Larger tumors, higher mitotic counts, and TERT mutations associate with metastasis in CRTC1::TRIM11 fusion tumorsSpecific Tumor Features May Predict Risk of Cancer Spreading

Since the original description of CRTC1::TRIM11 fusion cutaneous tumors (CTCT) in 2018, an increasing number of cases with metastatic behavior have been reported, yet there are limited studies analyzing prognostic parameters. This expanding data set presents an opportunity for reappraisal of clinical behavior. We present a series of 21 cases with detailed morphologic, molecular, clinical outcomes, and therapeutic response data. We utilize this data and a meta-analysis of all the cases in the literature to assess potential prognostic parameters to assist in clinical management. Primary tumors resulting in metastasis were larger ( P =0.038), had higher mitotic counts ( P <0.001), were more frequently ulcerated ( P =0.001), and exclusively harbored TERT promoter mutations ( P =0.005). A functional analysis of mixed data demonstrated a clear clustering pattern in which metastatic cases had larger diameters and were more mitotically active compared with nonmetastatic cases. Inclusion of TERT promoter mutational status further improved the model. There were no metastatic events among cases meeting all the following criteria: size <1.2 cm, <7 mitoses/mm 2 , and absent TERT promoter mutation. Metastatic events frequently involved regional lymph nodes, and all patients with distant metastasis had pulmonary involvement. Considering metastatic events in 23% of cases, sentinel lymph node biopsy and imaging studies may be considered in some cases, while, in cases with smaller size, low mitotic counts, and no evidence of a TERT promoter mutation, excision alone may be adequate. Given poor therapeutic responses in reported metastatic cases, more therapeutic options should be explored.