American Journal of Dermatopathology最新文献

Abstract: BAP1-inactivated melanocytic tumor (BIMT) represents a distinct subtype of melanocytoma, with characteristic morphologic features. These lesions are associated with inactivation of the BAP1 tumor suppressor gene. Although there are frequently histologic features that might otherwise cause concern for malignancy, including enlarged cells with nuclear variability, prominent nucleoli, and a lymphocytic inflammatory infiltrate, empirical data suggest that the majority behave in a clinically benign fashion. We report 2 cases of cutaneous BIMT with a distinctive morphologic pattern of clonal expansion with p16 loss. In both cases, there was liver metastasis after complete excision, in the absence of locoregional recurrence. These rare cases highlight the possibility of a distinct pathway of malignant progression in BIMT.

Abstract: Melanoma is known to have a high prevalence of somatic mutations, leading to a wide range of clinical and histological variability. This genetic plasticity can result in the partial or total loss of typical diagnostic clinical and immunohistochemical features of melanoma. Undifferentiated melanoma (UM) and dedifferentiated melanoma (DM) pose a significant diagnostic challenge due to their histological atypia and the absence of conventional melanocytic markers, often making them indistinguishable from pleomorphic dermal sarcoma (PDS). Accurate differentiation, however, is critical as UM and DM, unlike PDS, display a higher metastatic potential. Molecular analysis plays a crucial role in accurate diagnosis, particularly through the detection of mutations such as BRAF and NRAS, which are rarely found in true sarcomas. We present 2 cases of primary cutaneous UM initially misdiagnosed as PDS and later reclassified based on molecular findings. A comprehensive review of the literature was performed of reported cases of primary cutaneous undifferentiated and DM. Timely diagnosis is vital to allow access to effective targeted therapies, such as immune checkpoint inhibitors and BRAF/MEK inhibitors, which have shown promising responses, suggesting that undifferentiated and DM respond similarly to conventional melanoma despite their atypical presentation.

Abstract: Cutaneous metastases of breast neoplasms indicate advanced disease with poor prognosis. The role of Preferentially Expressed Antigen in Melanoma (PRAME) expression in breast cancer skin metastases remains poorly understood. In this study, we investigate PRAME expression in breast carcinoma metastatic to the skin, particularly triple-negative breast cancers (TNBC). A retrospective review of breast cancer cases with skin metastasis was conducted from January 2005 to March 2023. PRAME immunostaining was performed on skin metastatic lesions and corresponding primary tumors. A comparison group of noncutaneous metastases (n = 11) was included. Thirty patients with cutaneous metastasis were identified (29 women, 1 man; mean age 63 years). The most common site of skin metastasis was chest (25 cases, 83%). Histologically, 25 cases (83%) were invasive ductal carcinoma. Eleven cases (37%) were TNBC. PRAME positivity was observed in 10 skin metastases (33%) with 70% being triple negative. Among 20 available primary samples, only 3 were PRAME positive with corresponding positive metastases. Comparison group showed minimal PRAME expression. In total, 40% of patients died, with TNBC associated with higher mortality ( P = 0.04). All PRAME-positive TNBC patients with follow-up were deceased. In conclusion, PRAME expression occurred in approximately one-third of breast cancer skin metastases, with predominance in triple-negative breast cancer. These findings warrant further investigation of PRAME's role in cutaneous metastasis and its diagnostic implications.

Abstract: Granulomatous dermatitis within tattoos is most often attributed to pigment reactions, infection, or sarcoidosis. We report 2 patients of secondary syphilis presenting as granulomatous inflammation confined to black tattoo ink, an uncommon manifestation. Both patients demonstrated histologic features of granulomatous dermatitis with plasma cells, spirochetes confirmed by special staining, and complete resolution after penicillin therapy. These patients highlight syphilis as an important consideration in the differential diagnosis of papules within a tattoo.

Abstract: Giant cellular blue nevi (CBN) are rare melanocytic proliferations that may mimic melanoma, posing diagnostic challenges. We report a case of a 22-year-old woman with a 6-cm bluish-gray mass on the left medial buttock that had been present since childhood. An incisional punch biopsy performed at an outside facility demonstrated a dermal proliferation of heavily pigmented and densely cellular spindled and epithelioid melanocytes that were negative for PRAME. Comprehensive molecular profiling showed a low tumor mutational burden and identified an activating GNAQ p.Q209L mutation with no alterations in BRAF , NRAS , or KIT . Further workup at our institution included a pelvic MRI that showed no evidence of invasion into adjacent muscle or bone; however, the lesion's size warranted complete surgical excision. Final pathology analysis demonstrated a large circumscribed neoplasm consisting of both spindled and epithelioid melanocytes with no significant pleomorphism, a low proliferative index, and BRAF and PRAME negativity, though perineural involvement was noted. In the context of the imaging and molecular study results, a diagnosis of giant cellular blue nevus was made. This case highlights a rare presentation of giant CBN and the utility of integrating next-generation sequencing with histopathologic evaluation to distinguish the latter from melanoma and support clinical decision making.

Abstract: Solar elastotic bands (Raimer's bands) represent a rare clinical variant of severe solar elastosis that often affects forearms. Solar elastotic bands and keratoelastoidosis marginalis are associated with extensive chronic sun exposure (actinic damage). Repetitive trauma is also suspected of playing a causative role. We present a case of solar elastotic band of the forearm in which cytokeratin AE1/AE3 stains reveal positive staining in the dermis. This finding supports the hypothesis that trauma plays a role. We explore and review the histologic and clinical findings of several forms of solar elastosis, suggesting that these entities share many features in common.

Abstract: 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.

Abstract: 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.

Abstract: 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.