Case Of Pleomorphic Rhabdomyosarcoma Research Articles

PD-1 and PD-L1 expression in bone and soft tissue sarcomas

PD-1 and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the Unites States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently expanded the use of immunotherapy for metastatic urothelial cell carcinoma and Hodgkin lymphoma. However, studies on expression of PD-1 and its ligand in malignant bone and soft tissue sarcoma are sparse. In this study, we evaluated PD-1 and PD-L1 expression on variants of liposarcomas and rhabdomyosarcomas, osteosarcomas and chondrosarcomas. Tissue microarrays (TMAs) for liposarcomas (well differentiated, myxoid/round cell, and pleomorphic), rhabdomyosarcomas (alveolar, embryonal, pleomorphic, and spindle cell), conventional osteosarcomas and chondrosarcomas were stained for PD-1 and PD-L1 antibodies. Adipose tissue, skeletal muscle, bone, osteochondroma and lipoma were used as control and benign counterparts. Western blot was performed to evaluate expression of PD-1 and PD-L1 in four sarcoma cell lines. Osteosarcomas, chondrosarcomas, and all variants of liposarcomas and rhabdomyosarcomas over-expressed PD-1 relative to normal tissue. Expression of PD-1 in rhabdomyosarcomas was associated with higher tumour stage. Only one case of pleomorphic liposarcoma, one case of pleomorphic rhabdomyosarcoma and two cases of alveolar rhabdomyosarcomas were positive for PD-L1. Normal adipose tissue, skeletal muscle, and bone were negative for both PD-1 and PD-L1 and lipomas and osteochondroma weakly expressed PD-1 but not PD-L1. Western blot confirmed the presence of PD-1 protein in all four sarcoma cell lines. Overall, our results showed cytoplasmic expression of PD-1 in the bone and soft tissue sarcomas, while PD-L1 was negative. Whether these data are an indication for effectiveness of immunotherapy in the management of malignant bone and soft tissue sarcomas remains to be elucidated.

Pleomorphic Rhabdomyosarcoma in upper limb in an adult

Rhabdomyosarcoma (RMS) is the most common form of soft tissue sarcoma in the first 2 decades of life, with a peak age incidence in very young children. Due to the rarity of adult RMS, information regarding its clinical and biologic characteristics is very limited. We report a case of pleomorphic RMS of upper extremity in a 50-year-old man. There was no metastasis of the tumor. The patient underwent surgery with enbloc excision of the tumor. Histopathological examination showed typical features of pleomorphic RMS composed of large polygonal pleomorphic cells with eosinophilic cytoplasm and plenty of large multinucleated tumor giant cells having bizarre nuclei. Postoperatively patient took radiotherapy. There was no recurrence of tumor with follow-up of 2 years.

Rb1 loss modifies but does not initiate alveolar rhabdomyosarcoma

BackgroundAlveolar rhabdomyosarcoma (aRMS) is a myogenic childhood sarcoma frequently associated with a translocation-mediated fusion gene, Pax3:Foxo1a.MethodsWe investigated the complementary role of Rb1 loss in aRMS tumor initiation and progression using conditional mouse models.ResultsRb1 loss was not a necessary and sufficient mutational event for rhabdomyosarcomagenesis, nor a strong cooperative initiating mutation. Instead, Rb1 loss was a modifier of progression and increased anaplasia and pleomorphism. Whereas Pax3:Foxo1a expression was unaltered, biomarkers of aRMS versus embryonal rhabdomyosarcoma were both increased, questioning whether these diagnostic markers are reliable in the context of Rb1 loss. Genome-wide gene expression in Pax3:Foxo1a,Rb1 tumors more closely approximated aRMS than embryonal rhabdomyosarcoma. Intrinsic loss of pRb function in aRMS was evidenced by insensitivity to a Cdk4/6 inhibitor regardless of whether Rb1 was intact or null. This loss of function could be attributed to low baseline Rb1, pRb and phospho-pRb expression in aRMS tumors for which the Rb1 locus was intact. Pax3:Foxo1a RNA interference did not increase pRb or improve Cdk inhibitor sensitivity. Human aRMS shared the feature of low and/or heterogeneous tumor cell pRb expression.ConclusionsRb1 loss from an already low pRb baseline is a significant disease modifier, raising the possibility that some cases of pleomorphic rhabdomyosarcoma may in fact be Pax3:Foxo1a-expressing aRMS with Rb1 or pRb loss of function.

Diagnostic evaluation of metastatic rhabdomyosarcoma in effusion specimens

Sarcomas, including rhabdomyosarcoma (RMS), are rarely encountered in effusion specimens; therefore, difficulties in the accurate diagnosis of metastatic sarcomas in effusions can occasionally arise. Immunohistochemistry for myogenin has emerged as a useful adjunct in the diagnosis of RMS, especially in small biopsy specimens. To date, there are no published series describing the utility of immunocytochemistry for myogenin in the diagnosis of RMS in effusion specimens. A total of 15 patients, for whom metastatic sarcomas were diagnosed in effusion specimens between 1998 and 2012, were identified for analysis: alveolar RMS (n = 5); embryonal RMS (n = 1); pleomorphic RMS (n = 1); angiosarcoma (n = 1); Ewing's sarcoma (n = 2); osteosarcoma (n = 1); endometrial stromal sarcoma (n = 1); unclassified spindle cell sarcoma (n = 1); unclassified/undifferentiated pleomorphic sarcoma (n = 1); and leiomyosarcoma (n = 1). Immunocytochemistry for myogenin was performed for each of these cases as well as for 102 effusions that were positive for metastatic carcinoma. Immunocytochemistry for myogenin diffusely and strongly highlighted the nuclei of the tumor cells in six (86%) of seven cases of metastatic RMS; specifically, the five alveolar RMS and one embryonal RMS cases. The one case of pleomorphic RMS, the eight remaining metastatic sarcoma cases, and all 102 cases of metastatic carcinoma were completely negative for myogenin expression. In conclusion, immunocytochemistry for myogenin is a sensitive and specific ancillary adjunct in the diagnostic evaluation of metastatic RMS in effusion specimens.

高齢者の頬部に発生した多形型横紋筋肉腫の1例

高齢者の頬部に発生した多形型横紋筋肉腫の1例

Cytogenetic and real-time quantitative reverse-transcriptase polymerase chain reaction analyses in pleomorphic rhabdomyosarcoma

Pleomorphic rhabdomyosarcoma (PRMS) is a rare variant of rhabdomyosarcoma that occurs mostly in adults. A few cytogenetic studies of PRMS have been reported, but no consistent specific chromosome aberrations were detected. We herein report a cytogenetic study of three cases of pleomorphic rhabdomyosarcoma using a conventional G-banded karyotyping analysis. The three cases appeared to exhibit an extremely complex karyotype with numeric and structural rearrangements. Although the three cases displayed several common aberrations, including –2, –4, –9, –13, –14, –15, –19, –21, add(X)(p11), add(1)(q11), add(7)(p11), and add(13)(p11), no recurrent characteristic chromosomal aberrations could be detected. In addition, among these cases and seven other cases of previously reported PRMS, the most frequent chromosomal alterations were –2, –13, –14, –15, –16, and –19. No obviously consistent structural alterations can be found in these 10 PRMS cases, however, thereby suggesting that it is difficult to confirm whether these complex karyotypes correlated with the diagnosis or clinical outcome in PRMS. In this study, we detected MyoD1 and myogenin gene transcripts at the mRNA level in four cases of PRMS together with other soft-tissue sarcomas, including seven cases of malignant fibrous hitiocytoma, five cases of liposacroma, and three cases of leiomyosacroma using a real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. High-level expressions of MyoD1 and myogenin gene transcripts were determined in all cases of PRMS. In contrast, the other non-PRMS sarcomas showed either no expression or extremely weak expressions for both genes. Our findings suggest that the detections of MyoD1 and myogenin transcripts using real-time quantitative RT-PCR, combined with immunohistochemical stains, are extremely sensitive and useful for the diagnosis of PRMS.

A Case of Pleomorphic Rhabdomyosarcoma of Maxillary Sinus Accompanied with Inverted Papilloma

Rhabdomyosarcoma is an aggressive malignant tumor rarely developing in the head and neck in adults. In the sinonasal region, rhabdomyosarcoma constitutes a clinically important group because of the difficulty of surgical resection and its generally poor prognosis. Inverted papilloma is a relative rare and benign sinonasal lesionconstituting 0.5% to 4% of all nasal tumors that has a known propensity for recurrence, local aggressiveness, and association with transformation to malignancy. Squamous cell carcinoma is the major malignancy that is associated with inverted papilloma. To our knowledge, this is the first case report of pleomorphic rhabdomyosarcoma accompanied with inverted papilloma, and we represent the case with a review of the related literatures. (Korean J Otorhinolaryngol-Head Neck Surg 2009;52:70-4)

胸壁に発生した多形型横紋筋肉腫の１例

胸壁に発生した多形型横紋筋肉腫の１例