Kerri E. Rieger, MD, PhD

All Publications

• Immunotherapy for Keratinocyte Cancers. Part 1: Immune-Related Epidemiology, Risk Factors, Pathogenesis, and Immunotherapy Management of Keratinocytic Cancers Journal of the American Academy of Dermatology Neuner, R., Lee, J., Park, C., Rieger, K. E., Colevas, A. D., Chang, A. S. 2023; 88 (6): 1225-1240

  View details for DOI 10.1016/j.jaad.2022.06.1206

• Livedoid vasculopathy Dermatology Online Journal Leeolou, M. C., Rieger, K. E., Yeh, J. E. 2023; 29 (5)

  View details for DOI 10.5070/D329562414

• 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

• Subcutaneous Sweet Syndrome Successfully Treated With Ustekinumab in a Patient With Ulcerative Colitis. ACG case reports journal Hu, K. A., Shen, J., Rieger, K., Wei, M. T., Gubatan, J. 2022; 9 (11): e00881

  Abstract

  Ustekinumab, an inhibitor of the interleukin-12/23 pathway, received Food and Drug Administration (FDA) approval in 2019 for induction and maintenance therapy in patients with moderate-to-severe ulcerative colitis (UC). Data regarding the efficacy of ustekinumab in the treatment of extraintestinal manifestations of UC are unclear. Sweet syndrome, an acute febrile neutrophilic dermatosis, is a cutaneous manifestation of inflammatory bowel disease that parallels disease activity. In this study, we present the first case of subcutaneous Sweet syndrome with sterile osteomyelitis in a patient with UC successfully treated with ustekinumab.

  View details for DOI 10.14309/crj.0000000000000881

  View details for PubMedID 36447766

  View details for PubMedCentralID PMC9699508

• Evanescent, episodic salmon-colored macules in a young woman. JAAD case reports Leeolou, M. C., Young, P. A., Dear, A. L., Narala, S., Saleem, A., Rieger, K. E., Bae, G. H. 2022; 29: 30-32

  View details for DOI 10.1016/j.jdcr.2022.08.022

  View details for PubMedID 36186409

• Nontender white papule of the areola in a middle-aged female. JAAD case reports Young, P. A., Narala, S., Brown, R. A., Saleem, A., Rieger, K. E., Bae, G. H. 2022; 27: 6-8

  View details for DOI 10.1016/j.jdcr.2022.05.047

  View details for PubMedID 35941842

• Clinical and Pathological Characteristics and Outcomes Among Patients With Subcutaneous Panniculitis-like T-Cell Lymphoma and Related Adipotropic Lymphoproliferative Disorders. JAMA dermatology Guitart, J., Mangold, A. R., Martinez-Escala, M. E., Walker, C. J., Comfere, N. I., Pulitzer, M., Rieger, K. E., Torres-Cabala, C. A., Pincus, L. B., Kumar, E. S., Wang, E. B., Park, K. E., Espinosa, M. L., Duvic, M., Kim, Y. H., Horwitz, S. 2022

  Abstract

  There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date.To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions.This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort was classified as (1) SPTCL or (2) adipotropic lymphoproliferative disorder (ALPD) for similar cases with incomplete histopathological criteria for SPTCL designation.Cases of SPTCL diagnosed between 1998 and 2018.The main outcome was disease presentation and evolution, including response to therapy, disease progression, and development of hemophagocytic lymphohistiocytosis.The cohort of 95 patients (median [range] age, 38 [2-81] years; female-to-male ratio, 2.7) included 75 cases of SPTCL and 20 cases of ALPD. The clinical presentation was similar for both groups with multiple (61 of 72 [85%]) or single (11 of 72 [15%]) tender nodules mostly involving extremities, occasionally resulting in lipoatrophy. Hemophagocytic lymphohistiocytosis (HLH) was only observed in SPTCL cases. With a mean follow-up of 56 months, 60 of 90 patients (67%) achieved complete remission with a median (range) of 3 (1-7) cumulative therapies. Relapse was common. None of the patients died of disease progression or HLH. Two patients with ALPD eventually progressed to SPTCL without associated systemic symptoms or HLH.In this case series of patients initially diagnosed as having SPTCL, results showed no evidence of systemic tumoral progression beyond the adipose tissue. The SPTCL experience in this study confirmed an indolent course and favorable response to a variety of treatments ranging from immune modulation to chemotherapy followed by hematopoietic stem cell transplantation. Morbidity was primarily associated with HLH.

  View details for DOI 10.1001/jamadermatol.2022.3347

  View details for PubMedID 36001337

• Firm Red-Brown Plaques in a Patient With Systemic Scleroderma. JAMA dermatology Zacher, N. C., Rieger, K. E., Bailey, E. E. 2022

  View details for DOI 10.1001/jamadermatol.2022.3241

  View details for PubMedID 35976623

• New-onset pemphigus vegetans and pemphigus foliaceus following SARS-CoV-2 vaccination: a case series. JAAD case reports Gui, H., Young, P. A., Sox, J., Pol-Rodriguez, M., Rieger, K. E., Lewis, M. A., Winge, M. C., Bae, G. H. 2022

  View details for DOI 10.1016/j.jdcr.2022.07.002

  View details for PubMedID 35845348

• Acanthosis nigricans in the setting of severe pulmonary disease exacerbated by COVID-19 infection. JAAD case reports Hirotsu, K. E., Chiang, A., Bahrani, E., Cloutier, J. M., Rieger, K. E., Kwong, B. Y., Aleshin, M. 2022

  View details for DOI 10.1016/j.jdcr.2022.04.017

  View details for PubMedID 35529073

• Gastrointestinal Perforation in a patient with Anti-nuclear Matrix Protein 2 Antibody Positive Dermatomyositis. Arthritis care & research Valenzuela, A., Rieger, K. E., Blish, C. A., Chung, L., Fiorentino, D. 2022

  View details for DOI 10.1002/acr.24879

  View details for PubMedID 35287251

• Exploring Potential Innate Immune Targets to Treat Fibrosis and Chronic Inflammation in Chronic Graft-Versus-Host Disease Paulson, N., De Souza, C., Cui, L., Lerbs, T., Poyser, J., Kooshesh, M., Saleem, A., Rieger, K., Brown', R., Kwong, B., Fernandez-Po, S., Arai, S., Shizuru, J., Mueller, A., Wernig, G. SPRINGERNATURE. 2022: 557

  View details for Web of Science ID 000770361801147

• Spitz nevus with EHBP1-ALK fusion and distinctive membranous localization of ALK. Journal of cutaneous pathology Bahrani, E., Kunder, C. A., Teng, J. M., Brown, R. A., Rieger, K. E., Novoa, R. A., Cloutier, J. M. 1800

  Abstract

  ALK rearrangements define a histopathologically distinctive but diverse subset of Spitz tumors characterized by fusiform to epithelioid melanocytes with frequent fascicular growth and ALK overexpression. Molecularly, these tumors are characterized by fusions between ALK and a variety of other genes, most commonly TPM3 and DCTN1. We describe an unusual case of a Spitz nevus occurring in a 13-year-old female that manifested ALK immunopositivity with cell membrane localization. The proliferation was polypoid and composed of elongated nests of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and abundant cytoplasm without significant atypia and lacking mitotic figures. The nevus exhibited strong and diffuse expression of p16. Targeted next-generation RNA sequencing revealed an in-frame EHBP1-ALK fusion, which has been reported only once in the literature. EHBP1 encodes an adaptor protein with plasma membrane targeting potential. Together, these findings suggest that the 5' ALK fusion partner in Spitz tumors may dictate the subcellular localization of the ALK chimeric oncoprotein. In summary, this case highlights a rare ALK fusion associated with a distinct immunohistochemical staining pattern and further expands the spectrum of ALK-rearranged melanocytic tumors. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/cup.14209

  View details for PubMedID 35113459

• Intestinal Failure in Junctional Epidermolysis Bullosa: Mild Skin Disease, Severe Diarrhea. Digestive diseases and sciences DeMaria, K. A., Fink, C., Pepper, M., Rieger, K., Tan, S. Y., Namjoshi, S. S. 2022

  View details for DOI 10.1007/s10620-022-07410-1

  View details for PubMedID 35147818

• Histologic subtype of cutaneous immune-related adverse events predicts overall survival in patients receiving immune checkpoint inhibitors. Journal of the American Academy of Dermatology Hirotsu, K. E., Scott, M. K., Marquez, C., Tran, A. T., Rieger, K. E., Novoa, R. A., Robinson, W. H., Kwong, B. Y., Zaba, L. C. 2021

  View details for DOI 10.1016/j.jaad.2021.11.050

  View details for PubMedID 34875301

• Selective Targeting of Immune Modulatory Proteins to Mitigate Fibrosis and Inflammation in Sclerodermatous Graft-Vs-Host Disease Cui, L., De Souza, C., Lerbs, T., Poyser, J., Kooshesh, M., Saleem, A., Rieger, K., Brown, B., Kwong, B., Fernandez-Pol, S., Arai, S., Shizuru, J. A., Mueller, A. S., Wernig, G. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-151223

  View details for Web of Science ID 000736398802184

• Two Cases of Mycosis Fungoides With PCM1-JAK2 Fusion. JCO precision oncology Fernandez-Pol, S., Neishaboori, N., Chapman, C. M., Khodadoust, M. S., Kim, Y. H., Rieger, K. E., Suarez, C. J. 2021; 5: 646-652

  View details for DOI 10.1200/PO.20.00366

  View details for PubMedID 34994608

• Cutaneous Reactive Angiomatosis associated with Intravascular Cryoprotein Deposition as the Presenting Finding in a Patient with Underlying Lymphoplasmacytic Lymphoma: A Case Report and Review of the Literature. Journal of cutaneous pathology Zacher, N. C., Bailey, E. E., Kwong, B. Y., Rieger, K. E. 2021

  Abstract

  Cutaneous reactive angiomatosis, a group of disorders defined by benign vascular proliferation, is associated with a number of systemic processes, including intravascular occlusion by cryoproteins. We report a case of a 64-year-old female patient who presented with a one-year history of non-tender petechiae of the bilateral arms and lower legs. Dermoscopic evaluation showed increased vascularity with a globular pattern. Over a period of months, her findings progressed to erythematous to violaceous plaques with admixed hypopigmented stellate scarring of the bilateral lower extremities, forearms, and lateral neck. Biopsy showed increased thin-walled, small dermal blood vessels with focal inter-anastamosis. Some vessels were occluded by eosinophilic globules suspicious for cryoprotein. Subsequent laboratory studies confirmed a diagnosis of type 1 cryoglobulinemia, prompting a bone marrow biopsy that revealed lymphoplasmacytic lymphoma. Herein we report the fourth case of angiomatosis secondary to intravascular cryoproteins as the initial presentation of an underlying hematologic malignancy. We also present a review of the literature and emphasize the need for thorough initial work-up and close and prolonged clinical monitoring for underlying systemic disease in these patients. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/cup.14144

  View details for PubMedID 34617316

• NUTRITIONAL DEFICIENCY CONTRIBUTING TO REFRACTORY ERYTHRODERMA IN HEMATOPOETIC CELL TRANSPLANT PATIENTS: DISTINCTIVE CLINICAL AND HISTOPATHOLOGICAL FINDINGS. Journal of the American Academy of Dermatology Winge, M. C., Rieger, K. E., Kim, J., Weng, W., Johnston, L. J., Miklos, D. B., Strelo, J., Zaba, L. C., Pugliese, S. B., Novoa, R. A., Kwong, B. Y. 2021

  View details for DOI 10.1016/j.jaad.2021.07.077

  View details for PubMedID 34450206

• Histopathologic correlation of skin manifestations of multisystemic inflammatory syndrome in adults (MIS-A) associated with SARS-CoV-2 infection. JAAD case reports So, N. A., So, J., Centkowski, S., Rana, J., Aleshin, M., Kwong, B. Y., Rieger, K., Zaba, L. C., Chiou, A. S. 2021

  View details for DOI 10.1016/j.jdcr.2021.06.031

  View details for PubMedID 34405113

• Drug-induced hypersensitivity syndrome like reaction with angioedema and hypotension associated with BRAF inhibitor use and antecedent immune checkpoint therapy. JAAD case reports Rana, J., Maloney, N. J., Rieger, K. E., Pugliese, S. B., Strelo, J. L., Liu, A., Zaba, L. C., Kwong, B. Y. 2021; 13: 147-151

  View details for DOI 10.1016/j.jdcr.2021.04.033

  View details for PubMedID 34195327

• 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

• Clinical Characterization of Mogamulizumab-Associated Rash During Treatment of Mycosis Fungoides or Sezary Syndrome. JAMA dermatology Hirotsu, K. E., Neal, T. M., Khodadoust, M. S., Wang, J. Y., Rieger, K. E., Strelo, J., Hong, E., Kim, Y. H., Kwong, B. Y. 2021

  Abstract

  Importance: Mogamulizumab is a monoclonal antibody against CCR4 approved for treatment for mycosis fungoides (MF) and Sezary syndrome (SS). Mogamulizumab-associated rash (MAR) is difficult to differentiate from cutaneous MF or SS, which can lead to unnecessary discontinuation of drug use because of concern for severe drug reaction or incorrect presumption of disease relapse or progression in the skin.Objective: To examine the most common clinical presentations of MAR in patients with MF or SS and the diagnostic and management challenges.Design, Setting, and Participants: This retrospective case series assessed patients from a multidisciplinary cutaneous lymphoma clinic and supportive oncodermatology clinic at a major academic referral center who had a diagnosis of MF or SS and received mogamulizumab from January 1, 2013, to January 1, 2020. Treatment was followed by new or worsening rash with skin biopsy results compatible with drug eruption determined by clinicopathologic correlation and molecular testing to exclude active malignant disease.Exposures: At least 1 dose of mogamulizumab.Main Outcomes and Measures: Mogamulizumab-associated rash was characterized by clinical features, including time to onset, clinical presentation, histopathologic features, and management approach.Results: The study included 19 patients with MF or SS who developed MAR (median age, 65 years; age range, 38-82 years; 10 [52.6%] male). Median time to MAR onset was 119 days (range, 56 days to 3.8 years). Patients with MAR exhibited 4 predominant clinical presentations: (1) folliculotropic MF-like scalp plaques with alopecia, (2) papules and/or plaques, (3) photoaccentuated dermatitis, and (4) morbilliform or erythrodermic dermatitis. The most common anatomical region involved was the head and neck, including the scalp. Histopathologic findings were variable and did not correspond to primary clinical morphologic findings. Immunohistochemistry and T-cell clonality ancillary testing were helpful to distinguish MAR from disease. Most patients with MAR (14 of 19) discontinued mogamulizumab treatment; however, no life-threatening severe cutaneous adverse drug reactions occurred, and the decision for drug therapy cessation was usually multifactorial. Four patients were treated again with mogamulizumab with no life-threatening drug-related events. Approaches to management of MAR include topical corticosteroids, systemic corticosteroids, and/or methotrexate.Conclusions and Relevance: This case series found that mogamulizumab-associated rash had a heterogeneous clinical presentation with variable and delayed onset in patients with MF or SS. Mogamulizumab-associated rash exhibited a predilection for the head and neck and was difficult to clinically distinguish from relapse or progression of disease. Recognition of the most common clinical presentations can help prevent unnecessary discontinuation of mogamulizumab treatment. The presence of MAR does not necessitate permanent discontinuation of or avoidance of retreatment with mogamulizumab.

  View details for DOI 10.1001/jamadermatol.2021.0877

  View details for PubMedID 33881447

• Two Cases of Mycosis Fungoides With PCM1-JAK2 Fusion JCO PRECISION ONCOLOGY Fernandez-Pol, S., Neishaboori, N., Chapman, C. M., Khodadoust, M. S., Kim, Y. H., Rieger, K. E., Suarez, C. J. 2021; 5: 646-652

  View details for DOI 10.1200/PO.20.00366

  View details for Web of Science ID 000721836700009

• Multiple Mucosal Papules in a Pediatric Patient: Challenge. The American Journal of dermatopathology Ransohoff, K., Teng, J., Rieger, K. E. 2021; 43 (4): e45

  View details for DOI 10.1097/DAD.0000000000001675

  View details for PubMedID 33743004

• Multiple Mucosal Papules in a Pediatric Patient: Answer. The American Journal of dermatopathology Ransohoff, K., Teng, J., Rieger, K. E. 2021; 43 (4): 312

  View details for DOI 10.1097/DAD.0000000000001674

  View details for PubMedID 33743001

• An ulcerated violaceous nodule on the thigh. JAAD case reports Hirotsu, K. E., Kumar, A. M., Rieger, K. E., Chen, J. K. 2021; 9: 61–63

  View details for DOI 10.1016/j.jdcr.2021.01.011

  View details for PubMedID 33665278

• 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

• Reactivation of Chagas Disease in a Patient With an Autoimmune Rheumatic Disease: Case Report and Review of the Literature. Open forum infectious diseases Czech, M. M., Nayak, A. K., Subramanian, K. n., Suarez, J. F., Ferguson, J. n., Jacobson, K. B., Montgomery, S. P., Chang, M. n., Bae, G. H., Raghavan, S. S., Wang, H. n., Miranti, E. n., Budvytiene, I. n., Shoor, S. M., Banaei, N. n., Rieger, K. n., Deresinski, S. n., Holubar, M. n., Blackburn, B. G. 2021; 8 (2): ofaa642

  Abstract

  Reactivation of Chagas disease has been described in immunosuppressed patients, but there is a paucity of literature describing reactivation in patients on immunosuppressive therapies for the treatment of autoimmune rheumatic diseases. We describe a case of Chagas disease reactivation in a woman taking azathioprine and prednisone for limited cutaneous systemic sclerosis (lcSSc). Reactivation manifested as indurated and erythematous cutaneous nodules. Sequencing of a skin biopsy specimen confirmed the diagnosis of Chagas disease. She was treated with benznidazole with clinical improvement in the cutaneous lesions. However, her clinical course was complicated and included disseminated CMV disease and subsequent septic shock due to bacteremia. Our case and review of the literature highlight that screening for Chagas disease should be strongly considered for patients who will undergo immunosuppression for treatment of autoimmune disease if epidemiologically indicated.

  View details for DOI 10.1093/ofid/ofaa642

  View details for PubMedID 33575423

  View details for PubMedCentralID PMC7863873

• 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

• Next generation sequencing confirms T-cell clonality in a subset of pediatric pityriasis lichenoides. Journal of cutaneous pathology Raghavan, S. S., Wang, J. Y., Gru, A. A., Marqueling, A. L., Teng, J. M., Brown, R. A., Novoa, R. A., Kim, Y., Zehnder, J., Zhang, B. M., Rieger, K. E. 2021

  Abstract

  Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR based assays. In this study, we sought to implement next generation sequencing as a more sensitive and specific test to examine for T-cell clonality within the pediatric population.We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with next generation sequencing of T-cell receptor beta (TRB) and gamma (TRG) genes.Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites.T-cell clonality is a common finding in PL, likely representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/cup.14143

  View details for PubMedID 34614220

• Dermatologic Events Associated with the Anti-CCR4 Antibody Mogamulizumab: Characterization and Management. Dermatology and therapy Musiek, A. C., Rieger, K. E., Bagot, M., Choi, J. N., Fisher, D. C., Guitart, J., Haun, P. L., Horwitz, S. M., Huen, A. O., Kwong, B. Y., Lacouture, M. E., Noor, S. J., Rook, A. H., Seminario-Vidal, L., Vermeer, M. H., Kim, Y. H. 2021

  Abstract

  The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event. The objective of this report was to combine results from published literature with experiences and recommendations from multiple investigators and institutions into clinical best practice recommendations to assist healthcare providers in identifying and managing mogamulizumab-associated rash. Optimal management, which includes biopsy confirmation and steroid treatment, requires a multidisciplinary approach among oncology, dermatology, and pathology practitioners. INFOGRAPHIC.

  View details for DOI 10.1007/s13555-021-00624-7

  View details for PubMedID 34816383

• Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor. The American Journal of dermatopathology Brown, R. A., Cloutier, J. M., Bahrani, E. n., Liman, A. n., Tasso, D. n., Palmer, A. n., Manning, M. A., Galperin, I. n., Rieger, K. E., Novoa, R. A., Lau, H. n., Louie, C. Y. 2021

  Abstract

  Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.

  View details for DOI 10.1097/DAD.0000000000001931

  View details for PubMedID 33767072

• Histopathology of primary cutaneous adenoid cystic carcinoma of the scrotum presenting with predominantly solid growth. Journal of cutaneous pathology Gradecki, S. E., Gru, A. A., Rieger, K. E., Raghavan, S. S. 2020

  View details for DOI 10.1111/cup.13928

  View details for PubMedID 33314272

• Concurrent Trypanosoma cruzi and Cytomegalovirus Reactivation in an Immunosuppressed Patient With Limited Cutaneous Systemic Sclerosis. The American Journal of dermatopathology Chang, M. S., Bae, G. H., Almazan, T., Raghavan, S. S., Wang, J. Y., Czech, M. M., Wang, H., Banaei, N., Blackburn, B. G., Novoa, R. A., Rieger, K. E. 2020

  Abstract

  Chagas disease, a multisystem infection caused by the protozoan Trypanosoma cruzi, is primarily found in Latin America. In recent years, prevalence has increased in the United States, where reactivation is the most common clinical scenario. Here, we describe cutaneous reactivation of T. cruzi in a patient with limited cutaneous systemic sclerosis on immunosuppression therapy who simultaneously presented with cytomegalovirus reactivation. Histopathology showed parasitized histiocytes in the superficial and deep dermis. Occasional epidermal keratinocytes were also parasitized, and rare organisms were also seen in the walls of blood vessels. Also noted were viral cytopathic changes within the vascular endothelium, and immunostaining confirmed cytomegalovirus. In this report, we describe the difference in cutaneous findings between reactivated and acute Chagas disease, and we also review the histopathologic features that help distinguish T.cruzi from other intracellular organisms.

  View details for DOI 10.1097/DAD.0000000000001842

  View details for PubMedID 33201010

• Two Cases With Features of Lymphocyte Variant Hypereosinophilic Syndrome With STAT3 SH2 Domain Mutations. The American journal of surgical pathology Fernandez-Pol, S., Petersen, B., Murphy, J., Oak, J. S., Wang, E. B., Rieger, K. E., Kim, Y. H., Khodadoust, M. S., Suarez, C. J. 2020

  Abstract

  Lymphocyte variant hypereosinophilic syndrome (LV-HES) is a rare cause of eosinophilia that is due to eosinophilipoietic cytokine production by an immunophenotypically abnormal T-cell clone. The molecular pathogenesis of this disorder is largely unknown and only 1 case of LV-HES with a pathogenic STAT3 mutation has been described thus far. Here we report 2 cases of LV-HES with STAT3 SH2 domain mutations. These cases further support the model that activation of STAT3 signaling through STAT3 SH2 domain mutations is a recurrent event in LV-HES.

  View details for DOI 10.1097/PAS.0000000000001604

  View details for PubMedID 33060403

• ALK-positive compound Spitz nevus with extensive perineural and intraneural neurotropism. Journal of cutaneous pathology Brown, R. A., Wang, J. Y., Raghavan, S. S., Zhang, J., Wan, D. C., Born, D., Koo, M., Hazard, F. K., Novoa, R. A., Rieger, K. E. 2020

  View details for DOI 10.1111/cup.13890

  View details for PubMedID 33034114

• Cutaneous T-cell lymphomas with pathogenic somatic mutations and absence of detectable clonal T-cell receptor gene rearrangement: two case reports. Diagnostic pathology Rojansky, R., Fernandez-Pol, S., Wang, E., Rieger, K. E., Novoa, R. A., Zehnder, J. L., Kunder, C. A., Kim, Y. H., Khodadoust, M. S., Brown, R. A. 2020; 15 (1): 122

  Abstract

  BACKGROUND: Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin lymphomas for which diagnosis can be challenging given the potential for overlap with inflammatory dermatoses. Current diagnostic criteria for CTCL incorporate clinical and histopathologic findings as well as results of T-cell receptor (TCR) gene sequencing. Molecular interrogation of TCR genes, TRG and TRB, has provento be a critical tool for confirming diagnoses of CTCL and for disease tracking after initiation of therapy or after stem cell transplant. Methods for confirming a diagnosis of lymphoma in the absence of TCR gene clonality are lacking. We present two patients with CTCL with pathogenic somatic mutations in the absence of TRG and TRB clonality.CASE PRESENTATIONS: Case 1: A 38-year-old male had a 19-year history of a diffuse skin rash with papulosquamous, granulomatous, and verrucous features and progressive ulcerated plaques and tumors demonstrating an atypical CD4+ T-cell infiltrate with expression of cytotoxic markers CD56, TIA-1, granzyme, and perforin on histopathology. No definitive evidence for T-cell clonality was detected by conventional PCR of 6 biopsies or by next-generation sequencing (NGS) of 14 biopsies. Somatic mutational profiling of a skin biopsy revealed pathogenic mutations in PIKC3D and TERT promoter hotspots, confirming the presence of a clonal process. Case 2: A 69-year-old male with a 13-year history of progressive, diffuse hypertrophic and eroded plaques showed an atypical CD4+ T-cell infiltrate with subset expression of TIA-1 and granzyme on histopathology. No TCR clonality was detected by TCR-NGS of 6 biopsies. Somatic mutational profiling of a skin biopsy detected a pathogenic mutation in TP53, confirming the presence of a clonal process.CONCLUSIONS: These cases highlight how detection of pathogenic somatic mutations can confirma diagnosis of lymphoma in a clinically and histopathologically suspicious cutaneous lymphoid proliferation without detectable TCR clonality.

  View details for DOI 10.1186/s13000-020-01022-x

  View details for PubMedID 32988392

• CD47 prevents the elimination of diseased fibroblasts in scleroderma. JCI insight Lerbs, T., Cui, L., King, M. E., Chai, T., Muscat, C., Chung, L., Brown, R., Rieger, K., Shibata, T., Wernig, G. 2020; 5 (16)

  Abstract

  Scleroderma is a devastating fibrotic autoimmune disease. Current treatments are partly effective in preventing disease progression but do not remove fibrotic tissue. Here, we evaluated whether scleroderma fibroblasts take advantage of the "don't-eat-me-signal" CD47 and whether blocking CD47 enables the body's immune system to get rid of diseased fibroblasts. To test this approach, we used a Jun-inducible scleroderma model. We first demonstrated in patient samples that scleroderma upregulated transcription factor JUN and increased promoter accessibilities of both JUN and CD47. Next, we established our scleroderma model, demonstrating that Jun mediated skin fibrosis through the hedgehog-dependent expansion of CD26+Sca1- fibroblasts in mice. In a niche-independent adaptive transfer model, JUN steered graft survival and conferred increased self-renewal to fibroblasts. In vivo, JUN enhanced the expression of CD47, and inhibiting CD47 eliminated an ectopic fibroblast graft and increased in vitro phagocytosis. In the syngeneic mouse, depleting macrophages ameliorated skin fibrosis. Therapeutically, combined CD47 and IL-6 blockade reversed skin fibrosis in mice and led to the rapid elimination of ectopically transplanted scleroderma cells. Altogether, our study demonstrates the efficiency of combining different immunotherapies in treating scleroderma and provides a rationale for combining CD47 and IL-6 inhibition in clinical trials.

  View details for DOI 10.1172/jci.insight.140458

  View details for PubMedID 32814713

• PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features. Journal of cutaneous pathology Raghavan, S. S., Wang, J. Y., Kwok, S., Rieger, K. E., Novoa, R. A., Brown, R. A. 2020

  Abstract

  BACKGROUND: PRAME (PReferentially expressed Antigen in MElanoma) has shown utility in distinguishing melanoma from benign melanocytic lesions, but knowledge of its expression pattern in intermediate melanocytic and spitzoid proliferations is limited.METHODS: Immunohistochemical expression of PRAME was examined in 112 melanocytic proliferations with intermediate histopathologic or spitzoid features.RESULTS: Any intensity of PRAME staining in at least 60% of lesional melanocytes was determined as the best threshold for diffuse staining in this cohort. Nearly all non-spitzoid melanomas (23/24; 95.8%) demonstrated diffuse PRAME expression. PRAME was completely negative in 95.6% (43/45) of mitotically-active nevi, traumatized nevi, nevi with persistent/recurrent features, and dysplastic nevi. Most Spitz nevi (15/20) and atypical Spitz tumors (10/13) entirely lacked PRAME expression. One Spitz nevus, one atypical Spitz tumor, and one case of spitzoid melanoma (1/2) demonstrated diffuse PRAME expression.CONCLUSIONS: Although diffuse PRAME expression is generally limited to malignant melanoma, benign Spitz nevi and atypical Spitz tumors can infrequently express diffuse PRAME. PRAME immunohistochemistry can be useful in the evaluation of atypical melanocytic proliferations with intermediate histopathologic features but should be interpreted with caution in the setting of spitzoid neoplasms. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/cup.13818

  View details for PubMedID 32700786

• Diagnostic Utility of LEF1 Immunohistochemistry in Differentiating Deep Penetrating Nevi From Histologic Mimics. The American journal of surgical pathology Raghavan, S. S., Saleem, A., Wang, J. Y., Rieger, K. E., Brown, R. A., Novoa, R. A. 2020

  Abstract

  Deep penetrating nevi (DPNs) are intermediate grade lesions which have the capacity to recur, metastasize, or progress to melanoma. Differentiating DPN from other melanocytic lesions including blue and cellular blue nevi can be diagnostically challenging, and markers to distinguish these entities can be useful. Mutations of the beta-catenin and mitogen-activated protein kinase pathways have recently been elucidated as distinctive of DPN. This pathway can subsequently activate lymphoid enhancer-binding factor 1 (LEF1), a transcription factor shown to facilitate the epithelial-mesenchymal transition to propagate tumorigenesis. Seventy-two cases in total were examined on hematoxylin and eosin sections and with beta-catenin and LEF1 immunohistochemistry. This included: DPN (14), cellular blue nevi (19), blue nevi (15), congenital melanocytic nevi (12), and melanoma (12). Nuclear expression of LEF1, present throughout the entire depth of the lesion, was noted in 13/14 (93%) of DPN, 0/19 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 9/12 (75%) of melanoma cases. Nuclear expression of beta-catenin, present throughout the entire depth of the lesion, was noted in 14/14 (100%) of DPN, 0/18 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 1/12 (8%) of melanoma cases. A majority of congenital melanocytic nevi demonstrated a gradient of LEF1 and beta-catenin expression with more intense staining superficially and loss of staining with increasing depth. Deep, uniform nuclear LEF1 combined with beta-catenin immunohistochemical staining can be useful in distinguishing DPN from histologic mimics.

  View details for DOI 10.1097/PAS.0000000000001513

  View details for PubMedID 32520758

• Clinicopathologic characterization of enfortumab vedotin-associated cutaneous toxicity in patients with urothelial carcinoma. Journal of the American Academy of Dermatology Hirotsu, K. E., Rana, J. n., Wang, J. Y., Raghavan, S. S., Rieger, K. E., Srinivas, S. n., Fan, A. C., Kwong, B. Y., Novoa, R. A., Zaba, L. n. 2020

  View details for DOI 10.1016/j.jaad.2020.11.067

  View details for PubMedID 33301805

• Diffuse PRAME expression is highly specific for malignant melanoma in the distinction from clear cell sarcoma. Journal of cutaneous pathology Raghavan, S. S., Wang, J. Y., Toland, A. n., Bangs, C. D., Rieger, K. E., Novoa, R. A., Charville, G. W., Brown, R. A. 2020

  View details for DOI 10.1111/cup.13812

  View details for PubMedID 32681554

• 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

• Venetoclax monotherapy for cutaneous blastic plasmacytoid dendritic cell neoplasm. Annals of hematology Schwede, M. n., Tan, I. T., Atibalentja, D. F., Dickman, M. M., Rieger, K. E., Mannis, G. N. 2020

  View details for DOI 10.1007/s00277-020-04276-z

  View details for PubMedID 32968828

• Histopathologic Characterization of Mogamulizumab-associated Rash. The American journal of surgical pathology Wang, J. Y., Hirotsu, K. E., Neal, T. M., Raghavan, S. S., Kwong, B. Y., Khodadoust, M. S., Brown, R. A., Novoa, R. A., Kim, Y. H., Rieger, K. E. 2020

  Abstract

  Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient's previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient's MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR.

  View details for DOI 10.1097/PAS.0000000000001587

  View details for PubMedID 32976123

• Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa. JCI insight Eichstadt, S., Barriga, M., Ponakala, A., Teng, C., Nguyen, N. T., Siprashvili, Z., Nazaroff, J., Gorell, E. S., Chiou, A. S., Taylor, L., Khuu, P., Keene, D. R., Rieger, K., Khosla, R. K., Furukawa, L. K., Lorenz, H. P., Marinkovich, M. P., Tang, J. Y. 2019; 4 (19)

  Abstract

  BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy.METHODSAutologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 * 7 cm (35 cm2) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years.RESULTSNo participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019).CONCLUSIONC7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.TRIAL REGISTRATIONClinicaltrials.gov identifier: NCT01263379.FUNDINGEpidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH R01 AR055914, Office of Research and Development at the Palo Alto Veteran's Affairs Medical Center, and the Dermatology Foundation.

  View details for DOI 10.1172/jci.insight.130554

  View details for PubMedID 31578311

• Eosinophilic Granulomatosis With Polyangiitis: Histopathological Confirmation Despite Negative Serology AMERICAN JOURNAL OF MEDICINE Kumar, A. M., Bae, G. H., Besen, J., Kwong, B. Y., Rieger, K. E. 2019; 132 (10): E741–E743

  View details for DOI 10.1016/j.amjmed.2019.04.032

  View details for Web of Science ID 000493949700008

• A phase 1b, open-label, investigator-initiated, proof-of-concept study of pembrolizumab for advanced basal cell carcinomas Chang, A., Duy Tran, Cannon, J., Li, S., Jeng, M., Rieger, K., Reddy, S., Sarin, K., Colevas, D. MOSBY-ELSEVIER. 2019: AB8

  View details for Web of Science ID 000482195000029

• Angiodestructive lymphomatoid papulosis lasting more than 45years. JAAD case reports Lee, G. H., Bae, G. H., Rieger, K. E., Kim, Y. H., Chiou, A. S. 2019; 5 (9): 767–69

  View details for DOI 10.1016/j.jdcr.2019.06.027

  View details for PubMedID 31516992

• Intralymphatic Rosai-Dorfman Disease Associated With Vulvar Lymphedema: A Case Report of an Extremely Rare Phenomenon. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Saleem, A., Hoffmann, J., Warnke, R., Rieger, K. E., Longacre, T. 2019

  Abstract

  Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a self-limited histiocytic disorder of unclear etiology which most commonly presents with cervical lymphadenopathy. Purely extranodal presentation of RDD is uncommon, and isolated intralymphatic/intravascular confinement of this entity has not previously been described. We report a 16-yr-old female who presented with vaginal swelling and mass-like enlargement of the right labia. The mass had been present for nearly a year without pain or tenderness. Clinically, the lesion was thought to be a Bartholin gland cyst. Following surgical resection, histologic examination demonstrated a hypocellular myxedematous stroma with a mixture of ectatic thin and thick-walled vessels within which there were numerous collections of histiocytes, lymphocytes, and plasma cells. The histopathologic differential diagnosis included localized vulvar lymphedema, a specialized genital tract neoplasm, and childhood asymmetric labium majus enlargement. The histiocytes showed occasional plasma cells and lymphocytes within their cytoplasm, consistent with emperipolesis. Immunohistochemical studies showed that the histiocytes expressed CD163 and S100, while ERG and D2-40 highlighted their intralymphatic confinement, ultimately leading to the diagnosis of intralymphatic RDD. Intralymphatic RDD may present as vulvar lymphedema and can potentially mimic other myxedematous neoplasms of the vulvovaginal region.

  View details for DOI 10.1097/PGP.0000000000000619

  View details for PubMedID 31274698

• Loss of Primary Cilia Drives Switching from Hedgehog to Ras/MAPK Pathway in Resistant Basal Cell Carcinoma JOURNAL OF INVESTIGATIVE DERMATOLOGY Kuonen, F., Huskey, N. E., Shankar, G., Jaju, P., Whitson, R. J., Rieger, K. E., Atwood, S. X., Sarin, K. Y., Oro, A. E. 2019; 139 (7): 1439–48

  View details for DOI 10.1016/j.jid.2018.11.035

  View details for Web of Science ID 000472234100017

• Clinical factors associated with cutaneous histopathologic findings in dermatomyositis JOURNAL OF CUTANEOUS PATHOLOGY Wolstencroft, P. W., Rieger, K. E., Leatham, H. W., Fiorentino, D. F. 2019; 46 (6): 401–10

  View details for DOI 10.1111/cup.13442

  View details for Web of Science ID 000466179800002

• Persistent Upper Lip Swelling in a Young Woman: Answer. The American Journal of dermatopathology Wang, J. Y., Rieger, K. E. 2019; 41 (5): 386–87

  View details for PubMedID 31009412

• Persistent Upper Lip Swelling in a Young Woman: Answer AMERICAN JOURNAL OF DERMATOPATHOLOGY Wang, J. Y., Rieger, K. E. 2019; 41 (5): 386–87

  View details for DOI 10.1097/DAD.0000000000001048

  View details for Web of Science ID 000480719200015

• Biomarker discovery analysis: Alterations in p14, p16, p53, and BAP1 expression in nevi, cutaneous melanoma, and metastatic melanoma PIGMENT CELL & MELANOMA RESEARCH Sargen, M. R., Cloutier, J. M., Sarin, K. Y., Rieger, K. E., Chu, P., Swetter, S. M., Novoa, R. A. 2019; 32 (3): 474–78

  View details for DOI 10.1111/pcmr.12768

  View details for Web of Science ID 000465607700016

• Persistent Upper Lip Swelling in a Young Woman: Challenge AMERICAN JOURNAL OF DERMATOPATHOLOGY Wang, J. Y., Rieger, K. E. 2019; 41 (5): E43–E44

  View details for DOI 10.1097/DAD.0000000000001047

  View details for Web of Science ID 000480719200001

• Digital papillary adenocarcinoma: a case review CURRENT ORTHOPAEDIC PRACTICE Ziino, C., Rieger, K. E., Sen, S. 2019; 30 (2): 102–5

  View details for DOI 10.1097/BCO.0000000000000722

  View details for Web of Science ID 000460435800003

• Clinical factors associated with cutaneous histopathologic findings in dermatomyositis. Journal of cutaneous pathology Wolstencroft, P. W., Rieger, K. E., Leatham, H. W., Fiorentino, D. F. 2019

  Abstract

  BACKGROUND: Common histopathologic findings in cutaneous dermatomyositis include vacuolar interface with dyskeratosis, mucin, and perivascular inflammation. Data examining the relationships between these and other histologic abnormalities, or their dependence on biopsy site, and medications are limited.METHODS: Using 228 dermatomyositis skin biopsies and statistical analyses including Chi-squared analyses, calculations of relative risk, and adjusted generalized estimating equation regressions, we investigated relationships between 14 histopathologic findings and the impact of clinical factors on these findings.RESULTS: In biopsies taken from sites of visible rash, interface dermatitis was seen in 91%, and 95% had at least one of perivascular inflammation, mucin, or basal vacuolization. Vascular abnormalities were not closely associated with epidermal or inflammatory findings. Concomitant prednisone significantly decreased the odds of basal vacuolization (odds ratio [OR]=0.34, 95% confidence interval [CI]: 0.12-0.98, P-value=0.05), perivascular inflammation (OR=0.19, 95% CI: 0.07-0.53, P-value=0.002), and vessel damage (OR=0.81, 95% CI: 0.68-0.96, P-value=0.02).CONCLUSION: Vasculopathy and classic findings of interface dermatitis may be driven by unique pathways in dermatomyositis. Corticosteroid use may impact skin biopsy findings. There is a need for clinicopathologic correlation when diagnosing dermatomyositis.

  View details for PubMedID 30737826

• Pembrolizumab for advanced basal cell carcinoma: An investigator-initiated, proof-of-concept study JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Chang, A. S., Tran, D. C., Cannon, J. D., Li, S., Jeng, M., Patel, R., Van der Bokke, L., Pague, A., Brotherton, R., Rieger, K. E., Satpathy, A. T., Yost, K. E., Reddy, S., Sarin, K., Colevas, A. 2019; 80 (2): 564–66

  View details for DOI 10.1016/j.jaad.2018.08.017

  View details for Web of Science ID 000455473200042

• Loss of primary cilia drives switching from Hedgehog to Ras/MAPK pathway in resistant basal cell carcinoma. The Journal of investigative dermatology Kuonen, F., Huskey, N. E., Shankar, G., Jaju, P., Whitson, R. J., Rieger, K. E., Atwood, S. X., Sarin, K. Y., Oro, A. E. 2019

  Abstract

  Basal cell carcinomas (BCCs) rely on Hedgehog (HH) pathway growth signal amplification by the microtubule-based organelle, the primary cilium. Despite naive tumors responsiveness to Smoothened inhibitors (Smoi), resistance in advanced tumors remains frequent. While the resistant BCCs usually maintain HH pathway activation, squamous cell carcinomas with Ras/MAPK pathway activation also arise, with the molecular basis of tumor type and pathway selection still obscure. Here we identify the primary cilium as a critical determinant controlling tumor pathway switching. Strikingly, Smoi-resistant BCCs possess an increased mutational load in ciliome genes, resulting in reduced primary cilia and HH pathway activation compared to naive or Gorlin patient BCCs. Gene set enrichment analysis of resistant BCCs with a low HH pathway signature reveals increased Ras/MAPK pathway activation. Tissue analysis confirms an inverse relationship between primary cilia presence and Ras/MAPK activation, and primary cilia removal in BCCs potentiates Ras/MAPK pathway activation. Moreover, activating Ras in HH-responsive cell lines confers resistance to both canonical (vismodegib) and non-canonical (aPKC and MRTF inhibitors) HH pathway inhibitors, while conferring sensitivity to MAPK inhibitors. Our results provide insights into BCC treatment and identify the primary cilium as an important lineage gatekeeper, preventing HH to Ras/MAPK pathway switching.

  View details for PubMedID 30707899

• Biomarker discovery analysis: Alterations in p14, p16, p53, and BAP1 expression in nevi, cutaneous melanoma, and metastatic melanoma. Pigment cell & melanoma research Sargen, M. R., Cloutier, J. M., Sarin, K. Y., Rieger, K. E., Chu, P., Swetter, S. M., Novoa, R. A. 2019

  Abstract

  Protein biomarkers for diagnosis and prognosis are currently lacking for melanoma, which predominantly relies on histologic features for diagnosis (cytologic and nuclear pleomorphism, growth pattern) and staging (Breslow depth, ulceration). In many cases, the histology of the primary tumor is an unreliable predictor of tumor behavior, and consequently sentinel lymph node biopsy along with imaging studies are often necessary to predict likelihood of mortality from disease. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30672662

• The Reply. The American journal of medicine Kumar, A. M., Bae, G. H., Besen, J. n., Kwong, B. Y., Rieger, K. E. 2019; 132 (11): e812

  View details for DOI 10.1016/j.amjmed.2019.07.027

  View details for PubMedID 31779785

• Eosinophilic granulomatosis with polyangiitis: histopathological confirmation despite negative serology. The American journal of medicine Kumar, A. M., Bae, G. H., Besen, J. n., Kwong, B. Y., Rieger, K. E. 2019

  View details for PubMedID 31100285

• Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma Journal of INVESTIGATIVE DERMATOLOGY | Original Article | Carcinogenesis/Tumorigenesis Chiang, A., Tan, C. Z., Kuonen, F., Hodgkinson, L. M., Chiang, F., Cho, R. J., South, A. P., Tang, J. Y., Chang, A. S., Rieger, K. E., Oro, A. E., Sarin, K. Y. 2019; 139 (11): 2263-2271. E5

  View details for DOI 10.1016/j.jid.2019.03.1163

• Pachydermodactyly: Case report including clinical and histopathologic diagnostic pitfalls JOURNAL OF CUTANEOUS PATHOLOGY Barnes, L. A., Bae, G. H., Lewis, M. A., Rieger, K. E. 2018; 45 (12): 949–53

  View details for DOI 10.1111/cup.13359

  View details for Web of Science ID 000450005800014

• Cross-contamination of Pathology Specimens: A Cautionary Tale CUTIS Lewellis, S. W., Roy, K., Gojenola, L., Swetter, S. M., Rieger, K. E. 2018; 102 (4): E12–E14

  View details for Web of Science ID 000447978900005

• Pachydermodactyly: case report including clinical and histopathologic diagnostic pitfalls. Journal of cutaneous pathology Barnes, L. A., Bae, G. H., Lewis, M. A., Rieger, K. E. 2018

  Abstract

  Pachydermodactyly is a rare, benign condition characterized by swelling and thickening of the periarticular skin, most commonly at the proximal interphalangeal joints. Diagnosis is routinely made through correlation of clinical, histopathologic, and radiographic findings. Here we report a case of pachydermodactyly in a 25 year-old male, with emphasis on the clinical and histopathologic differential diagnosis and potential diagnostic pitfalls. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30221379

• Well-Appearing Newborn With a Vesiculobullous Rash at Birth PEDIATRICS Stewart, S. E., Lin, J. L., Everhart, J. L., Pham, T. H., Marqueling, A. L., Rieger, K. E., Hilgenberg, S. L. 2018; 141 (3)

  View details for DOI 10.1542/peds.2017-0236

  View details for Web of Science ID 000426361800040

• Well-Appearing Newborn With a Vesiculobullous Rash at Birth. Pediatrics Stewart, S. E., Lin, J. L., Everhart, J. L., Pham, T. H., Marqueling, A. L., Rieger, K. E., Hilgenberg, S. L. 2018

  Abstract

  A term, appropriate-for-gestational-age, male infant born via normal spontaneous vaginal delivery presented at birth with a full-body erythematous, vesiculobullous rash. He was well-appearing with normal vital signs and hypoglycemia that quickly resolved. His father had a history of herpes labialis. His mother had an episode of herpes zoster during pregnancy and a prolonged rupture of membranes that was adequately treated. The patient underwent a sepsis workup, including 2 attempted but unsuccessful lumbar punctures, and was started on broad-spectrum antibiotics and acyclovir, given concerns about bacterial or viral infection. The rash evolved over the course of several days. Subsequent workup, with particular attention to his history and presentation, led to his diagnosis.

  View details for PubMedID 29437933

• Pembrolizumab for advanced basal cell carcinoma: an investigator-initiated, proof-of-concept study. Journal of the American Academy of Dermatology Chang, A. L., Tran, D. C., Cannon, J. G., Li, S. n., Jeng, M. n., Patel, R. n., Van der Bokke, L. n., Pague, A. n., Brotherton, R. n., Rieger, K. E., Satpathy, A. T., Yost, K. E., Reddy, S. n., Sarin, K. n., Colevas, A. D. 2018

  View details for PubMedID 30145186

• An adolescent with granulomatous mycosis fungoides infiltrating skeletal muscle successfully treated with oral prednisone. JAAD case reports Lewis, D. J., Turkeltaub, A. E., Dai, J., Nagarajan, P., Rieger, K. E., Nunez, C. A., Kim, Y. H., Duvic, M. 2017; 3 (4): 276–79

  View details for PubMedID 28653029

• Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy. JAMA dermatology Freites-Martinez, A., Kwong, B. Y., Rieger, K. E., Coit, D. G., Colevas, A. D., Lacouture, M. E. 2017

  Abstract

  To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab.To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management.Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs.All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery.Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1-positive) T cells, an immunophenotypic pattern also observed in other cases of anti-PD-1-induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers.Pembrolizumab is used in advanced melanoma, advanced non-small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.

  View details for DOI 10.1001/jamadermatol.2017.0989

  View details for PubMedID 28467522

• Intraepidermal Type VII Collagen by Immunofluorescence Mapping: A Specific Finding for Bullous Dermolysis of the Newborn. Pediatric dermatology Heinecke, G., Marinkovich, M. P., Rieger, K. E. 2017; 34 (3): 308-314

  Abstract

  Bullous dermolysis of the newborn (BDN) is a subtype of dystrophic epidermolysis bullosa (DEB) characterized by skin fragility and blister formation at birth that typically resolves within the first year of life. Abnormal intraepidermal retention of type VII collagen (C7) has been reported as a characteristic feature of BDN, but few studies have investigated the specificity of this finding.We retrospectively reviewed pathology reports of patients diagnosed with DEB using immunofluorescence mapping from January 2001 to January 2015. For cases describing intraepidermal accumulation of C7, we collected information on patient characteristics, including genetic testing results, clinical outcome, and concurrent electron microscopy findings, where available.Of the 143 cases of DEB with immunofluorescence mapping, eight patients had intracytoplasmic epidermal retention of C7. Of these eight patients, two were lost to follow-up, four had complete resolution of bullae, and two had marked improvement with rare residual bullae. Concurrent electron microscopic findings available for three patients were consistent with BDN.Our review of immunofluorescence mapping findings in patients with DEB found that 5.6% had abnormal intracytoplasmic epidermal retention of C7, a finding previously reported in BDN. All such patients with clinical outcomes available had resolution or marked improvement of bullae, consistent with clinical outcomes expected in BDN.

  View details for DOI 10.1111/pde.13132

  View details for PubMedID 28523885

• Correlates of multiple basal cell carcinoma in a retrospective cohort study: Sex, histologic subtypes, and anatomic distribution. Journal of the American Academy of Dermatology Kuo, K. Y., Batra, P., Cho, H. G., Li, S., Chahal, H. S., Rieger, K. E., Tang, J. Y., Sarin, K. Y. 2017

  View details for DOI 10.1016/j.jaad.2017.02.047

  View details for PubMedID 28392289

• Postzygotic Mutations in Beta-Actin are Associated with Becker's Nevus and Becker's Nevus Syndrome. journal of investigative dermatology Cai, E. D., Sun, B. K., Chiang, A., Rogers, A., Bernet, L., Cheng, B., Teng, J., Rieger, K. E., Sarin, K. Y. 2017

  View details for DOI 10.1016/j.jid.2017.03.017

  View details for PubMedID 28347698

• Zosteriform Mycosis Fungoides: A New Clinical Presentation With a Dermatomal Distribution. The American Journal of dermatopathology Rieger, K. E., Kim, J., Kim, Y. H. 2017; 39 (2): e17-e18

  Abstract

  Classic mycosis fungoides (MF) presents with patches and plaques on the trunk and proximal extremities. However, numerous clinicopathologic variants have been described, making diagnosis challenging. Here, the authors report a 21-year-old woman with immunophenotypically and molecularly confirmed MF occurring in a dermatomal distribution. Awareness of this and other rare variants of MF is critical to avoid misdiagnosis.

  View details for DOI 10.1097/DAD.0000000000000652

  View details for PubMedID 28134736

• Incidence ratio of basal cell carcinoma to squamous cell carcinoma equalizes with age. Journal of the American Academy of Dermatology Chahal, H. S., Rieger, K. E., Sarin, K. Y. 2017; 76 (2): 353-354

  View details for DOI 10.1016/j.jaad.2016.08.019

  View details for PubMedID 28089000

• Basosquamous Carcinoma: Controversy, Advances, and Future Directions. Dermatologic surgery Tan, C. Z., Rieger, K. E., Sarin, K. Y. 2017; 43 (1): 23-31

  Abstract

  Basosquamous carcinoma is a rare cutaneous neoplasm that has caused considerable controversy as to its classification, pathogenesis, and management.To review and summarize current literature on the definition, pathogenesis, incidence, and management of basosquamous carcinoma.Through December 2015, an electronic search of the Pubmed database was performed using combinations of basosquamous carcinoma and metatypical basal cell carcinoma as search terms.A selection of 39 publications including case reports and series, retrospective studies, and systematic reviews of the literature were included. Descriptions of the definition of basosquamous carcinoma, clinical behavior, histopathological characteristics, current treatment therapies, and future advances are summarized.This systematic review provides a comprehensive overview of the current understanding of basosquamous carcinoma. Further study is required to elucidate the mechanisms driving the formation of this aggressive tumor.

  View details for DOI 10.1097/DSS.0000000000000815

  View details for PubMedID 27340741

• Persistent Upper Lip Swelling in a Young Woman. The American Journal of dermatopathology Wang, J. Y., Rieger, K. E. 2017

  View details for PubMedID 29140807

• Zosteriform Mycosis Fungoides: A New Clinical Presentation With a Dermatomal Distribution. The American Journal of dermatopathology Rieger, K. E., Kim, J., Kim, Y. H. 2016

  Abstract

  Classic mycosis fungoides (MF) presents with patches and plaques on the trunk and proximal extremities. However, numerous clinicopathologic variants have been described, making diagnosis challenging. Here, the authors report a 21-year-old woman with immunophenotypically and molecularly confirmed MF occurring in a dermatomal distribution. Awareness of this and other rare variants of MF is critical to avoid misdiagnosis.

  View details for DOI 10.1097/DAD.0000000000000652

  View details for PubMedID 28157131

• Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa. JAMA Siprashvili, Z., Nguyen, N. T., Gorell, E. S., Loutit, K., Khuu, P., Furukawa, L. K., Lorenz, H. P., Leung, T. H., Keene, D. R., Rieger, K. E., Khavari, P., Lane, A. T., Tang, J. Y., Marinkovich, M. P. 2016; 316 (17): 1808-1817

  Abstract

  Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating, often fatal, inherited blistering disorder caused by mutations in the COL7A1 gene encoding type VII collagen. Support and palliation are the only current therapies.To evaluate the safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with RDEB.Single-center phase 1 clinical trial conducted in the United States of 4 patients with severe RDEB with a measured area of wounds suitable for grafting of at least 100 cm2. Patients with undetectable type VII collagen keratinocyte expression were excluded.Autologous keratinocytes isolated from biopsy samples collected from 4 patients with RDEB were transduced with good manufacturing practice-grade retrovirus carrying full-length human COL7A1 and assembled into epidermal sheet grafts. Type VII collagen gene-corrected grafts (approximately 35 cm2) were transplanted onto 6 wounds in each of the patients (n = 24 grafts).The primary safety outcomes were recombination competent retrovirus, cancer, and autoimmune reaction. Molecular correction was assessed as type VII collagen expression measured by immunofluorescence and immunoelectron microscopy. Wound healing was assessed using serial photographs taken at 3, 6, and 12 months after grafting.The 4 patients (mean age, 23 years [range, 18-32 years]) were all male with an estimated body surface area affected with RDEB of 4% to 30%. All 24 grafts were well tolerated without serious adverse events. Type VII collagen expression at the dermal-epidermal junction was demonstrated on the graft sites by immunofluorescence microscopy in 9 of 10 biopsy samples (90%) at 3 months, in 8 of 12 samples (66%) at 6 months, and in 5 of 12 samples (42%) at 12 months, including correct type VII collagen localization to anchoring fibrils. Wounds with recombinant type VII collagen graft sites displayed 75% or greater healing at 3 months (21 intact graft sites of 24 wound sites; 87%), 6 months (16/24; 67%), and 12 months (12/24; 50%) compared with baseline wound sites.In this preliminary study of 4 patients with RDEB, there was wound healing in some type VII collagen gene-corrected grafts, but the response was variable among patients and among grafted sites and generally declined over 1 year. Long-term follow-up is necessary for these patients, and controlled trials are needed with a broader range of patients to better understand the potential long-term efficacy of genetically corrected autologous epidermal grafts.clinicaltrials.gov Identifier: NCT01263379.

  View details for DOI 10.1001/jama.2016.15588

  View details for PubMedID 27802546

• Ovoid Palatal Patch in Dermatomyositis: A Novel Finding Associated With Anti-TIF1? (p155) Antibodies. JAMA dermatology Bernet, L. L., Lewis, M. A., Rieger, K. E., Casciola-Rosen, L., Fiorentino, D. F. 2016; 152 (9): 1049-1051

  View details for DOI 10.1001/jamadermatol.2016.1429

  View details for PubMedID 27224238

• PUF60: a prominent new target of the autoimmune response in dermatomyositis and Sjogren's syndrome ANNALS OF THE RHEUMATIC DISEASES Fiorentino, D. F., Presby, M., Baer, A. N., Petri, M., Rieger, K. E., Soloski, M., Rosen, A., Mammen, A. L., Christopher-Stine, L., Casciola-Rosen, L. 2016; 75 (6): 1145-1151

  Abstract

  Autoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60 kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient's serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody.A new 60 kDa specificity was detected by immunoblotting HeLa cell lysates. The targeted autoantigen was identified as poly(U)-binding-splicing factor 60 kDa (PUF60) using (i) a human protein array and (ii) two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing. Anti-PUF60 antibodies were assayed by ELISA using sera from patients with primary Sjögren's syndrome (SS; n=84), systemic lupus erythematosus (SLE; n=71), DM (n=267), polymyositis (n=45), inclusion body myositis (n=45) and healthy controls (n=38).PUF60 was identified as a new autoantigen. Anti-PUF60 antibodies were present in 25/84 (30%) patients with SS, 6/71 (8.5%) patients with SLE and 2/38 (5.0%) control subjects (SS vs controls, p=0.002; SLE vs controls, p=0.711). Anti-PUF60 antibodies were present in 48/267 (18.0%) patients with DM versus 4/45 (8.9%) and 5/45 (11.1%) patients with inclusion body myositis and polymyositis, respectively. The antibody was significantly associated with anti-Ro52 antibodies, rheumatoid factor and hyperglobulinemia in the patients with primary SS. In patients with DM, the antibody was associated with anti-transcription intermediary factor 1 gamma seropositivity and Caucasian race.PUF60 represents a novel autoantigen in patients with SS and DM. PUF60 antibodies are associated with distinct clinical features and different immune responses in different diseases.

  View details for DOI 10.1136/annrheumdis-2015-207509

  View details for Web of Science ID 000376440900033

  View details for PubMedID 26253095

• New-onset cutaneous lichen planus following therapy for hepatitis C with ledipasvir-sofosbuvir JOURNAL OF CUTANEOUS PATHOLOGY Scott, G. D., Rieger, K. E. 2016; 43 (4): 408–9

  View details for PubMedID 26816004

• JAK2-positive cutaneous myelofibrosis presenting as sclerosing extramedullary hematopoietic tumors on the scalp: case presentation and review of the literature. Journal of cutaneous pathology LeBlanc, R. E., Lester, L., Kwong, B., Rieger, K. E. 2015; 42 (11): 858-862

  Abstract

  We report the second case of cutaneous myelofibrosis with a documented JAK2 activating mutation involving the scalp of a 67-year-old woman with primary myelofibrosis in her marrow. In contrast to the previous case, the biopsy revealed extensive lesional collagen deposition and closely mimicked a fibrohistiocytic proliferation. Similar rare lesions occurring in the setting of myeloproliferative neoplasms have been called sclerosing extramedullary hematopoietic tumors. These entities appear histomorphologically and etiologically distinct from extramedullary hematopoiesis, and their diagnosis should prompt the workup for a myeloproliferative neoplasm in the absence of an antecedent diagnosis. The presence of the JAK2 mutation in our case confirmed that the lesions represented skin involvement by a neoplastic myeloid proliferation and not compensatory extramedullary hematopoiesis. Our patient died of disease several months following the appearance of her lesions, which is in keeping with other reports that suggest that cutaneous myelofibrosis may serve as an independent poor prognostic sign in otherwise advanced primary myelofibrosis. A review of the literature further emphasizes the importance of distinguishing this entity from mesenchymal neoplasms and acute myeloid leukemia involving the skin.

  View details for DOI 10.1111/cup.12553

  View details for PubMedID 26153565

• JAK2-positive cutaneous myelofibrosis presenting as sclerosing extramedullary hematopoietic tumors on the scalp: case presentation and review of the literature JOURNAL OF CUTANEOUS PATHOLOGY LeBlanc, R. E., Lester, L., Kwong, B., Rieger, K. E. 2015; 42 (11): 858-862

  Abstract

  We report the second case of cutaneous myelofibrosis with a documented JAK2 activating mutation involving the scalp of a 67-year-old woman with primary myelofibrosis in her marrow. In contrast to the previous case, the biopsy revealed extensive lesional collagen deposition and closely mimicked a fibrohistiocytic proliferation. Similar rare lesions occurring in the setting of myeloproliferative neoplasms have been called sclerosing extramedullary hematopoietic tumors. These entities appear histomorphologically and etiologically distinct from extramedullary hematopoiesis, and their diagnosis should prompt the workup for a myeloproliferative neoplasm in the absence of an antecedent diagnosis. The presence of the JAK2 mutation in our case confirmed that the lesions represented skin involvement by a neoplastic myeloid proliferation and not compensatory extramedullary hematopoiesis. Our patient died of disease several months following the appearance of her lesions, which is in keeping with other reports that suggest that cutaneous myelofibrosis may serve as an independent poor prognostic sign in otherwise advanced primary myelofibrosis. A review of the literature further emphasizes the importance of distinguishing this entity from mesenchymal neoplasms and acute myeloid leukemia involving the skin.

  View details for DOI 10.1111/cup.12553

  View details for Web of Science ID 000368293300010

• Activity of Type I and Type II Interferons in Dermatomyositis Skin Is Correlated with Characteristic Pathologic Features Leatham, H. W., Rieger, K., Chung, L., Li, S., Higgs, B. W., Yao, Y., Sarin, K., Fiorentino, D. WILEY-BLACKWELL. 2015

  View details for Web of Science ID 000370860202208

• A subdermal source: contact dermatitis. American journal of medicine Fogel, A. L., Longmire, M., Rieger, K. E., Sarin, K. Y. 2015; 128 (6): 578-581

  View details for DOI 10.1016/j.amjmed.2015.02.005

  View details for PubMedID 25747191

• ETV3-NCOA2 in indeterminate cell histiocytosis: clonal translocation supports sui generis. Blood Brown, R. A., Kwong, B. Y., McCalmont, T. H., Ragsdale, B. n., Ma, L. n., Cheung, C. n., Rieger, K. E., Arber, D. A., Kim, J. n. 2015

  View details for PubMedID 26438513

• Localized cutaneous fibrosing disorders. Rheumatic diseases clinics of North America Yaqub, A., Chung, L., Rieger, K. E., Fiorentino, D. F. 2013; 39 (2): 347-364

  Abstract

  This article acquaints the reader with disorders of the skin that might mimic systemic sclerosis but whose pathology is localized to the skin and/or has extracutaneous manifestations that are different than systemic sclerosis. These disorders include localized scleroderma (morphea), eosinophilic fasciitis, scleredema, scleromyxedema, nephrogenic systemic fibrosis, and chronic graft-versus-host disease. Particular emphasis is placed on clinical and histopathologic features that help the clinician differentiate between these disorders. Treatment options are briefly reviewed.

  View details for DOI 10.1016/j.rdc.2013.02.013

  View details for PubMedID 23597968

• Localized cutaneous fibrosing disorders. Rheumatic diseases clinics of North America Yaqub, A., Chung, L., Rieger, K. E., Fiorentino, D. F. 2013; 39 (2): 347-364

  View details for DOI 10.1016/j.rdc.2013.02.013

  View details for PubMedID 23597968

• Reconsidering the Diagnostic and Prognostic Utility of LN-2 for Undifferentiated Pleomorphic Sarcoma and Atypical Fibroxanthoma AMERICAN JOURNAL OF DERMATOPATHOLOGY Hollmig, S. T., Rieger, K. E., Henderson, M. T., West, R. B., Sundram, U. N. 2013; 35 (2): 176-179

  Abstract

  The topic of distinguishing atypical fibroxanthoma (AFX) from undifferentiated pleomorphic sarcoma (UPS), formerly malignant fibrous histiocytoma, is highly controversial. Although their clinical behavior is disparate, AFX and UPS commonly appear nearly identical on routine histopathologic examination. Although conceptually useful, subcategorization of UPS into superficial (confined to the dermis and subcutaneous tissue) and deep (involvement of fascia and deeper structures) types has not improved our ability to differentiate UPS from AFX. Numerous authors have purported LN-2 (CD74) immunopositivity as able to distinguish UPS from AFX and to predict those rare AFX likely to behave aggressively, although only a single prior study has been dedicated to evaluating this marker. We performed LN-2 staining of 14 AFX, 8 superficial UPS, and 65 deep UPS specimens using an identical protocol as described by prior authors. Of the 73 total UPS specimens, only 1 (1.4%) stained strongly with LN-2, as compared with 3 of 14 (21%) AFX (P = 0.012). One of 2 (50%) clinically aggressive AFX tumors that later exhibited both local recurrence and metastasis stained strongly for LN-2, whereas 2 of 12 (17%) of the more indolent tumors stained strongly with this marker (P = 0.40). Our data do not replicate prior reports of LN-2 as a sensitive and specific marker for UPS, or as indicative of prognosis for AFX, and therefore does not support the use of LN-2 as either a diagnostic or prognostic marker.

  View details for DOI 10.1097/DAD.0b013e318265fb9e

  View details for Web of Science ID 000316941200009

  View details for PubMedID 23000905

• ALK-negative systemic intravascular anaplastic large cell lymphoma presenting in the skin JOURNAL OF CUTANEOUS PATHOLOGY Rieger, K. E., POLIDORE, T., Warnke, R., Kim, J. 2011; 38 (2): 216-220

  Abstract

  Systemic cases of the CD30-positive T-cell neoplasm, anaplastic large cell lymphoma (ALCL), are typically anaplastic lymphoma kinase (ALK)-positive. The failure to express ALK protein has been shown to portend a worse prognosis. We describe a case of ALK-negative systemic ALCL that presented as a violaceous plaque on the scalp of a 79-year-old man. Interestingly, the neoplastic cells were confined largely within vascular spaces, a configuration that is exceedingly rare in the skin and is more typically seen with intravascular large B-cell lymphoma. In addition, bcl-2 immunohistochemical staining was strongly positive in this case, which may portend a more aggressive clinical course. To our knowledge, this report represents the first case of an ALK-negative ALCL to present intravascularly in the skin. Therefore, the recognition of systemic anaplastic T-cell lymphoma present within the intravascular spaces is important to avoid misdiagnosis.

  View details for DOI 10.1111/j.1600-0560.2010.01528.x

  View details for Web of Science ID 000285754200009

  View details for PubMedID 20236372

• Skin Nodules in a Patient With Acute Myeloid Leukemia and Neurological Deterioration - Disseminated fusariosis ARCHIVES OF DERMATOLOGY Rieger, K. E., Ridky, T. W., Sundram, U. N. 2010; 146 (9): 1037-1042

  View details for Web of Science ID 000282004600028

  View details for PubMedID 20855710

• Recurrence rates associated with incompletely excised low-risk nonmelanoma skin cancer JOURNAL OF CUTANEOUS PATHOLOGY Rieger, K. E., Linos, E., Egbert, B. M., Swetter, S. M. 2010; 37 (1): 59-67

  Abstract

  Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities.Retrospective review of dermatopathology records from January 1999 to January 2005 was conducted to identify biopsies or excision specimens with histologically transected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which were not subsequently excised. Patient and tumor characteristics associated with recurrence were analyzed in a subgroup of patients with predominantly 'low-risk' and/or minimally transected NMSCs. Prospective follow up was performed through March 31, 2008. Data was analyzed with Chi-square and Fishers exact tests and multivariate logistic regression.Of 376 transected NMSCs, 27 (7.2%) recurred, including 20 (9%) of 223 BCCs and 7 (4.6%) SCCs in situ of 153 SCCs. The overall recurrence rate of the 124 minimally transected NMSCs was even lower (5.6%). Multivariate logistic regression identified three significant predictors of recurrence: tumor location on the head and neck (p = 0.041), tumor size (p = 0.00741) and superficial subtype of BCC (p = .035).Although surgical excision of NMSC remains the standard of care, observation or nonsurgical treatment may be acceptable in many cases of incompletely excised low-risk or minimally transected NMSCs.

  View details for DOI 10.1111/j.1600-0560.2009.01340.x

  View details for PubMedID 19615009

• Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rieger, K. E., Hong, W. J., Tusher, V. G., Tang, J., Tibshirani, R., Chu, G. 2004; 101 (17): 6635-6640

  Abstract

  Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity. The analysis used heterogeneity-associated transformation of the data to account for a clinical outcome arising from more than one underlying cause. To compute the risk of toxicity for each patient, we applied nearest shrunken centroids, a method that identifies and cross-validates predictive genes. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of 14 patients with no false positives among 43 controls (P = 2.2 x 10(-7)). The responses of these nine patients displayed significant heterogeneity. Of the five patients with toxicity and normal responses, two were treated with protocols that proved to be highly toxic. These results may enable physicians to predict toxicity and tailor treatment for individual patients.

  View details for DOI 10.1073/pnas.0307761101

  View details for PubMedID 15096622

• Portrait of transcriptional responses to ultraviolet and ionizing radiation in human cells NUCLEIC ACIDS RESEARCH Rieger, K. E., Chu, G. 2004; 32 (16): 4786-4803

  Abstract

  To understand the human response to DNA damage, we used microarrays to measure transcriptional responses of 10 000 genes to ionizing radiation (IR) and ultraviolet radiation (UV). To identify bona fide responses, we used cell lines from 15 individuals and a rigorous statistical method, Significance Analysis of Microarrays (SAM). By exploring how sample number affects SAM, we rendered a portrait of the human damage response with a degree of accuracy unmatched by previous studies. By showing how SAM can be used to estimate the total number of responsive genes, we discovered that 24% of all genes respond to IR and 32% respond to UV, although most responses were less than 2-fold. Many genes were involved in known damage-response pathways for cell cycling and proliferation, apoptosis, DNA repair or the stress response. However, the majority of genes were involved in unexpected pathways, with functions in signal transduction, RNA binding and editing, protein synthesis and degradation, energy metabolism, metabolism of macromolecular precursors, cell structure and adhesion, vesicle transport, or lysosomal metabolism. Although these functions were not previously associated with the damage response in mammals, many were conserved in yeast. These insights reveal new directions for studying the human response to DNA damage.

  View details for DOI 10.1093/nar/gkh783

  View details for Web of Science ID 000224207500009

  View details for PubMedID 15356296

  View details for PubMedCentralID PMC519099