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HMGA2 overexpression is found in 10-15% of leiomyomas (LM). HMGA2 overexpression is common in variants of hydropic, intravenous and lipo-LM. Cellular or highly cellular LM (CLM) is a LM variant with a less well-defined molecular nature. In this study, we identified and examined 52 hypercellular LM with sclerotic collagen, herein defined as cellular leiomyoma with sclerosis (CLM-S). CLM-S shows large tumour size (average 12.2 cm) and characteristic histology of tumour cells, arranged in cellular fascicles, sheets and trabeculae with abundant dense, pink sclerotic extracellular matrix in bands and nodules and increased vascularity. Tumour cells are uniform with small, round-oval nuclei and scant, pale-eosinophilic to vacuolated cytoplasm reminiscent of pericytes. The differential diagnosis of CLM-S includes conventional CLM, endometrial stromal tumours and perivascular epithelioid cell tumour. Immunohistochemical profile [HMGA2, fumarate hydratase, smooth muscle markers, Melan A and HMB-45] and molecular alterations [by HMGA2 mRNA reverse transcription-polymerase chain reaction (RT-PCR), HMGA2 fluorescence in-situ hybridisation and MED12 sequencing] were analysed in comparison to matched myometrium and CLM controls. Remarkably, 96% (50 of 52) of CLM-S demonstrated diffuse positive immunoreactivity for HMGA2 and up to an 80-fold increase in HMGA2 mRNA, determined by RT-PCR. FISH analysis with break-part probes at intron 3 and the 5' UTR detected HMGA2 rearrangements in 47% (18 of 38) of CLM-S. All CLM-S retained expression of fumarate hydratase. No MED12 mutations were found in any CLM-S. Our findings show that CLM-S has unique and characteristic histomorphology probably driven by HMGA2 overexpression., (© 2022 John Wiley & Sons Ltd.)

Aims: Blue naevi are uncommon dermal melanocytic neoplasms characterised by GNAQ/GNA11 mutations, which very rarely progress to melanoma. Such melanomas also often have BAP1 mutations, and lack genetic events associated with conventional melanoma. Exceptionally, blue naevi arise in extracutaneous locations; one melanoma arising in this setting has been reported. We report the clinicopathological, immunohistochemical and molecular genetic features of two cases of melanoma arising in extracutaneous blue naevus., Methods and Results: Both arose in males, aged 25 and 63 years, with no history of other melanocytic lesions, and presented as large, painful intra-abdominal masses. The tumours were dark-brown/black, multilobulated, involved small intestinal mesentery and consisted of a predominantly fascicular and spindled, but occasionally nested and epithelioid, proliferation of variably pigmented, relatively monotonous cells with pale cytoplasm and ovoid nuclei with mild to moderate atypia. Mitotic activity was variable but generally low. Both cases showed areas of conventional and cellular blue naevus. Recurrent tumour in one case showed predominantly epithelioid morphology and greater cytological atypia and mitotic activity. One case expressed Melan-A, SOX10 and CD117, with absent expression of S100 protein and DOG1; the other expressed Melan-A, HMB45 and S100 protein. Next-generation sequencing identified GNAQ and BAP1 mutations in one case and GNA11 mutation in the other. Both patients developed widespread metastatic disease., Conclusion: Exceptionally rare, aggressive melanomas arising in extracutaneous blue naevi should be distinguished from metastatic melanoma, gastrointestinal stromal tumour and malignant melanotic nerve sheath tumour, especially given the significant therapeutic and prognostic differences between these different entities., (© 2020 John Wiley & Sons Ltd.)

Objectives: To describe the cytopathological features of clear cell sarcomas (CCSs), including immunohistochemical and molecular results, the latter in selected cases., Methods: Sixteen consecutively diagnosed cases of CCS of soft tissue, over 6-year duration were included. Fine needle aspiration cytology was performed for primary diagnosis in three and for recurrent/metastatic lesions in 12 cases. Cytopathological features in 16 cases (conventional Papanicolaou- and May-Grünwald Giemsa-stained smears) were critically analysed. Corresponding histopathological and immunostained sections were available in 15 cases. Two cases were tested for EWSR1 gene rearrangement by fluorescence in-situ hybridisation., Results: Sixteen tumours occurred in patients with age ranging from 18 to 56 years (median = 33.5); M: F ratio = 1:1; in deep soft tissues, mostly in extremities. Primary cytopathological diagnosis (3 cases) was CCS with a differential diagnosis of melanoma (1 case) and poorly differentiated malignant tumour (2 cases). On review, smears were predominantly hypercellular (n = 14), invariably composed of monomorphic appearing epithelioid/polygonal cells (n = 16), including spindle cells (n = 6); mostly singly scattered (n = 16), in loose clusters (n = 12); with prominent nucleolisation (n = 16); granular to vacuolated, well-defined cytoplasm (n = 12), binucleation/multinucleation (n = 9); mitoses (n = 6); sudden anisonucleosis; racquet-shaped cells (n = 3), against a tigroid background (n = 2), along with focal intracytoplasmic pigment deposition (n = 2). Immunohistochemically, tumour cells were positive for S-100P (15/15), HMB-45 (15/15) and melan-A(6/12). Two cases tested for EWSR1 rearrangement displayed red-green split signals., Conclusions: This constitutes one of the largest series describing the cytomorphological spectrum of CCS of soft tissue. Certain features, such as singly scattered monomorphic, epithelioid cells with prominent nucleolisation are useful diagnostic clues. Immunohistochemical stains are necessary and molecular testing is further helpful in reinforcing a diagnosis in certain cases. A correct diagnosis has crucial treatment implications., (© 2020 John Wiley & Sons Ltd.)