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Aims Methods and Results Conclusion Pleomorphic adenoma (PA) with a prominent trabecular/canalicular morphology has consistent HMGA2 protein expression, and association with HMGA2 fusions. We report our experience with this subtype, with emphasis on the carcinomas that can arise in this context.A retro‐ and prospective review (2013–2024) of major salivary gland tumours with prominent trabecular/canalicular morphology was performed. Twenty‐one parotid tumours met the criteria: 14 benign (66.7%), six carcinomas (28.6%), and one of uncertain behaviour (4.7%). HMGA2 immunohistochemistry (IHC) was performed on all cases. Next‐generation sequencing was successfully performed on 18. Seven benign cases had a conventional PA component. In all cases, the tumour cells in these trabecular/canalicular areas demonstrated variable papillary thyroid carcinoma‐like nuclear changes, including chromatin clearing, overcrowding, membrane irregularities, and intranuclear pseudoinclusions. Benign tumours were well‐demarcated, whereas carcinomas demonstrated either a multinodular pattern of invasion or subtle infiltration. Two carcinomas showed increased cytologic atypia and architectural complexity and one had perineural invasion. By IHC, all were positive for HMGA2. In the trabecular/canalicular areas, there was consistent strong expression of CAM5.2, S‐100, and SOX‐10 and variable expression of p63 but negative p40. HMGA2 alterations were detected in 16 of 18 cases (89%). Follow‐up was available on two carcinomas, with one being locally recurrent.While most HMGA2‐positive salivary gland neoplasms with a prominent trabecular/canalicular growth pattern are benign, they, like traditional PAs, may give rise to carcinomas that can locally recur. These carcinomas can be deceptively bland, subtly infiltrative, or have a multinodular pattern of invasion. [ABSTRACT FROM AUTHOR]

Introduction: Solitary fibrous tumor (SFT) is a fibroblastic tumor with malignant potential that is underpinned by a recurrent inv12(q13q13)-derived NAB2::STAT6 fusion. Breast and axilla are uncommon locations for this entity. Methods: Records of two academic institutions were electronically searched for breast and axillary SFTs. Clinical and pathologic data were reviewed. Literature review for breast or axillary SFTs was performed. Present study and previously reported tumors were stratified using five SFT risk models: original and modified Demicco metastatic risk, Salas local recurrence risk, Salas metastatic risk, and Thompson local recurrence risk. Results: Five patients with breast or axillary SFT were identified. Median age was 49 years, and median follow-up (available for four patients) was 82 months. Three patients showed no evidence of disease, and one developed recurrence. Literature review identified 58 patients with breast or axillary SFT. Median age was 54 years, and median follow-up (available for 35 patients) was 24 months. Thirty-one patients showed no evidence of disease, three developed recurrence, and one developed metastasis. Original and modified Demicco models and Thompson model showed the highest sensitivity; original and modified Demicco models and Salas metastatic risk model demonstrated the highest specificity. Kaplan–Meier models were used to assess recurrence-free probability (RFP). Original and modified Demicco models predicted RFP when stratified by "low risk" and "moderate/intermediate and high risk" tumor, though sample size was small. Conclusions: While many SFTs of breast and axilla remain indolent, a subset may develop recurrence and rarely metastasize. The modified Demicco risk model demonstrated optimal performance characteristics. [ABSTRACT FROM AUTHOR]

Background: Giant cell tumor of soft tissue (GCT‐ST) is a rare soft tissue neoplasm that is morphologically similar to but genetically distinct from giant cell tumor of bone. A novel keratin‐positive GCT‐ST (KPGCT‐ST) harboring HMGA2::NCOR2 fusions was recently discovered. Fewer than 30 cases have been described; herein is reported an additional seven. Methods: Cases diagnosed as GCT‐ST were retrieved from institutional archives and consultation files. The histopathologic characteristics were assessed, and the electronic medical record was reviewed. Results: Seven tumors were identified in six women and one man with a median age of 23 years. All patients underwent excision; no recurrences or metastases were noted during a median follow‐up period of 7 months. Histopathologically, the tumors were characterized by a multinodular proliferation of keratin‐positive mononuclear cells with evenly admixed osteoclast‐like giant cells and absent neoplastic bone. A fibrous capsule with lymphoid cuffing was frequently seen. Foamy macrophages, inflammation, hemorrhage, and hemosiderin were variably present. The HMGA2::NCOR2 fusion was detected in all cases. Conclusions: Our findings support previously reported hypotheses that KPGCT‐ST is a spectrum of the same entity as the recently described xanthogranulomatous epithelial tumor. Although follow‐up data are limited, to date, KPGCT‐ST appears to follow an indolent course. [ABSTRACT FROM AUTHOR]

Background: Spitzoid melanocytic neoplasms are diagnostically challenging; criteria for malignancy continue to evolve. The ability to predict chromosomal abnormalities with immunohistochemistry (IHC) could help select cases requiring chromosomal evaluation. Methods: Fluorescence in situ hybridization (FISH)‐tested spitzoid neoplasms at our institution (2013–2021) were reviewed. p16, BRAF V600E, and preferentially expressed antigen in melanoma (PRAME) IHC results were correlated with FISH. Results: A total of 174 cases (1.9F:1M, median age 28 years; range, 5 months–74 years) were included; final diagnoses: Spitz nevus (11%), atypical Spitz tumor (47%), spitzoid dysplastic nevus (9%), and spitzoid melanoma (32%). Sixty (34%) were FISH positive, most commonly with absolute 6p25 gain (RREB1 > 2). Dermal mitotic count was the only clinicopathologic predictor of FISH. Among IHC‐stained cases, p16 was lost in 55 of 134 cases (41%); loss correlated with FISH positive (p < 0.001, Fisher exact test). BRAF V600E (14/88, 16%) and PRAME (15/56, 27%) expression did not correlate with FISH alone (p = 0.242 and p = 0.359, respectively, Fisher exact test). When examined together, however, p16‐retained/BRAF V600E‐negative lesions had low FISH‐positive rates (5/37, 14%; 4/37, 11% not counting isolated MYB loss); all other marker combinations had high rates (56%–75% of cases; p < 0.001). Conclusions: p16/BRAF V600E IHC predicts FISH results. "Low‐risk" lesions (p16+/BRAF V600E−) uncommonly have meaningful FISH abnormalities (11%). PRAME may have limited utility in this setting. [ABSTRACT FROM AUTHOR]