This case represents the second inguinal pleomorphic RMS ever reported in the international literature [5
]. RMSs are a group of different pathobiologic entities linked by a common characteristic: to form neoplastic skeletal muscle. This is derived from biological forces related to aberrant transcription signals that lead to the production of myogenic proteins. These differing morphologic features were recognized in the mid-1900s by Horn and Enterline, who divided RMSs into embryonal, alveolar, botryoid, and pleomorphic subtypes [6
]. However, recent histologic and molecular studies led to the description of additional entities, such as spindle cell and anaplastic RMSs. Following further refinements of the original entities, using molecular biology, the International Classification of Rhabdomyosarcomas separated the histological subtypes according to their prognostic significance [6
]. As a consequence, botryoid and spindle cell RMSs were assigned to the superior-prognosis group, embryonal RMSs to the intermediate-prognosis group, and alveolar RMSs to the poor-prognosis group. However, pleomorphic RMSs were not included in this classification, as they concerned the paediatric population in which the pleomorphic subtype is a very rare entity [3
Pleomorphic RMSs occur predominately in middle-aged men (median age: 54–56 years) and are mostly located in the lower extremity. Less frequent sites of presentation are the abdomen, retroperitoneum, chest wall, spermatic cord/testes, upper extremity, mouth, and orbit [8
]. They typically have an aggressive clinical course, demonstrating an overall poor prognosis [8
Given the rarity of the disease and the lack of large prospective controlled studies, very few related data are available, deriving from studies with small numbers of patients. Furlong et al. [8
] reported 38 pleomorphic RMS cases (28 men and 10 women). These patients presented with a rapidly growing mass (with a median size of 6.9 cm) involving mainly the lower extremity. The response to treatment was rather poor as approximately 70% of the patients died of the disease within 20 months. The progression-free survival of 45% of these patients was reported to be 9 months. Gaffney et al. [9
] reported 11 pleomorphic RMS cases (10 men and 1 woman; median age: 56 years) with the thigh being the most common site of disease presentation. From the 8 cases that had clinical follow-up, 1 patient was alive 20 months after the initial diagnosis, whereas the remaining 7 patients had died 2–28 months following diagnosis.
In the study by Ferrari et al. [2
], localized pleomorphic RMS was found in 37 patients (20% of the total RMS population), and complete surgical resection was possible for 74% of these patients (compared to 30% for other RMS histologic subtypes). Only 12 patients received chemotherapy. Overall, the 5-year event-free survival and overall survival rates were 29.9 and 53.4% for the pleomorphic RMSs compared to 32.9 and 45.7%, respectively, for the non-pleomorphic RMSs. However, these results correspond to the localized rather than the metastatic setting, which was the case in our patient. In the same study, it has been suggested that when the paediatric treatment guidelines are followed in adult patients, the response rates are comparable to those observed in children. According to the major conclusions derived from the meta-analysis of the Intergroup RMS Studies I–IV, VAC remains the standard regimen for patients with advanced disease [4
The underlying aetiology of the poor prognosis in this disease is not yet well understood. Reports regarding prognostic and predictive factors of adult pleomorphic RMS patients are very few and contradictory. Little et al. [10
] suggest that pleomorphic RMS is the most common RMS subtype in adults, accounting for 43% of the RMS population with locoregional disease. Pleomorphic RMSs were grouped and analyzed together with embryonal RMSs (a total of 63 patients) and did not show significant differences in terms of progression-free survival or overall survival compared to the alveolar subtype. Nevertheless, metastasis-free survival was slightly higher for the pleomorphic/embryonal group (58 vs. 32% for the alveolar group, p = 0.04). In another study, Joshi et al. [11
] reported that increasing age is a negative prognostic factor among children with RMSs.
On the other hand, a retrospective analysis from the Surveillance, Epidemiology and End Results database of 205 adults and 17 children with pleomorphic RMSs, which was recently published by Sultan et al. [3
], concluded that adult patients with pleomorphic RMSs demonstrate a worse prognosis, and that this is irrespective of the site of origin of the tumour or the histological subtype. It is noteworthy that there were exceptionally few children with pleomorphic RMSs in this database, and that these had a risk to die twice as high as adults (HR 3.73 vs.1.79, p < 0.001).