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Primary cerebral lymphoma is a unique and infrequent CNS malignancy in which the B lymphocyte subtype constitutes most cases.1 B cell neoplasms other than multiple myeloma including non-Hodgkin’s lymphomas, and acute and chronic leukaemias might also exhibit lytic bone lesions, hypercalcaemia, and monoclonal gammopathy via the particular actions of interleukin (IL-1), IL-6, or tumour necrosis factor-α secreted by the neoplastic B cell clone, but not reported previously secondary to a primary cerebral lymphoma.2 We describe an unusual presentation of a B cell primary cerebral lymphoma mimicking a plasma cell dyscrasia.
A 64 year old woman was admitted with complaints of headache, ataxia, and urinary incontinence. Physical examination disclosed motor dysfunction in the legs, dysphasia, and impaired cerebellar function. On initial evaluation, a mass of 6×4 cm in diameter was shown in the left frontal lobe by MRI of the cranium (fig 1). Haematological and blood biochemistry values were within normal limits. Direct skull radiography disclosed multiple lytic lesions (fig 2). Serum immunoglobulin (Ig) G concentration was high (3400 mg/dl; normal<1800) and a monoclonal protein band of IgG-κ type was detected by immunoelectrophoresis. Total excision of the lesion disclosed large lymphocytes with oval and vesicular nuclei, and prominent nucleoli consistent with “intermediate grade large cell malignant lymphoma” according to the working formulation.3 Methyl green pyronine stain was positive indicating cytoplasmic RNA accumulation and lymphoplasmocytoid differentiation. Staining with CD10 was also positive confirming the diagnosis of B cell lymphoma. The tumour margins showed infiltration into the surrounding white matter and extending to perivascular spaces with absence of involvement of subarachnoid spaces, dura, or bony structures. Pathological examination of the largest lytic skull lesion disclosed “osteolysis without a neoplastic infiltration”. Immunoelectrophoresis of CSF showed a monoclonal IgG-κ band similar to the results of serum assays whereas biochemical and cytopathological CSF examinations were normal. Enzyme linked immunosorbent assay (ELISA) tests for HIV and antibody titres against Epstein-Barr virus were also negative in both serum and CSF samples. Slit lamp examination was normal, with no lymphomononuclear deposits in the uvea or vitreous fluid. Staging procedures including CT of the abdomen and pelvis, bilateral bone marrow aspiration, and biopsies were within normal limits precluding the diagnosis of primary cerebral lymphoma. She received 4920 cGy radiotherapy to the whole cranium followed by COPP (cyclophosphamide, vincristine, procarbazine and prednisone) chemotherapy, repeated every fourth week. By the third month of follow up, serum and CSF paraprotein disappeared and lytic skull lesions regressed. Concurrent cranium MRI disclosed no residual or recurrent mass and repeated investigation for systemic lymphoma was also negative. She is still being followed up and has so far survived more than a year.
MRI of cranium showing a mass of 6×4 cm in diameter, located in the left frontotemporal lobe, showing moderate enhancement after intravenous contrast material injection.
Direct lateral radiography of the skull of the patient, showing multiple punched out lytic lesions of the cranial vault, with no evidence of a periosteal reaction.
Despite the differences in localisation and biology, non-Hodgkin’s lymphomas arising from the CNS are not histologically different from the ones arising at extraneural sites, except that almost all have intermediate or high grade histology, predominantly of B cell subtype.4 The monoclonality of intracellular immunoglobulins and cell lines obtained from primary cerebral lymphoma tissue cultures is well established.5 These specific clonal products might be detected in CSF but not reflected in systemic circulation probably owing to the presence of an intact blood-brain barrier that, to the our knowledge, a B cell primary cerebral lymphoma with raised serum monoclonal paraprotein and lytic skull lesions simulating multiple myeloma has not been previously reported. The probable factors of disturbed blood-brain barrier, tumorous penetration of vascular spaces, or stimulation of angiogenetic collateral formation secondary to neoplastic outgrowth might be, alone or in combination, responsible for those remote effects of primary cerebral lymphoma. This remains to be verified. The contradictory pattern of overlapping symptomatology of B cell neoplasms makes it obligatory to achieve the definitive histopathological diagnosis particularly in the case of primary cerebral lymphoma , in which the therapeutic algorithm as well as the prognosis have diverse features.