Diagnosis

Ewing's sarcoma of the thumb

CASE FOLLOW-UP

A technetium bone scan revealed very high tracer uptake in the affected bone but no other abnormal foci in the rest of the skeleton (not shown). A chest radiograph showed no metastatic lesions (not shown). All laboratory data were within normal limits. Disarticulation through the metacarpophalangeal joint of the thumb was successfully performed, followed by chemotherapy.

Findings

X-rays of the right hand showed a purely lytic lesion of the distal phalanx without periosteal reaction, which was accompanied by a huge soft tissue tumor (Figure 1).

Considering the age of the patient and the clinical findings, primitive neuroectodermal tumor (PNET)/ Ewing's sarcoma (ES) of the thumb was the most probable radiologic diagnosis.

PATHOLOGY

An incisional biopsy was performed. Under the light microscope, the neoplasm was seen to be composed of sheets of tumor cells with round-to-oval nuclei. The cytoplasm was scant, and the cell margins were ill- defined. Periodic acid-Schiff (PAS) staining revealed prominent cytoplasmic glycogen (Figure 2). Immunohistochemically, the tumor cells expressed vimentin and MIC2, while desmin, myoglobin, keratin, and S100 were negative.

Discussion

Ewing's sarcoma, a highly malignant primary bone tumor, was first described by James Ewing in 1921. The tumor is derived from red bone marrow. Most frequently, it is observed in children and young adults from 5 to 25 years of age. Ewing's sarcoma accounts for approximately 5% of biopsy-analyzed bone tumors in patients of all ages. It is the second most common malignant bone tumor in young patients. Males are affected more frequently than females, with a ratio of approximately 1.5/1.^1,2

An association exists between ES and PNET. The majority of both of these tumors (90%) share the cytogenetic translocation t(11;22) (q24;q12) or (21;22) (q22;q12), with occasional variations, and a characteristic immunohistochemical staining profile. Both of these tumors are believed to show neuroectodermal differentiation, albeit in different degrees. Ewing's sarcoma tends to be poorly differentiated, whereas PNET most often shows definite neuroectodermal differentiation. Although once viewed as distinct entities, ES of bone, extraosseus ES, Askin's tumor, and PNET are now considered together as members of the Ewing's family of tumors.^3,4As such, they are increasingly grouped together for both treatment and prognostic factor analysis.

The histogenesis of ES remains controversial, and current wisdom as to the cellular origin is divided between mesenchymal cells, possibly osteoprogenitor cells of the bone marrow, or neuroectodermal cells.^3,4 Most frequently, the tumor is diagnosed as a monostotic lesion in the metaphysis or diaphysis of the long bones of the extremities. The tumor also may occur, although less frequently, in the pelvic area, ribs, and scapulae.^1,2 Ewing's sarcoma rarely affects the hand. Kissane and coworkers¹ indicated the incidence of ES involving the hands to be 0.3% of all cases of ES, and Dahlin² reported the figure as 1%.

In ES of the hands, the middle and index fingers are the most commonly involved. The metacarpals are more commonly affected than the phalanges.⁵ As with tumors in other locations, pain and swelling are the 2 most common presenting complaints, and they may tend to be progressive. Low-grade fever is common, and these patients may have elevated erythrocyte sedimentation rate and leukocytosis. Few patients have a history of local trauma, and the symptoms may vary in duration from a few weeks to many months.^6,7

The classic radiographic features of ES-namely, lytic permeative destruction, aggressive periosteal reaction, cortical violation, and a soft tissue mass-are also typically present in lesions of the hands. A purely lytic lesion is less common in the small bones of the hands than in other bones. Within the short tubular bones of the hands, most ES tumors are centered in the metadiaphyseal region, similar to the trend in long bones.^5-

The definitive diagnosis of ES requires a biopsy specimen. Morphologically, the neoplasm is characterized by monotonous sheets of hyperchromatic cells with round-to-oval nuclei, high nuclear-to-cytoplasmic ratios, and scant cytoplasm. Cytoplasmic glycogen can often be detected by PAS stain or electron microscopy. Afiligree pattern of infiltration in soft tissue is associated with an adverse prognosis. The immunohistochemical profile usually exhibits immunopositivity to vimentin and the MIC2 gene product. The MIC2 gene product is a cell surface glycoprotein found on ES cells and is very useful in the differential diagnosis. Antibodies to the MIC2 gene product include 12E7, O13, and HBA71 (CD99). Specimens of ES may mark for S100 protein and neuron-specific enolase.⁹ The immunohistochemical features of the presented cases correspond well to those of conventional ES.

The treatment of ES continues to be controversial. Recent reports have emphasized the role of surgical extirpation and adjunctive chemotherapy, especially in the absence of metastatic disease. In the hand bones, resection removes the tumor with radical margins and preserves the function, and the results are cosmetically satisfactory.⁶

The prognosis of ES involving the digits seems to be even better than that of ES that involves more usual sites. This is probably because the phalanges are the most peripheral bone; tumors can be excised with a wide margin. Consequently, ES of the digit may lead to an excellent prog-nosis.⁷

CONCLUSION

Ewing's sarcoma is a highly malignant, small, round-cell neoplasm that usually arises in the medullary cavity of bone. The most common sites for the primary lesion are the long bones, pelvis, and ribs. The case described here is unusual because of its location and the volume of the extraskeletal mass.

1. Kissane JM, Askin FB, Foulkes M, et al. Ewing's sarcoma of bone: Clinicopathologic aspects of 303 cases from the intergroup Ewing's sarcoma study. Hum Pathol. 1983;14:773-779.
2. Dahlin DC, Unni KK.Bone Tumors:General Aspects and Data on 8,542 cases. 4th ed. Springfield, IL: Charles C. Thomas Publishers, Ltd.; 1986.
3. Delattre O, Zucman J, Melot T, et al. The Ewing's family of tumors- A subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med.1994; 331:294-299.
4. Baldini EH, Demetri GD, Fletcher CD, et al. Adults with Ewing's sarcoma/primitive neuroectodermal tumor: Adverse effect of older age and primary extraosseous disease on outcome. Ann Surg. 1999; 230:79-86.
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9. Llombart-Bosch A, Contesso G, Peydro-Olaya A. Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone. Semin Diagn Pathol. 1996;13:153-170.