Endemic Burkitt's lymphoma [s8]common in the Burkitt zone

Burkitt's lymphoma is a non-Hodgkin's lymphoma, but because it behaves differently from the other lymphomas in this group, it has to be considered separately. There are two types: (1) The type which is endemic in highly malarial areas, mostly in Africa, and which is associated with the Epstein[nd]Barr virus. (2) The rare sporadic type seen all over the world, which is not associated with this virus. Here, we are only concerned with the endemic type.

Burkitt's lymphoma is a high grade tumour of B lymphocytes, and is the fastest growing tumour in man[md]it can double in size in 24 hours. It afflicts children from 2 to 16 (mean age 7); is unknown under 1, and is rare over 20. It is the commonest children's cancer in Africa, and in some areas it is as common as all other childhood cancers combined. In endemic areas the genome of the Epstein[nd]Barr virus is present in 80% of tumours. 80% of well children have serological evidence of the virus, those with high titres being at much greater risk of developing the disease.

It presents as: (1) Swelling of the mandible or maxillae (one to four quadrants)[md]the commonest presentation in Africa. The earliest sign is loosening, or displacement, of a child's molar, or premolar teeth. (2) Proptosis, which may be marked, but is usually not painful. (3) Intra-abdominal tumours, especially of the retroperitoneal lymph nodes or ovaries. (4) Extradural lesions causing spinal cord compression and paraplegia. (5) Enlargement of the parotid glands, breasts (usually both), testes, thyroid, and kidneys, all of which are uncommon. Lymphomatous masses can also occasionally occur in skin or bone. (6) Lymph node enlargement is also uncommon, except in the abdomen. (7) Firm, painless, non-tender swellings, sometimes of huge size, anywhere in the body (rare). In spite of all this, the child's general health is usually remarkably good. When his bone is involved, X-rays show osteolytic lesions.

Burkitt's tumour is among the dozen tumours that can be cured by chemotherapy alone. Even involvement of the central nervous system is compatible with long survival. It responds so dramatically, that a child with Burkitt's lymphoma should have the highest priority for chemotherapy. His prognosis is inversely proportional to the volume of his tumour, hence the importance of:

(1) Early urgent treatment. If you can treat him before his central nervous system is involved, he has about a 50% chance of surviving 4 years, and will probably survive indefinitely.

(2) If he presents late, try, if possible, to remove the large bulk of his tumour surgically first. If you can remove more than 90% of it, you will double his survival time. Unfortunately, you are unlikely to be able to do this, except perhaps by removing a girl's ovary, or her breasts, or a mass in the mesentery. If you try, spilling the tumour is unimportant, because there will be a malignant ascites anyway.

If a child is to be treated early, and perhaps if he is to be treated at all, you will probably have to treat him yourself. There is no time for a leisurely workup[md]try to start treatment in 24 to 48 hours.

There are two important complications: (1) The acute tumour lysis syndrome is a combination of lactic acidosis, hyperkalaemia, and hyperuricaemia, and is the result of the rapid destruction of a large mass of tumour. Resection of most of the tumour before chemotherapy reduces this risk. This syndrome, and the post-surgical complications of far advanced disease, are the common causes of an early death. (2) The excretion of cyclophosphamide in the urine can cause a haemorrhagic cystitis. You can reduce both these dangers by maintaining a high urine output and by alkalizing his urine.

Williams EH, et al., ''Results of treatment of Burkitt's Lymphoma in the West Nile District of Uganda at Kuluva Hospital'. East African Medical Journal. 1982;785[nd]92.[-3] Williams EH, ''Rapid diagnosis of Burkitt's Lymphoma (and other soft tissue sarcomas)'. Tropical Doctor. 1981;11:68[nd]70.[-3] Ziegler JH, ''Cure of Burkitt's Lymphoma'. Lancet 1979;ii:936[nd]39.[-3] Fig. 32-3 BURKITT'S LYMPHOMA. A, a child's first complaint may be a loose tooth or displaced teeth, and the first X-ray sign, an erosion of the lamina dura of a tooth. B, a child with Burkitt's lymphoma, showing proptosis and swelling of both his upper and lower jaw on the right side. C, prompt chemotherapy is effective in over 50% of cases. D, massive involvement of a kidney. E, the characteristic ''starry sky' histology of Burkitt's lymphoma. F, if you aspirate a tumour and stain the cells with a Romanowsky stain, you may see cells like this. G, the ''Burkitt zone' in Africa, which is coincident with that of holoendemic or hyperendemic malaria. (1) a mass of retroperitoneal lymph nodes. (2) a spinal mass causing paraplegia.

BURKITT'S LYMPHOMA DIAGNOSIS. The fact that you are in an endemic area, the child's age, and the site of a rapidly growing tumour should alert you to the diagnosis. X-ray him. Take a standard biopsy, or a smear biopsy. If possible, send a bone marrow smear for histology, and examine his CSF for malignant cells.

RAPID CYTOLOGICAL DIAGNOSIS. Approach the tumour from the most convenient direction, usually through his mouth. Take a dry syringe and a 0.8 mm needle. Using local anaesthesia for the skin only, plunge the needle into the tumour. Withdraw the plunger a few times to draw the cells into the needle, detaching it each time to expel the air. Remove the needle and squirt its contents on to a slide, dry it, but don't smear it because this might destroy the cells. Fix it in methanol, or absolute ethanol, for 3 minutes, and stain it with Field's stain, or, better, any of the Romanowsky blood stains, such as those of Lieshman, Wright, or Giemsa.

The cells of Burkitt's lymphoma are fairly uniform in size. The cytoplasm of the cells forms a thin eccentric rim round the nucleus, is basophilic, non-granular, and usually contains some small vacuoles. The nucleus is slightly indented, and has 2 to 5 nucleoli, evenly distributed chromatin, and occasionally mitoses. You will not see the ''starry sky' appearance, because this is a histological, not a cytological finding.

THE DIFFERENTIAL DIAGNOSIS. varies with the site.

A swelling of the jaws[md]an infected tooth socket (5.8), perhaps with osteomyelitis (7.14a), injury (62.1), maxillary sinusitis (25.9), a dentigerous cyst or an adamantinoma (26.7), or a nasopharyngeal carcinoma (32.28). Burkitt's lymphoma usually displaces the teeth.

An abdominal swelling[md]tuberculous lymph nodes (29.2), other lymphomata (32.4), a mass of worms (10.6), Hirschsprung's disease (28.6a).

Other sites[md]inflammatory conditions and other fast-growing tumours.

STAGING. Here is Zeigler's method of staging.

Stage A One extra-abdominal tumour.

Stage B Multiple extra-abdominal tumours.

Stage C An intra-abdominal tumour with or without facial tumours.

Stage D Intra-abdominal tumours (Stage C) with tumours elsewhere other than in the face.

Stage AR An intra-abdominal tumour, but with [mt]90% resected.

PROGNOSIS. Both cyclophosphamide alone, and the three- drug regime described below, give a complete response rate of 85%. Cyclophosphamide alone gives a relapse rate of 50 to 60%; the three-drug regime reduces this to 30%. These figures are for all stages combined. Stages A and B have a better prognosis.

If he does not relapse within 6 months of starting treatment, there is a 90% chance of a complete cure. He is unlikely to relapse after one year, if he responded completely to the initial treatment.

CHEMOTHERAPY [s7]FOR BURKITT'S LYMPHOMA If you cannot obtain very rapid histological or cytological confirmation, and the clinical presentation is typical, start treatment without them[md]the tumour may grow dramatically in a few days.

Prepare him for chemotherapy as in Section 32.2.

If he has a large intra-abdominal mass, or an accessible mass elsewhere, try to resect it urgently, or refer him to have it resected. If this is impractical, start chemotherapy alone. Don't delay chemotherapy if early resection is impossible.

Triple therapy reduces the relapse rate at all stages, especially in less favourable cases (stage D), or when there is meningeal involvement, or in stage C when there is a very large tumour. Stop treatment at the end of the course[md]maintenance therapy is of no value.

CYCLOPHOSPHAMIDE. Give cyclophosphamide intravenously 1 to 1.5 g/m['2] every 14 to 21 days, up to 6 courses.

TRIPLE THERAPY. Give cyclophosphamide 1 to 1.5 g/m['2] on day one. Vincristine 1.4 mg/m['2] on day one. Tab methotrexate 15 mg/m['2] daily for 4 days. Start subsequent courses on the 21st day following the start of the first treatment, and repeat them until six courses have been given. If the tumour has not completely responded by this time, continue until it does so, and then give one more course. If there is no toxicity, you can give courses every 14 days.

CAUTION ! (1) Beware of the acute tumour lysis syndrome (see above), especially if he has a large tumour burden. During the first 24 hours maintain a high urine output, and alkalinize his urine with sodium bicarbonate (the adult dose is 3 g in water every 2 hours until the urinary pH exceeds 7, followed by 5 to 10 g daily). (2) If the mass is large give him allopurinol 10 to 20 mg/kg daily.

As always, explain to his parents what has happened, and what you are going to do. Tell them his prognosis, and that if his tumour does return, you may be able to treat him[md]but he must come for follow-up. Try to see him monthly for the first year.

PROGNOSIS [s7]WITH BURKITT'S LYMPHOMA If he fails to respond to the initial treatment, he is sure to die in a few months, whatever you do.

If his airway, his ureters, or his gut are obstructed, the obstruction may respond to chemotherapy.

If he has had no relapse during a year after triple therapy, he has about a 90% chance of surviving indefinitely. About a third of all children have no relapses for at least 2 years, and should survive indefinitely. His prognosis with cyclophosphamide alone is less favourable.

If he has an ''early relapse' within the first 3 months of treatment, it is usually in the same site. This is common with abdominal tumours, and is probably a regrowth of the original tumour. The results of repeating chemotherapy are likely to be poor.

If he has a ''late relapse' more than 3 months after treatment, the tumour is likely to arise in a previously uninvolved site, and will probably respond rapidly to the same agent(s) used initially. A few patients have multiple successfully treated relapses, at intervals which may be as long as 10 years.

CAUTION ! Don't neglect the opportunity of saving patients in relapse. Refer them if you can. Follow them up carefully, and and treat late relapses ([mt] 3 months) aggressively, if necessary several times[md]vigorous treatment in relapse can nearly double the chances of survival.

DIFFICULTIES [s7]WITH BURKITT'S LYMPHOMA If he has CRANIAL NERVE PALSIES (often multiple) or MENINGEAL INVOLVEMENT his central nervous system is involved. This becomes increasingly common as the number of relapses increase.

If he presents with PARAPLEGIA, and you suspect Burkitt's lymphoma, treat him. If you can start treatment in the first 3 or 4 days, he is likely to do well. If you can refer him for laminectomy, do so urgently; the less the delay, the better his prognosis.

Fig. 32-4 THE AGE DISTRIBUTION OF HODGKIN'S LYMPHOMA is bimodal with two peaks. After Mould RF, ''Cancer Statistics'. Bristol, Adam Hilger, with kind permission.