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Differential Diagnosis

Burkitt's lymphoma causes an osteolytic lesion in bone, followed by a bone reaction, periosteal elevation, and new bone formation: therefore the commonest error is to suspect osteomyelitis. In the early stages the appearances are similar, but in children the diaphyseal site and the lack of pain or systemic reaction should lead to the correct interpretation. Because the disease is multifocal, and because the soft tissues are often swollen, but painless, osteomyelitis can be excluded in many patients if the possibility of Burkitt's tumor is remembered. Ultrasound will show soft tissue tumor, rather than the edema of early infection. Yaws and syphilis may have to be considered in countries where they are common. Tuberculosis of bone occasionally induces a periosteal reaction, but the multifocal, osteolytic pattern of Burkitt's lymphoma with tumors at different stages is quite unlike the usual pattern of skeletal tuberculosis. Nevertheless, careful clinical and imaging correlation is necessary until there is a tissue diagnosis.

Radiologically, the "moth-eaten" osteolytic defects, together with laminated or spiculated periosteal reaction suggest osteolytic osteosarcoma, Ewing's tumor and neuroblastoma; all may produce changes that resemble Burkitt's lymphoma. Concomitant soft tissue tumors, in the abdomen, face or elsewhere may establish the correct diagnosis. An ultrasound scan of the abdomen is essential, but only biopsy may differentiate these entities.

In the spine, the soft paravertebral shadow can easily be mistaken for a tuberculous paraspinal abscess, but clinically the paraplegia of Pott's disease is nearly always spastic, whereas in Burkitt's lymphoma it is almost always flaccid. Tuberculosis of the spine usually (but not always) shows marked involvement of bone and the disc spaces are eventually narrowed, whereas Burkitt's tumor does not involve the disc spaces and, at the time of paraplegia, the amount of bone involvement on plain radiographs may be surprisingly little. Unless CT or MRI scans are available to provide more information, this discrepancy between the apparently normal vertebrae and the clinical neurological involvement is significant. Widening of the interpedicular space is infrequent in any type of spinal tuberculosis, but is more common in Burkitt's lymphoma. The marked anterior wedging of tuberculosis is contrary to the more common posterior deformity in Burkitt's tumor, and the involvement of several contiguous vertebrae is more likely to indicate infection than lymphoma. Nevertheless, because tuberculosis in the spine is often multifocal, but can involve the pedicles and may be localized, there will be patients in whom the correct radiological interpretation will not be easy; close correlation with ultrasound, CT, MRI and the clinical findings is then essential.

Within the brain and meninges, CT and MRI show solid tumors, usually multiple. The differential diagnosis of central nervous system involvement may be extremely difficult if it is not known that the patient has Burkitt's tumor; however primary CNS presentation is very rare, so that in the vast majority of patients, the disease will already have been recognized. Whatever the radiological extent of the tumor, 65% of CNS-lymphoma patients will have a raised CSF protein and in 30% of these there will be neoplastic cells: in the remaining 35% the CSF can be normal even when there are advanced neurological signs. There is no correlation between the extent of the Burkitt's tumor in the CNS and the lymphoma elsewhere in the body, nor is there any prognostic correlation between the extent of the disease and the likelihood of subsequent CNS spread.

Renal involvement may be the first sign of Burkitt's tumor and, when this happens, the diagnosis can be difficult if this possibility is not considered. The urographic differential diagnosis of Burkitt's lymphoma in the kidneys will usually include multiple simple cysts or other forms of cystic disease. Ultrasound will differentiate cysts from solid tumors. Metastases and non-Burkitt's lymphoma, especially Hodgkin's disease, can be less easy to differentiate. Burkitt's tumors appear well defined and cause tissue displacement rather than invasion; they lack calcification, are solid on ultrasound or CT, and are avascular on angiography. In this way renal cell carcinoma and angiomyolipoma can be excluded with certainty. A search elsewhere will nearly always provide further evidence of Burkitt's tumor. Ultrasound and CT scans should include the liver, ovaries and spleen when Burkitt's lymphoma is suspected.

Burkitt's tumors in the gastrointestinal tract cannot be reliably differentiated from other lymphomas, from other causes of intestinal obstruction or from intrinsic gastric or bowel tumors of other cell types. The presence of multiple tumors, usually clinically silent, rarely causing intussusception, and a chance finding on imaging, may suggest the possible diagnosis. Alimentary tract involvement nearly always occurs late in the disease.

The rare case of Burkitt's lymphoma involving the lungs may be mistaken for pneumonic consolidation or any interstitial disease, including leukemic infiltration. On plain chest radiographs mediastinal Burkitt's tumors will simulate lymphoma or lymphadenopathy. It may be possible by CT or MRI to differentiate tumors from enlarged mediastinal lymph nodes. Extranodal mediastinal masses are very uncommon in tuberculosis.

The radiological findings in Burkitt's lymphoma seen in North America and elsewhere are not intrinsically different, although the variation in sites of involvement causes different presentations. Intrathoracic involvement is a little more common in the North American and European patients than in those from tropical Africa. The visceral pleura may be densely infiltrated with tumor and in these patients the underlying lung may be spared. The chest radiographs demonstrate scattered interstitial infiltration: the pleura may be thickened, nodular or contain an effusion. It is important to note that lung and pleura may be separately or independently involved. The heart may become infiltrated and show similar small irregular nodules: there may be intracardiac masses or a pericardial effusion.

Tumors have been reported in skeletal muscles and in the neck and may present as nonspecific soft tissue tumors. Bone, central nervous system, renal, ovarian and other tumors do not differ radiologically in nonendemic areas compared with the findings in the tropical cases.

A constant awareness of the possibility of Burkitt's lymphoma is the most important aid to accurate diagnosis. The jaw tumors will seldom cause difficulty, and any unusual tumor in children or young adults, especially in the abdomen, should raise a high index of suspicion. Because of the nature of the disease, an early accurate diagnosis is essential because radiotherapy may be harmful and the correct chemotherapy may be lifesaving. The prognosis is better than might be expected.

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Copyright: Palmer and Reeder