Fusion-driven Spindle Cell Rhabdomyosarcomas of Bone and Soft Tissue: A Clinicopathologic and Molecular Genetic Study of 25 Cases

Dehner, Carina; Broski, Stephen M.; Meis, Jeanne M.; Murugan, Paari; Chrisinger, John S.A.; Sosa, Carlos; Petersen, Matthew J.; Halling, Kevin C.; Gupta, Sounak; Folpe, Andrew L.

doi:10.1016/j.modpat.2023.100271

Cited by 11 publications

(5 citation statements)

References 50 publications

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“…TFCP2 -RMS tumors are predominantly localized in the jaws and the skull of young adults. The tumors have a rapid clinical course with a poor prognosis of 3-year overall survival at 28% [ 102 ]. Treatment options include surgery.…”

Section: Soft Tissue Neoplasms With Head and Neck Predilectionmentioning

confidence: 99%

Molecular pathology in diagnosis and prognostication of head and neck tumors

Skálová,

Bradová,

Michal

et al. 2024

Virchows Arch

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Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal tract, oropharynx, nasopharynx, and soft tissue. Availability of new molecular techniques allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, the expanding spectrum of immunohistochemical markers facilitates a rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined classifications, while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review highlights some principal molecular alterations in head and neck neoplasms presently available to assist pathologists in the practice of diagnosis, prognostication and prediction of response to treatment.

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Section: Soft Tissue Neoplasms With Head and Neck Predilectionmentioning

confidence: 99%

Molecular pathology in diagnosis and prognostication of head and neck tumors

Skálová,

Bradová,

Michal

et al. 2024

Virchows Arch

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“…TFCP2 -RMS tumors are predominantly localized in the jaws and the skull of young adults, often with secondary involvement of soft tissues. The tumors are usually diagnosed at an advanced stage and have a rapid clinical course with a dismal prognosis and a 3-year overall survival of 28% despite aggressive multimodal therapy [ 89 ]. Treatment options include surgery which may not be indicated if massive tumor spread has occurred by the time of diagnosis.…”

Section: Soft Tissue Neoplasms With Sinonasal Predilectionmentioning

confidence: 99%

Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities

Skálová,

Agaimy,

Bradova

et al. 2024

Virchows Arch

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Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.

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“…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%

“…39 In two cases, SNVs were reported, including CDC73 and SETD2 in the first case and AMER1, PREX2, TFE3, along with a deletion in the APC gene in the second case. 19 The therapeutic approach included surgery in 26 cases, combined with chemotherapy and/or radiotherapy in 17 cases, which in two cases was followed by tyrosinkinase inhibitors (TRKi). In 20 patients surgery was not performed due to advanced disease and 18 of these patients received chemotherapy and/or radiotherapy and six cases additionally received TRKi.…”

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

confidence: 99%

“…[16][17][18] A subset of SS-RMS usually harbouring EWSR1/FUS::TFCP2 or MEIS1::NCOA1/2 gene fusions shows a strong predilection for primary bone involvement. 19 EWSR1/FUS::TFCP2 rearranged SS-RMS were first described by Watson et al 13 They show spindle to epithelioid morphology, tend to affect craniofacial bones, especially the jaws of young adults, and are often associated with a rapid clinical course, resistance to adjuvant treatment, and poor prognosis.…”

Section: Introductionmentioning

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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Fusion-driven Spindle Cell Rhabdomyosarcomas of Bone and Soft Tissue: A Clinicopathologic and Molecular Genetic Study of 25 Cases

Cited by 11 publications

References 50 publications

Molecular pathology in diagnosis and prognostication of head and neck tumors

Molecular pathology in diagnosis and prognostication of head and neck tumors

Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities

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

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