American Journal of Dermatopathology最新文献

Abstract: Scurvy is an uncommon diagnosis in developed countries, yet it remains an important clinical consideration in patients with restrictive diets. In this study, we report a case of a male patient with a history of sclerosing mesenteritis and chronic dietary restriction who presented with bilateral leg purpura, perifollicular hemorrhage, and gingival bleeding. His cutaneous findings initially raised concern for vasculitis or coagulopathy. However, histopathology revealed classic features of scurvy and an undetectable vitamin C level confirmed the diagnosis. Oral vitamin C supplementation led to rapid clinical improvement. This case emphasizes the importance of a thorough dietary history and skin examination in patients presenting with mucocutaneous bleeding.

Abstract: Tumor of follicular infundibulum (TFI) is a rare cutaneous lesion of unclear histogenesis. Various benign and malignant cutaneous neoplasms have been reported in association with TFI, including most commonly basal cell carcinoma (BCC). Indeed, some authors have suggested that TFI may represent a variant of BCC. Because BCC are well established to be driven by alterations in the Hedgehog signaling pathway, most often secondary to ultraviolet (UV)-induced mutagenesis, we undertook next-generation DNA sequencing of a cohort of TFI to determine their molecular relatedness to BCC. Four TFI cases were successfully sequenced, with 3 of the 4 patients being men, and a mean age at diagnosis of 57.8 years (range: 46-68 years). All 4 tumors were located on the face and showed typical histologic features of TFI, including a plate-like proliferation of bland keratinocytes with peripheral palisading and multiple points of connection to the epidermis. Two of the lesions were solitary and 2 occurred as part of eruptive TFI. No recurrences were reported. Molecular profiling failed to reveal Hedgehog pathway alterations, TP53 mutations, or a UV mutation signature in any case. In contrast, 3 cases demonstrated recurrent SLX4 mutations. In total, 18 unique mutations in 15 genes spanning an array of cellular functions including DNA repair and cell signaling were identified. Overall, the histomorphologic, clinical, and molecular features of TFI support its classification as a distinct and benign entity from BCC. In addition, the presence of recurrent SLX4 alterations suggests that TFI are likely not reactive but rather may represent a true neoplasm.

Abstract: Rosai-Dorfman disease (RDD) is a rare histiocytic disorder that most commonly affects lymph nodes but can also present in extranodal sites, including the breast. Immune-related RDD may be associated with increased plasma cells, with a significant proportion of the plasma cells expressing IgG4. These cases typically lack the other features of IgG4-related disease. We report a case of a 20-year-old woman who presented with a painless mass in the left breast. Prior biopsy was diagnosed as RDD with increased plasma cells. Ultrasound scan showed a well-circumscribed hypoechoic hypervascular solid subcutaneous mass with preservation of the surrounding breast parenchyma. Clinical assessment and imaging showed no evidence of regional lymphadenopathy or involvement of other organ systems. A wide local excision was performed. The excision showed a firm, unencapsulated fibrotic subcutaneous nodule. The histopathology revealed an expansion of the subcutaneous tissue, characterized by sheets of large histiocytes with round-to-oval nuclei and abundant pale to eosinophilic cytoplasm, set against a background of lymphoplasmacytic inflammation and stromal fibrosis. Several histiocytes demonstrated emperipolesis. The lesion was completely excised with clear margins. Immunohistochemistry showed that the histiocytes were positive for S100 and CD68, and negative for CD1a and AE1/AE3. The morphology and immunohistochemistry confirmed the diagnosis of extranodal RDD limited to the subcutaneous tissue of the breast. Extranodal RDD involving the breast is exceedingly rare and can mimic carcinoma both clinically and radiologically. Accurate diagnosis requires histologic and immunohistochemical confirmation.

Abstract: Basomelanocytic tumors are rare cutaneous neoplasms characterized by an intimate admixture of basal cell carcinoma and melanoma. Although basal cell carcinoma (BCC) and melanoma are commonly encountered individually, only a limited number of basomelanocytic tumors have been documented. We report the clinical and histologic features and molecular findings of 2 combined basomelanocytic tumors: 80-year-old man and 91-year-old-man, presented with lesions on the left upper lip and left forehead, respectively. The first tumor consisted of a close admixture of BCC, highlighted by p63 and keratin immunostains, and melanoma, highlighted by Melan-A and SOX10, with abundant melanoma in situ within the lobules of BCC. The second tumor exhibited 2 different neoplastic populations: 1 component of a nodular proliferation of basaloid epithelial nests with peripheral palisading, characteristic of BCC and stained positive for keratin 5/6, keratin 17, and p63. Scattered within these basaloid nests were melanocytes highlighted by Sox10, Melan-A, MiTF, and HMB-45. Molecular analyses of Case 1 show 11 identical variants with similar allelic frequencies detected in both the nodules of invasive melanoma and the remaining surrounding basal cell carcinoma with admixed melanoma cells. In addition, high-level NRAS amplification, and variants of KDR and TRAF7 variants were restricted to the nodules of invasive melanoma, possibly reflecting molecular progression. CDKN2A and PCTH1 mutations, frequently detected in melanoma and basal cell carcinoma, respectively, were detected in the second case. The presence of 2 components with distinct immunoprofile yet with some common genetic aberration suggests that basomelanocytic tumors may arise from a common progenitor.

Abstract: 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.

Abstract: Eccrine syringofibroadenoma was initially described by Mascaró in 1963 as a possible "eccrine" counterpart of Pinkus fibroepithelioma. Later, Nomura et al, reported a case of bullous pemphigoid associated to syringofibroadenomatous hyperplasia of the palms and soles, suggesting that this entity corresponds to hyperplasia of the eccrine ducts rather than a true neoplasm. There are currently numerous publications that support this hypothesis, describing similar changes induced by different alterations of the papillary dermis, either associated to inflammatory reactions or even neoplastic diseases. Despite the fact that these changes are already well-known, there are very few published cases of this condition in its subungual location. We believe that it is important to highlight this information so dermatologists and pathologists can include it among their differential diagnoses. Histopathological findings can be very subtle, and if not known, they can go unnoticed, leading to a nonspecific diagnosis, creating uncertainty for both the patient and the treating physician.

Abstract: Malignant melanomas can adopt characteristics of nonmelanocytic cells or tissue components, a rare phenomenon called divergent differentiation. Melanoma with rhabdomyosarcomatous differentiation is rare with 19 documented cases in the literature. We describe a 69-year-old man with a cutaneous lesion on his left cheek initially diagnosed as a primary rhabdomyosarcoma. Re-examination of the initial biopsy and the subsequent excision with additional stains and molecular tests revealed primary cutaneous melanoma with rhabdomyosarcomatous differentiation. This case highlights the diagnostic challenges associated with this rare melanoma subtype. A review of the literature follows with emphasis on immunohistochemical findings, molecular studies, and follow-up care.

Abstract: Epithelioid fibrous histiocytoma (EFH) is a rare, benign cutaneous neoplasm, thought to be distinct from benign fibrous histiocytoma because of its characteristic anaplastic lymphoma kinase (ALK) gene rearrangements. This article presents 3 cases of EFH with unusual multinucleated giant cells, all located on acral sites. The patients, 2 women and 1 man, ranged from 24 to 63 years of age. Histopathologically, these cases exhibited well-circumscribed lesions in the dermis, composed of sheets of epithelioid cells with abundant eosinophilic cytoplasm and round nuclei within a fibrous stroma. Notably, numerous multinucleated giant cells were present, all showing ALK positivity. Clinical follow-up, ranging from 3 to 120 months, revealed no recurrence, reinforcing the benign nature of EFH. These findings highlight the importance of distinguishing EFH from other cutaneous epithelioid neoplasms with multinucleated giant cells. The presence of ALK rearrangement serves as a critical diagnostic marker. This case series expands the histopathologic spectrum of EFH and emphasizes the need for awareness of its diverse presentations to avoid misdiagnosis.

Abstract: CRTC1::TRIM11 cutaneous tumor (CTCT) is a newly identified dermal amelanotic tumor that shows epithelioid to spindle cell morphology with melanocytic differentiation and harbors an in-frame translocation, CRTC1::TRIM11 . Given the limited number of reported cases describing its biologic behavior, it is crucial to distinguish this entity from histopathologic mimics, including clear cell sarcoma and metastatic or primary dermal melanoma. Herein, we report a 39-year-old woman with CTCT on the left leg histopathologically mimicking dermal melanoma. The patient developed a tender nodule on the left lateral malleolus 1 year before presentation, which enlarged gradually. A punch biopsy from the lesion and subsequent excision demonstrated a dense spindle cell tumor in the dermis. There were fascicles of achromic spindle cells, some of which showed mildly enlarged nuclei. A mitotic rate of 4/mm 2 was noted. The lesional cells were diffusely positive with SOX10 and MITF, with rare S100 and HMB45 staining. Melan-A, pan cytokeratin, p63, and smooth muscle actin were negative. With detection of CRTC1::TRIM11 by next-generation sequencing and lack of CCS-associated cytogenetic translocations, a diagnosis of CTCT was established. She was treated with Mohs micrographic surgery. No metastasis or local recurrence has been found in the 22 months since treatment. Although CTCT was once thought to behave more indolently than melanoma or clear cell sarcoma, recent reports with long-term follow-up detail occurrence of regional and/or distant metastases. Further studies on treatment and follow-up management strategy are warranted.

Abstract: Sitosterolemia is a rare autosomal recessive lipid disorder characterized by markedly elevated plasma plant sterol levels, premature atherosclerosis, and cutaneous xanthomas. Adult-onset orbital xanthogranuloma (AOX) is an uncommon non-Langerhans cell histiocytosis marked by xanthogranulomatous infiltration of the orbital tissues. We report the case of a 49-year-old woman with bilateral periorbital tumors and tendinous xanthomas who remained undiagnosed for >2 decades. Histopathologic examination of multiple biopsies for a 15-year period revealed xanthogranulomatous infiltrates consistent with AOX, accompanied by intracytoplasmic eosinophilic bodies not previously described. Imaging revealed severe stenosis of both cardiac and cerebral vessels. Laboratory testing showed markedly elevated levels of β-sitosterol, campesterol, and stigmastanol. Genetic analysis identified a homozygous nonsense mutation in the ABCG5 gene, confirming the diagnosis of sitosterolemia. This represents only the third reported case of AOX associated with sitosterolemia. The significance of the eosinophilic bodies observed in this patient remains unclear. Our findings highlight AOX as a rare but potentially under-recognized cutaneous manifestation of sitosterolemia. Importantly, measurement of plant sterol levels and genetic testing should be considered in patients with unexplained xanthogranulomatous lesions, particularly when accompanied by vascular disease or atypical lipid profiles. Recognizing this association may lead to earlier diagnosis and targeted treatment, potentially reducing the risk of life-threatening complications associated with this treatable metabolic disorder.