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Context.--A variety of uncommon malignant endometrial tumors can be challenging to diagnose because of overlapping morphology with more common entities. In some cases, immunohistochemical stains and/or molecular testing allow for more definitive diagnosis or prognostication. Objective.--To review classic morphologic features of uncommon endometrial tumors, pathologic features of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in the diagnosis of these tumors. Data Sources.--University of Michigan (Ann Arbor) cases and review of pertinent literature about each entity. Conclusions.--Although each of these uncommon endometrial tumors has morphologic mimics, key histologic features, immunohistochemical stains, and molecular testing allow for accurate classification. doi: 10.5858/arpa.2023-0098-RA, Although endometrial carcinoma is a common gynecologic malignancy, (1) there is suboptimal interobserver reproducibility in the diagnosis of high-grade endometrial cancers (ECs). (2-5) Historically, risk has been determined based on [...]

* Context.--Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva's anatomic location. Objectives.--To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties. Design.--One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6). Results.--Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95,1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96,1.20, and 1.08, respectively; P < .001). Conclusions.--There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN. (Arch Pathol Lab Med. 2023;147:1431-1437; doi: 10.5858/arpa.2022-0088-OA), Differentiated vulvar intraepithelial neoplasia (dVIN) has been well accepted as a precursor lesion of human papillomavirus (HPV)-independent squamous cell carcinoma (SCC) of the vulva. (1,2) Recognition of dVIN and its [...]

* Context.--While the vast majority of cervical tumors consist of human papillomavirus (HPV)-related squamous cell carcinoma or adenocarcinoma, a subset of rare tumor types, frequently unrelated to HPV, does occur in this location. These tumors vary widely in prognostic and therapeutic implications, and accurate recognition is crucial to providing appropriate treatment. Some are benign or portend a favorable prognosis (adenoid basal carcinoma, ectopic prostate tissue), while others are frankly malignant lesions with a less favorable prognosis (adenoid cystic carcinoma, HPV-negative endocervical adenocarcinoma, mesonephric adenocarcinoma, clear cell carcinoma, small cell carcinoma, and adenosquamous carcinoma). Objective.--To review the morphologic features of uncommon cervical lesions, the utility of immunohistochemistry for distinction between these entities, and the clinical and prognostic implications of accurate diagnosis. Data Sources.--University of Michigan cases and review of the pertinent literature regarding the entities described. Conclusions.--Key morphologic and immunohistochemical features detailed herein will allow for the accurate distinction between these uncommon cervical lesions. Morphology is most useful in discriminating between the entities, as there is frequent immunohistochemical overlap between them; however, in rare instances immunohistochemistry can be useful in resolving the diagnosis. (Arch Pathol Lab Med. 2021;145:891-902; doi: 10.5858/arpa.2020-0327-RA), Cervical cancer, a disease that has rapidly declined in incidence owing to the advent of routine screening with the Papanicolaou test and high-risk human papillomavirus (HPV) testing, primarily consists of [...]

* Context.--Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course that can arise de novo or from a low-grade B-cell lymphoma. In particular, chronic lymphocytic leukemia/small lymphocytic lymphoma is a very common malignancy in the Western hemisphere, and most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma have an indolent course and behavior. However, 2% to 8% of chronic lymphocytic leukemia/small lymphocytic lymphoma cases transform. Histiocytic sarcomatous transformation is rare and portends poor prognosis.Objective.--To review the clinical features, morphology, and key points related to the differential diagnosis for histiocytic sarcoma. We discuss recent understanding of the biology underlying transformation.Data Sources.--University of Michigan case and review of pertinent literature about histiocytic sarcoma and morphologic differential diagnosis.Conclusions.--Histiocytic sarcoma is a rare histiocytic neoplasm that can arise as a result of trans-differentiation from low-grade B-cell lymphomas, and has a wide differential diagnosis including other histiocytic/dendritic cell neoplasms, myeloid neoplasms, lymphomas, melanoma, and carcinoma. However, some key morphologic and immunohistochemical features allow for accurate classification.(Arch Pathol Lab Med. 2018;142:1322-1329; doi: 10.5858/arpa.2018-0220-RA), Histiocytic sarcoma is a rare neoplasm of mature histiocytes, and is considered to be a true hematopoietic tumor. (1,2) It can present as a primary malignancy or, less commonly, a [...]

* Context.--Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma that is limited to the skin at diagnosis. It has a differential diagnosis that includes systemic/nodal follicular lymphoma secondarily involving the skin; primary cutaneous diffuse large B-cell lymphoma leg type; reactive lymphoid hyperplasia; and primary cutaneous marginal zone lymphoma. Objective.--To review the clinical, morphologic, immunophenotypic, and genetic features of primary cutaneous follicle center lymphoma; its differential diagnosis; and the evidence that supports use of immunohistochemistry and genetic testing in the diagnosis and prognosis of this entity. Data Sources.--Pertinent literature regarding cutaneous B-cell lymphomas is summarized and University of Michigan cases are used to highlight characteristics of primary cutaneous follicle center lymphoma. Conclusions.--Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma with distinctive features, although some cases may have elements that overlap with other lymphomas, complicating interpretation. (Arch Pathol Lab Med. 2018;142:1313-1321; doi: 10.5858/arpa.2018-0215-RA), By definition, primary cutaneous follicle center lymphoma (PCFCL) is a lymphoma of follicle center B cells without evidence of systemic/nodal involvement at the time of diagnosis. (1-5) It is a [...]

Context.--Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is an uncommon disorder with germline-inactivating mutations in the fumarate hydratase (FH) gene. The kidney cancers that develop in patients with HLRCC are often unilateral and solitary, with a potentially aggressive clinical course; morphologic identification of suspicious cases is of the utmost importance. Objective.--To review classic morphologic features of HLRCC-associated renal cell carcinoma, the reported morphologic spectrum of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in diagnosis of these tumors. Data Sources.--University of Michigan cases and review of pertinent literature about HLRCC and the morphologic spectrum of HLRCC-associated renal cell carcinoma. Conclusions.--Histologic features, such as prominent nucleoli with perinucleolar halos and multiple architectural patterns within one tumor, are suggestive of HLRCC-associated renal cell carcinoma. However, the morphologic spectrum is broad. Appropriate use of FH immunohistochemistry and referral to genetic counseling is important for detection of this syndrome. doi: 10.5858/arpa.2018-0216-RA, Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), also referred to as Reed syndrome, (1-4) is a rare familial cancer disorder caused by a germline mutation in the fumarate hydratase [...]