Colbert MD, Holder K, Tekin B
… +4 more, Buonaccorsi JN, Geiersbach KB, Guo RR, Camilleri MJ
Am J Dermatopathol
· 2026 May · PMID 41650288
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Melanoma exhibits a broad spectrum of histopathologic variations, including rare forms with neural differentiation. Neurotropism in melanoma encompasses both perineural invasion and neural-like transformation, but the pr...Melanoma exhibits a broad spectrum of histopathologic variations, including rare forms with neural differentiation. Neurotropism in melanoma encompasses both perineural invasion and neural-like transformation, but the prognostic implications of these features remain uncertain. Although (peri)neural invasion is well documented, true neural differentiation in melanomas is exceedingly rare. In this study, we describe an unusual case of primary cutaneous malignant melanoma exhibiting extensive Wagner-Meissner-like bodies, a feature more commonly associated with benign neural tumors and nevi. In this case, histopathology revealed a dual-component lesion with a neurotized and an epithelioid melanocytic component, both showing PRAME expression and p16 loss. Chromosomal microarray identified heterozygous loss of 9p22.1p13.1 (including CDKN2A / CDKN2B ), and loss of 10q22.2q26.3 (including PTEN ), supporting malignancy. These findings suggest that in this case, Wagner-Meissner-like bodies likely represent neurotization rather than a benign or collision lesion, highlighting the need for integrated histopathologic, immunohistochemical, and molecular analysis in challenging melanocytic neoplasms.
Russolillo JK, Schaedler A, Hsia B
… +3 more, Silberstein PT, Tauseef A, Torbenson E
Am J Dermatopathol
· 2026 May · PMID 41650285
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BACKGROUND: Acral melanoma (AM) is a rare but aggressive melanoma subtype that arises on palmoplantar surfaces and nail units. It disproportionately affects individuals with darker skin tones and is frequently diagnosed...BACKGROUND: Acral melanoma (AM) is a rare but aggressive melanoma subtype that arises on palmoplantar surfaces and nail units. It disproportionately affects individuals with darker skin tones and is frequently diagnosed at advanced stages. Limited genomic data have hindered the development of effective targeted therapies. METHODS: A retrospective genomic analysis of AM was conducted using the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange repository, evaluating 212 tumor samples from 203 patients for somatic mutations, copy number alterations, and mutational patterns across demographic and clinical variables. Co-occurrence, mutual exclusivity, and survival analyses were also performed. RESULTS: NRAS (21.2%), BRAF (18.3%), and KIT (9.0%) were the most common mutations. CDKN2A and CDKN2B deletions occurred in over 20% of the samples, along with recurrent amplifications in CDK4 , CCND1 , and TERT . Significant comutation patterns included NF1 - PTPRT and KRAS - TERT . Mutation frequencies varied across sex and racial groups, and NAB2 mutations were exclusive to metastatic tumors. CONCLUSION: This study provides a comprehensive genomic overview of AM, highlighting recurrent alterations in the MAPK and cell cycle pathways, and potential demographic-specific molecular signatures. These findings support the need for expanded molecular profiling to improve prognostic accuracy and identify targets for future therapy.
Wong S, Sorial C, Siddiqui F
… +2 more, Fernandez C, Saeed S
Am J Dermatopathol
· 2026 Jun · PMID 41649408
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Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma classically characterized by small blue cell morphology and a distinctive perinuclear dot-like cytokeratin 20 (CK20) staining pa...Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma classically characterized by small blue cell morphology and a distinctive perinuclear dot-like cytokeratin 20 (CK20) staining pattern. Rare histologic variants, however, may deviate from these defining features and pose significant diagnostic challenges. We report a diagnostically challenging case of large-cell variant MCC arising on the left distal dorsal forearm of a 61-year-old man, highlighting its distinctive morphologic and immunophenotypic features. Histopathologic examination revealed a predominantly dermal-based neoplasm composed of pleomorphic large epithelioid cells with abundant cytoplasm, enlarged nuclei, frequent mitotic figures, and focal architectural patterns mimicking adnexal differentiation, including tubule-like structures and sebocyte-like cells. Classic finely stippled "salt-and-pepper" chromatin was inconspicuous. Immunohistochemical analysis demonstrated diffuse pankeratin positivity and strong diffuse cytoplasmic CK20 staining, obscuring the characteristic perinuclear dot-like accentuation typically associated with MCC. The tumor also showed diffuse expression of neuroendocrine markers, including insulinoma-associated protein 1 (INSM1), neurofilament, chromogranin, and synaptophysin, with rare tumor cells exhibiting aberrant CK5/6 and CK7 expression. These findings expanded the differential diagnosis to include sebaceous carcinoma, porocarcinoma, and metastatic carcinoma. Integration of histomorphology with a comprehensive immunohistochemical panel supported a final diagnosis of large-cell variant MCC. This case underscores the importance of recognizing atypical morphologic and immunophenotypic presentations of MCC and reinforces the need for broad immunohistochemical evaluation to ensure appropriate management of this aggressive malignancy.
Mucinous syringometaplasia is a rare adnexal process that may mimic mucinous carcinoma or metastatic mucinous adenocarcinoma, creating diagnostic challenges. After reviewing the recent report by Furtado et al, we present...Mucinous syringometaplasia is a rare adnexal process that may mimic mucinous carcinoma or metastatic mucinous adenocarcinoma, creating diagnostic challenges. After reviewing the recent report by Furtado et al, we present a brief additional case involving a longstanding ulcerated plaque on the dorsal hand of a 61-year-old man. Histology demonstrated an epidermal invagination connected to eccrine ducts lined by nonkeratinizing squamous epithelium with abundant goblet cells, strongly positive with Alcian blue, and negative for CDX2, supporting a primary cutaneous eccrine-derived mucinous metaplasia. We emphasize 2 practical considerations: the limited sensitivity and specificity of CDX2 in excluding gastrointestinal primaries, and the importance of correlating morphology with mucin stains and a focused immunohistochemical panel to avoid overdiagnosis. We further note that mucinous syringometaplasia is likely a reactive/metaplastic phenomenon related to local irritation or trauma, and encourage standardized diagnostic criteria and multicenter registries to improve understanding of its incidence, behavior, and diagnostic pitfalls.
Lymphomatoid papulosis (LyP) type E is a rare form of primary cutaneous CD30 + lymphoproliferative disorder characterized by recurrent ulcerative lesions on the skin and/or mucous membranes, after a course of remissions...Lymphomatoid papulosis (LyP) type E is a rare form of primary cutaneous CD30 + lymphoproliferative disorder characterized by recurrent ulcerative lesions on the skin and/or mucous membranes, after a course of remissions and relapses; however, it is a localized disease with a good prognosis. We have previously reported 2 cases of LyP types C and D with exclusively intraoral involvement. To date, 32 cases of intraoral LyP have been reported. Of them, only 3 cases were diagnosed as LyP type E. We report a 17-year-old Mexican female patient who developed multiple intraoral lesions, without skin or other mucosal surface involvement, with episodes of remission and exacerbation. Histopathologic analysis revealed infiltrates of small-to-medium-sized atypical lymphoid cells, with foci of angiocentric and angioinvasive pattern. By immunohistochemistry, the atypical lymphoid cells were positive for CD3, CD5, CD7 (partial loss), and CD8. Unlike TCRD, TCRBF1 highlighted numerous atypical lymphoid cells, which were also CD30, granzyme B, perforin, TIA-1, and MUM1 positive, and whose angiocentric and angioinvasive pattern was evidenced through CD34 and α-SMA markers. EBER1/2 was negative, with Ki-67 highlighting most atypical lymphoid cells. Treatment with topical corticosteroids has provided considerable improvements, showing resolution of lesions. To the best of our knowledge, this is the first case of LyP type E affecting a pediatric patient with lesions confined to the oral mucosa.
Hamilton L, Jimenez A, Linfante A
… +4 more, Kelly B, Gibson B, Torres-Cabala CA, Curry JL
Am J Dermatopathol
· 2026 Feb · PMID 41592302
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Interdigitating dendritic cell sarcoma (IDCS) is a rare tumor derived from dendritic cells and has been reported in slightly more than 100 cases in literature. IDCS of the skin is an exceedingly rare presentation, noted...Interdigitating dendritic cell sarcoma (IDCS) is a rare tumor derived from dendritic cells and has been reported in slightly more than 100 cases in literature. IDCS of the skin is an exceedingly rare presentation, noted in 8 case reports in published literature. We present a rare case of a 44-year-old man who presented with primary cutaneous IDCS on his posterior neck, who was later discovered to have biopsy-confirmed IDCS lung metastases. Secondary to this, the patient was found to have a superficial spreading melanoma on his left shoulder, consistent with the notion that cutaneous IDCS increases a patient's risk of secondary malignancies. Upon further investigation of his IDCS, bilateral lung metastases of IDCS were identified and the patient received several cycles of chemotherapy. This case contributes to the limited body of knowledge on cutaneous IDCS and its treatment modalities. The poor prognosis associated with metastatic IDCS highlights the importance for further research to identify treatment regimens that lead to better prognosis.
Am J Dermatopathol
· 2026 Feb · PMID 41592301
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The "clown nose" is a rare clinical presentation characterized by reddish-brown nodular lesions localized to the nasal tip. This distinctive sign has been associated with metastatic malignancies, genetic syndromes, and p...The "clown nose" is a rare clinical presentation characterized by reddish-brown nodular lesions localized to the nasal tip. This distinctive sign has been associated with metastatic malignancies, genetic syndromes, and primary dermatologic conditions. We describe a rare case of metastatic eccrine porocarcinoma manifesting as a clown nose in a 54-year-old man with a history of metastatic lung squamous cell carcinoma. In addition, we performed a systematic literature review through PubMed to evaluate infiltration of the nose as a potential indicator of underlying tumor metastasis.
Gandhi I, Adler R, Fishman C
… +3 more, Islam Z, Zhou L, Phelps R
Am J Dermatopathol
· 2026 Feb · PMID 41592300
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We present a rare case of squamous cell carcinoma with rhabdoid features (SCCR), an aggressive histological variant of SCC, in a 63-year-old man with a history of liver transplantation, alongside a review of the literatu...We present a rare case of squamous cell carcinoma with rhabdoid features (SCCR), an aggressive histological variant of SCC, in a 63-year-old man with a history of liver transplantation, alongside a review of the literature on previously reported cases (n = 14). SCCR is characterized by large, ovoid, or polygonal carcinoma cells with eosinophilic cytoplasmic inclusions, eccentric nuclei, and prominent nucleoli. While typically associated with INI-1-inactivating mutations and linked to immunosuppression, particularly post-transplantation, the exact pathogenesis of SCCR remains unclear.The patient presented with an ulcerating, elevated mass on the right parietal scalp 5 months post-transplant, while on tacrolimus and mycophenolate therapy. Pathological analysis revealed moderately differentiated SCC with rhabdoid morphology, measuring 13 mm in thickness, extending close to the specimen's base. Immunohistochemistry demonstrated positivity for INI-1, EMA (focal), and CK5/6, with negative staining for desmin, CK18, and CK19.This case highlights the distinct clinical and pathological manifestations of SCCR and underscores the potential for its development following immunosuppression. Increased awareness of this rare and aggressive entity is crucial for timely diagnosis and management.
Am J Dermatopathol
· 2026 May · PMID 41568758
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Myxofibrosarcoma is a malignant fibroblastic neoplasm characterized by cellular pleomorphism, myxoid stroma, distinctive curvilinear vessels, nonspecific immunophenotype, and complex karyotype. The epithelioid variant is...Myxofibrosarcoma is a malignant fibroblastic neoplasm characterized by cellular pleomorphism, myxoid stroma, distinctive curvilinear vessels, nonspecific immunophenotype, and complex karyotype. The epithelioid variant is a rare subtype composed of atypical cells featuring abundant eosinophilic cytoplasm and vesicular nuclei, closely mimicking nonmesenchymal malignancies. We report an exceptionally rare case of cutaneous epithelioid myxofibrosarcoma on the face of a 70-year-old man. The patient presented with a progressively enlarged cheek mass. Histopathologic examination revealed a dermal and subcutaneous tumor with a multinodular growth pattern and significant heterogeneity. It featured peripheral low-grade areas with myxoid stroma and curvilinear vessels and a central high-grade component (>50%) composed of solid sheets of epithelioid cells with severe nuclear atypia, prominent macronucleoli, and a high mitotic rate (>20 mitoses per 10 HPF). Tumor cells were focally positive for smooth muscle actin but negative for melanocytic, epithelial, myoepithelial, and lymphoid markers. CD34 highlighted the characteristic curvilinear vasculature of the tumor. Molecular analysis showed no mutations in BRAF, NRAS, or KIT genes, ultimately resulting in the diagnosis of high-grade epithelioid myxofibrosarcoma (FNCLCC grade 3). No recurrence or metastasis occurred within 9 months of follow-up. This case underscores the diagnostic challenge of cutaneous sarcomas in the head and neck region and highlights the necessity of a multimodal approach for an accurate diagnosis.