American Journal of Dermatopathology最新文献

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.

Abstract: Characterizing the typical clinical, morphologic, and molecular findings of distinct subtypes of Spitz neoplasms may help facilitate diagnosis and management of these cases. Approximately 1%-2% of Spitz neoplasms have a MET fusion driver. However, there is minimal data in the current literature regarding this specific subtype of Spitz neoplasm. Most cases in our series (9/10) were diagnosed as atypical Spitz tumors, whereas 1 case was diagnosed as a Spitz nevus. We found 3 characteristic morphologic patterns, the first consisted of either expansile nests of spindle shaped spitzoid melanocytes with plexiform arrangement in the dermis forming a large nodular lesion or thin chords and fascicles of spindle shaped spitzoid melanocytes with a tightly interwoven plexiform pattern in the dermis forming a plaque-like architecture. The second pattern consisted of sheets of epithelioid melanocytes with spitzoid cytology, and the third pattern consisted of a both epithelioid and spindle shaped cytology with plexiform arrangement in the dermis as seen in various subtypes of Spitz neoplasms. Compared to a cohort of 81 control Spitz neoplasms, MET fusions were more likely to have spindle cytology and a plexiform growth pattern in the dermis. The most common fusion pattern was ZKSCAN1 (4/10). Copy number gains of the fusion gene were frequent, seen in 61% of cases. None of our cases had a TERT promoter mutation or homozygous deletions of CDKN2A . All of our patients had an uneventful clinical course with no evidence of recurrence after reexcision with average follow-up time of 35 months.

Abstract: Neurotrophic tyrosine receptor kinase-rearranged spindle cell neoplasms (NTRK-RSCN) are rare soft tissue sarcomas distinguished by various NTRK gene fusions. These tumors display a range of histologic features and tumor characteristics, with NTRK fusion genes serving as critical oncogenic drivers. We present the case of a 44-year-old woman who presented with a several-year history of a slowly enlarging, 1.3 cm, erythematous nodule on the right medial breast. A punch biopsy revealed a dermal proliferation of bland, monomorphic, spindled cells infiltrating the subcutaneous fat with admixed lymphoplasmacytic inflammation. Lesional cells were positive for S100, CD34, and Pan-TRK. Next-generation sequencing identified an EML4-NTRK3 rearrangement. Given that NTRK-RSCN tends to be locally aggressive and there are rare reports of metastasis, complete surgical excision was recommended. The patient underwent wide local excision with positive margins that were subsequently cleared after re-excision. Next-generation sequencing played a crucial role in reaching the correct diagnosis in this case. This is the first reported case of a cutaneous EML4-NTRK3 fusion spindle cell neoplasm located on the cutaneous breast.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare malignant soft tissue neoplasm typically found in the distal extremities of middle-aged adults. Histologically, MIFS presents with a myxoid stroma, a mixed inflammatory infiltrate, epithelioid/spindle cells resembling virocytes, pseudolipoblasts, and emperipolesis. Genetic alterations commonly include TGFBR3-MGEA5 rearrangements and VGLL3 amplifications. Recently, YAP1::MAML2 fusions have been identified in nodular necrotizing variants of MIFS. We report a case of a 40-year-old man presenting with right thumb pain initially suspected to be tendovaginitis. Histopathologic examination revealed a variably cellular proliferation in a fibrosclerotic-myxoid stroma with epithelioid cells displaying vesicular nuclei, spindle cells, and inflammatory infiltrates. Focal extensive necrosis was present. Immunohistochemical analysis was negative for SOX10, S100, SMA, desmin, MDM2, ALK, and CD20. Molecular genetic testing identified 2 variants of YAP1::MAML2 gene fusions and an additional TRIM24::BRAF fusion. Although BRAF rearrangements have previously been reported in MIFS, identification of TRIM24 as a fusion partner represents a novel finding. The presence of YAP1::MAML2 fusions, especially in combination with a TRIM24::BRAF fusion, has not been previously described in MIFS. TRIM24 is a transcriptional coregulator involved in p53 ubiquitination and tumorigenesis. The TRIM24::BRAF fusion has been detected in various malignancies, suggesting its potential oncogenic role. This case underscores the genetic heterogeneity of MIFS and suggests the need for further studies to elucidate the clinical implications of these molecular alterations. This report expands the molecular spectrum of MIFS and highlights the diagnostic utility of advanced sequencing technologies in identifying rare gene fusions. The TRIM24::BRAF fusion may represent a potential therapeutic target, warranting further investigation.

Abstract: Diagnosing a case of patchy alopecia in the setting of lupus erythematosus (LE) can be clinically challenging. Of the various causes of LE-specific alopecias, lupus panniculitis of the scalp is rarely reported. A 40-year-old woman presented with a nonscarring patch of alopecia over the scalp. Trichoscopy showed multiple follicular plugging, multiple thin and dystrophic hair shafts, empty follicles, and regularly distributed pinpoint white dots within the lesion. The clinical diagnoses of alopecia areata or early discoid LE were considered. However, the histopathological examination of the scalp biopsy showed typical hyaline-type fat necrosis of the subcutis along with moderate perivascular and perifollicular inflammatory infiltrate without any interface dermatitis. On direct immunofluorescence, staining for IgG, IgA, IgM, and C3 was negative. A diagnosis of lupus panniculitis of the scalp, presenting as patchy nonscarring alopecia, was rendered. Treatment with oral prednisolone and methotrexate led to complete recovery of alopecia. In conclusion, we report a rare case of lupus panniculitis of the scalp and discuss its differential diagnosis in the setting of LE.