From the Archives of the AFIP: Genitourinary Rhabdomyosarcoma in Children

Radiologic-Pathologic Correlation

Abstract Introduction Clinical Features

Pathologic Features Radiologic Features Differential Diagnosis Treatment and Prognosis

Summary Source Information References

Pathologic Features

Microscopic and Gross Features

The tumor cells of rhabdomyosarcoma are analogous to the various maturational stages of fetal muscle cells (rhabdomyoblasts). Thus, the histologic appearance of rhabdomyosarcoma ranges from primitive mesenchymal tumors with stellate cells to well-differentiated lesions with myofiber-like cells and cross striations. The diagnosis of rhabdomyosarcoma may be confirmed with light microscopy, which reveals cellular cross striations (Figure 1), or with electron microscopy, which demonstrates thick (myosin) and thin (actin) myofilaments or Z-band material. Newer diagnostic techniques use immunohistochemical markers of myogenic differentiation, including antibodies directed toward myoglobin, desmin, actin, and the MyoD1 gene product (17,20). Cytogenetic evaluation may prove useful in the future (21,22). Despite these techniques, accurate diagnosis is difficult in a small number of cases. The microscopic differential diagnosis of rhabdomyosarcoma includes primitive neuroectodermal tumor, extraosseous Ewing sarcoma, synovial cell sarcoma, fibrosarcoma, alveolar soft part sarcoma, hemangiopericytoma, undifferentiated sarcoma, and neuroblastoma (23).

The most widely used classification system for rhabdomyosarcoma was proposed in 1958 by Horn and Enterline (24), who divided rhabdomyosarcomas into embryonal, botryoid, alveolar, and pleomorphic subtypes (Table 1). Embryonal histologic characteristics are most commonly found in genitourinary rhabdomyosarcoma. Light microscopy typically demonstrates variable proportions of loose myxoid foci containing primitive cells and regions of dense spindle cells. The small primitive cells frequently display thin cytoplasmic processes, producing a stellate, bipolar, tadpole, "racquet," or"strap" cell appearance (Figure 1). Some embryonal tumors with a pure spindle cell component may mimic the appearance of smooth muscle tumors and have been subtyped as spindle cell rhabdomyosarcomas (25,26). Botryoid rhabdomyosarcoma, which is generally considered a subtype of embryonal rhabdomyosarcoma, shows polypoid growth with a myxoid histologic pattern and a characteristic submucosal zone of increased cellularity referred to as the "cambium layer" (Figure 1). Alveolar rhabdomyosarcomas are composed of larger, round or oval cells separated into nests or "alveoli" by fibrous septa. The peripheral cells in alveolar rhabdomyosarcoma frequently assume a well-organized "picket fence" arrangement, whereas the central cells appear loose and necrotic. A "solid" variant of alveolar rhabdomyosarcoma has been proposed (27). Pleomorphic rhabdomyosarcoma is a highly cellular lesion composed of haphazardly arranged, round and pleomorphic cells with hyperchromatic nuclei and bizarre mitoses. These tumors rarely occur in the pediatric age group.

Modifications of the conventional histologic classification have been proposed in an effort to optimize prognostic information (12,28). Despite attempts to refine histologic classification, the wide spectrum of appearances and the absence of universally accepted criteria may lead to errors in diagnosis.

The gross appearance of rhabdomyosarcoma is variable. The margins of the tumor may be infiltrative or well defined by a compressive pseudocapsule. Botryoid rhabdomyosarcoma represents an exception to this nonspecific morphologic appearance. In this variant of embryonal rhabdomyosarcoma, the tumor does not penetrate the overlying epithelium as it protrudes into hollow organs such as the urinary bladder or vagina, and it appears as an intraluminal mass composed of smooth, grapelike clusters (Figure 2). Paratesticular rhabdomyosarcoma is often well circumscribed by tunica vaginalis or tunica albuginea. Cut sections of rhabdomyosarcoma typically appear firm, fleshy, and lobulated and may display gelatinous myxoid areas (Figure 3) orregions of secondary hemorrhage and necrosis.

Clinical Staging

The Intergroup Rhabdomyosarcoma Study, a collaborative study designed to evaluate the response of patients with rhabdomyosarcoma to chemotherapy and radiation therapy (29), used a clinical staging system with a strong reliance on surgical outcome (Table 2). Clinical stage varies with the anatomic site of the primary tumor, a characteristic that reflects the relative ease or difficulty of surgical resection. The genitourinary system is a relatively favorable anatomic site for rhabdomyosarcoma in terms of staging. Although less than 50% of all children with rhabdomyosarcoma have clinical stage I or II disease, 43% of patients with genitourinary primary rhabdomyosarcoma have stage I disease, and, of those children with paratesticular rhabdomyosarcoma, 59% have stage I and 21% have stage III or IV disease (3). A new complex staging system that integrates clinical, radiologic, and laboratory findings with histologic features at biopsy has been proposed for future studies (Table 3).

Metastases

Between 10% and 20% of all patients with rhabdomyosarcoma will have metastases at the time of diagnosis. Although rhabdomyosarcoma can metastasize to almost any site, metastatic disease is most commonly found in the lungs, cortical bone, and lymph nodes and is less frequently seen in the bone marrow and liver. However, the incidence and pattern of metastatic spread vary with the anatomic location of the primary tumor (7). For example, rhabdomyosarcoma of the prostate is more likely to disseminate to the lungs or bone marrow than are tumors confined to the urinary bladder (23). In patients with paratesticular rhabdomyosarcoma, regional lymph nodes, lungs, and cortical bone are the most common sites of metastatic spread at clinical presentation (15). Of gynecologic cases of rhabdomyosarcoma, lesions of the cervix are more likely to have metastasized to the lungs or bone marrow at the time of diagnosis than are vaginal tumors (30).

Abstract Introduction Clinical Features

Pathologic Features Radiologic Features Differential Diagnosis Treatment and Prognosis

Summary Source Information References