Primary Cutaneous Ewing Sarcoma (PCES) is exceptionally rare and represent a notorious diagnostic mimicker of Merkel cell carcinoma (MCC), particularly when it aberrantly expresses neuroendocrine markers. This pitfall ca...Primary Cutaneous Ewing Sarcoma (PCES) is exceptionally rare and represent a notorious diagnostic mimicker of Merkel cell carcinoma (MCC), particularly when it aberrantly expresses neuroendocrine markers. This pitfall can lead to significant diagnostic error and inappropriate management. A 73-year-old woman presented with a progressive, FDG-avid nodule on the left upper arm. An initial punch biopsy revealed a malignant small round cell tumor with a classic neuroendocrine immunophenotype, including dot-like positivity for CK20 and Neurofilament, which did not allow distinction between PCES and MCC. Subsequently, wide local excision was performed. Histological and extensive immunohistochemical analyses were conducted on the excision specimen, and fluorescence in situ hybridization (FISH) was employed for molecular confirmation. Examination of the resectate showed a multinodular dermal tumor composed of uniform round cells. Immunohistochemistry revealed diffuse positivity for CD99 and NKX2.2, whereas S100 and SOX10 were negative. Crucially, FISH analysis confirmed an EWSR1::FLI1 gene fusion. The sentinel lymph node was negative for metastasis. This case exemplifies a profound diagnostic pitfall in which PCES closely mimicked the immunoprofile of MCC. It underscores that dot-like CK20 and Neurofilament staining are not entirely pathognomonic for MCC diagnosis. In the differential diagnosis of cutaneous round cell tumors, which includes metastases, melanoma, and several sarcoma types, the present case reveals the diagnostic challenges of cutaneous sarcomas and highlights the necessity of a multimodal approach for accurate diagnosis.
Synovial sarcoma is a malignant soft tissue neoplasm that can closely mimic carcinoma by histology and immunohistochemistry, making accurate diagnosis challenging in small or superficial biopsies. In this study, we repor...Synovial sarcoma is a malignant soft tissue neoplasm that can closely mimic carcinoma by histology and immunohistochemistry, making accurate diagnosis challenging in small or superficial biopsies. In this study, we report a rare case of a superficial biphasic synovial sarcoma with striking neuroendocrine differentiation, a biopsy of which was initially interpreted as a poorly differentiated carcinoma due to diffuse cytokeratin and neuroendocrine marker expression. Resection subsequently revealed a biphasic morphology, and molecular testing confirmed the presence of an SS18::SSX fusion, confirming the diagnosis of synovial sarcoma. This case highlights a potential diagnostic pitfall in dermatopathology and stresses the importance of confirmatory molecular testing in cases where both sarcoma and carcinoma are included in the differential diagnosis.
Am J Dermatopathol
· 2026 Mar · PMID 41524681
·
Publisher ↗
Periungual Bowen disease is an uncommon form of squamous cell carcinoma in situ that may mimic benign pigmented lesions, such as melanocytic nevi. We report a case of a 36-year-old man who presented with an irregularly s...Periungual Bowen disease is an uncommon form of squamous cell carcinoma in situ that may mimic benign pigmented lesions, such as melanocytic nevi. We report a case of a 36-year-old man who presented with an irregularly shaped brown macule on the periungual area of the right third finger, with a history of gradual enlargement over 8 years. The patient reported occasional periungual trauma because of nail picking but had no significant medical history. A punch biopsy was performed, and histopathological examination confirmed the diagnosis of Bowen disease. The lesion was completely excised, and no recurrence was observed during follow-up. This case highlights the importance of clinical suspicion and histological evaluation for chronic pigmented periungual lesions that may resemble benign conditions.
Wong S, Bhukhan A, Siddiqui F
… +1 more, Dominguez P
Am J Dermatopathol
· 2026 Jun · PMID 41494201
·
Publisher ↗
Fibroepithelioma of Pinkus (FEP) is an uncommon histologic variant of basal cell carcinoma that classically arises on the trunk and proximal extremities. We present the case of a 59-year-old Hispanic man with a 15-year h...Fibroepithelioma of Pinkus (FEP) is an uncommon histologic variant of basal cell carcinoma that classically arises on the trunk and proximal extremities. We present the case of a 59-year-old Hispanic man with a 15-year history of a slowly enlarging, intermittently painful nodule on the left plantar foot. Clinical examination revealed a pearly, telangiectatic, hyperkeratotic nodule, and biopsy demonstrated anastomosing cords of basaloid cells within a fibromyxoid stroma, consistent with FEP. This case highlights an atypical acral presentation of FEP and contributes to the limited literature documenting its occurrence on the plantar foot. Recognition of this rare variant in unusual anatomic locations is important, because persistent acral lesions may seem clinically benign yet require timely biopsy to ensure accurate diagnosis and appropriate surgical management.
Am J Dermatopathol
· 2026 May · PMID 41489577
·
Publisher ↗
Sweat gland (SG) neoplasms encompass a wide variety of benign or malignant adnexal skin tumors differentiating into the various segments of SG. Their diagnosis and classification are often difficult, and have relied main...Sweat gland (SG) neoplasms encompass a wide variety of benign or malignant adnexal skin tumors differentiating into the various segments of SG. Their diagnosis and classification are often difficult, and have relied mainly on histologic and immunohistochemical criteria. Several genomic alterations have been more recently discovered in SG tumors, and have been used as additional diagnostic criteria. Among them, fusions of the MYBL1 or the MYB gene (namely MYB::NFIB or MYBL1::NFIB ) have been detected in a significant proportion of cutaneous and extracutaneous (breast and salivary gland) adenoid cystic carcinomas (AdCC), and have been regarded specific of this tumor type. We report here an exceedingly rare case of a benign neoplasm diagnosed as benign tubular SG adenoma that was unexpectedly found to harbor a MYBL1::NFIB fusion gene. This case expands the spectrum of SG tumors driven by fusions of MYBL1 , and challenges the specificity of MYBL1 fusions for cutaneous AdCC.
Am J Dermatopathol
· 2026 Mar · PMID 41489496
·
Publisher ↗
Cutaneous adnexal tumors are a heterogeneous group of neoplasms with diverse histopathologic features. Clear cell hidradenoma (CCH) and cutaneous mixed tumors are benign adnexal neoplasms that may share overlapping morph...Cutaneous adnexal tumors are a heterogeneous group of neoplasms with diverse histopathologic features. Clear cell hidradenoma (CCH) and cutaneous mixed tumors are benign adnexal neoplasms that may share overlapping morphologic characteristics, making diagnosis challenging, particularly at uncommon acral sites. We report the case of a 60-year-old man who presented with a long-standing nodule on the hand. Histopathologic evaluation suggested a possible diagnosis of clear cell hidradenoma. There were also myxoid areas and a focal chondroid area as well, which are features seen in cutaneous mixed tumors. To further clarify the diagnosis, next-generation sequencing identified an in-frame TRPS1-PLAG1 gene fusion, confirming a diagnosis of cutaneous mixed tumor with phenotypic features of clear cell hidradenoma. This case highlights the diagnostic complexity of acral adnexal tumors with overlapping morphologic features. Molecular testing, such as next-generation sequencing, can be an essential adjunct in distinguishing between morphologically similar adnexal neoplasms, thereby guiding accurate diagnosis and management.
Am J Dermatopathol
· 2026 Mar · PMID 41481331
·
Publisher ↗
BRCA1-associated protein (BAP1)-inactivated melanocytoma (BIM) exhibits a unique, biphasic cellular composition. The tumor comprises 2 distinct melanocytic populations: a cytologically bland nevoid of aggregated nests an...BRCA1-associated protein (BAP1)-inactivated melanocytoma (BIM) exhibits a unique, biphasic cellular composition. The tumor comprises 2 distinct melanocytic populations: a cytologically bland nevoid of aggregated nests and a more distinctive group of larger, epithelioid melanocytes with prominent eosinophilic cytoplasm. Both cell populations typically test positive for BRAF V600E, with the epithelioid component demonstrating biallelic BAP1 inactivation, which can be demonstrated by loss of BAP1 nuclear expression by immunohistochemistry within the epithelioid melanocytes. Most cases are sporadic; however, some patients have an underlying BAP1 germline mutation. We report a case of a 15-year-old girl with a strong family history of breast cancer and a brown to pink, dome-shaped nodule on the left wrist. A shave biopsy of the nodule showed a dermal-based melanocytic proliferation with features like those described in BAP-1 inactivated melanocytoma with BRAF V600E expression; however, BAP-1 expression was retained. Furthermore, molecular testing of the lesion revealed BRAC2 and CHEK2 germline mutations. This case highlights that the histopathologic features of BAP-1-inactivated melanocytoma can be seen in the setting of an underlying germline mutation other than BAP-1 inactivation. Further study of melanocytic tumors showing BIMT-like histology but with normal BAP1 immunostaining is warranted, because some may contain clues to underlying germline mutations related to family cancer predisposition.
Magro CM, Kessler E, Foster K
… +1 more, Shapiro L
Am J Dermatopathol
· 2026 Mar · PMID 41474865
·
Publisher ↗
BACKGROUND: Kohlmeier-Degos disease is a potentially severe multiorgan thrombotic vascular injury syndrome with characteristic cutaneous lesions characterized by depressed porcelain white plaques with telangiectatic rims...BACKGROUND: Kohlmeier-Degos disease is a potentially severe multiorgan thrombotic vascular injury syndrome with characteristic cutaneous lesions characterized by depressed porcelain white plaques with telangiectatic rims. This occlusive vasculopathy involves the microvasculature but also extends to affect arterioles and small arteries where a peculiar intravascular and intimal fibrosing reaction occurs. We discovered in earlier studies that complement pathway activation and enhanced type I interferon signaling are held to be a critical impetus for the endothelial cell injury. Significant upregulation of type I interferon signaling is also responsible for the neointimal expansion and fibrosis. We had the opportunity of examining before and after treatment biopsies in a pediatric patient receiving the 3-drug protocol for the treatment of Kohlmeier-Degos disease. RESULTS: The patient was a 13-year-old girl who presented with a few months history of depressed white macular skin lesions and abdominal pain. A laparotomy revealed multiple serosal porcelain plaques and evidence of acute severe intestinal ischemia. The patient's pretreatment skin and intestinal resection samples showed a striking pauci-inflammatory microangiopathy associated with endothelial cell necrosis and microvascular thrombosis and arteriolar and arterial neointimal hyperplasia with intimal fibrosis, extensive vascular C5b-9 deposition and enhanced type I interferon signaling in the skin and intestine. Extravascular fibrosis with a loss in the expression of CD34 amid fibroblasts was observed. A diagnosis was made of Kohlmeier-Degos disease. The post-treatment biopsies of the skin and intestine demonstrated complete abrogation of both endothelial cell injury and intravascular fibrin thrombi. There was no evidence of neointimal fibrosis. The CD34 negative procollagen scleroderma phenotype was not observed in fibroblasts. A discernible but less intense type I interferon signal was present while the C5b-9 studies were negative in the post-treatment skin biopsy. The intestinal resection specimen obtained several months later had a negative interferon signature. Fibrous intravascular occlusion was limited to rare vessels in the intestinal resection specimen. CONCLUSIONS: The cutaneous and extracutaneous lesions of Kohlmeier-Degos disease are potentially reversible. The combination of therapeutic complement inhibition, downregulation of type I interferon expression, and the promotion of vascular patency and reduced platelet activation through prostacyclin administration define the cornerstone of treatment.
Diaz D, Makkar T, Tanko F
… +3 more, Bender J, Fitzhugh V, Guo Y
Am J Dermatopathol
· 2026 Mar · PMID 41468562
·
Publisher ↗
Spindle cell lipoma (SCL) is a benign adipocytic tumor commonly occurring in the neck, back, and shoulder of middle-aged men. Although often straightforward, SCL can exhibit unusual histologic patterns that pose diagnost...Spindle cell lipoma (SCL) is a benign adipocytic tumor commonly occurring in the neck, back, and shoulder of middle-aged men. Although often straightforward, SCL can exhibit unusual histologic patterns that pose diagnostic challenges. Verocay bodies, characterized by palisading nuclei around acellular zones, are a classic feature of schwannoma but are not pathognomonic. We report a SCL on the posterolateral neck of a 48-year-old man that showed prominent palisaded arrangements reminiscent of Verocay bodies, prompting a differential that included schwannoma. Immunohistochemical studies were performed, and the spindle cells were negative for S100 (only scattered adipocytes highlighted), and positive for CD34, and showed loss of nuclear RB staining. These findings are characteristic of SCL and the case underscores the importance of integrating microscopy, immunohistochemical panel selection, and terminology discipline. Recognizing the pitfalls of indiscriminate "Verocay-like body" nomenclature in nonschwannomatous neoplasms is crucial for avoiding misdiagnosis.
Hu AY, Wang X, Jorgensen J
… +4 more, Nagarajan P, Leventaki V, Hu S, Torres-Cabala CA
Am J Dermatopathol
· 2026 Mar · PMID 41468560
·
Publisher ↗
Myeloid sarcoma and blastic plasmacytoid dendritic cell neoplasm (BPDCN) are hematologic malignancies of immature cells that frequently involve the skin. In the absence of bone marrow involvement or an associated myeloid...Myeloid sarcoma and blastic plasmacytoid dendritic cell neoplasm (BPDCN) are hematologic malignancies of immature cells that frequently involve the skin. In the absence of bone marrow involvement or an associated myeloid neoplasm, distinguishing myeloid sarcoma with disseminated cutaneous involvement (leukemia cutis) from BPDCN is particularly challenging because of overlapping clinical and immunophenotypic features. We report a case of NPM1-mutated myeloid sarcoma presenting with rapidly progressive cutaneous lesions and no initial medullary disease, resulting in an initial misdiagnosis of BPDCN and treatment accordingly. The clinicopathologic evolution over an 8-month period is detailed through analysis of 8 skin biopsies and 5 bone marrow examinations. The disease ultimately progressed to refractory acute myeloid (monoblastic) leukemia, and the patient died approximately 8 months after initial presentation.