TFCP2 (Transcription Factor CP2)

The patient succumbed to the disease 4 months after surgery. RMS with FUS-TFCP2 fusion is rare, highly aggressive and associated with a poor prognosis.

He was treated with vincristine, dactinomycin, and cyclophosphamide, followed by cabozantinib and pembrolizumab, and finally pembrolizumab and concurrent radiation therapy to the targetable lesions. He had a continual, rapid progression of disease and expired 2 months following radiation. This case is notable because it presents a rare example of an aggressive, TFCP2::FUS gene fusion-positive RMS presenting with multiple cutaneous metastases, and highlights that this entity is highly resistant to multiple chemotherapies, immunotherapy, and radiation therapy.

All four patients are alive at follow-up, two on treatment for metastatic disease. This is the first Indian case series reporting the clinicopathological details in patients with TFCP2 mutations.

We also demonstrated that FQIs directly bind to TFCP2 with affinities in the nanomolar ranges. Our results suggest that FQIs are promising chemotherapeutics for TFCP2-driven cancer, especially HCC.

We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.

We found clinical, histological, and molecular evidence demonstrating the efficacy of cyclosporine in reducing the expanded malignant clone and achieving durable clinical remission for more than a year. Our findings highlight the complex interplay between CAR T-cell therapy, pre-existing genetic vulnerabilities, and the GI microenvironment, emphasizing the need for vigilant monitoring and tailored therapeutic strategies to address the risks associated with CAR-T lymphomagenesis.

The rarity and atypical presentation of spindle cell rhabdomyosarcoma in adults highlight the importance of thorough histopathological examination and immunohistochemistry in diagnosis. This case emphasizes the complexity of managing such tumors, showcasing the combination of surgical and chemotherapeutic interventions.

Ectopic expression of Dusp27 enhanced the transcriptional activity of Tfcp2l1 and promoted features associated with the naïve pluripotent state, while suppressing meso-endodermal lineage differentiation. The present study demonstrates that Dusp27 is a novel positive regulator of Tfcp2l1 through a physical interaction and thereby fine-tunes the pluripotency status and meso-endodermal differentiation of murine ESCs.

We conclude that SCRMS with ZFP64::NCOA2/3 fusions represent a distinct, clinically aggressive sarcoma, characterized by fascicular and sometimes round cell morphology, occasional chondro-osseous differentiation and variable skeletal muscle marker expression. Recognition of this emerging subtype of SCRMS may have prognostic and therapeutic implications.

We illustrate case examples demonstrating how a combined morphological and molecular approach with targeted RNA-Seq can aid in diagnosis and identify clinically actionable alterations in pediatric FN-RMS.

Detection of FUS signals using FISH led to the diagnosis of FUS::TFCP2-rearranged rhabdomyosarcoma. In cases of ALK positivity and spindle cell or epithelioid cell morphology, FUS::TFCP2-rearranged rhabdomyosarcoma should be considered in the differential diagnosis using staining for rhabdomyoblastic markers other than desmin.

Under circumstances, identification of the exact fusion may have therapeutic and/ or prognostic implications. This overview discusses the main ALK fusion entities with emphasis on differential diagnosis.