American Journal of Dermatopathology最新文献

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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Background: Dermatomyositis is an autoimmune disease characterized by heterogeneous clinical and histopathologic features. Myositis-specific antibodies and myositis-associated antibodies have been linked to distinct clinical phenotypes, but their relationship with specific histopathologic features is unclear. This study aimed to characterize cutaneous histologic patterns in dermatomyositis patients with known autoantibody profiles.

Methods: We conducted a retrospective review of patients with positive myositis-specific antibody/myositis-associated antibody serology, a clinical diagnosis of dermatomyositis, and skin biopsies of lesional dermatomyositis-affected skin. Clinical data were extracted from medical records, and histopathologic features were recorded after masked review by 3 subspecialized dermatopathologists. Associations between antibody subtypes and histopathologic features were analyzed using Fisher exact test.

Results: The cohort comprised 30 patients who underwent 47 biopsies between 2009 and 2024. The most prevalent features were vacuolar interface dermatitis (70.4%), dermal mucin (71.1%), and mild superficial perivascular inflammation (81.5%). Perivascular inflammation without associated interface dermatitis was associated with nuclear matrix protein 2 positivity ( P < 0.01). Transcriptional intermediary factor 1γ-positive biopsies were less likely to demonstrate dermal mucin ( P < 0.01). No significant associations were found between antibodies and adnexal inflammation or the type of interface dermatitis (vacuolar or lichenoid).

Conclusions: Variability in skin biopsy findings from dermatomyositis patients with specific autoantibodies is limited. Perivascular inflammation without interface change and an absence of dermal mucin may be more common in patients with nuclear matrix protein 2 and TIF1γ autoantibodies, respectively. These observations may aid diagnosis in cases with atypical histologic features.

Abstract: We report an exceptional case of a neoplasm with myoepithelial differentiation arising in the eyelid of a 50-year-old woman, representing the first documented instance of a HAS2::PLAG1 gene fusion in this anatomical location. The tumor exhibited a biphasic morphology with both spindle and epithelioid cell components and demonstrated aberrant immunohistochemical expression of ALK protein, although molecular analysis did not reveal any ALK gene rearrangements. This case underscores the importance of comprehensive molecular diagnostics in resolving immunophenotypic ambiguities and accurately classifying rare adnexal tumors.

Abstract: Cutaneous melanomas are most commonly driven by somatic mutations in genes such as BRAF , NRAS , KIT , or NF1 , with kinase fusions being rare in conventional melanomas of non-Spitz lineage. RAF1 , a key upstream regulator of the mitogen-activated protein kinase pathway, is infrequently rearranged in non-Spitz melanomas (ie, bona fide melanomas without Spitz-nevus-like cytomorphology), with a reported frequency of less than 1%. As a result, the clinicopathologic features and prognostic implications of RAF1 -rearranged melanomas remain poorly defined. We report a case of melanoma harboring a MAP4::RAF1 fusion in a 24-year-old man who presented with a 1-cm papule on the left ankle. Histopathologically, the tumor was an ulcerated nodular melanoma with a Breslow thickness of 4.1 mm. The tumor cells were predominantly epithelioid and amelanotic, arranged in large and small nests, without definitive spitzoid cytomorphologic features. Sentinel lymph node biopsy revealed metastatic melanoma, resulting in a final stage of pT4bN1a. Molecular profiling demonstrated a triple wild-type melanoma harboring a MAP4::RAF1 fusion, a TERT promoter mutation, and several additional previously undescribed somatic mutations, with a panel-derived tumor mutational burden of 7 mutations/Mb, as estimated using a targeted next-generation sequencing assay with an approximately 2.1 Mb capture region. The disease was refractory to multiple lines of treatment, including dual immunotherapy and chemotherapy, and the patient died 18 months after diagnosis. This case represents a rare and fatal example of a triple wild-type cutaneous melanoma with a MAP4::RAF1 fusion in a young adult, thereby expanding the clinicopathologic and prognostic spectrum of RAF1 -fused melanomas of non-Spitz lineage.