Acta haemat. 54: 115-119 (1975)
Burkitt’s Lymphoma Presenting as Acute Leukaemia F. J aiyesimi, O. O luboyede , D. T aylor and J. B. F amilusi Departments of Paediatrics, Haematology and Pathology, University College Hospital, Ibadan
Key Words. Burkitt’s tumour • Epstein-Barr virus • Leukaemia in Burkitt’s lym phoma • Methylgreen-pyronine Abstract. A Nigerian male child presented with extensive superficial lymphadenopathy, a bleeding diathesis, and numerous tumour cells in blood and bone marrow. Further characterization of the tumour cells confirmed the diagnosis of Burkitt’s lymphoma. The main unusual features shown by this patient are discussed.
Burkitt’s lymphoma is the commonest childhood tumour in Africa, ac counting for 53.4%> of all malignant tumours and leukaemia seen in chil dren in Ibadan, Western Nigeria [8]. Leukaemic features are rare in Burkitt’s lymphoma and, to the best of our knowledge, the presence of Burkitt's lymphoma cells in large quantities in the peripheral circulation has only once been reported [9]. The present communication concerns another ease of Burkitt’s lymphoma presenting as acute leukaemia.
Case R eport
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K. S. (UCH No. 321382), an 8-year-old Nigerian male child, presented at the University College Hospital, Ibadan on August 20, 1973. The complaints were swelling of both cheeks for 2 weeks, bleeding from the gums for 1 week, blood in the stools for 5 days, and protrusion of both eyes for 5 days. There was no previous ill-health. Physical examination revealed pallor of mucous membranes, swollen and bleed ing gums, multiple purpuric spots, and right subconjunctival haemorrhage. There was marked facial swelling with bilateral proptosis. The superficial lymph nodes in the submental, cervical, axillary and inguinal regions were enlarged and discrete
116
J aiyesimi/O luboyede/T aylor/F amilusi
but non-tender. The liver was 7 cm enlarged and the spleen 8 cm. Both organs were firm and non-tender. Packed cell volume 15°/o, haemoglobin 4.5 g/100 ml, white cell count 59,700/«l, platelet count less than 10,000/« 1. The blood film showed numerous blast cells each measuring 10-15 «m in diameter with multiple vacuolations in the cytoplasm and 2-3 nucleoli in each nucleous (fig. 1). Marrow aspiration from the left iliac crest showed a very cellular marrow appearance with complete bone marrow replacement by Burkitt’s lymphoma cells morphologically identical to those found in the peri pheral film (fig. 2). Methylgreen-pyronine staining of bone marrow aspirate revealed intense pyroninophilia of the cytoplasm of all the blast cells, a feature which is characteristic of Burkitt’s lymphoma [2], Phase contrast cytology of peripheral blood cells showed blast cells with dark scanty cytoplasm containing conspicuous lipid granules. The patient was transfused with 500 ml of fresh whole blood and with 2 units of platelets. In addition, intravenous vincristine 1.5 mg/m2, intravenous cyclophos phamide 500 mg/m2 and oral prednisolone 40 mg/m2/day were administered. How ever, he deteriorated very rapidly and died on the fourth day of admission. Autopsy confirmed the diagnosis of Burkitt’s lymphoma. There was involvement of the jaws, orbits and the long bones. The liver, spleen, intestines, and the lymph glands in the cervical, axillary, inguinal and retroperitoneal areas were all diffusely infiltrated with Burkitt’s lymphoma cells.
Discussion
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The present case of Burkitt’s lymphoma is noteworthy because of the prominence of clinical and haematological features usually associated with acute leukaemia and the extensive involvement of the superficial lymph nodes. Various authors have stressed the rarity of leukaemic mani festations in Burkitt’s lymphoma [4, 10]. However, O 'C onor and D avies [6] have reported evidence of leukaemia in the peripheral blood as a ter minal event in one patient; and C lift et al. [3] also reported four patients with Burkitt’s tumour who developed bone marrow infiltration with tum our cells terminally. Only one of these patients had a substantial number of malignant cells in the peripheral blood, and this was following chemo therapy and surgical excision of the tumour. It has been suggested that chemotherapy and surgical excision might have caused the spread of tum our into the blood stream in that particular patient. In contrast, tumour cells were found in the bone marrow and peripheral blood of our patient on admission, prior to any chemotherapy or surgical procedures. Extensive superficial lymph node involvement is rare in Burkitt’s lym phoma [1, 4], Even when the periheral ymph nodes are swolen, histolo-
•
j Mqi«
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Fig. I. Burkitt’s tumour cells in peripheral blood film. The cells measure 1015 «m in diameter and have numerous cytoplasmic vacuolations. Leishman’s stain. X 1,000. Fig. 2. Iliac marrow aspirate: the marrow is crowded with tumour cells mor phologically identical to those in the peripheral blood. Leishman’s stain. X 270.
118
J aiyesimi/O luboyede /T aylor/F amilusi
gy usualy shows reactive hyperplasia only, and the enlargements have been regional rather than generalized [2]. However, in our patient, as well as in the report by Stevens et al. [9], the superficial lymphadenopathy was generalized and the lymph nodes showed extensive infiltration with tumour cells. The rapidly fatal course of the disease in our patient is in accord with the experience of other workers [10]. The very poor prognosis may be due to a deficiency in the immunological competence of these children. African children with Burkitt’s tumour have high titres of Epstein-Barr virus (EBV) antibodies [5]. In Ibadan, titres of antibodies to viral capsid antigens of the EBV in children with Burkitt’s lymphoma are usually over 1:5,120 [7], In our patient the level was significantly lower (1:2,560). This might be due to either some impairment of the patient’s ability to produce antibodies to this virus, or to mopping up of the antibodies by the Burkitt’s tumour cells. Further immunological studies in patients with similar presentations of Burkitt’s tumour are required.
Acknowledgement. We thank Prof. A. U. A ntia, L. L uzzatto and B. O. O sunfor their advice. The EBV antibody titre was estimated by Prof. O sunkoya.
koya
References
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1 Burkett, D.: A sarcoma involving the jaws in African children. Br. J. Surg. 46: 218-223 (1958). 2 Burkitt, D. P. and W right, D. H.: Burkin’s lymphoma, pp. 17, 213 (Living stone, Edinburgh 1970). 3 C lift , R. A.; W right, D. H., and C lifford, P.: Leukaemia in Burkitt’s lym phoma. Blood 22: 243-251 (1963). 4 Edington, G. N. and G illes, H. M.: Pathology in the tropics, pp. 440-441 (Arnold, London 1969). 5 H enle, G.; H enle, W.; C lifford , P.; D iehl, V.; K afuko, G. W.; K irya, B. G.; K lein, G.; Morrow, R. H.; M unuba, G. M. R.; P ike, P.; T ukei, P. M., and Z ie gler, J. L.: Antibodies to Epstein-Barr virus in Burkitt’s lymphoma and control groups. J. natn. Cancer Inst. 43: 1147-1157 (1969). 6 O’C onor, G. T. and D avies, J. N. P.: Malignant tumours in African children with special reference to malignant lymphoma. J. Pediat. 56: 526-535 (1960). 7 Osunkoya, B. O.: Personal commun. 8 Osunkoya, B. O. and A jayi, O. O.: Burkitt’s lymphoma. A clinico-pathological review of Ibadan cases. Paediatrician I: 261-272 (1973).
Leukaemia in Burkitt’s Tumour
119
9 Stevens, D. A.; O’Conor, G. T.; Levine, P. H., and Rosen, R. B.: Acute leu kaemia with ‘Burkitt’s lymphoma cells’, and Burkitt's lymphoma. Ann. intern. Med. 76: 967-973 (1972). 10 Wright, D. H. and P ike, P. A.: Bone marrow involvement in Burkitt’s tumour. Br. J. Haemat. 15: 409-416 (1968).
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Dr. F. J aiyesimi, Department of Paediatrics, University College Hospital, Ibadan (Nigeria)
Burkitt’s Lymphoma Presenting as Acute Leukaemia F. J aiyesimi, O. O luboyede , D. T aylor and J. B. F amilusi Departments of Paediatrics, Haematology and Pathology, University College Hospital, Ibadan
Key Words. Burkitt’s tumour • Epstein-Barr virus • Leukaemia in Burkitt’s lym phoma • Methylgreen-pyronine Abstract. A Nigerian male child presented with extensive superficial lymphadenopathy, a bleeding diathesis, and numerous tumour cells in blood and bone marrow. Further characterization of the tumour cells confirmed the diagnosis of Burkitt’s lymphoma. The main unusual features shown by this patient are discussed.
Burkitt’s lymphoma is the commonest childhood tumour in Africa, ac counting for 53.4%> of all malignant tumours and leukaemia seen in chil dren in Ibadan, Western Nigeria [8]. Leukaemic features are rare in Burkitt’s lymphoma and, to the best of our knowledge, the presence of Burkitt's lymphoma cells in large quantities in the peripheral circulation has only once been reported [9]. The present communication concerns another ease of Burkitt’s lymphoma presenting as acute leukaemia.
Case R eport
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/11/2019 12:14:02 AM
K. S. (UCH No. 321382), an 8-year-old Nigerian male child, presented at the University College Hospital, Ibadan on August 20, 1973. The complaints were swelling of both cheeks for 2 weeks, bleeding from the gums for 1 week, blood in the stools for 5 days, and protrusion of both eyes for 5 days. There was no previous ill-health. Physical examination revealed pallor of mucous membranes, swollen and bleed ing gums, multiple purpuric spots, and right subconjunctival haemorrhage. There was marked facial swelling with bilateral proptosis. The superficial lymph nodes in the submental, cervical, axillary and inguinal regions were enlarged and discrete
116
J aiyesimi/O luboyede/T aylor/F amilusi
but non-tender. The liver was 7 cm enlarged and the spleen 8 cm. Both organs were firm and non-tender. Packed cell volume 15°/o, haemoglobin 4.5 g/100 ml, white cell count 59,700/«l, platelet count less than 10,000/« 1. The blood film showed numerous blast cells each measuring 10-15 «m in diameter with multiple vacuolations in the cytoplasm and 2-3 nucleoli in each nucleous (fig. 1). Marrow aspiration from the left iliac crest showed a very cellular marrow appearance with complete bone marrow replacement by Burkitt’s lymphoma cells morphologically identical to those found in the peri pheral film (fig. 2). Methylgreen-pyronine staining of bone marrow aspirate revealed intense pyroninophilia of the cytoplasm of all the blast cells, a feature which is characteristic of Burkitt’s lymphoma [2], Phase contrast cytology of peripheral blood cells showed blast cells with dark scanty cytoplasm containing conspicuous lipid granules. The patient was transfused with 500 ml of fresh whole blood and with 2 units of platelets. In addition, intravenous vincristine 1.5 mg/m2, intravenous cyclophos phamide 500 mg/m2 and oral prednisolone 40 mg/m2/day were administered. How ever, he deteriorated very rapidly and died on the fourth day of admission. Autopsy confirmed the diagnosis of Burkitt’s lymphoma. There was involvement of the jaws, orbits and the long bones. The liver, spleen, intestines, and the lymph glands in the cervical, axillary, inguinal and retroperitoneal areas were all diffusely infiltrated with Burkitt’s lymphoma cells.
Discussion
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/11/2019 12:14:02 AM
The present case of Burkitt’s lymphoma is noteworthy because of the prominence of clinical and haematological features usually associated with acute leukaemia and the extensive involvement of the superficial lymph nodes. Various authors have stressed the rarity of leukaemic mani festations in Burkitt’s lymphoma [4, 10]. However, O 'C onor and D avies [6] have reported evidence of leukaemia in the peripheral blood as a ter minal event in one patient; and C lift et al. [3] also reported four patients with Burkitt’s tumour who developed bone marrow infiltration with tum our cells terminally. Only one of these patients had a substantial number of malignant cells in the peripheral blood, and this was following chemo therapy and surgical excision of the tumour. It has been suggested that chemotherapy and surgical excision might have caused the spread of tum our into the blood stream in that particular patient. In contrast, tumour cells were found in the bone marrow and peripheral blood of our patient on admission, prior to any chemotherapy or surgical procedures. Extensive superficial lymph node involvement is rare in Burkitt’s lym phoma [1, 4], Even when the periheral ymph nodes are swolen, histolo-
•
j Mqi«
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/11/2019 12:14:02 AM
Fig. I. Burkitt’s tumour cells in peripheral blood film. The cells measure 1015 «m in diameter and have numerous cytoplasmic vacuolations. Leishman’s stain. X 1,000. Fig. 2. Iliac marrow aspirate: the marrow is crowded with tumour cells mor phologically identical to those in the peripheral blood. Leishman’s stain. X 270.
118
J aiyesimi/O luboyede /T aylor/F amilusi
gy usualy shows reactive hyperplasia only, and the enlargements have been regional rather than generalized [2]. However, in our patient, as well as in the report by Stevens et al. [9], the superficial lymphadenopathy was generalized and the lymph nodes showed extensive infiltration with tumour cells. The rapidly fatal course of the disease in our patient is in accord with the experience of other workers [10]. The very poor prognosis may be due to a deficiency in the immunological competence of these children. African children with Burkitt’s tumour have high titres of Epstein-Barr virus (EBV) antibodies [5]. In Ibadan, titres of antibodies to viral capsid antigens of the EBV in children with Burkitt’s lymphoma are usually over 1:5,120 [7], In our patient the level was significantly lower (1:2,560). This might be due to either some impairment of the patient’s ability to produce antibodies to this virus, or to mopping up of the antibodies by the Burkitt’s tumour cells. Further immunological studies in patients with similar presentations of Burkitt’s tumour are required.
Acknowledgement. We thank Prof. A. U. A ntia, L. L uzzatto and B. O. O sunfor their advice. The EBV antibody titre was estimated by Prof. O sunkoya.
koya
References
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/11/2019 12:14:02 AM
1 Burkett, D.: A sarcoma involving the jaws in African children. Br. J. Surg. 46: 218-223 (1958). 2 Burkitt, D. P. and W right, D. H.: Burkin’s lymphoma, pp. 17, 213 (Living stone, Edinburgh 1970). 3 C lift , R. A.; W right, D. H., and C lifford, P.: Leukaemia in Burkitt’s lym phoma. Blood 22: 243-251 (1963). 4 Edington, G. N. and G illes, H. M.: Pathology in the tropics, pp. 440-441 (Arnold, London 1969). 5 H enle, G.; H enle, W.; C lifford , P.; D iehl, V.; K afuko, G. W.; K irya, B. G.; K lein, G.; Morrow, R. H.; M unuba, G. M. R.; P ike, P.; T ukei, P. M., and Z ie gler, J. L.: Antibodies to Epstein-Barr virus in Burkitt’s lymphoma and control groups. J. natn. Cancer Inst. 43: 1147-1157 (1969). 6 O’C onor, G. T. and D avies, J. N. P.: Malignant tumours in African children with special reference to malignant lymphoma. J. Pediat. 56: 526-535 (1960). 7 Osunkoya, B. O.: Personal commun. 8 Osunkoya, B. O. and A jayi, O. O.: Burkitt’s lymphoma. A clinico-pathological review of Ibadan cases. Paediatrician I: 261-272 (1973).
Leukaemia in Burkitt’s Tumour
119
9 Stevens, D. A.; O’Conor, G. T.; Levine, P. H., and Rosen, R. B.: Acute leu kaemia with ‘Burkitt’s lymphoma cells’, and Burkitt's lymphoma. Ann. intern. Med. 76: 967-973 (1972). 10 Wright, D. H. and P ike, P. A.: Bone marrow involvement in Burkitt’s tumour. Br. J. Haemat. 15: 409-416 (1968).
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Dr. F. J aiyesimi, Department of Paediatrics, University College Hospital, Ibadan (Nigeria)
