Original ArticlesPleomorphic rhabdomyosarcoma in children: Four cases in the pediatric age group
Abstract
Pleomorphic rhabdomyosarcoma is considered rare and controversial, especially in children. Although pleomorphic rhabdomyosarcoma has been observed in children, its sparcity has taken it out of current childhood rhabdomyosarcoma classifications. We report four pediatric cases of pleomorphic rhabdomyosarcoma, review morphologic, immunohistochemical, and ultrastructural features, and discuss the rare need to include this category in children. The Soft Tissue Registry of the Armed Forces Institute of Pathology was searched for cases coded as “pleomorphic rhabdomyosarcoma” from 1970 to the present. Only cases in patients less than 21 years old were included. Clinical data, morphology, and immunohistochemical stains were reviewed and follow-up was obtained. Electron microscopy was performed on two cases. Molecular analysis by polymerase chain reaction was performed on one case with available material. Of four patients included, there were three boys and one girl. Patient ages ranged from 9 months to 10 years (median, 4.5 years). Tumors were located on the chest wall (n = 2) and one each on the upper and lower extremities. Tumor size ranged from 4.0 to 10.0 cm (median, 7 cm). Grossly, the tumors were lobulated and circumscribed. Microscopically, architectural patterns varied from solid to fascicular or storiform. All tumors had large, often multinucleated, polygonal, spindled or strap-like rhabdomyoblasts with abundant eosinophilic cytoplasm. Nuclear characteristics ranged from hyperchromatic to vesicular. Most tumor cells had large prominent nucleoli. Background rhabdomyoblasts varied from spindled to polygonal. No tumors displayed areas typical of embryonal or alveolar rhabdomyosarcoma. All tumors exhibited atypical mitotic figures. Immunohistochemistry revealed that the tumors were positive for the following markers: desmin (), myoglobin (4/4), myoD1 (3/3), myf4 (3/3), and MSA (4/4). The two cases studied by electron microscopy both showed evidence for skeletal muscle differentiation. One case showed no evidence for a t(2;13) or t(1;13) translocation. Two patients were alive with no evidence of disease at 12 and 25 years. One patient was dead of disease at 9 years. Pleomorphic rhabdomyosarcoma is rare but exists in children. The diagnosis should be considered in pleomorphic sarcomas exhibiting skeletal muscle differentiation, which are otherwise devoid of typical areas or chromosomal changes of embryonal or alveolar rhabdomyosarcoma. Ann Diagn Pathol 5: 199-206, 2001. This is a US government work. There are no restrictions on its use.
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Rhabdomyosarcoma: Updates on classification and the necessity of molecular testing beyond immunohistochemistry
2024, Human PathologyRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents under the age of 20. The current World Health Organization (WHO) classification for soft tissue and bone tumors recognizes 4 distinct subtypes of RMS based on clinicopathological and molecular genetic features: embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. However, with the increased use of molecular techniques, the classification of rhabdomyosarcoma has been evolving rapidly. New subtypes such as osseus RMS harboring TFCP2/NCOA2 fusions or RMS arising in inflammatory rhabdomyoblastic tumor have been emerging within the last decade, adding to the complexity of diagnosing skeletal muscle tumors. This review article provides an overview of classically recognized distinctive subtypes as well as new, evolving subtypes and discusses important morphologic, immunophenotypic and molecular genetic features of each subtype including recommendations for a diagnostic approach of malignant skeletal muscle neoplasms.
We present our experience with seven cases of epithelioid rhabdomyosarcoma (RMS) to further characterise its clinicopathological features. There were five males and two females with ages ranging from 19 to 84 years (mean 56 years). Four tumours occurred in the somatic soft tissue, two in organs and one in the bone. The mean tumour size was 10.7 cm (range 3.5–15 cm). Histologically, six tumours were characterised by sheet-like growth of uniform epithelioid cells with large vesicular nuclei, prominent nucleoli, high mitotic activity and moderate to abundant amphophilic-to-eosinophilic cytoplasm. One tumour was composed of dyscohesive cells with rhabdoid appearance embedded in a myxoid matrix. Features suggestive of rhabdomyoblastic differentiation were absent. However, immunohistochemical study revealed skeletal muscle differentiation in all cases. Of note, focal expression of epithelial markers with co-expression of neuroendocrine markers was noted in five and three cases, respectively. Of six patients with follow-up, one experienced local recurrence and three developed metastases. To date, three patients have died of disease within 14 months. This study further demonstrates that epithelioid RMS represents a distinct variant of RMS with an aggressive behaviour. It may be misdiagnosed as poorly differentiated neuroendocrine carcinoma due to co-expression of epithelial and neuroendocrine markers.
Diagnostic Pathology: Soft Tissue Tumors
2015, Diagnostic Pathology: Soft Tissue TumorsDystrophin and dysferlin double mutant mice: A novel model for rhabdomyosarcoma
2012, Cancer GeneticsAlthough researchers have yet to establish a link between muscular dystrophy (MD) and sarcomas in human patients, literature suggests that the MD genes dystrophin and dysferlin act as tumor suppressor genes in mouse models of MD. For instance, dystrophin-deficient mdx and dysferlin-deficient A/J mice, models of human Duchenne MD and limb-girdle MD type 2B, respectively, develop mixed sarcomas with variable penetrance and latency. To further establish the correlation between MD and sarcoma development, and to test whether a combined deletion of dystrophin and dysferlin exacerbates MD and augments the incidence of sarcomas, we generated dystrophin and dysferlin double mutant mice (STOCK-Dysfprmd Dmdmdx-5Cv). Not surprisingly, the double mutant mice develop severe MD symptoms and, moreover, develop rhabdomyosarcoma (RMS) at an average age of 12 months, with an incidence of >90%. Histological and immunohistochemical analyses, using a panel of antibodies against skeletal muscle cell proteins, electron microscopy, cytogenetics, and molecular analysis reveal that the double mutant mice develop RMS. The present finding bolsters the correlation between MD and sarcomas, and provides a model not only to examine the cellular origins but also to identify mechanisms and signal transduction pathways triggering development of RMS.
Skeletal Muscle Tumors
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