Related Experiment Video
Updated: Apr 23, 2026
Combining Reflectance Confocal Microscopy with Optical Coherence Tomography for Noninvasive Diagnosis of Skin Cancers via Image Acquisition
Published on: August 18, 2022
CRTC1::TRIM11 Cutaneous Tumors With Atypia: Melanoma Mimicry, Aggressive Potential, and Methylation Classifier
Bethany Batson1, Arivarasan Karunamurthy1,2, Azfar Neyaz1
1Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
CRTC1::TRIM11 cutaneous tumors are an emerging subset of MITF pathway-activated neoplasms that typically present as dermal nodules and can closely mimic clear cell sarcoma or malignant melanoma. Most reported tumors behave in an indolent manner, yet rare malignant cases have been documented. We report three additional CRTC1::TRIM11 cutaneous tumors with atypical features, including two patients with nodal or visceral disease at presentation. Histologically, all three tumors showed marked cytologic atypia with prominent nucleoli, and the usual nested and short-fascicular architecture was largely replaced by broad sheet-like growth, raising concern for melanoma. The tumors expressed SOX10 (diffuse) and S100 protein (patchy) with focal to absent expression of Melan-A and HMB45. PRAME was negative. CRTC1::TRIM11 was confirmed in all tumors. Two tumors harbored TERT promoter mutations, and one showed additional low-level copy-number gains of 1q, 8q, and 12q with 14q loss. In one case, methylation profiling yielded a clear cell sarcoma score of 0.885, just below the confidence threshold, likely due to shared CREB-MITF pathway activation and the lack of a dedicated CRTC1::TRIM11 reference class. A literature review identified nine previously reported metastatic CRTC1::TRIM11 cutaneous tumors. When combined with our series, extremities were the predominant primary site, and metastases most often involved regional lymph nodes and the lung. Fusion status remains the molecular gold standard, while secondary events such as TERT promoter mutations and 8q gains may contribute to aggressive behavior in a subset of tumors.
Insights
CRTC1::TRIM11 cutaneous tumors, a subset of MITF-activated neoplasms, can present atypically with aggressive features. Molecular analysis, including fusion status, is key for diagnosis and understanding potential for metastasis.
Area of Science:
- Oncology
- Dermatopathology
- Molecular Pathology
Background:
- CRTC1::TRIM11 cutaneous tumors are a rare neoplasm subset activated by the MITF pathway.
- These tumors typically present as dermal nodules, mimicking other malignancies like melanoma or clear cell sarcoma.
- While often indolent, rare aggressive and metastatic cases have been documented.
Purpose of the Study:
- To describe three CRTC1::TRIM11 cutaneous tumors with atypical features, including advanced disease at presentation.
- To analyze the histological and molecular characteristics of these atypical tumors.
- To review the literature on metastatic CRTC1::TRIM11 tumors and identify factors associated with aggressive behavior.
Main Methods:
- Histopathological examination including immunohistochemistry for SOX10, S100, Melan-A, and HMB45.
- Molecular testing for CRTC1::TRIM11 fusion, TERT promoter mutations, and copy-number alterations.
- Methylation profiling for tumor classification.
- Comprehensive literature review of metastatic CRTC1::TRIM11 cutaneous tumors.
Main Results:
- The three reported tumors exhibited marked cytologic atypia and sheet-like growth, raising concern for melanoma.
- Immunohistochemistry showed diffuse SOX10, patchy S100, and variable Melan-A/HMB45 expression.
- CRTC1::TRIM11 fusion was confirmed; TERT promoter mutations and 1q, 8q, 12q gains were noted in two cases.
- Literature review identified nine prior metastatic cases, with extremities as the common primary site and lymph nodes/lung as frequent metastatic sites.
Conclusions:
- CRTC1::TRIM11 cutaneous tumors can display significant atypia and advanced disease at presentation, challenging initial diagnosis.
- Molecular confirmation of the CRTC1::TRIM11 fusion remains crucial.
- TERT promoter mutations and chromosomal gains (e.g., 8q) may correlate with aggressive behavior in a subset of these tumors.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:23Abnormal Proliferation
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...