 2014; 71 (5): 904-U304

  Abstract

  Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4±2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval -45.7% to -7.9%; P=.006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.Short follow-up time and no placebo control are limitations.Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.

  View details for DOI 10.1016/j.jaad.2014.05.020

  View details for Web of Science ID 000343918200035

• An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma. Journal of the American Academy of Dermatology Ally, M. S., Aasi, S., Wysong, A., Teng, C., Anderson, E., Bailey-Healy, I., Oro, A., Kim, J., Chang, A. L., Tang, J. Y. 2014; 71 (5): 904-911 e1

  Abstract

  Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4±2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval -45.7% to -7.9%; P=.006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.Short follow-up time and no placebo control are limitations.Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.

  View details for DOI 10.1016/j.jaad.2014.05.020

  View details for PubMedID 24929884

• Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma NATURE GENETICS Lee, C. S., Bhaduri, A., Mah, A., Johnson, W. L., Ungewickell, A., Aros, C. J., Nguyen, C. B., Rios, E. J., Siprashvili, Z., Straight, A., Kim, J., Aasi, S. Z., Khavari, P. A. 2014; 46 (10): 1060-1062

  Abstract

  Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo. These findings suggest a role for KNSTRN mutagenesis in SCC development.

  View details for DOI 10.1038/ng.3091

  View details for Web of Science ID 000342554100007

  View details for PubMedCentralID PMC4324615

• Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma. Nature genetics Lee, C. S., Bhaduri, A., Mah, A., Johnson, W. L., Ungewickell, A., Aros, C. J., Nguyen, C. B., Rios, E. J., Siprashvili, Z., Straight, A., Kim, J., Aasi, S. Z., Khavari, P. A. 2014; 46 (10): 1060-1062

  Abstract

  Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo. These findings suggest a role for KNSTRN mutagenesis in SCC development.

  View details for DOI 10.1038/ng.3091

  View details for PubMedID 25194279

• The Role of Vismodegib in the Management of Advanced Basal Cell Skin Cancers: A Review CURRENT DERMATOLOGY REPORTS Ally, M. S., Aasi, S. Z. 2014; 3 (2): 98–102

  View details for DOI 10.1007/s13671-014-0073-2

  View details for Web of Science ID 000218755500004

• Recurrent point mutations in KNSTRN and disruption of multiple notch signaling genes in cutaneous squamous cell carcinoma Lee, C., Bhaduri, A., Mah, A., Ungewickell, A., Aros, C., Nguyen, C., Siprashvili, Z., Johnson, W., Straight, A., Kim, J., Aasi, S., Khavari, P. NATURE PUBLISHING GROUP. 2014: S35

  View details for Web of Science ID 000334560400201

• Single-stage turn-over muscular hinge flap with Burow's full-thickness skin graft to repair oral commissure defect. Dermatologic surgery Wysong, A., Aasi, S. Z. 2013; 39 (10): 1530-1534

  View details for DOI 10.1111/dsu.12216

  View details for PubMedID 23590278

• Comment on basal cell carcinoma rebound after cessation of vismodegib in an individual with basal cell nevus syndrome. Dermatologic surgery Ally, M. S., Wysong, A., Tang, J. Y., Aasi, S. 2013; 39 (9): 1413-1414

  View details for DOI 10.1111/dsu.12250

  View details for PubMedID 23682843

• Update on metastatic basal cell carcinoma: a summary of published cases from 1981 through 2011. JAMA dermatology Wysong, A., Aasi, S. Z., Tang, J. Y. 2013; 149 (5): 615-616

  View details for DOI 10.1001/jamadermatol.2013.3064

  View details for PubMedID 23677097

• New Onset of Keratoacanthomas After Vismodegib Treatment for Locally Advanced Basal Cell Carcinomas: A Report of 2 Cases JAMA DERMATOLOGY Aasi, S., Silkiss, R., Tang, J. Y., Wysong, A., Liu, A., Epstein, E., Oro, A. E., Chang, A. L. 2013; 149 (2): 242-243

  View details for DOI 10.1001/jamadermatol.2013.1798

  View details for Web of Science ID 000317672300031

  View details for PubMedID 23426496

• Atlas of Practical Mohs Histopathology Aasi, S. Z., Leffell, D. J., Lazova, R. Z. 2013

  View details for DOI 10.1007/978-1-4614-5161-7

• Is Tanning Bed Exposure Associated With Aggressive Basal Cell Carcinoma? JOURNAL OF CLINICAL ONCOLOGY Gamba, C. A., Wysong, A., Million, L., Aasi, S., Kim, J., Tang, J. Y. 2012; 30 (32): E333-E336

  View details for DOI 10.1200/JCO.2012.42.1008

  View details for Web of Science ID 000310914800006

  View details for PubMedID 23008324

• Hemorrhagic complications in dermatologic surgery DERMATOLOGIC THERAPY Bunick, C. G., Aasi, S. Z. 2011; 24 (6): 537-550

  Abstract

  The ability to recognize, manage, and, most importantly, prevent hemorrhagic complications is critical to performing dermatologic procedures that have safe and high quality outcomes. This article reviews the preoperative, intraoperative, and postoperative factors and patient dynamics that are central to preventing such an adverse outcome. Specifically, the role that anticoagulants and anti-platelet agents, hypertension, and other medical conditions play in the development of postoperative hemorrhage are discussed. In addition, this article provides practical guidelines on managing bleeding during and after surgery.

  View details for DOI 10.1111/j.1529-8019.2012.01454.x

  View details for Web of Science ID 000303004600004

  View details for PubMedID 22515669

• Cosmetic concerns and management strategies to combat aging MATURITAS Robinson, D. M., Aasi, S. Z. 2011; 70 (3): 256-260

  Abstract

  Multiple modalities with varying degrees of complexity and risks exist in the treatment of the aging face. Paramount to all treatment paradigms is photoprotection to prevent further damage. Intervetions should be geared towards addressing the intrinsic and extrinsic signs of aging and can include topical retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and soft tissue fillers. The combination of these primary, secondary, and tertiary therapies will address the underlying pathophysiologic changes of the aging face and thus will provide the optimal aesthetic outcome.

  View details for DOI 10.1016/j.maturitas.2011.07.020

  View details for Web of Science ID 000296684900009

  View details for PubMedID 21873005

• Cancer of the skin Cancer Principles and Practice of Oncology Reszko A, Aasi SZ, Wilson LD, Leffell DJ 2011; 9: 1610-1633
• Melanoma and Non-melanoma Skin Cancer Dermatology A Pictorial Review Aasi SZ, Cox KM 2010; 2: 193-206
• Commentary: Expanding the Donor Site Options for Full-Thickness Skin Grafts Dermatol Surg. Aasi SZ 2010; 36: 532-533
• Z-plasty made simple. Dermatology research and practice Aasi, S. Z. 2010; 2010: 982623-?

  Abstract

  A Z-plasty is a critical and reliable technique that is useful for scar revisions and correction of free margin distortion. A Z-plasty can help lengthen a contracted scar, change the direction of a scar so that it is better aligned with the relaxed skin tension lines, or interrupt and break a scar for better camouflage. This article will review the technique of a basic Z-plasty as well as provide case examples of its use in free margin distortion and scar revision.

  View details for DOI 10.1155/2010/982623

  View details for PubMedID 21789038

• Mohs micrographic surgery histopathology concordance Annual Meeting of the American-College-of-Mohs-Micrographic-Surgery-and-Cutaneous-Oncology Mariwalla, K., Aasi, S. Z., Glusac, E. J., Leffell, D. J. MOSBY-ELSEVIER. 2009: 94–98

  Abstract

  The low recurrence rate and tissue-sparing benefit associated with Mohs micrographic surgery (MMS) requires accurate interpretation of frozen sections by the MMS surgeon.We sought to assess concordance between dermatopathologists and MMS surgeons when reporting cutaneous malignancy in the MMS setting.This study is a retrospective analysis of 1156 slides submitted during 10 years as part of a pre-existing randomized, blinded, quality assurance protocol. Slides were read by one of 5 dermatopathologists and represent cases from 3 MMS surgeons and 5 MMS fellows. Agreement or disagreement was recorded.Of the 1156 slides, 32 slides (2.8%) were disparate. Aside from differences regarding intraepidermal neoplasia, the concordance rate was 99.7%.This study represents data collected at a single institution in the United States alone.There was statistically significant concordance between MMS surgeons and dermatopathologists in frozen section interpretation in the MMS setting. Discordance was primarily related to the interpretation of in situ malignancy.

  View details for DOI 10.1016/j.jaad.2008.09.061

  View details for Web of Science ID 000262261700010

  View details for PubMedID 19103361

• Skin cancer prevention and photo protection in organ transplant recipients Skin Diseases in Organ Transplantation Aasi SZ 2008: 295-301
• Dermatologic surgery: introduction to anatomy and approach Fitzpatrick's Dermatology in General Medicine Aasi SZ, Pennington B 2008; 7: 2289-2301
• Free margin distortion Complications in Cutaneous Surgery Aasi SZ 2008: 95-114
• Cancer of the skin Cancer Principles and Practice of Oncology Thomas VD, Aasi SZ, Wilson LD, Leffel DJ 2008; 8: 863-1888
• Dermatologic diseases and disorders Geriatrics Review Syllabus Aasi SZ 2006; 6: 309-319
• Multiple facial angiofibromas: A cutaneous manifestation of Birt-Hogg-Dube syndrome Meeting of the New-England-Dermatological-Society Schaffer, J. V., Gohara, M. A., McNiff, J. M., Aasi, S. Z., Dvoretzky, I. MOSBY-ELSEVIER. 2005: S108–S111

  Abstract

  Birt-Hogg-Dubé syndrome (BHDS) is an uncommon autosomal dominant genodermatosis characterized by a triad of skin tumors--fibrofolliculomas, trichodiscomas, and acrochordons--together with an increased risk of renal tumors and spontaneous pneumothoraces. This report describes multiple facial angiofibromas as the predominant initial manifestation of BHDS. The patient had a total of 41 facial papules removed via shave excision, initially for diagnostic and then for therapeutic purposes; histologic evaluation revealed diagnostic features of angiofibroma in 39 lesions and fibrofolliculoma in only 2. BHDS should be considered, along with tuberous sclerosis and multiple endocrine neoplasia type 1, in the differential diagnosis of multiple facial angiofibromas, particularly when onset is in adulthood.

  View details for DOI 10.1016/j.jaad.2004.11.021

  View details for Web of Science ID 000231081400003

  View details for PubMedID 16021156

• Bilobed transposition flap DERMATOLOGIC CLINICS Aasi, S. Z., Leffell, D. J. 2005; 23 (1): 55-?

  Abstract

  This article reviews the indications and techniques for performing a bilobed flap for reconstruction of surgical wounds. Various examples of surgical defects where a bilobed flap can be used are shown. Possible complications and pitfalls are also reviewed.

  View details for DOI 10.1016/j.det.2004.08.004

  View details for Web of Science ID 000226324900006

  View details for PubMedID 15620619

• Cancer of the skin Cancer Principles and Practice of Oncology Aasi SZ, Leffell DJ 2005; 7: 1717-1744
• Ellipse, ellipse variations and dog-ear repairs Surgery of the Skin Book SE, Aasi SZ, Leffell DJ 2005: 259-272
• Idiopathic eruptive macular pigmentation: A case of 21 years' duration JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Mehta, S., Aasi, S., Cole, R., Chu, P., Weinberg, J. M. 2003; 49 (5): S280-S282

  Abstract

  Idiopathic eruptive macular pigmentation is a rare condition characterized by asymptomatic pigmented macules involving the neck, trunk, and proximal portions of the extremities. Age at onset usually varies from 1 to 20 years. The lesions usually appear abruptly and remit spontaneously over months to years. An unusual case of a 24-year-old woman with idiopathic eruptive macular pigmentation lasting 21 years was characterized by several periods of spontaneous resolution followed by recurrences.

  View details for DOI 10.1067/S0190-9622(03)00745-X

  View details for Web of Science ID 000186362900017

  View details for PubMedID 14576654

• Complications in dermatologic surgery - How safe is safe? ARCHIVES OF DERMATOLOGY Aasi, S. Z., Leffell, D. J. 2003; 139 (2): 213-214

  View details for Web of Science ID 000180971400012

  View details for PubMedID 12588228

• Dermatologic diseases and disorders Geriatrics Review Syllabus Aasi SZ, Cook B 2002; 5: 390-399
• Aquagenic palmoplantar keratoderma J Am Acad Dermatol Yan AC, Aasi SZ, Alms DJ, Heymann WR, Paller AS, Honig PJ 2001: 696-699
• Autoantibodies to type VII collagen have heterogeneous subclass and light chain compositions and their complement-activating capacities do not correlate with the inflammatory clinical phenotype. J Clinical Immunol. Gandhi K, Chen M, Aasi SZ, Lapiere JC, Woodley DT, Chan LS 2000; 20: 416-423
• Successful correction of depressed scars of the forehead secondary to trauma and morpheme en coup de saber by autologous free dermal-fat graft. Dermatol Surg. Lapiere JC, Aasi SZ, Cook B, Montalvo A 2000: 793-796