Rhabdomyosarcoma with TFCP2 Rearrangement or Typical Co-expression of AE1/AE3 and ALK: Report of Three New Cases in the Head and Neck Region and Literature Review

Gallagher, Karen Patricia Domínguez; Roza, Ana Luiza Oliveira Corrêa; Tager, Elena María José Román; Mariz, Bruno Augusto Linhares Almeida; Soares, Ciro Dantas; Rocha, André Caroli; Abrahão, Aline Corrêa; Romañach, Mário José; Carlos, Román; Hunter, Keith D.; Lopes, Márcio Ajudarte; Vargas, Pablo Agustín; Santos‐Silva, Alan Roger

doi:10.1007/s12105-022-01507-9

Cited by 15 publications

(8 citation statements)

References 19 publications

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“…Twenty‐three articles reporting 66 cases of TFCP2 ‐rearranged SS‐RMS (our three cases included) were found in the English literature 13–15,19,25–40 . There were 39 female and 25 male patients (the gender was unknown in two cases).…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-three articles reporting 66 cases of TFCP2rearranged SS-RMS (our three cases included) were found in the English literature. [13][14][15]19,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] There were 39 female and 25 male patients (the gender was unknown in two cases). The average age at The tumours were composed of admixture of different cell phenotypes including spindle, epithelioid, and round cells.…”

Section: R E V I E W O F T H E L I T E R a T U R Ementioning

confidence: 99%

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Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature

Bradová,

Mosaieby,

Michal

et al. 2023

Histopathology

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AimsSpindle‐cell/sclerosing rhabdomyosarcomas (SS‐RMS) are clinically and genetically heterogeneous. They include three well‐defined molecular subtypes, of which those with EWSR1/FUS::TFCP2 rearrangements were described only recently. This study aimed to evaluate five new cases of SS‐RMS and to perform a clinicopathological and statistical analysis of all TFCP2‐rearranged SS‐RMS described in the English literature to more comprehensively characterize this rare tumour type.Methods and ResultsCases were retrospectively selected and studied by immunohistochemistry, fluorescence in situ hybridization with EWSR1/FUS and TFCP2 break‐apart probes, next‐generation sequencing (Archer FusionPlex Sarcoma kit and TruSight RNA Pan‐Cancer Panel). The PubMed database was searched for relevant peer‐reviewed English reports. Five cases of SS‐RMS were found. Three cases were TFCP2 rearranged SS‐RMS, having FUSex6::TFCP2ex2 gene fusion in two cases and triple gene fusion EWSR1ex5::TFCP2ex2, VAX2ex2::ALKex2 and VAX2intron2::ALKex2 in one case. Two cases showed rhabdomyoblastic differentiation and spindle‐round cell/sclerosing morphology, but were characterized by novel genetic fusions including EWSR1ex8::ZBTB41ex7 and PLOD2ex8::RBM6ex7, respectively. In the statistical analysis of all published cases, CDKN2A or ALK alterations, the use of standard chemotherapy and age at presentation in the range of 18–24 years were negatively correlated to overall survival.ConclusionEWSR1/FUS::TFCP2‐rearranged SS‐RMS is a rare rhabdomyosarcoma subtype, affecting predominantly young adults with average age at presentation 34 years (median 29.5 years; age range 7–86 years), with a predilection for craniofacial bones, rapid clinical course with frequent bone and lung metastases, and poor prognosis (3‐year overall survival rate 28%).

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Section: Resultsmentioning

confidence: 99%

Section: R E V I E W O F T H E L I T E R a T U R Ementioning

confidence: 99%

Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature

Bradová,

Mosaieby,

Michal

et al. 2023

Histopathology

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“…Among them, MYOD1 mutation is the most commonly reported mutation phenotype to date, and can occur at any age. MyoD1 -mutated tumors tend to follow a more aggressive process, which is mostly associated with poor prognosis ( 2 , 6 ). VGLL2 – NCOA2 fusion occur almost exclusively in infantile patients and are detected in up to 50% of spindle cell/sclerotic RMS in infancy.…”

Section: International Multidisciplinary Team (Imdt) Discussionmentioning

confidence: 99%

“…Previous studies have shown that this subtype is almost exclusively intraosseous RMS, which has extremely strong invasiveness and poor prognosis ( 3 , 4 ). However, in most previous reports, the focus was on describing the clinical and pathological characteristics of tumors ( 4 - 6 ), with little detailed description of their treatment process, resulting in insufficient management experience and reference for this subtype.…”

Section: Introductionmentioning

confidence: 99%

Pediatric spindle cell/sclerosing rhabdomyosarcoma with FUS–TFCP2 fusion: a case report and literature review

Fang,

Duan,

Wang

et al. 2024

Transl Pediatr

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Background FUS–TFCP2 gene fusion is a recently identified and highly distinct molecular subtype of spindle cell/sclerosing rhabdomyosarcoma (RMS), with fewer than 40 cases being reported to date. Due to its low incidence, clinical studies on this subtype are limited. Here, we report a new case of this rare entity to describe and summarize its unique clinical characteristics and treatment process, aiming to emphasize the importance of molecular testing for spindle cell/sclerosing RMS and increase the understanding of this subtype. By summarizing and comparing with previous reports on RMS with the EWSR1/FUS–TFCP2 fusion mutation, we hope to make some new hints for its management. Case Description In this report, we describe a rare case of spindle cell/sclerosing RMS in a 13-year-old boy, who had a massive destructive lesion involving the mandible. Next-generation sequencing of tumor tissue revealing a FUS–TFCP2 fusion. The tumor was extremely aggressive and showed resistance to polychemotherapy, after 4 cycles of multi drug combined chemotherapy, the primary tumor still continued to grow, and suspicious chest metastasis occurred. Even after aggressive total resection of the primary tumor and postoperative chemotherapy, systemic metastasis to the vertebra and chest could not be prevented yet, ultimately with a fatal outcome within 6 months. We additionally summarize 37 cases of RMS with the EWSR1/FUS–TFCP2 fusion mutation reported in the literature. This subtype was found to be almost exclusively primary in bone and histologically showed a common origin of epithelium and muscle. The high aggressiveness made the conventional standard chemoradiotherapy ineffective. Because most tumors of this subtype express ALK protein, ALK inhibitors seem to be a new target for its therapy. Conclusions Spindle cell/sclerosing RMS with FUS–TFCP2 fusion has its unique clinical characteristics and progression. It shows a marked skeletal predilection and an aggressive clinical course, typically resistant to traditional standard treatments for RMS. Therefore, molecular detection is crucial in managing this subtype. Once the diagnosis is clear, a more aggressive treatment plan is needed. In addition, almost all cases were found to have a positive expression of ALK. So ALK inhibitors can be a choice of targeted therapy.

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“…1 RMS with TFCP2 fusion is rare, with 53 cases including 52 cases reported in the literature and the present case (Table 1). [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] The mean age was 28 years (range: 8-86 years) and the median age at diagnosis was 33.5 years. Approximately 70% cases occurred <40 years.…”

Section: Discussionmentioning

confidence: 99%

Rhabdomyosarcoma With FUS::TFCP2 Fusion in the Mandible: A Rare Aggressive Subtype, but Can Be Misdiagnosed as Ossifying Fibroma

Zhong,

Wei,

Xiao

et al. 2023

Int J Surg Pathol

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Rhabdomyosarcoma (RMS) with TFCP2 rearrangement has been identified recently. This entity has a distinctive clinicopathologic features: a rapidly aggressive clinical course, a preference for the craniofacial bones, a spindle and epithelioid histomorphology, and positive immunohistochemistry for epithelial markers, ALK, and myogenic markers. RMS with TFCP2 rearrangement is rare and may be misdiagnosed as other spindle cell tumors. Here, we report a case of this entity arising in the mandible, which was initially diagnosed as ossifying fibroma in primary tumor in another hospital. A 26-year-old man presented with a recurred mass in the mandible for 1 month after the operation of mandibular tumor. The first excisional specimen was initially diagnosed as ossifying fibroma in another hospital. Histopathologic examination revealed the tumor with a hybrid spindle cell and epithelioid cytomorphology, spindle cells and spindle-to-epithelioid cells with eosinophilic and rich cytoplasm, with high-grade features, prominent nucleoli and some atypical mitosis. Immunohistochemical analysis revealed positivity for desmin, MYOD1, pan-keratin, ALK (5A4), ALK (D5F3). Based on the morphology and immunophenotype, molecular studies were performed, which revealed a FUS::TFCP2 fusion transcript, confirming the diagnosis of Rhabdomyosarcoma with FUS::TFCP2 fusion. Making a correct diagnosis is primarily dependent on awareness by the pathologist of this rare subtype of RMS and careful histopathological evaluation, supported by immunohistochemical and molecular analysis, to avoid potential diagnostic pitfalls.

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Rhabdomyosarcoma with TFCP2 Rearrangement or Typical Co-expression of AE1/AE3 and ALK: Report of Three New Cases in the Head and Neck Region and Literature Review

Cited by 15 publications

References 19 publications

Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature

Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature

Pediatric spindle cell/sclerosing rhabdomyosarcoma with FUS–TFCP2 fusion: a case report and literature review

Rhabdomyosarcoma With FUS::TFCP2 Fusion in the Mandible: A Rare Aggressive Subtype, but Can Be Misdiagnosed as Ossifying Fibroma

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