<i>CRTC1::TRIM11</i> cutaneous tumor: An update with local recurrence and lung metastasis in a pediatric patient

Abstract

We recently reported a case of CRTC1::TRIM11 fusion with prominent epidermal involvement mimicking a Spitz tumor arising on the arm in a 5-year-old female.1 The latest edition of the WHO Classification of Skin Tumors has removed the term “melanocytic”, and the official name is now “CRTC1::TRIM11 cutaneous tumor” (CTCT). Briefly, CTCT is a newly described entity with reproducible histopathologic and molecular characteristics. Histopathologically, it is invariably a circumscribed dermal tumor composed of nests and bundles of epithelioid to spindled cells with prominent nucleoli and abundant pink to pale cytoplasm.2 Although morphologically, CTCT resembles clear cell carcinoma and malignant melanoma, it possesses a distinct genetic fusion, and its biological behavior remains under investigation, given the limited follow-up data currently available. At the time of our article's publishing, only 13 cases had been reported in the literature. All but one case displayed indolent behavior. Since then, 34 new cases have been published.3-5 Although 21 of these patients have remained disease free with no evidence of recurrence after a median follow-up of 37 months (range: 12–168 months), three cases displayed aggressive behavior. One completely excised lesion had local recurrence at 6 months after initial diagnosis, and the patient subsequently remained disease free following re-excision after 30 months of follow-up. Another case had multiple positive regional lymph node metastases. Notably, neither of these tumors displayed any defining features that would otherwise predict an aggressive course.3, 4 However, a 30-year-old man with CTCT on the hip harboring TERT promoter variant developed regional inguinal lymph node and pulmonary metastases at 18 and 36 months, respectively.5 We now report that our case developed local recurrence and lung metastasis despite wide local excision with 1.5 cm margins of the original tumor (0.5 cm margins initially, followed by 1 cm margins on re-excision). Nineteen months after the original diagnosis (14 months after re-excision), biopsy-proven metastasis was identified locally in two lymph nodes in the right upper arm and right axilla. The tumor cells morphologically resembled those present in the original neoplasm and demonstrated mitotic figures (up to 3/mm2) (Figures 1-4). Clinically, the recurrence presented as painless subcutaneous nodularity adjacent to the surgical scar (Figure 5). There was no detectable clinical lymphadenopathy. Imaging with positron emission tomography and computed tomography was also consistent with metastatic disease to the lung. Despite this visceral metastasis, the patient did not experience pulmonary or other systemic symptoms. The patient was started on the PD-1 inhibitor, pembrolizumab. Before initiation of immunotherapy, immunohistochemistry demonstrated a low positive PD-L1 tumor proportion score and positive PD-L1 immune cell staining. Unfortunately, the metastatic lesions have continued to progress with an increase in size despite 6 months of PD-1 inhibitor therapy. In summary, we report a case of CTCT in a pediatric patient with rapid recurrence and visceral metastasis. This represents the fourth of a total of 47 cases that have demonstrated aggressive behavior and the only pediatric case thus far that has subsequently developed metastatic disease to a visceral site (lung). Given the rarity of this entity, no consensus guidelines exist for management. However, this case highlights that CTCT can behave aggressively in children and suggests that clinical and radiographic follow-up should be implemented following definitive surgical treatment to monitor for disease recurrence or progression. Finally, as the experience with this tumor increases, there should be further efforts to determine staging and/or prognostic parameters to determine the risk of aggressive behavior for individual cases. The authors would like to extend their best wishes to the patient and her family. The authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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