Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 46, Num. 3, 2000, pp. 187-188

Journal of Postgraduate Medicine, Vol. 46, No. 3, July-September, 2000, pp. 187-188

Case Report

Waldenstrom's Macroglobulinaemia with Intracerebral Haemorrhage

Khan GQ, Hassan DG, Masood T, Khan AR*

Departments of Medicine and Pathology*, Government Medical College and SMHS Hospital, Srinagar, Kashmir, India.
Address for correspondence: G. Q. Khan, MD, 3-School Enclave, Rawalpora P.O. Sanatnagar, Srinagar - 190 005, Kashmir, India.

Code Number: jp00067

Abstract:

A 65-year-old male was admitted for evaluation of severe anaemia, recurrent epistaxis, axillary lymphadenopathy, and hepatomegaly. The diagnosis of Waldenstrom's macroglobulinaemia was made on the basis of clinical and laboratory findings. The patient developed intracerebral haemorrhage without associated hypertension and with normal coagulation profile. (J Postgrad Med 2000; 46:187-188)

Key words: Hyperviscosity syndrome, immunoglobulins, multiple myeloma, Waldenstrom's Macroglobulinaemia.

Waldenstrom's Macroglobulinaemia (WM), first described by Waldenstrom in 1948, is a disorder of unknown aetiology characterised by malignant proliferation of lymphoplasma-cytoid cells that secrete IgM immunoglobulin. This is a rare disorder with a wide spectrum of presentations, course and complications.¹ We report the disorder in an elderly male with WM with intracerebral haemorrhage. Only few cases of WM have appeared in Indian literature.^2-5

Case Report

A 65-year-old male was admitted with easy fatigability, weakness and recurrent epistaxis. The patient was normotensive, severely anaemic, had firm, mobile and non-tender lymph nodes in left axilla, palpable liver five cm below the right costal margin. No features of Raynaud's phenomenon were present, and other systemic examination was unremarkable except changes in the fundus, which showed large physiological cup, venous tortuosity and haemorrhages all over the fundus (Figure 1). Fluorescein angiography showed prolonged `arm retinal time' (20 seconds), sluggish flow of dye through the vessels (remaining in the vessels after 20 minutes).

Investigations revealed, a haemoglobin of 4.5 g/dL (normochromic/normocytic erythrocytes), white blood cell count of 8.3 x 10⁹/L with 51% lymphocytes, erythrocyte sedimentation rate (ESR) of 175 mm after one hour, and normal platelet counts. Serum viscosity was 8 (normal, 1.4-1.8). The blood smear showed marked rouleaux formation. Serum albumin was 2.9 g/dL and globulin 7.8 g/dL. Serum electrophoresis revealed markedly elevated IgM, 2850 mg/dL (normal 45-150 mg/dL). Urine analysis showed Bence-Jones protein and 24 hours' protein of 3.6g.

Haemolytic and coagulation profiles were normal and endocrinological investigations failed to reveal any other abnormality. Skeletal survey did not show lytic lesions. Bone marrow aspiration smear showed predominantly, lymphocytes, lymphoplasmacytoid cells and plasma cells. Some cells showed intranuclear (Dutcher) and intracytoplasmic (Russel) bodies. The normal elements were reduced and crowded out by the lymphoproliferative infiltrates. Fine needle aspiration cytology of lymphnode showed mature lymphocytes with some lymphoplasmacytoid cells and plasma cells (Figure 2). Histopathological examination of the lymph node showed lymphocytes, lympho-plasmacytoid cells and plasma cells. On the basis of clinical picture and investigations, the diagnosis of WM was made.

Because of non-availability of facility for plasmapheresis, the patient was treated with cyclophosphamide and prednisolone. Patient was given blood transfusions as well, and was discharged in a stable condition. After 8 weeks, the patient showed significant clinical improvement with decrease in liver size by 3 cm, absence of haemorrhages on fundus examination, haemoglobin 7.3 g/dl and IgM of 1370 mg/dl. During hospital stay, he got generalized tonic clonic convulsions, was managed with anticonvulsant therapy, computed tomography (CT) scan revealed normal study, and was again discharged after he got stabilised. Later, he was admitted for reassessment and during hospital stay he got cerebrovascular accident, CT scan revealed intracerebral haemorrhage on right side in the territory of middle cerebral artery. He was treated conservatively, but died after 18 hours of this episode.

Discussion

WM is a disease of old age, more common in men during the 5^th to 7^th decade with a median age of 64 years. Besides the usual presentations of weakness, fatigability, weight loss, hepatosplenomegaly, lymphadenopathy, recurrent infections and visual disturbances; hyperviscosity syndrome with bleeding from mucous membranes, is the main manifestation of this disorder,^6,7 However, there has been variable clinical spectrum of the disorder.^1,8 Markedly elevated IgM, has been considered as the major diagnostic criterion,¹ and is well differentiated from closely related disorders like multiple myeloma, chronic lymphocytic leukaemia and IgM myeloma. In addition to the neurological complications like focal brain syndromes, retinopathy, myelopathy, and neuropathy, epistaxis, bleeding from gastrointestinal tract, subarachnoid haemorrhage has been described in the literature.^1,5 Our patient had intracerebral haemorrhage in absence of the usual risk factors, like hypertension, which seems unusual and this can be explained on the basis of hyperviscosity syndrome where excessive production of the intravascular paraprotein leads to increased red cell aggregation and plasma viscosity causing reduction in the blood flow leading to vascular stasis, occlusion and ischaemia with eventual bleeding tendency due to interference with coagulation factors and platelet function.⁹

Our patient showed fair response to chemotherapy, however, plasmapheresis has been found highly beneficial in patients with hyperviscosity syndrome. Several trials with different chemotherapeutic agents like cyclophosphamide, chlorambucil and melphalan have been conducted so far and variable results and toxicities have been observed. More recently agents like fludarabine and cladribine have been shown to be highly effective; around 80% of patients respond to chemotherapy with median survival of more than 3 years.^1,6

Acknowledgement

The authors acknowledge the help of Dr. Javid Iqbal, Biomedicare Laboratories, for various investigations; Drs. Tariq Qureshi and S. Fazili, Ophthalmologists, Government Medical College, for Ophthalmologic studies and fundus photographs; and Dr. M. Sidiqi, Immunologist, Sher-i-Kashmir Institute of Medical Sciences, for electrophoretic studies.

References

1. MacKenzie MR, Fudenberg HH. Macroglobulinemia: An analysis for forty patients. Blood 1972; 39:874-889.
2. Malaviya AN, Mangalik A. Macroglobulinemia: report of first three cases from India. J Assoc Physicians India 1971; 19:571-577.
3. Jayapal V, Thomas M, Mathew S, Augustine J, Santhamma K, Vijayalekshmi N, et al. Waldenstrom's macroglobulinemia. J Assoc Physicians India 1990; 38:510-512.
4. Karmarkar T, Saha A, Verma N, Walker R, Sakhuja V, Datta U. Waldenstrom's macroglobulinemia: a case with lymphocytosis. J Assoc Physicians India 1993; 41:458-459
5. Lekhra OP, Sawhney IM, Gupta A, Varma S, Chopra JS. Venous retinopathy in Waldenstrom's macroglobulinemia. J Assoc Phys Ind 1996; 44:61-62.
6. Longo DL. Plasma cell disorders. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, editors. Harrison's Principles of Internal Medicine. 14th Ed. New York: McGraw Hill; 1998. pp 712-718.
7. Tumours of lymphoid tissues: the paraproteinemias. In: Penington D, Rush B, Castaldi P, editors. GC de Gruchy Clinical Haematology in Medical practice. 4th Ed. Delhi: CBS Publishers 1985. pp 502-553.
8. Mc Callister BD, Bayrd ED, Harrison EG, Mc Guckin WF. Primary Macroglobulinemia: review with a report of thirty-one cases and notes on the value of continuous chlorambucil therapy. Am J Med 1967; 43:394-434.
9. MacKenzie MR, Lee TK. Blood viscosity in Waldenstrom's Macroglobulinaemia. Blood 1977; 49:507-510.

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