Am J Dermatopathol
· 2026 May · PMID 42012242
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Onychopapilloma (OP) is a benign tumor of the nail. In all studies of the literature including the World Health Organization new classification of nail tumor, OP is proposed as a tumor originating in the distal matrix an...Onychopapilloma (OP) is a benign tumor of the nail. In all studies of the literature including the World Health Organization new classification of nail tumor, OP is proposed as a tumor originating in the distal matrix and defined histologically by its onychogenic property as "matrix metaplasia of the nail bed."The aim of this study is to clarify the origin and type of keratinization of OP, to emphasize the application of clear histological criteria according to the type of surgical procedure, to present new clinical and histological subtypes of OP, and to discuss the differential diagnosis.Eighty-six cases were available for clinicopathologic review. Detailed clinicopathological analysis could be performed on 56 cases.In addition to the classic clinical presentations of longitudinal erythronychia, longitudinal leukonychia, longitudinal melanonychia, 2 cases presented an unusual band pattern in the form of xanthonychia. Histological interpretation was more difficult for samples obtained by tangential longitudinal excision than for those obtained by longitudinal monobloc excision. The superficial eosinophilic layer of the nail bed was either clearly identified by its round to oval nuclei or showed features simulating a keratogenous zone by foci of irregularly contoured pycnotic nuclei. In all cases, the so-called matrix metaplasia of the nail bed corresponded to an onycholemmal keratinization with 2 types of cornified cells: clear cells either parakeratotic or orthokeratotic, and eosinophilic cells. The clear orthokeratotic cornified cells sometimes simulated abnormal enlarged onychocytes. The onychogenic marker including hair related keratin (HK) 31, HK85, HK86, LEF-1, and beta-catenin were not expressed in the nail bed. The samples obtained by tangential longitudinal excision frequently showed incomplete or complete deepithelialization. In incomplete deepithelialization, 2 clues suggested a diagnosis of OP: numerous filiform superficial papillae and remnants of nail bed epithelium with a superficial eosinophilic layer. In complete deepithelialization, only examination of the nail plate allowed the diagnosis to be established. Loss of the organization of the suprabasal layers, dyskeratosis, and keratinocytes with clear cytoplasm were occasionally observed. However, the absence of nuclear atypia confirmed by the normal expression of Ki67 and p53 ruled out in situ onycholemmal carcinoma/malignant OP. Two new histological subtypes have been observed. OP with lesions resembling seborrheic keratosis. OP with an overexpression of CD10 simulating the stroma of OM. Nail clipping has proven to be potentially useful in the differential diagnosis between OP with seborrheic keratosis-like lesions and onychogenic tumor such as onychocytic matricoma and onychomatricoma. In contrast to the thick nail plate perforated by cavities of onychogenic tumors, OP was characterized by a focal thin nail plate with longitudinal groove. On excised lesion, the negativity of the onychogenic markers such as LEF-1 or beta-catenin led to a definitive diagnosis of OP.OP is a nail bed onycholemmal papilloma. Numerous whorls of fusiform eosinophilic cells and true dyskeratotic cells could raise concern for the possibility of a low-grade in situ onycholemmal carcinoma. Awareness of this distinctive pattern of OP along with supplemental immunostaining will assist in enabling the correct diagnosis to be made. The KS-like variant could cause a diagnostic pitfall with onychocytic matricoma. The lack of white dots and rounded white clods on clinical examination and the focal thinning of the nail plate, on histological examination of nail clipping, provide clues for the diagnosis.
BAP1 (BRCA 1-associated protein 1)-inactivated melanocytic tumor (BIMT) is a melanocytic neoplasm characterized histologically by large epithelioid cells and is commonly associated with a conventional nevus component. Th...BAP1 (BRCA 1-associated protein 1)-inactivated melanocytic tumor (BIMT) is a melanocytic neoplasm characterized histologically by large epithelioid cells and is commonly associated with a conventional nevus component. The defining molecular alteration is inactivation of the BAP1 gene. Initiating mutations in BIMT include BRAF p.V600E, or less commonly RAS mutations and fusions involving RAF1 . In this article, we report a case of BIMT with a BAP1 mutation and a novel PDZRN3::BRAF fusion. Histologic examination revealed an intradermal melanocytic neoplasm with nests and single units of large, atypical epithelioid cells with abundant amphophilic-eosinophilic cytoplasm, well-defined cell borders, large vesicular nuclei, and prominent nucleoli. Frequent binucleated and multinucleated melanocytes were present. There was no associated conventional nevus component. Scattered mitotic activity were identified. No evidence of maturation, necrosis, or lymphovascular or perineural invasion was seen. The lesional cells were immunoreactive for SOX10, Melan A, and HMB45 (focal, minimal, and weak), and were negative for PRAME. There was patchy loss of expression of p16 and complete loss of BAP1 expression. Molecular analysis demonstrated BAP1 mutation and a novel fusion involving PDZRN3::BRAF . Our finding expands our current understanding of the molecular landscape and pathogenesis of BIMT.
Systemic anaplastic large cell lymphoma with cutaneous involvement can mimic other malignancies and delay treatment. A 71-year-old Filipino woman had 18 months of minimally symptomatic plaques and nodules; a right-hip no...Systemic anaplastic large cell lymphoma with cutaneous involvement can mimic other malignancies and delay treatment. A 71-year-old Filipino woman had 18 months of minimally symptomatic plaques and nodules; a right-hip nodule enlarged to an 8 × 8 × 5-cm mass. She underwent radical wide excision of the right-hip mass and scalp nodules; only the hip specimen was submitted for histopathology and was read as a malignant spindle cell tumor favoring alveolar rhabdomyosarcoma, with rapid recurrence at the hip and scalp surgical sites. On referral, she had plaques and nodules, crusted scalp lesions, and lymphadenopathies. Repeat biopsies from scalp and recurrent hip lesions showed a dermal-subcutaneous infiltrate of large atypical lymphocytes with mitoses and periadnexal/intravascular involvement; immunohistochemistry was CD30/CD3/CD45 positive and ALK/EMA negative, consistent with ALK-negative systemic ALCL with cutaneous involvement. Staging revealed stage IV disease with extranodal metastases and elevated LDH. After a dose of ifosfamide/etoposide elsewhere, therapy was revised to ifosfamide, carboplatin, and etoposide plus brentuximab vedotin, with marked improvement by 2 cycles and cutaneous resolution by 5; she died of cardiopulmonary failure before the sixth cycle. This case underscores generous sampling, focused immunohistochemistry, and staging; negative ALK/EMA does not exclude systemic disease, and CD30-directed therapy can yield rapid cutaneous responses.
Squamoid eccrine ductal carcinoma (SEDC) is an exceptionally rare malignant adnexal tumor that remains frequently underrecognized due to its overlapping clinical and histopathologic features with more common cutaneous ne...Squamoid eccrine ductal carcinoma (SEDC) is an exceptionally rare malignant adnexal tumor that remains frequently underrecognized due to its overlapping clinical and histopathologic features with more common cutaneous neoplasms. This study presents a monocentric retrospective analysis of 16 patients with histologically confirmed SEDC diagnosed over a ten-year period. Clinical data, histopathologic parameters, immunohistochemical profiles, treatment approaches, and outcomes were systematically reviewed. The cohort predominantly comprised elderly individuals, with a male predominance and lesions arising mainly on sun-exposed areas of the head and neck. Clinically, SEDC manifested as erythematous or hyperkeratotic plaques or nodules often leading to an initial impression of squamous cell carcinoma. Histologically, tumors displayed the characteristic biphasic architecture with superficial squamoid differentiation and deeper ductal structures, frequently accompanied by subcutaneous infiltration or perineural involvement. Treatment consisted primarily of conventional excision, with complete margin clearance achieved in most cases; however, local recurrence occurred in 25% of patients, often within the first year. One patient developed distant metastases and died of disease. Clinical morphology, particularly erythematous plaque presentation, showed significant association with mortality, whereas deeper invasion demonstrated a trend toward worse outcomes. Despite its low metastatic potential, SEDC exhibits locally aggressive behavior, and diagnostic challenges remain common, especially on superficial biopsies. This series represents one of the largest single-center cohorts reported to date and underscores the importance of deep sampling, accurate histopathologic evaluation, and close clinical follow-up to optimize management of this rare adnexal carcinoma.
Pancreatic panniculitis is a rare cutaneous manifestation of pancreatic disease, most commonly occurring in patients with acute or chronic pancreatitis or pancreatic neoplasms. In most reported cases, pancreatic patholog...Pancreatic panniculitis is a rare cutaneous manifestation of pancreatic disease, most commonly occurring in patients with acute or chronic pancreatitis or pancreatic neoplasms. In most reported cases, pancreatic pathology is recognized before or concurrent with the onset of skin lesions; less commonly, panniculitis precedes the diagnosis. Histology demonstrates a lobular panniculitis with saponified fat necrosis and anucleate "ghost" adipocytes, findings that are pathognomonic. Clinically, pancreatic panniculitis presents as tender subcutaneous nodules, most often on the lower extremities, and may be accompanied by systemic manifestations such as fever and inflammatory arthritis. We report 2 cases of pancreatic panniculitis occurring in patients without abdominal pain.
BACKGROUND: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma and typically presents with erythematous or scaly patches in older adults with a CD4 + immunophenotype. In Sri Lanka, however, a hyp...BACKGROUND: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma and typically presents with erythematous or scaly patches in older adults with a CD4 + immunophenotype. In Sri Lanka, however, a hypopigmented variant with CD8 + predominance and an apparently indolent clinical course is frequently encountered. METHODS: A retrospective descriptive study was conducted on 243 patients with histologically confirmed MF diagnosed at the National Hospital, Kandy, between 2018 and 2024. Clinical, histopathologic, and immunophenotypic features were reviewed in all cases. A subset of 27 patients with a minimum follow-up of 2 years was analyzed for treatment modalities and clinical outcomes. Diagnoses were established according to WHO-EORTC 2018 criteria. RESULTS: Patients predominantly presented with hypopigmented patch-stage disease involving sun-protected sites. Histology showed subtle epidermotropism with small Pautrier microabscesses and a characteristic "eyeliner" pattern. Immunohistochemistry demonstrated a CD8 + -predominant infiltrate in 95.9% of cases, with absent or reduced CD4 expression. Most patients achieved complete or partial remission with topical therapy or phototherapy, and no progression to plaque or tumor stage was observed. CONCLUSIONS: Hypopigmented CD8 + MF in Sri Lanka represents an indolent clinicopathologic variant within the MF spectrum, recognition of which is essential to avoid misdiagnosis and overtreatment.
Divergent differentiation in primary cutaneous malignant melanoma is a rare phenomenon that can pose a significant diagnostic challenge. We present two new cases of primary cutaneous malignant melanoma with rhabdomyosarc...Divergent differentiation in primary cutaneous malignant melanoma is a rare phenomenon that can pose a significant diagnostic challenge. We present two new cases of primary cutaneous malignant melanoma with rhabdomyosarcomatous differentiation, highlighting its aggressive nature. Thorough histological sampling and inclusion of skeletal muscle immunostains are essential for accurate diagnosis, particularly when rhabdoid morphology is identified.
BACKGROUND: Ber-EP4 is an immunohistochemical marker targeting epithelial cell adhesion molecule and is widely applied in the diagnosis of cutaneous basal cell carcinoma (BCC). Although highly sensitive, variability in e...BACKGROUND: Ber-EP4 is an immunohistochemical marker targeting epithelial cell adhesion molecule and is widely applied in the diagnosis of cutaneous basal cell carcinoma (BCC). Although highly sensitive, variability in expression level and staining distribution may complicate interpretation in routine practice. OBJECTIVE: This study aimed to characterize Ber-EP4 expression and staining patterns in cutaneous BCC and to assess their associations with clinicopathological features. MATERIALS AND METHODS: Sixty surgically excised cases of cutaneous BCC were retrospectively analyzed. Ber-EP4 immunohistochemistry was performed using an automated staining platform. Expression was evaluated according to the proportion of positive tumor cells, and staining patterns were classified based on spatial distribution. Associations between Ber-EP4 expression and clinicopathological features were analyzed. RESULTS: All cases demonstrated Ber-EP4 positivity, with a mean percentage of Ber-EP4-positive tumor cells per case of 78.1%. High-level expression was observed in 68.3% of cases. Diffuse staining was the predominant pattern, identified in 85.0% of tumors, while nondiffuse patterns accounted for the remaining 15.0%. Ber-EP4 expression showed no significant associations with most clinicopathological variables; however, ulceration was significantly associated with reduced Ber-EP4 expression (aOR = 12.05; 95% confidence interval, 2.41-60.15; P = 0.002). CONCLUSIONS: Ber-EP4 is a highly sensitive immunohistochemical marker for cutaneous BCC, showing predominantly diffuse expression across diverse clinicohistologic contexts. However, reduced expression in ulcerated tumors and the presence of nondiffuse staining patterns highlight potential diagnostic pitfalls, particularly in superficially sampled lesions. These findings underscore the need for cautious interpretation and integrated histomorphological and immunohistochemical assessment to ensure diagnostic accuracy.
BACKGROUND: Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm predominantly affecting elderly individuals in sun-exposed areas. Despite its alarming histopathological features, AFX typically exhibits an indo...BACKGROUND: Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm predominantly affecting elderly individuals in sun-exposed areas. Despite its alarming histopathological features, AFX typically exhibits an indolent clinical course. Diagnosis remains challenging due to overlapping features with other aggressive cutaneous malignancies, especially malignant melanoma. METHODS: We retrospectively analyzed 15 cases of AFX diagnosed between 2009 and 2024. Comprehensive immunohistochemical profiling was performed, including CD10, CD68, S100, Melan-A, HMB45, CD31, CD34, ERG, cytokeratins, P40, P63, SMA, Desmin, and newly, PRAME (clone EPR20330). Clinical and follow-up data were collected from medical records. RESULTS: The cohort had a mean age of 72.9 years, with a male predominance (66.7%). The scalp was the most frequent tumor site (40.0%). All cases demonstrated diffuse block-type CD10 positivity and were uniformly negative for PRAME. Occasional weak staining for melanocytic markers was observed in a minority of cases. After a mean follow-up of 84.0 months, all patients were alive. CONCLUSION: A comprehensive immunohistochemical panel is essential for the accurate diagnosis of AFX. The absence of PRAME expression, together with block-type CD10 positivity, supports the distinction of AFX from malignant melanoma and other histological mimics, facilitating appropriate clinical management.
BACKGROUND: Dermatofibromas are common benign dermal lesions with numerous histological variants. The combination of sclerotic and epithelioid features is extremely rare, with very few cases documented in the literature....BACKGROUND: Dermatofibromas are common benign dermal lesions with numerous histological variants. The combination of sclerotic and epithelioid features is extremely rare, with very few cases documented in the literature. CASE REPORT: We describe a 64-year-old male with a history of rheumatoid arthritis treated with methotrexate who presented with an asymptomatic 1-cm erythematous plaque on the chest. Histopathological examination revealed a symmetrical intradermal lesion composed of epithelioid cells with prominent nucleoli, dispersed between thick, hyalinized collagen bundles. No epidermal connection or cytological atypia was identified. Immunohistochemical analysis showed a unique profile: the neoplastic cells were positive for factor XIIIa, CD68, and vimentin, but also demonstrated strong, aberrant expression of cytokeratins (AE1/AE3, CK8/18) and the epithelial markers p40 and p63. Markers for muscle, vascular, melanocytic, and neural differentiation were negative. CONCLUSION: This is the first reported case of sclerosing epithelioid dermatofibroma exhibiting diffuse cytokeratin and p40/p63 expression. Recognizing this atypical immunophenotype is crucial to avoid diagnostic pitfalls, as it may mimic malignant epithelial or mesenchymal neoplasms such as sarcomatoid squamous cell carcinoma or epithelioid sarcoma. The expression likely reflects phenotypic plasticity rather than true epithelial malignancy.
Drug-induced hypersensitivity syndrome (DIHS) is a rare, severe cutaneous adverse reaction that presents with rash, fever, and multiorgan involvement after medication or supplement exposure. Diagnosis is primarily clinic...Drug-induced hypersensitivity syndrome (DIHS) is a rare, severe cutaneous adverse reaction that presents with rash, fever, and multiorgan involvement after medication or supplement exposure. Diagnosis is primarily clinical, although a skin biopsy may provide supportive evidence. Histologic features vary but generally reflect nonspecific epidermal and dermal inflammatory patterns. Rarely, DIHS presents with atypical features such as pustules, imitating acute generalized exanthematous pustulosis. We describe a case of a 68-year-old man who was started on carbamazepine for postoperative seizures and subsequently presented with a diffuse morbilliform rash with pustular components and distributive shock. He also displayed fever, lymphadenopathy, eosinophilia, acute kidney injury, and hepatitis, leading to a diagnosis of DIHS. A biopsy revealed interface dermatitis with eosinophils, subcorneal neutrophilic pustules, and dermal granulomatous inflammation. Although DIHS displays a broad spectrum of histologic features, a granulomatous reaction has been rarely reported. Herein, we describe a case of DIHS with granulomatous features.
Carbonell-Zamorano J, Santonja-López N, Navarro L
… +3 more, Fernandez A, Calabuig-Fariñas S, Sabater-Marco V
Am J Dermatopathol
· 2026 Mar · PMID 41894668
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Isocitrate dehydrogenase 1 (IDH1) mutations are well-established oncogenic drivers in several malignancies, including gliomas and hematologic neoplasms, but are rarely reported in melanoma and remain poorly characterized...Isocitrate dehydrogenase 1 (IDH1) mutations are well-established oncogenic drivers in several malignancies, including gliomas and hematologic neoplasms, but are rarely reported in melanoma and remain poorly characterized in this tumor type. Their clinicopathological and molecular significance in cutaneous melanoma is not well-defined. We retrospectively analyzed 9 cases of cutaneous melanoma harboring IDH1 mutations identified by next-generation sequencing from a larger institutional cohort. Clinicopathological characteristics, immunohistochemical profiles (including p16, PRAME, Ki-67, and PD-L1), and associated molecular alterations were evaluated. Eight tumors carried the pathogenic IDH1 p.R132C mutation and one harbored p.V178I. Most cases corresponded to nodular melanomas with epithelioid morphology, increased Breslow thickness (median 2.87 mm), high mitotic activity, and frequent ulceration. Tumor-infiltrating lymphocytes were weak or absent in most tumors. All cases expressed S100 and Melan-A; PRAME was strongly positive in 6 cases, while partial or complete loss of p16 expression was observed in all tumors. PD-L1 expression (tumor proportion score 1%-49%) was detected in 3 cases. Co-occurring mutations in the MAPK pathway were identified in 8 tumors, and 5 cases also harbored TERT promoter mutations (c.-146C>T, C228T). Comparable variant allele frequencies of IDH1 and associated mutations suggest an early oncogenic role. IDH1-mutated melanomas represent a rare molecular subset frequently associated, in this limited series, with established high-risk clinicopathological features. The recurrent coexistence of IDH1 mutations with MAPK pathway and TERT promoter alterations supports a potential cooperative role within melanoma oncogenesis. These findings are descriptive and hypothesis-generating, and further studies with larger cohorts are required to clarify the biological and clinical relevance of IDH1 mutations in melanoma.
Zou Y, Xia R, Li S
… +5 more, Li L, Zhu D, Ma Y, Wang P, Wang F
Am J Dermatopathol
· 2026 Jun · PMID 41869737
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BACKGROUND: The correct diagnosis of basal cell carcinoma (BCC) histopathological subtype is crucial for treatment design. Although the diagnostic accuracy of reflectance confocal microscopy (RCM) and dermoscopy for BCC...BACKGROUND: The correct diagnosis of basal cell carcinoma (BCC) histopathological subtype is crucial for treatment design. Although the diagnostic accuracy of reflectance confocal microscopy (RCM) and dermoscopy for BCC has been studied, the literature of RCM and dermoscopy in predicting BCC subtype remain limited. OBJECTIVES: To assess the diagnostic accuracy of confocal and dermoscopic criteria for predicting BCC subtype. METHODS: Confocal and dermoscopic images of histopathologically confirmed BCC were retrospectively analyzed. Multivariate and adjusted odds ratios were computed, along with sensitivity and specificity. Receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) was calculated. RESULTS: The study included 103 patients with 124 lesions. And 84 (105 lesions) were assigned to the confocal analysis group and 49 (62 lesions) to the dermoscopic analysis group. Multivariate analysis yielded three confocal models for predicting a diagnosis of nodular BCC (nBCC) with sensitivity of 91.7% and specificity of 80.7% (AUC, 0.913), superficial BCC (sBCC) with sensitivity of 82.3% and specificity of 91.5% (AUC, 0.932), and aggressive BCC (aBCC) with sensitivity of 87.5% and specificity of 97.8% (AUC, 0.945). We developed three dermoscopic models for diagnosing nBCC with sensitivity of 76.5% and specificity of 82.1% (AUC, 0.891), sBCC with sensitivity of 95.0% and specificity of 95.2% (AUC, 0.973), and aBCC with sensitivity of 62.5% and specificity of 90.7% (AUC, 0.849). CONCLUSION: Both RCM and dermoscopy are reliable tools for the identification of BCC subtypes. RCM is more accurate for nBCC and aBCC, whereas dermoscopy is more accurate for sBCC.