COL1A1::PDGFB fusion-associated uterine fibrosarcoma: A case report and review of the literature

Abstract

Background: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation.

Case: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment.

Conclusions: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Keywords: COL1A1::PDGFB; Imatinib; fibrosarcoma; soft tissue sarcomas; translocation t(17;22)(q22;q13); uterus.

FIGURE 1

Morphological and immunohistochemical features of the primary tumor. (A) Uterine mesenchymal tumor composed by spindle cells with a storiform to whorled pattern (H&E, 10×). (B) Spindle cells show eosinophilic cytoplasm, monomorphic and ovoid nuclei, very low to absent mitotic activity (H&E., 20×). (C) Patch positivity for CD10 (10×); (D) Strong and diffuse positivity for CD34 (10×).

FIGURE 2

(A) “Break apart PDGFB FISH figure”: here it is represented an unbalanced translocation with loss of the 5′ probe part of the PDGFB gene (green one) and gain of probe copies at 3′ (orange). This pattern is typical of DFSP. (1000×). (B) “Dual fusion‐dual color COL1A1::PDGFB FISH figure.” Here it is possible to see the fusion: (orange: COL1A1/ green: PDGFB). (1000×).

FIGURE 3

CT scan and FDG PET of the local recurrence. (A) June 2020: CT scan showing local recurrence in the right pelvis; (B) June 2020: CT scan: evidence of local recurrence in the left pelvis; (C) June 2020: PET with FDG showing local recurrence in the right pelvis; (D) July 2020: PET with FDG: evidence of initial response after few days of therapy.