JBJS | Article

The Journal of Bone & Joint Surgery, Volume 84, Issue 5

Case Reports | May 01, 2002

Primary Rhabdomyosarcoma of the Humerus : A Case Report and Review of the Literature

Frank Thomas, MD; Jeffrey F. Lipton, MD; Carl Barbera, MD; Vincent J. Vigorita, MD; Eli Bryk, MD

Frank Thomas, MD
Department of Orthopedic Surgery, Kingsbrook Jewish Medical Center, 585 Schenectady Avenue, Brooklyn, NY 11203

Jeffrey F. Lipton, MD
Department of Pathology, Maimonides Medical Center, 4802 10th Avenue, Brooklyn, NY 11219. E-mail address: jlipton@maimonidesmed.org

Carl Barbera, MD
Richmond Bone and Joint, 3311 Hylan Boulevard, Staten Island, NY 10306

Vincent J. Vigorita, MD
Department of Pathology, Lutheran Medical Center, 150 55th Street, Brooklyn, NY 11220

Eli Bryk, MD
Department of Orthopedic Surgery, Beth Israel Medical Center, 10 Union Square East, New York, NY 10003

The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

The Journal of Bone & Joint Surgery. 2002; 84:813-817

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Introduction

Introduction | Case Report | Discussion | References

Rhabdomyosarcoma is primarily a neoplasm of the soft tissue in children ¹ . Osseous involvement is most often due to metastasis ^2-6 . Primary rhabdomyosarcoma of bone has most frequently been reported in the facial bones ^7,8 . To our knowledge, only six cases of primary rhabdomyosarcoma involving a long bone have been described in the English-language literature ^2-6,9 . The purpose of this report is to increase awareness of this uncommon entity by describing the clinical, surgical, radiographic, and pathologic findings in our patient as well as in cases that have been reported previously.

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Fig. 1:: Anteroposterior radiograph of the right humerus, demonstrating a destructive lesion of the proximal part of the shaft, with soft-tissue extension. Associated calcification and periosteal reaction are present. A permeative pattern is seen proximal and distal to the area of destruction.

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Fig. 2:: T2-weighted fast-spin-echo coronal magnetic resonance image (repetition time, 4000 msec; echo time, 95 msec). Note the soft-tissue extension as well as the central area of increased signal intensity representing central necrosis.

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Fig. 3:: Photomicrograph of the tumor, showing pleomorphic round and spindle-shaped cells with abundant amphophilic cytoplasm and a high mitotic rate (hematoxylin and eosin, 400).

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Fig. 4:: Photomicrograph showing immunohistochemical reactivity for myoglobin in a subset of tumor cells (400).

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Fig. 5:: Electron microscopic image demonstrating the characteristic thin and thick filaments and Z bands of skeletal muscle cells (37,000).

Case Report

Introduction | Case Report | Discussion | References

A twenty-two-year-old man presented with a six-month history of pain in the proximal part of the right arm that had been exacerbated by a recent fall. Physical examination revealed an enlargement of the proximal part of the arm. Radiographs revealed a pathologic fracture through a lytic lesion in the proximal part of the right humerus, with a periosteal reaction ( Fig. 1 ).

Magnetic resonance imaging demonstrated an expansile, intramedullary, poorly defined neoplasm in the proximal part of the humerus, with diffuse erosion of the cortex and involvement of the surrounding soft tissue ( Fig. 2 ). Computed tomography demonstrated soft-tissue extension and humeral destruction. The intraosseous central location and uniform cortical destruction indicated that the lesion was not a soft-tissue sarcoma invading bone. A bone scan did not reveal distant metastases. Computed tomography of the chest did not reveal any thoracic abnormality.

An incisional biopsy showed a high-grade sarcoma with muscle differentiation. Histologic analysis revealed a population of multinucleated and mononucleated giant tumor cells, with abundant eosinophilic cytoplasm. Immunohistochemical studies were positive for vimentin, desmin, myoglobin, and MyoD1, a profile consistent with rhabdomyosarcoma ( Figs. 3 and 4 ).

The patient received two weeks of chemotherapy consisting of vincristine, actinomycin D (dactinomycin), and cyclophosphamide (Cytoxan) prior to undergoing forequarter amputation. He tolerated the procedure well, but he was lost to follow-up after leaving the hospital against medical advice on the second postoperative day. Subsequent investigation revealed that the patient died in November 1998, eleven months after the operation, evidently without having received further treatment for the tumor. Examination of the resection specimen showed a soft, light-yellow, gelatinous tumor measuring 20 cm along the long axis of the arm and 15 cm transversely. The tumor was centered in the proximal part of the humerus, with involvement of the surrounding soft tissues. A central hemorrhagic and necrotic area contained serosanguineous fluid. No intra-articular extension was seen, and dissection of nineteen axillary lymph nodes revealed no evidence of regional metastasis. The lesion was diagnosed as embryonal rhabdomyosarcoma on the basis of the histologic evaluation.

Electron microscopic evaluation of the surgical specimen was performed to provide further confirmation of the diagnosis. Z-band and M-band architecture, thick and thin filaments, basement-membrane material, and glycogen were all clearly demonstrated ( Fig. 5 ).

This tumor could have originated in one of three ways: as a metastasis from an occult primary tumor located elsewhere, as a local extension of a soft-tissue sarcoma, or as a primary intraosseous tumor. The magnetic resonance imaging and pathologic findings supported the diagnosis of primary rhabdomyosarcoma of bone.

Discussion

Introduction | Case Report | Discussion | References

Primary rhabdomyosarcoma involving the appendicular skeleton is extremely rare, with only five cases having been described in previous reports ^2,3,5,9,10 . The cause is unknown. The lesion has been reported with greater frequency in the facial bones ^7,11 and can certainly involve the bones of the extremities as a component of a dedifferentiated chondrosarcoma or malignant mesenchymoma. Osseous involvement more commonly is the result of metastasis ^4,12,13 or local extension ^2,5,14,15 , in which cases the proportion of bone that is affected is small compared with the size of the primary site ⁵ . However, there have been several reports in which the first manifestation of metastatic rhabdomyosarcoma was in bone ^12,13,16 . Technetium bone scans can aid in identifying these metastases ¹⁵ and may indicate the location of the primary tumor in these unusual cases.

Rhabdomyosarcoma more commonly appears as a primary soft-tissue tumor in children ¹⁷ , with the most common sites of metastases being the lungs and the lymph nodes ^18,19 . Other sites of metastases have included the brain, skull, pancreas, gallbladder, liver, pericardium, and other abdominopelvic viscera ¹⁹ . Areas of rhabdomyosarcomatous differentiation are seen in nephroblastomas, Triton tumors (i.e., tumors with mixed neural and myogenic differentiation), thymic neoplasms, and mixed mï¿½llerian tumors ¹⁸ . Rhabdomyosarcoma was even identified as a component of a primary myxoid liposarcoma in the mouth of a thirty-four-year-old man ²⁰ . Odd primary locations have included the sternum ⁸ , temporal bone ^2,7 , mandible ¹¹ , iliac bone ¹ , breast ²¹ , and brain ¹⁰ .

Clinically, primary rhabdomyosarcoma of the appendicular skeleton can be mistaken for osteosarcoma, Ewing sarcoma, plasmacytoma, or lymphoma ^14,22 . Primary leiomyosarcoma, although also uncommon, is more prevalent ²² and should be higher on the list of potential diagnoses ^23,24 . Unlike rhabdomyosarcoma, leiomyosarcoma has a predilection for long bones ²² . The differential diagnosis of osseous sarcomas with rhabdomyoblastic differentiation includes malignant fibrous histiocytoma, malignant mesenchymoma ^25,26 , dedifferentiated chondrosarcoma ^4,6 , metastatic rhabdomyosarcoma, rhabdomyosarcoma with local osseous extension, and malignant Triton tumor. Primary malignant mesenchymoma of the bone is rare ⁴ . Van Dorpe et al., in a review of the literature, identified only fifteen previous cases, six of which had a rhabdomyosarcomatous component ²⁶ . Dedifferentiated chondrosarcoma with a rhabdomyosarcomatous component is an unusual occurrence but was well described by Reith et al. ⁶ . Otsuka et al. reported that rhabdomyosarcoma was identified in the lung of a patient who had metastasis of osteosarcoma following chemotherapy ²⁷ . It is evident that rhabdomyosarcoma can present in a large variety of situations and that mesenchymal tumors of varied histogenesis may have an element of rhabdomyosarcomatous differentiation.

The international classification system for rhabdomyosarcoma divides the lesion into several types, including botryoid, embryonal, spindle cell, alveolar, undifferentiated, and rhabdoid ¹⁷ . The worst prognosis is seen in association with the alveolar and undifferentiated subtypes, and the best is seen in association with the botryoid and spindle-cell subtypes, the latter of which has an excellent prognosis (as indicated by an 88% survival rate at five years ¹⁷ ). Most of the previously described cases of primary rhabdomyosarcoma of bone were reported to be of the embryonal variant.

The diagnosis of rhabdomyosarcoma can be difficult, especially in sites in which the lesion is rare. Horn and Enterline ¹⁹ , in their 1958 report of thirty-nine cases, were unable to delineate any characteristic macroscopic features of rhabdomyosarcoma. Light microscopic evaluation of a pleomorphic or embryonal specimen stained with hematoxylin and eosin will usually demonstrate abundant spindle-shaped cells with strongly eosinophilic cytoplasm. Small round cells with occasional multinucleation are characteristic of the alveolar type, while prevalent cross-striations are observed in some alveolar and embryonal types ^4,19 . The botryoid features noted by Horn and Enterline ¹⁹ were similar to those of the embryonal type with high mitotic activity. Nevertheless, a variety of cell patterns have been described ²⁸ .

Immunohistochemical studies may show positive staining for desmin ^25,28 , vimentin, HHF-35, myosin, titin Z-band protein, S-100 protein, sarcomeric actin, and/or creatine kinase. Fetal heavy-chain myosin, skeletal muscle actin ²⁵ , cardiac alpha-actin, myoglobin, MyoD1, and titin have all been described as specific to skeletal muscle ¹⁸ but are not always reproducibly positive. Tallini et al. ²⁹ and Wesche et al. ³⁰ , however, documented the high specificity and sensitivity of the MyoD1 antibody to skeletal muscle, and focal nuclear reactivity for MyoD1 was observed in the case of our patient. The actin antibody HHF-35 and the desmin antibody clone der11 have been claimed to be the most specific ^18,28 .

Ultrastructural analysis is the most sensitive and specific means for diagnosing rhabdomyosarcoma. Thick and thin filaments, Z-band material ^25,28 , basement-membrane material ¹⁸ , and glycogen should all be noted ¹⁷ , as they were prominently in the case of our patient ( Fig. 5 ). So-called myosin/ribosome complexes have also been described as a requisite for identification ¹⁸ . Gruchala et al. ²⁸ noted poorly developed rough endoplasmic reticulum in some cases. In addition, electron microscopy is useful for distinguishing rhabdomyosarcoma from leiomyosarcoma by identifying a lower actin-to-myosin ratio (6:1 vs. 15:1) ¹⁸ .

Surgical resection is the mainstay of treatment. A review of the other published reports ^1,9 suggests that wide resection, at a minimum, provides the best chance for a cure. Because of the low number of cases of rhabdomyosarcoma of the long bones, it is difficult to formulate an effective treatment protocol.

The embryonal subtypes as a whole are associated with a more favorable prognosis than the alveolar subtypes, and the spindle variants have the best prognoses of all ^17,18 . The initial lesion described by Deb and Kundu ² was considered "nonaggressive" and was managed with local excision and bone-grafting, as was the recurrent lesion nine months later. No further follow-up was mentioned in that report. The patient reported on by Pasquel et al. ¹⁰ had distant metastases at the time of the last reported follow-up, eight months after the operation. The patient described by Hsueh et al. ³ was lost to follow-up. Lucas et al. ¹⁴ stated that their patient had no evidence of disease at seven months, while Rashid et al. ⁵ reported that their patient died one year after the initial operative intervention. The patient described by Wang et al. ⁹ had a good outcome after intra-arterial chemotherapy. Our patient failed to return for follow-up, but further investigation revealed that he died eleven months after the operation. In general, primary bone sarcomas that have these patterns of cortical destruction may be considered higher-grade lesions ³¹ . As a note, DNA aneuploidy that is observed after chemotherapy has been regarded as a favorable finding ³² . Because of the low number of cases of primary osseous rhabdomyosarcoma and the inadequate duration of follow-up in most of those cases, few conclusions can be made regarding prognosis.

Marcial-Seoane et al. ⁴ postulated that the lesions described by Hsueh et al. ³ and Pasquel et al. ¹⁰ were not pure rhabdomyosarcomas, but instead were primary osteorhabdomyosarcomas characterized by the presence of an osteogenic sarcomatous component. This reinterpretation was based on the identification of neoplastic bone formation in the tumors that had been called pure rhabdomyosarcomas. It should be noted that the patients reported on by Deb and Kundu ² , Rashid et al. ⁵ , and Lucas et al. ¹⁴ also presented with radiographic evidence of periosteal reaction. The neoplasm in our patient showed no such findings, and the large intraosseous proportion of the tumor, the absence of known metastases, and the lack of a separate identifiable primary site led us to believe that the lesion was in fact a primary rhabdomyosarcoma. All of the radiographic, clinical, and pathologic evidence supported a primary bone origin. The diagnosis was substantiated by histopathological, immunohistochemical, and ultrastructural studies.

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Introduction | Case Report | Discussion | References

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