Lymph node metastases of rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft tissue sarcoma occurring in children under 15 years old (1,2). Rhabdomyosarcoma also occurs in young adults, but it is uncommon after 45 years of age (1,3). There are three major histologic types of rhabdomyosarcoma, and patient age and outcome correlate with histologic classification (1,4).

Embryonal rhabdomyosarcoma accounts for 50–60% of all rhabdomyosarcomas (1,5). The relative frequency of embryonal rhabdomyosarcoma has decreased in recent years as the criteria and methods used to establish the diagnosis of rhabdomyosarcoma in general, and the alveolar type in particular, have improved. Embryonal rhabdomyosarcoma occurs predominantly in young children, mostly under 10 years of age, but can occur with decreasing frequency in adolescents and younger adults. This type is truly rare in patients over 40 years. Botryoid rhabdomyosarcoma and spindle cell rhabdomyosarcoma are considered variants of embryonal rhabdomyosarcoma; accounting for approximately 10% of all embryonal rhabdomyosarcomas. Alveolar rhabdomyosarcoma accounts for approximately one-third of all cases of rhabdomyosarcoma (1,5). These neoplasms most commonly affect older children and young adults, ages 10 to 25 years of age. Pleomorphic rhabdomyosarcoma is the least frequent type, representing less than 5% of all rhabdomyosarcomas. These tumors occur almost exclusively in adults, and are truly rare in younger patients.

The median age of patients with rhabdomyosarcoma varies with histologic type. The overall male-to-female ratio for all patients with rhabdomyosarcoma is 1.3:1 (1). Patients with embryonal rhabdomyosarcoma most often have tumors involving the head and neck region, particularly involving the parameningeal structures or orbit, the genitourinary region, and the extremities (1,2). Botryoid rhabdomyosarcoma arises beneath a mucosal surface and grossly forms polypoid mass(es) resembling a bunch of grapes—and hence derives its name from the Greek word botryos. Spindle cell rhabdomyosarcoma, which histologically has a smooth muscle–like appearance, most often occur in males in the paratesticular region and has a favorable prognosis (6). With current therapeutic strategies, including excision, radiation therapy, and chemotherapy, current survival rates approach 75% to 80%, and most patients who present with localized embryonal rhabdomyosarcoma can be cured (7,8).

Alveolar rhabdomyosarcoma appears to have a predilection for deep soft tissues of the extremities, but also commonly involves the head and neck, trunk, pelvis, and perineum/anus (1). Pleomorphic rhabdomyosarcoma most often arises in large muscles of the extremities, particularly the thigh, but can involve other sites (1). The prognosis of patients with the alveolar and pleomorphic types of rhabdomyosarcoma is worse than for patients with the embryonal type (3,8,9). With therapy, the overall survival for patients with alveolar rhabdomyosarcoma approaches 50%, and survival is lower for patients with pleomorphic rhabdomyosarcoma.

Rhabdomyosarcomas have high metastatic potential and can disseminate early and widely through both lymphatic and blood vessels. When metastases occur, regional lymph nodes are commonly involved. However, the frequency of lymph node metastases appears to be higher in the older literature, or this frequency is presently much lower in the era of modern, curative therapy. For example, in a study of 110 patients with alveolar rhabdomyosarcoma published in 1969, 92% of patients died of widespread metastases within the first 4 years after diagnosis (10). Most of these patients had metastases to the regional lymph nodes and a median survival of less than 9 months. Not infrequently, lymph node metastases were detected before the primary tumor was identified. In contrast, in more recent studies, less than 5% of patients with sarcomas of all types developed regional lymph node metastases (11). Among all types of sarcoma, rhabdomyosarcoma (along with epithelioid sarcoma and angiosarcoma) has the highest frequency of regional lymph node metastases (11,12).

Metastases of rhabdomyosarcoma to lymph nodes are histologically similar to the primary neoplasms. Embryonal rhabdomyosarcomas resemble the embryogenetic stages of normal skeletal muscle, ranging from poorly differentiated tumors, which are very difficult to diagnose without the help of electron microscopy (EM) and immunohistochemistry, to well-differentiated tumors, in which cross-striations and other features of fetal skeletal muscle can be recognized (Fig. 98.1) (1,2,13). The neoplastic cells are generally small to medium in size and usually many cells are spindled. Highly cellular areas alternating with hypocellular or myxoid areas can be present. Mitotic figures are common, and necrosis can be present. In some cases, the neoplastic cells have abundant glycogen and lipid and have a clear cell appearance. Alveolar rhabdomyosarcomas, in contrast, differ from embryonal rhabdomyosarcoma in pattern and cytologic features in most cases. In the best known pattern, the neoplastic cells are separated into an alveolar pattern, or nests, by connective tissue septa, and cells within the centers of these nests are discohesive with pyknotic nuclei (Figs. 98.2 and 98.3) (1,3,10,13). However, the alveolar pattern, although helpful, is not required for the diagnosis if the cells have the characteristic cytologic features. (Neoplasms without the alveolar pattern are known as the solid variant.) The cells of alveolar rhabdomyosarcoma are medium-sized or larger polygonal cells that often have distinctly visible
nucleoli and eosinophilic cytoplasm. Mitotic figures are numerous, and foci of necrosis are frequent. The neoplastic cells are usually not spindled (unlike embryonal rhabdomyosarcoma). Pleomorphic rhabdomyosarcoma is composed of numerous spindle cells and tumor giant cells, histologically resembling other types of spindle cell sarcoma (1,3,14).