Billings, Steven D

AimsOssifying fibromyxoid tumour is a rare mesenchymal neoplasm predominantly affecting adults characterised by a multinodular growth pattern and the presence of a fibrous pseudocapsule with areas of ossification. Prompted by the recognition of a non‐ossifying ossifying fibromyxoid tumour with lipomatous differentiation which caused diagnostic difficulty, we sought to further explore cases of ossifying fibromyxoid tumour with non‐osseous heterologous elements.Methods and ResultsA search of our institutional and consultation archives revealed three additional cases that demonstrated lipomatous components and two cases with cartilaginous differentiation. RNA‐sequencing revealed fusions involving PHF1 (n = 4) or EPC1 (n = 1) in all (five of five) cases tested, including EPC1::PHC1 and JAZF1::PHF1 fusions, which have not been reported before in ossifying fibromyxoid tumour.ConclusionThese six cases expand the histomorphological spectrum of ossifying fibromyxoid tumour, introducing lipomatous differentiation as a hitherto undocumented feature. Awareness of these rare variants will ensure appropriate diagnosis and clinical management.

AimsThe majority of dermatofibrosarcoma protuberans (DFSP) harbour PDGFB or PDGFD rearrangements. We encountered ALK expression/rearrangement in a PDGFB/D‐negative CD34‐positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of ALK‐rearrangements in DFSP and plaque‐like CD34‐positive dermal fibroma (P‐LDF).Methods and ResultsWe searched the archives of academic institutions for cases previously coded as DFSP and P‐LDF. NGS‐naïve or PDGFB‐negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or ALK FISH was performed on ALK‐positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of “DFSP” and two “P‐LDF” with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0–2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (n = 5), ALK fusion partners included DCTN1 (2), PLEKHH2, and CLIP2 in DFSP‐like cases and FLNA in P‐LDF‐like lesions. ALK FISH was positive in one (of two) cases previously labelled P‐LDF. Methylome profiling of two (of three) ALK‐rearranged DFSP‐like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (n = 2; 26, 27 months).ConclusionWe describe a cohort of novel ALK‐rearranged tumours with morphologic features similar to DFSP.

AbstractCIC rearranged sarcomas have significant overlap with Ewing sarcoma, are aggressive, and typically present in deep soft tissue. They most commonly have a t(4;19)(q35;q13) with CIC‐DUX4 fusion. Superficial presentation is rare. We report eight (6F, 2M; median 45‐years‐old, range 14‐65) superficial CIC‐rearranged sarcomas, involving the extremities (n = 4), vulva (n = 2), and trunk (n = 2). The tumors were composed of nodules/sheets of round cells with necrosis and hemorrhage separated by dense hyaline bands. Tumor cells had vesicular chromatin, prominent nucleoli and frequent mitotic figures. One showed pagetoid spread. Targeted next‐generation sequencing was positive for CIC‐DUX4 fusion (6/6); fluorescence in situ hybridization (FISH) was positive for CIC rearrangement (2/3). Eight of eight had evidence of CIC‐DUX4 fusion/rearrangement by molecular techniques. Immunohistochemistry was positive for CD99+ (8/8) and DUX4+ (4/4). FISH for EWSR1 rearrangement was negative (5/5). Of five patients with at least 6 months follow‐up, three of five died of disease, all within 2 years of presentation. One is alive with disease at 48 months. One is disease free at 3 months. Superficial CIC‐rearranged sarcomas should be considered in cases exhibiting features reminiscent of Ewing sarcoma, but with increased pleomorphism and/or geographic necrosis. In contrast to superficial Ewing sarcomas, superficial CIC‐rearranged sarcomas are aggressive.