Cooper Rutland

All Publications

• RNA in situ hybridization detection of CRTC1/3::MAML2 fusions and LINC00473 in mucoepidermoid carcinomas and hidradenomas of breast, salivary glands, and skin. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Rutland, C. D., Kingsley, L., Wang, A., Zdravkovic, S., Das, I., Bremer, R., Laser, J. S., Bridge, J. A., Bishop, J. A., Krings, G., Chen, Y. Y., Bean, G. R. 2025: 100756

  Abstract

  Genomic rearrangements involving MAML2 have been reported in mucoepidermoid carcinoma (MEC) arising in various anatomic sites, as well as the benign counterpart of hidradenoma. Depending on the location, MAML2-rearranged neoplasms may share morphologic overlap with additional diagnostic entities including other salivary gland malignancies and cutaneous mimics. In some cases, detection of a CRTC1::MAML2 or less common CRTC3::MAML2 rearrangement by fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) may be necessary to help confirm the diagnosis. However, such testing can be time consuming, relatively expensive, and unavailable in many pathology laboratories. We describe the development and validation of an in situ hybridization (ISH) custom BaseScope assay targeting the recurrent breakpoints of CRTC1::MAML2 and CRTC3::MAML2 rearrangements. Moreover, we investigated the diagnostic utility of LINC00473 RNAscope as a surrogate marker for MAML2 fusion status. LINC00473 is a long non-coding RNA reportedly downstream of the CRTC1::MAML2 oncoprotein. We evaluated 227 patient cases, including 30 salivary gland and 2 breast MEC, 14 cutaneous and 8 breast hidradenoma, and 173 cases representing >20 potential histologic entities in the differential diagnosis for the presence of each fusion transcript by BaseScope, and a subset of cases (n=205) for the detection of LINC00473 by RNAscope. RNA ISH was directly visualized by chromogenic signal, and the MAML2 fusion partner could be positively identified in the majority of cases. Overall, RNA ISH demonstrates high concordance with orthogonal testing, with CRTC1/3::MAML2 BaseScope showing 93% sensitivity and 100% specificity and LINC00473 RNAscope showing 92% sensitivity and 99% specificity. RNA ISH for CRTC1/3::MAML2 rearrangements and LINC00473 represent reasonable timely and cost-effective alternatives to FISH and NGS. Such markers may provide the means for accurate diagnosis to ensure appropriate therapy of MEC and HA-neoplasms that can arise in multiple anatomic sites and be encountered by a wide range of pathologists.

  View details for DOI 10.1016/j.modpat.2025.100756

  View details for PubMedID 40107452

• Acellular Dermal Matrix: Imaging Features With Histopathology Correlation. Journal of breast imaging Dhami, A., Rutland, C. D., Momeni, A., Waheed, U. 2024

  Abstract

  Acellular dermal matrix (ADM) is an immunologically inert graft, typically from cadaveric skin, often used in postmastectomy breast reconstruction. Created from decellularized dermal tissues that have been treated to remove DNA and antigenic donor cells (leaving extracellular matrix), ADM is often used as a structural scaffold or sling to reinforce and support the structure and position of a breast implant during postoperative integration in implant-based breast reconstruction; ADM can also be used to fill cosmetic defects. Advantages of ADM use include improved cosmesis and reduced capsular contracture rates. On US, ADM can be seen as a subtle band with variable echogenicity adjacent to the implant. When folded on itself or redundant, ADM may present as a palpable oval mass with indistinct or circumscribed margins and variable echogenicity. On mammography, ADM can be seen as a circumscribed oval equal density mass when redundant and folded on itself; a layered appearance may be evident on tomosynthesis. On MRI, presence and absence of enhancement have been documented. Imaging findings likely vary depending on the degree of host tissue remodeling and incorporation, and when biopsied, histopathologically, ADM may be difficult to distinguish from scarring. Successful imaging diagnosis of ADM is aided by clinical knowledge of the intraoperative use and configuration of ADM, which may help differentiate ADM from new or recurrent malignancy and avoid unnecessary biopsy.

  View details for DOI 10.1093/jbi/wbae054

  View details for PubMedID 39248808

• Targeted DNA sequencing in diagnosis of malignant phyllodes tumors with emphasis on tumors with keratin and p63 expression. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Ye, J., Theparee, T., Bean, G. R., Rutland, C. D., Schwartz, C. J., Vohra, P., Allard, G., Wang, A., Hosfield, E. M., Peng, Y., Chen, Y. Y., Krings, G. 2024: 100593

  Abstract

  The differential diagnosis of malignant spindle cell neoplasms in the breast most frequently rests between malignant phyllodes tumor (MPT) and metaplastic carcinoma (MBC). Diagnosis of MPT can be challenging due to diffuse stromal overgrowth, keratin (CK) and/or p63 immunopositivity, and absent CD34 expression, which can mimic MBC, especially in core biopsies. Distinction of MPT from MBC has clinical implications, with differences in surgical approach, chemotherapy, and radiation. In this study, we evaluated MPT (78 tumors, 64 patients) for stromal CK, p63, and CD34 expression and profiled a subset (n=31) by targeted next-generation DNA sequencing (NGS), with comparison to MBC (n=44). Most MPT (71%) were CK+ and/or p63+, including 32% CK+ (25/77 focal) and 65% p63+ (32/66 focal, 10/66 patchy, 1/66 diffuse). Thirty-percent of MPT expressed both CK and p63 (20/66), compared to 95% of MBC (40/42, p<0.001). CK and/or p63 were positive in CD34+ and CD34- MPT. Recurrent genetic aberrations in MPT involved TERT, TP53, MED12, CDKN2A, chromatin modifiers, growth factor receptors/ligands, and PI-3K and MAPK pathway genes. Only MED12 (39%, 12/31) and SETD2 (13%, 4/31) were exclusively mutated in MPT and not MBC (p<0.001 and p=0.044, respectively), whereas PIK3R1 mutations were only found in MBC (35%, 13/35, p<0.001). Comparative literature review additionally identified ARID1B, EGFR, FLNA, NRAS, PDGFRB, RAD50, and RARA alterations enriched or exclusively in MPT versus MBC. MED12 was mutated in MPT with diffuse stromal overgrowth (53%, 9/17), CD34- MPT (41%, 7/17), and CK+ and/or p63+ MPT (39%, 9/23), including 36% of CD34- MPT with CK and/or p63 expression. Overall, MED12 mutation and/or CD34 expression were observed in 68% (21/31) MPT, including 61% (14/23) of CK+ and/or p63+ tumors. Our results emphasize the prevalence of CK and p63 expression in MPT and demonstrate diagnostic utility of NGS, especially in MPT with confounding factors that can mimic MBC.

  View details for DOI 10.1016/j.modpat.2024.100593

  View details for PubMedID 39154782

• Contemporary diagnostic approach to atypical vascular lesion and angiosarcoma. Seminars in diagnostic pathology Rutland, C. D., Bean, G. R., Charville, G. W. 2023

  Abstract

  Vascular neoplasms account for a substantial fraction of cutaneous mesenchymal tumors, spanning from clinically indolent benign lesions to highly aggressive malignancies. These neoplasms present a distinctive challenge in terms of their diagnostic histopathology, both because of the breadth of their morphological manifestations and because of the significant histological overlap between different entities, even benign and malignant ones. The post-radiotherapy setting is particularly problematic diagnostically, insofar as radiation exposure predisposes not only to secondary angiosarcoma, but also to atypical vascular lesion, a largely benign proliferation of cutaneous blood vessels typically affecting the breast. To address these challenges, we explore the clinical, histological, and molecular features of malignant vascular neoplasia, including primary and secondary subtypes, through the comparative lens of atypical vascular lesion. In addition to highlighting the key morphological indicators of malignancy in superficial vasoformative tumors, we offer an approach that integrates clinical characteristics and molecular genetic profiling to facilitate accurate classification. With this current knowledge as our foundation, we also look ahead in an effort to frame some of the key unanswered questions regarding superficial vascular malignancies and their natural history, clinical management, and molecular underpinnings.

  View details for DOI 10.1053/j.semdp.2023.04.017

  View details for PubMedID 37121782

• Diagnostic utility of FOXO1 immunohistochemistry for rhabdomyosarcoma classification. Histopathology Rutland, C. D., Gedallovich, J., Wang, A., Zdravkovic, S., Varma, S., Hornick, J. L., Charville, G. W. 2023

  Abstract

  AIMS: Rhabdomyosarcomas currently are classified into one of four subtypes (alveolar, embryonal, spindle cell/sclerosing, or pleomorphic) according to their morphological, immunohistochemical, and molecular genetic features. The alveolar subtype is characterized by a recurrent translocation involving PAX3 or PAX7 and FOXO1; identification of this translocation is important for appropriate classification and prognostication. In this study, we aimed to explore the diagnostic utility of FOXO1 immunohistochemistry for rhabdomyosarcoma classification.METHODS/RESULTS: A monoclonal antibody targeting a FOXO1 epitope retained in the fusion oncoprotein was used to study 105 rhabdomyosarcomas. FOXO1 was positive for expression by immunohistochemistry in all 25 alveolar rhabdomyosarcomas with 84% showing diffuse expression in greater than 90% of neoplastic cells; the remainder of alveolar rhabdomyosarcomas displayed at least moderate staining in a minimum of 60% of lesional cells. Apart from three spindle cell rhabdomyosarcomas showing heterogeneous nuclear immunoreactivity in 40-80% of tumor cells, the 80 cases of embryonal, pleomorphic, and spindle cell/sclerosing rhabdomyosarcoma were negative for FOXO1 expression (96.3% specific) when using a threshold of nuclear staining in 20% of neoplastic cells to determine positivity. Variable cytoplasmic staining was present in a fraction of all rhabdomyosarcoma subtypes. Non-neoplastic lymphocytes, endothelial cells, and Schwann cells also showed variably intense nuclear anti-FOXO1 immunoreactivity.CONCLUSIONS: Taken together, our findings suggest that FOXO1 immunohistochemistry is a highly sensitive and relatively specific surrogate marker of the PAX3/7::FOXO1 fusion oncoprotein in rhabdomyosarcoma. Cytoplasmic immunoreactivity, expression in non-neoplastic tissues, and limited nuclear staining of non-alveolar rhabdomyosarcomas represent potential pitfalls in interpretation.

  View details for DOI 10.1111/his.14898

  View details for PubMedID 36860202

• TRPS1 Immunohistochemical Evaluation of Paget Disease Rutland, C., Wang, A., Krings, G., Bean, G. ELSEVIER SCIENCE INC. 2023: S204-S205

  View details for Web of Science ID 000990969800216