A case report of cutaneous melanocytoma with CRTC1‐TRIM11 fusion: Is CMCT distinct from clear cell sarcoma of soft tissue?

Abstract

Pathological diagnosis of dermal melanocytic tumors is often problematic owing to histological resemblance. Recently, cutaneous melanocytoma with CRTC1-TRIM11 (CMCT) was added to this category. However, only six cases have been reported so far. We herein present a case of a 77-year-old Japanese man with CMCT. The patient presented a nodule in the right thigh and underwent surgical resection. Histological examination indicated a welldemarcated 6 × 5 mm-sized tumor nodule in the dermis and subcutis. The tumor was amelanotic, consisting of uniform nests and fascicles of spindled, or epithelioid cells. The melanocytic nature was evident by immunohistochemistry. The CRTC1-TRIM11 fusion was detected by TRIM11 immunostaining, chromogenic in situ hybridization, and RT-PCR/direct sequencing.He has been free from the tumor for 1 year after additional resection. The main differential diagnosis of CMCT includes primary and metastatic dermal malignant melanomas (MM) and dermal/subcutaneous clear cell sarcoma (CCS). Additionally, histological overlap with paraganglioma-like dermal melanocytic tumor was considered. Although some investigators argue that CMCT is a variant of CCS, we think it should be separated from CCS, and subcutaneous/dermal CCS should be confined to tumors with EWSR1-ATF1/ CREB1 fusion. However, longer follow-up and more case studies are needed for revealing the true prognosis of CMCT. K E Y W O R D S chromogenic in situ hybridization, clear cell sarcoma, CRTC1, cutaneous melanocytoma, fusion gene, malignant melanoma, RT-PCR, TRIM11 Figure 1 Histological findings of the tumor (HE staining) (a) An expansive cellular tumor nodule occupied the dermis and subcutis with a slightly invasive pattern in the deeper part. (b) Spindle to epithelioid tumor cells formed nests segmented with hyalinized collagenous fibers. (c) Nuclei of tumor cells were oval and showed fair atypia with large nucleoli.Cutaneous melanocytoma with CRTC-TRIM11 497

Dermal melanocytic tumor with CRTC1‐TRIM11 fusion: Report of two additional cases with review of the literature of an emerging entity

“…By immunohistochemistry, SOX10, MITF, and TRIM11 diffuse immunoreaction was a consistent finding in all cases examined 1‐4 . MelanA expression was more variable with nine cases exhibiting focal or patchy positivity whereas in four cases, there was a complete absence of expression.…”

“…“Cutaneous melanocytic tumor with CRTC1‐TRIM11 fusion (CMTCT)” is a recently described neoplasm with melanocytic differentiation that presents as a superficial nodule on varying anatomic sites. Thirteen cases 1‐4 (including ours) have been described so far, eight on the extremities, three on the head and neck, and two on the lower back. The lesions' median diameter was 10 mm (range 4–51 mm), whereas the patients' median age was 33 years (range 11‐82), including one 11‐year‐old child 3 .…”

“…The lesional cells commonly display mild to moderate atypia with prominent nucleoli. All reported cases 1‐4 were mitotically active and some displayed areas of necrosis, including one pediatric case that showed severe pleomorphism and increased mitotic activity (12 mitotic figures/10HPF).…”

“…RNA sequencing was performed in 10 cases (including current Case 1) 1,3,4 . Kashima et al 2 also used chromogenic in situ hybridization to detect TRIM11 rearrangements followed by RT‐PCR/direct sequencing to detect the CRTC1‐TRIM11 fusion. TRIM11 break‐apart FISH was performed in 10 cases total (including Case 2) and CRTC1‐TRIM11 fusion FISH in Case 1 of the present study.…”

“…In 2018, Cellier et al 1 reported a potentially new entity with a recurrent genetic signature that they termed “cutaneous melanocytoma with CRTC1‐TRIM11 fusion (CMCT).” It was described as a dermal proliferation composed of atypical epithelioid and spindle cells with a melanocytic immunophenotype resembling melanoma or CCS. Since then, six more cases harboring the same CRTC1‐TRIM11 fusion have been added to the literature 2‐4 and new nomenclature has been advocated. Bontoux et al, 4 who described a case of a CRTC1‐TRIM11 fused neoplasm that recurred and metastasized after 13 years, suggested that this entity represents a more aggressive cutaneous variant of CCS harboring a novel gene fusion other than the EWSR1‐ATF1 5,6 .…”