Focal Rhabdomyoblastic Differentiation Research Articles

Clinical diagnostic and radiographic features of recurrent intracranial malignant triton tumor in an adult: illustrative case.

Malignant triton tumors (MTTs) are a rare and aggressive type of malignant peripheral nerve sheath tumor identified histologically by focal rhabdomyoblastic differentiation. A 37-year-old female with a prior history of Hodgkin lymphoma presented with acute-onset confusion, cognitive deficits, and weakness. Brain magnetic resonance imaging revealed a hemorrhagic intracranial mass later confirmed to be a malignant triton tumor. The patient underwent two resections and several courses of chemoradiation for multiple tumor recurrences and metastases. Unfortunately, despite extensive treatment, she died 2 years after initial presentation from complications of this tumor. Her overall survival (OS) of 26.7 months was double that reported in historical cohorts (OS ∼13 mos). The diagnosis and treatment of central nervous system MTTs are difficult and require a multidisciplinary team of neurosurgeons, radiologists, and oncologists. Histopathological analysis is required for confirmation of diagnosis. Gross-total resection of tumor and adjuvant radiation therapy have been shown to give patients the highest rates of survival and improved outcomes. Further studies and clinical trials are warranted to investigate the efficacy of chemotherapeutic agents like temozolomide, bevacizumab, and abemaciclib.

DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor

The spectrum of neoplasms associated with DICER1 variants continues to expand, with the recent addition of primary “DICER1-associated central nervous system sarcoma” (DCS). DCS is a high-grade malignancy predominantly affecting pediatric patients. Six pediatric DCS were identified through a combination of clinical diagnostic studies, archival inquiry, and interinstitutional collaboration. Clinical, histologic, immunohistologic, and molecular features were examined. Genomic findings in the 6 DCS were compared with those in 14 additional DICER1-associated tumors sequenced with the same assay. The six patients presented at ages 3–15 years with CNS tumors located in the temporal (n = 2), parietal (n = 1), fronto-parietal (n = 1), and frontal (n = 2) lobes. All underwent surgical resection. Histologic examination demonstrated high-grade malignant spindle cell tumors with pleuropulmonary blastoma-like embryonic “organoid” features and focal rhabdomyoblastic differentiation; immature cartilage was seen in one case. Immunohistochemically, there was patchy desmin and myogenin staining, and patchy loss of H3K27me3, and within eosinophilic cytoplasmic globules, alfa-fetoprotein staining. Biallelic DICER1 variants were identified in all cases, with germline variants in two of five patients tested. DCS demonstrated genomic alterations enriched for Ras pathway activation and TP53 inactivation. Tumor mutational burden was significantly higher in the 6 DCS tumors than in 14 other DICER1-associated tumors examined (mean 12.9 vs. 6.8 mutations/Mb, p = 0.035). Postoperative care included radiation (n = 5) and chemotherapy (n = 3); at the last follow-up, three patients were alive without DCS, and three had died of disease. Our analysis expands the clinical, histologic, immunohistological, and molecular spectrum of DCS, identifying distinctive features that can aid in the diagnosis, multidisciplinary evaluation, and treatment of DCS.

Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum.

Biphenotypic sinonasal sarcoma (BSNS) is a locally aggressive tumor occurring in the sinonasal region. It harbors both myogenic and neural differentiation and is characterized by PAX3 rearrangement with MAML3 as the most frequent fusion partner, but the partner of PAX3 remains unidentified in a subset of cases. About 70 cases have been reported so far. In this study, we report a series of 41 cases with clinical, pathologic, and molecular description. Twenty-five (61%) patients were female individuals, and the median age was 49 years. Tumors arose predominantly in the nasal cavity and ethmoidal sinuses. Local recurrences occurred in 8 cases of the 25 (32%). Histologic features were characteristic of BSNS, with 5 cases showing focal rhabdomyoblastic differentiation. Immunohistochemistry showed a constant positivity of S100 protein and PAX3 and negativity of SOX10. MyoD1 was focally positive in 91% of cases, whereas only 20% were positive for myogenin. Molecular analysis showed a PAX3-MAML3 transcript in 37 cases (90%). RNA sequencing was performed in the 4 negative cases for PAX3-MAML3 fusion, and it showed that 1 case harbored a PAX3-FOXO1 fusion, as previously described in the literature, and 2 novel fusions: PAX3-WWTR1 fusion in 2 cases and PAX3-NCOA2 fusion in 1 case. RNA sequencing results were confirmed by fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and Sanger sequencing. The PAX3-NCOA2-positive case showed focal rhabdomyoblastic differentiation. In conclusion, we report 2 novel fusions (PAX3-WWTR1 and PAX3-NCOA2) in BSNS and show that MyoD1 is more sensitive than myogenin for demonstrating myogenic differentiation in this tumor.

Biphenotypic Sinonasal Sarcoma with Focal Rhabdomyoblastic Differentiation: Case Report of a Newly Described Malignancy with a Review of the Literature

Biphenotypic Sinonasal Sarcoma with Focal Rhabdomyoblastic Differentiation: Case Report of a Newly Described Malignancy with a Review of the Literature

Novel PAX3-NCOA1 Fusions in Biphenotypic Sinonasal Sarcoma With Focal Rhabdomyoblastic Differentiation.

Sarcomas arising in the sinonasal region are uncommon and encompass a wide variety of tumor types, including the newly described biphenotypic sinonasal sarcoma (BSNS), which is characterized by a monomorphic spindle cell proliferation with dual neural and myogenic phenotypes. Most BSNSs harbor a pathognomonic PAX3-MAML3 fusion driven by t(2;4)(q35;q31.1), whereas the alternative fusion partner gene remains unidentified in a subset of PAX3-rearranged cases. As NCOA1 on 2p23 is a known partner in PAX3-related fusions in other tumor types (ie, alveolar rhabdomyosarcoma), we investigated its status by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction assays in 2 BSNS cases showing only PAX3 gene rearrangements. Novel PAX3-NCOA1 fusions were identified in these 2 index cases showing an inv(2)(q35p23) by FISH and confirmed by reverse transcription polymerase chain reaction. Five additional BSNS cases with typical morphology were studied by FISH, revealing a PAX3-MAML3 fusion in 4 cases and only PAX3 rearrangement in the remaining case without abnormalities in MAML3 or NCOA1 gene. Except for 1 case with surface ulceration, all other tumors lacked increased mitotic activity or necrosis, and all cases immunohistochemically coexpressed S100 protein and actin, but lacked SOX10 reactivity. Interestingly, the 2 PAX3-NCOA1-positive cases showed desmin reactivity and displayed a small component of rhabdomyoblastic cells, which were not seen in the more common PAX3-MAML3 fusion cases. In conclusion, we report a novel PAX3-NCOA1 fusion in BSNS, which appears to be associated with focal rhabdomyoblastic differentiation and should be distinguished from PAX3-NCOA1-positive alveolar rhabdomyosarcoma or malignant Triton tumor. SOX10 immunohistochemistry is a useful marker in distinguishing BSNS from peripheral nerve sheath tumors.

Sclerosing Rhabdomyosarcoma: Report of a Case Arising in the Head and Neck of an Adult and Review of the Literature

Sclerosing rhabdomyosarcoma is a unique rhabdomyosarcoma variant, characterized by a prominent hyalinizing matrix. A notable pitfall is the potential for the unusual matrix and often pseudovascular growth pattern of this lesion to lead to confusion with other sarcoma types, including osteosarcoma, chondrosarcoma, and angiosarcoma. Here we report a case of sclerosing rhabdomyosarcoma arising in a 40-year old male. The tumor was centered in the pterygomaxillary fossa with extensive infiltration into adjacent structures. Fine needle aspiration yielded a preliminary diagnosis of high-grade pleomorphic undifferentiated sarcoma, for which he received neoadjuvant chemotherapy and surgical resection. Microscopic examination showed a malignant spindled to round cell neoplasm with prominent osteoid-like, hyaline stroma. Focal rhabdomyoblastic differentiation and diffuse immunoreactivity for desmin and myogenin aided in diagnosis. Nineteen months status post primary resection, the patient expired with multiple lung and bony metastases. Among 39 cases reported thus far (including the present case), there is a broad age range (0.3-79years), with an average age at presentation of 27years. The most commonly involved sites are the extremities (n=19) and head and neck (n=15). Most cases have been treated by resection, often combined with radiation and/or chemotherapy. Out of 31 cases with follow-up information provided, 6 patients developed local recurrence, 7 patients developed regional or distant metastasis, and 5 patients died of disease. Herein we discuss the ongoing controversy regarding how sclerosing rhabdomyosarcoma might best fit into existing rhabdomyosarcoma classification schemes, based upon current clinicopathologic and molecular genetic evidence.

A Rare Case of Primary Parapharyngeal Well Differentiated Liposarcoma with Rhabdomyoblastic Differentiation

Rhabdomyoblastic differentiation in liposarcoma is a rare entity, with only few cases being reported in the literature. These cases were reported in either dedifferentiated liposarcomas or in recurrent tumours which occurred in the retroperitoneum. The present case was a rare case of a primary parapharyngeal well differentiated liposarcoma with a focal rhabdomyoblastic differentiation.

Metastatic rhabdomyosarcomatous elements, mimicking a primary sarcoma, in the omentum, from a poorly differentiated ovarian Sertoli-Leydig cell tumor in a young girl: An unusual presentation with a literature review

Sertoli-Leydig cell tumors (SLCTs) of the ovary with mesenchymal heterologous elements are uncommon. Only few such cases have been documented, showing presence of only mesenchymal heterologous elements at the metastatic site. We report an unusual case in a young girl who presented with an omental mass that was consistent with histopathological features of a high-grade sarcoma, with prominent rhabdomyoblastic differentiation of the embryonal type. The sections from her ovarian mass for which she was operated a year back displayed features of a poorly differentiated SLCT with heterologous elements, including focal rhabdomyoblastic differentiation. This is one of the rare cases, to the best of our knowledge, where only rhabomyosarcomatous elements were identified at the metastatic site, mimicking a primary abdominal rhabdomyosarcoma, in a case of an ovarian SLCT. Further, this case reinforces the presence of rhabdomyosarcomatous elements in an ovarian SLCT to be associated with an aggressive disease course.

Dedifferentiated chordoma of the thoracic spine with rhabdomyosarcomatous differentiation. Report of a case and review of the literature

A case of spinal thoracic chordoma involving the T9 vertebra in a 70-year-old male patient, destroying the vertebral body and invading the vertebral canal with compression of the spinal cord, is presented. The patient was referred to our neurosurgical unit with a history of an irradiated metastatic adenocarcinoma to the thoracic vertebra, a diagnosis that was rendered 3 years earlier at another hospital on presentation. This misdiagnosis was likely due to the absolute rarity of thoracic vertebral chordomas (2%-3% of all chordomas), the higher frequency of metastatic deposits to the vertebrae from visceral cancers in the elderly, the limited amount of biopsy material available for histologic examination, and the epithelial phenotype of the tumor (keratin/EMA positive). The patient underwent second palliative surgery with subtotal piecemeal removal of the tumor bringing relief of the neurologic symptoms. The bulk of the tumor was represented by a high-grade pleomorphic sarcoma with adjacent areas of atypical chordoma. Small foci of conventional chordoma were also found. The previous histologic slides were also reviewed, which were consistent with the areas of atypical chordoma. Small targeted tissue fragments from areas of (atypical) chordoma and from sarcomatous areas were recovered for electron microscopy. The fine features of chordoma and focal rhabdomyoblastic differentiation were found with the latter retrospectively supported by immunohistochemical detection of striated muscle markers. A final diagnosis of dedifferentiated chordoma with rhabdomyoblastic differentiation was finally established. Rhabdomyoblastic metaplasia is a novelty in dedifferentiated chordoma. The patient died after 5 months. Autopsy was not requested.

Dedifferentiated liposarcoma of the cheek

Liposarcomas of the head and neck region are rare; only a few cases have been reported to arise in the cheek or buccal mucosa. Dedifferentiated liposarcoma has rarely been reported in the head and neck region and, to the best of our knowledge, this is the first reported case of dedifferentiated liposarcoma of the cheek. Dedifferentiated liposarcoma is a mixed histologic subtype defined by the association of an atypical lipomatous tumor or well-differentiated liposarcoma and a nonlipogenic sarcoma. The patient was a 61-year-old man who presented with a soft-tissue mass of the left cheek and a presumptive diagnosis of salivary neoplasm based on a fine needle aspiration. The tumor was excised and consisted histologically of an atypical lipomatous tumor/well-differentiated liposarcoma composed a well-differentiated lipomatous neoplasm with atypical cells and rare lipoblasts. The tumor recurred in the same location 5 months after surgery. The recurrent tumor was primarily composed of a nonlipogenic spindle sarcoma with focal rhabdomyoblastic differentiation associated with areas of an atypical lipomatous tumor/well-differentiated liposarcoma.

Leiomyosarcoma of the Female Breast: Report of Two New Cases and a Review of the Literature

We present the clinical, light microscopic, and immunohistochemical features of two new cases of leiomyosarcoma of the female breast. Both the patients were old (83 and 86 years) and were referred with a history of a long-standing breast lump. The results of the physical examination and the preoperative radiologic investigations suggested a phyllodes tumor. The patients were treated with mastectomy. The tumors measured 6 and 6.5 cm in the largest dimension, respectively, and were composed of fascicles of atypical, actively proliferating spindle cells, often intersecting at right angles. The axillary lymph nodes were free of tumor. Immunohistochemically, the tumor cells were positive for desmin, muscle-specific actin, and vimentin and negative for other markers, including keratins and hormone receptors. Focal rhabdomyoblastic differentiation was noted in one case. Follow up at 1 year is negative for metastases or local recurrences. Our study confirms that leiomyosarcoma of the breast is a locally invasive neoplasm and that it could represent a peculiar anatomic entity among mesenchymal tumors of the breast.