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Clear cell tumor with melanocytic differentiation and MITF::CREM translocation
Sanda Alexandrescu1, Alma Imamovic-Tuco2, Katherine Janeway3
1Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Abstract:
In addition to melanoma, a large and diverse family of tumors shows melanocytic differentiation. The best characterized member of this family is clear cell sarcoma, which is characterized by EWSR1::ATF1 and EWSR1::CREB1 fusions. These fusions drive the transcription of MITF, the master regulator of melanocytic differentiation. Clear cell tumor with melanocytic differentiation and MITF::CREM translocation is a recently described tumor with some similarities to clear cell sarcoma. However, only a single case has been reported. Here, we describe a second molecularly proven case that arose on the scalp of a newborn baby. In contrast to the prior reported case, the current case showed predominantly high-grade cytomorphologic features with only focal clear cell areas. Similar to the prior case, the tumor showed immunohistochemical evidence of neural crest origin/differentiation with prominent melanocytic differentiation. The fusion breakpoints were also similar and preserved the transcriptional activation domain of CREM, suggesting that CREM hyperactivity is a major feature of this tumor type. The current tumor showed a short-interval recurrence. These results expand the clinical and pathologic spectrum of this potentially new entity.
Insights
A rare clear cell tumor with melanocytic differentiation, featuring CREM translocation, was identified in a newborn. This case expands the understanding of this new entity and its potential for recurrence.
Area of Science:
- Oncology
- Molecular Pathology
- Dermatopathology
Background:
- Melanocytic differentiation is observed in various tumors beyond melanoma.
- Clear cell sarcoma is characterized by EWSR1::ATF1/CREB1 fusions, driving MITF transcription.
- Clear cell tumor with melanocytic differentiation and MITF::CREM translocation is a newly described entity with limited prior reporting.
Observation:
- A second molecularly confirmed case of clear cell tumor with melanocytic differentiation is presented, occurring on the scalp of a newborn.
- This case displayed predominantly high-grade cytomorphologic features with focal clear cell areas, differing from the initial report.
- Immunohistochemistry confirmed neural crest origin and prominent melanocytic differentiation.
Findings:
- The tumor harbored similar fusion breakpoints to the previously reported case, preserving the CREM transcriptional activation domain.
- This suggests that CREM hyperactivity is a key driver in this tumor type.
- The tumor exhibited rapid recurrence, indicating aggressive behavior.
Implications:
- This report expands the clinical and pathological spectrum of clear cell tumor with melanocytic differentiation.
- It highlights the importance of molecular analysis in characterizing rare tumors.
- Further research is needed to fully understand the biology and optimal management of this potentially new entity.
