Burkitt's Lymphoma in Colombia*GERMAN BEI .TRAN, M .D.,f ATILlo BAEZ, M .D .$ and PEI .AYO CORREA, M.D .

Cali, Colombia

ATYPE of lymphoma with unique clinical,histologic and epidemiologic features was

described in 1958 in East Africa [1] . It is foundmost commonly in children . It frequently in-volves the retroperitoneal area and the jaw, butusually spares the peripheral lymph nodes, thebone marrow and the spleen . It often invades thekidney, liver, ovary, adrenal, thyroid gland,testicle and gastrointestinal tract [2,3] . Thetumor has been found only in subjects residingin areas up to 1,500 meters above sea level,where the temperature never falls below ap-proximately 12°c., and where the annual rainfall is at least 60 cm. These last characteristicshave prompted investigators to consider thepossibility that the disease is produced by anarthropod-borne virus [4,5] .

Histologic studies of the tumor have shownthat it has a rather characteristic pattern con-sisting of a proliferation of immature lymphoidcells, among which are scattered histiocytes con-taining abundant cytoplasm . This has been de-scribed as the "starry-sky" appearance, which isgiven by the dark blue background due to thelymphoid cells, with scattered clear areas due tothe cytoplasm of the histiocytes [3] . The tumoris invasive and rapidly growing, and has a poorprognosis . In a few cases a terminal leukemicphase has been reported [6] .

There is a possibility that similar tumors havebeen observed in subjects residing in NewGuinea [5] but the majority have been reportedfrom equatorial Africa . A recent survey in thejungles of Central America and a review of therecords of the Department of Pathology of theGorgas Memorial Laboratory in Panama ha% efailed to uncover any case of Burkitt's lymphomain areas which geographically and climatologi-cally are similar to those regions of Africa inwhich the tumor is frequently found [71. The

present report describes six cases of Burkitt'slymphoma observed in Colombia .

CASE REPORTS

In the first case of our series the diagnosis wasmade clinically in the University Hospital ofCali .

CASE i . A four and a half year old mestizo girl(L. D . -M .) was brought to the University Hospital inJuly 1963 because of anorexia and fever of twomonths' duration . A small mass had been noticed inthe outer aspect of the right lower gingiva six weeksprior to admission . A similar mass had appeared onthe left lower jaw, and enlargement of the abdomenwas noticed two weeks later . Physical examinationrevealed an undernourished girl with a pulse rate of100 per minute, a blood pressure of 80, 50 mm . 11g, atemperature of 392°c . and body weight of 14,250gm. The right side of the mandible was prominent .(Fig . 1 .) Oral examination showed a large pinkishtumor mass arising from the right lower jaw. pro-truding into the mouth and extending to the sub-maxillary area. The abdomen was considerably en-larged, and several large, irregular, tender masses ofdifferent size were felt in each of the four quadrants .'the hemoglobin was 6.2 gm. per cent, hematocrit 19per cent, leukocytes 9,400 per cu. mm. with a normaldifferential count . The erythrocyte sedimentationrate was 52 mm . in 1 hour . The patient's blood groupwas A, Rh positive. Stool examination revealed eggsof Trichuris trichiura, trophozoites of Trichomonashominis and occult blood . Roentgenograms of theabdomen showed displacement of the viscera by aninfra-abdominal mass . (Fig . 2.) Bone marrow smearswere normal . A biopsy specimen of the oral tumorshowed the histologic characteristics of Burkitt'slymphoma. On the seventh hospital day the parentsremoved the patient from the hospital .

This and the following cases were discoveredduring a review of the records of the Depart-ment of Pathology of the Universidad del Valle,School of Medicine.

` From the Departments of Medicine and Pathology, Facultad de Medicina, Universidad del Valle, Cali, ColombiaManuscript received April 7, 1965 .

f Present address : Section of Hematology, Tulane University School of Medicine, New Orleans, LouisianaPresent address : Pondville Hospital, Boston, Massachusetts .

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Fin . 1 . Case I . Photograph showing tumorous en-largement of the left mandible .

FIG . 2 . Case I. Roentgenogram of the gastro-intestinal tract showing displacement of the bowelby a large mass .

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CASE ii . A five year old white bov (0 . A . A-) wasbrought to the University Hospital on August 10,1957, with a history of abdominal swelling and pain ofthree weeks' duration . He became sick in Sevilla, alocality approximately 110 miles from Cali . Lapa-rotomy performed locally showed a large abdominaltumor, and the patient was referred to the UniversityHospital. On admission the patient was critically illwith a pulse rate of 120 per minute, a blood pressureof 80/50 mm . Hg and a temperature of 38 °c. He wasdehydrated and pale. There were no palpable periph-eral lymph nodes . The abdomen was prominent andshowed an infected median surgical wound above andbelow the umbilicus. The hemoglobin was 9 gm . percent and the hematocrit 29 per cent . The white bloodcell count was 17,750 per cu . mm. with a differentialcount of 79 per cent polymorphonuclear leukocytes,19 per cent lymphocytes and 2 per cent monocytes . Achest roentgenogram showed bilateral infiltrates andenlargement of the hilum. A second exploratorylaparotomy was performed in this hospital and a largeretroperitoneal mass was found, encroaching uponthe anatomic structures of the abdomen . A biopsyspecimen was interpreted as showing lytnphoblasticlymphoma. Review of the slides showed the typicalpicture of Burkitt's lymphoma . On August 20 the pa-tient was discharged from the hospital . Outside thehospital he was given x-ray radiation . On September4 he was readmitted because of dehiscence of the ab-dominal wound and an intestinal fistula. After a pro-gressive downhill course, the patient died on thetwelfth hospital day . At autopsy there was a largeretroperitoneal tumor that surrounded the splenicand hepatic vessels, and the mesentery and colon ; itinvaded the greater omentum and pararectal tissue ;it penetrated the diaphragm and protruded throughthe anterior foramens of the diaphragm into thethoracic cavity. On the pleural surfaces there werediscrete whitish nodules . On histologic examination,the tumor had the characteristics of Burkitt's lym-phoma, with infiltration of the pancreas, stomach, duo-denum, jejunum, pericardium, lung, thyroid glandand periadrenal tissue . The spleen and the bonemarrow were normal .

CASE in . A four and a half year old white boy(W. L . J .) was brought to the University Hospital onApril 1, 1962, with a chief complaint of progressiveabdominal swelling, anorexia and weight loss of twomonths' duration. He was born in Cali and hadalways lived there. His family was from the loweconomic stratum. Physical examination revealed achronically ill, pale, undernourished patient with aprotruberant abdomen . The pulse rate was 140 perminute and temperature 36 .9 °c. Small lymph nodeswere found in the submaxillary areas . Several large,firm, irregular masses were palpated in the perium-bilical area. The liver extended 3 cm . below the costalmargin. The spleen was barely palpable . There was

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marked edema of the lower extremities. The hemo-globin was 7 .5 gm, per cent, the white blood cellcount 11,350 per cu . mm. with a differential countshowing 5t per cent polymorphonuclear leukocytesand 49 per cent lymphocytes . The erythrocyte sedi-mentation rate was 41 mm . in 1 hour . Blood groupwas 0, Rh positive. X-ray studies showed displace-ment of the stomach, jejunum and duodenum byintra-abdominal masses . Biopsy specimens of inguinaland cervical nodes showed lymphoid hyperplasia andfibrosis . After a rapid downhill course the patient diedon the sixth hospital day . The autopsy revealed anundernourished white boy with 1,500 ml . of whitishfluid in the abdomen . Large whitish masses werefound in the retroperitoneum, extending to and in-vading the pancreas, duodenal arch, mesentery,jejunum, ileuileum, hepatic hilum, both kidneys, andboth the parietal and visceral layers of the peri-toneum. The spleen weighted 157 gm . This organ andmany of the abdominal lymph nodes were surroundedby the tumor. Histologic examination showed a tumorwith the characteristics of the Burkitt's lymphomathat had invaded all the viscera mentioned, and alsothe urinary bladder and periadrenal tissue . Groups oftumor cells were found in the liver and lung . Thebone marrow was normal .

CASE iv. A three year old girl (L . M. A .) enteredthe University Hospital on April 25, 1959, with achief complaint of abdominal pain and fever of onemonth's duration . She was born in Carmen deAtrato (State of Choc6) but had been living in Cali .Physical examination showed a pale but comfortablegirl. Her pulse rate was 96 per minute, her tempera-ture 37 0c. and her weight 12,000 gm . A large, firm,tender periumbilical mass was felt in the abdomen .The liver and spleen were not palpable. The hemo-globin was 11 .2 gm . per cent and the leukocyte countwas 11,500 per cu . mm. with a differential countshowing 55 per cent polymorphonuclear leukocytes,1 per cent band forms, 40 per cent lymphocytes and 4per cent eosinophils . Blood group was 0, Rh positive .On the fourth hospital day, laparotomy revealed alarge tumor mass involving the mesentery, retro-peritoneum and small bowel . The liver was grosslynormal. Forty centimeters of the ileum was resected,followed by an end to end anastomosis. A histologicdiagnosis of malignant lymphoma was made . On re-view, the slides were typical of Burkitt's lymphoma .Postoperatively the patient was treated with roent-genotherapy without affecting the size of the tumor .On June 4 edema of the right lower gum was noticed .A rapidly growing tumor of the jaw was detected tendays later. Roentgenologic examinations failed toreveal any lesions at first, but an ostcolytic defect witha cystic appearance was seen on June 26 . (Fig . 3 .) OnJune 27 the patient was discharged from the hospital .She died four days later at home. No autopsy wasperformed .

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Do. 3 . Case tv. Ruentgenogram of the mandible.Arrows show a zone of rarefaction, one of several.

CASE v . A five year old white boy (C . A . V .) wasbrought to the University Hospital in May 1961 witha chief complaint of abdominal enlargement, anorexiaand dyspnea of twenty days' duration . Physicalexamination revealed a pale, sick boy . The pulse ratewas 140 per minute, blood pressure 90/60 mm . Hgand temperature 37 °c. The abdomen was enlargedand a fluid wave was present . Irregular, firm tendermasses were palpated in the four quadrants . Thehemoglobin was 7.4 gm . per cent, hematocrit 28 percent, leukocyte count 8,000 per cu . mm., with adifferential of 45 per cent polymorphonuclear leuko-cytes, 5 per cent band forms, 4 per cent eosinophils,40 per cent lymphocytes and 6 per cent monocytes .The erythrocyte sedimentation rate was 45 mm . in 1hour. Blood group was 0, Rh positive. An x-rayexamination of the small bowel showed irregularareas of stenosis and dilatation . Laparotomy revealedtwo large tumor masses, one involving a portion ofthe ileum and the other occupying the pelvic cavity .Several smaller masses were also seen . Subsequentreview of the biopsy specimen showed the picture ofBurkitt's lymphoma. The immediate postoperativecourse was uneventful and the patient was dischargedon the twelfth day . His subsequent course is unknown .He had come from Aguadas (State of Caldas), alocality amidst the Andes mountains more than 150miles north of Cali.

CASE vi . A four and a half year old boy (N . F .)was brought to the Childrens Hospital of Cali onJanuary 3, 1962, with the complaint of painful en-largement of the abdomen, and vomiting and diar-rhea of three weeks' duration . He was a pale boy. Hispulse rate was 125 per minute ; his blood pressure110/70 mm. Hg, his temperature 38 °c., his respira-tion rate 50 per minute and his weight 18 kg. Therewere two irregular, firm, tender masses occupying the

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FIG . 4 . Case vi . Roentgenogram of the stomachand duodenum showing displacement of the gastricantrum and broadening of the duodenal arch byan extrinsic tumoral mass .

umbilical region and the right lower quadrant of theabdomen. The hemoglobin was 10.7 gm. per cent,erythrocyte sedimentation rate 36 mm, in I hour,leukocyte count 10,200 per cu . mm. with a normaldifferential count. Blood group was 0, Rh positive .Roentgenograms of the stomach and small bowel re-vealed deformity of the gastric antrum and broaden-ing of the duodenal arch by an extrinsic mass . (Fig .4 .) Laparotomy on January 8 showed a large mesen-teric tumor that deformed the duodenum and in-vaded its wall. We originally made a diagnosis oflymphosarcoma from a biopsy specimen . On recentreview the slides were found to be typical of Burkitt'slymphoma . The patient was discharged on the tenthpostoperative day. His subsequent course is unknown .

COMMENTS

The clinical picture in these cases correspondsclosely with that reported by Burkitt in theAfrican cases . The age of the patients, the rapidand malignant progression of the disease, thepredominant involvement of the retroperitonealspace, the lack of primary compromise of thespleen and bone marrow and the lack ofleukemic patterns in the peripheral blood, arecharacteristics of the classic descriptions of thisdisease .

On histologic examination, the affected tissuesin our six cases have a characteristic appear-ance, like that described byO'Conor [3[ . (Fig . 5 .)The tumor is composed of homogeneous lym-phoid cells of primitive types, usually with dense,

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dark nuclei and scanty cytoplasm . Among thesecells there arc scattered histiocytes giving the"starry sky" appearance . These histiocytes con-tain nuclear and cytoplasmic debris, apparentlyphagocytized from the surrounding cells .

It is not clear where these tumor cells origi-nate. The histologic pattern of the tumor resem-bles that of germinal centers, and in some of ourcases the tumor is continuous with such centers .(Fig. 6 .) This continuity may mean that thetumor arises in germinal centers of lymphoidfollicles and from there spreads beyond thelymph node . In the interstitial spaces the tumorcells advance easily and invade all the surround-ing tissues . The capacity of the tumors to metas-tasize is less notorious than their capacity forlocal invasion . They seem to have predilectionfor some endocrine glands, such as the gonadsand the thyroid, and also for both skeletal andcardiac muscle . The turner cells surround, butusually do not penetrate the spleen . The bonemarrow may show focal lesions . The cells do notusually disseminate, as in leukemia, and do notdiffuse throughout the bone marrow. It seemsthat the tumor most frequently localizes in theretroperitoneal space, and in approximately halfof the cases it involves the jaw .

It is worth noting that the incidence rate of thelymphoreticular malignancies among childrenand young adults in Colombia [9] differsboth from that in the United States [8[ andother temperate zones, and from that in equa-torial Africa [10] . We have neither the highfrequency of leukemias such as reported in theUnited States nor the disproportionate fre-quency of lymphomas reported from CentralAfrica. Our incidence of Burkitt's lymphoma isintermediate between the extremely high ratesfor Africa and the rarity of the disease in theUnited States and Europe .

The localities from which our patients origi-nated have physical characteristics similar tothe areas of Africa in which this tumor occursfrequently. One patient (Case t) came fromDagua, a town which lies very close to a river ofthe same name, at an altitude of 826 meters(2,709 feet) above sea level, with an averagetemperature of 27°c. (80.6 °F .) and a yearlyrainfall of 680 mm . The town is surrounded bymountains of the Western range of the Andes .The Dagua river empties into the Pacific Oceanapproximately 35 miles from the town of Daguaand crosses the tropical rain forest of the Choc6system .

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Ftu . 5 . Case n. Photomicrograph o B

mphoma A, shos g h typical distribution of the two chief components of the tumor : lymphoid cells and histiocytes . Hema-mxylin and eosin stain, original magnification X 125 . B, showing details of the cellularcomponents : primitive lymphoid cells and a scattering of small, darkly stained histiocvteswith a pale-staining cytoplasm which contains inclusion bodies . llematnxylin and cosinstain, original magnification X 320 .

Another patient (Case is) came from Sevilla,a town on the skirts of the Central range of theAndes. It lies at 1,538 meters (5,044 feet) abovesea level, with a temperature ranging from13 °c. (55 .4°F .) to 28 °c. (82 .4°u.) and an aver-age of 19 .3°c. (66 .8 °F .) . The yearly rainfall is1,971 mm. This is a region of small hills, thecenter of a coffcc-growing area. The coffeeplantations are usually covered by shade treesand the vegetation is dense . Two patients (CasesItt and iv) became sick in Cali . This is a citywhich lies close to the Cauca river at 996 meters(3,257 feet) above sea level . The average tem-perature is 24 °c. (75 .2°F .) and the annual rain-fall is 1,153 mm . The family of one of these pa-tients (Case fit) had always lived near the Caucariver in the suburbs of the town . The house inwhich the boy became sick was separated fromthe river by a levee, with a nearby canal forsurface drainage . There were many ornamentalplants in the house . The other patient (Case iv)was born in Carmen de Atrato, a town lying inthe very hot and humid tropical forest of thestate of Choct .

It was not possible to obtain information aboutthe ecologic characteristics of the residence ofour fifth patient (Case v) .Our sixth patient (Case vi) came from

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Fm. 6 . Case Iv. Photomicrograph of mesentericlymph node surrounded by the tumor . The lymphsinuses are seen in the medullary portion of thenode in the lower part of the photograph, thetumor in the upper part . The cortical layer of thenode contains two germinal centers which arein continuity with the tumor. Hematoxylin andeosin stain, original magnification X 33 .

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Miranda, a town in the Valley of the Caucariver at an altitude of 1,060 meters (3,500 feet)above sea level and with an annual rain pre-cipitation of 1,500 mm . The average yearlytemperature is similar to that of Cali but exactfigures are not available .

The discovery of these cases outside Africacalls for further studies of the disease in equa-torial America and offers an opportunity toexplore further the possibility of a viral etiology .

SUMMARY

Six cases of Burkitt's lymphoma are reportedfor the first time from Colombia . The first casewas diagnosed clinically and the remaining fivewere found in the course of a review of therecords of the Department of Pathology of theUniversidad del Valle, School of Medicine, atCali, Colombia. The relevant clinical, pathologicand epidemiologic data are given .

ADDENDUM

After this manuscript was completed ourattention was called to publication of a clinico-pathologic conference in The American Journal ofMedicine in which mention was made of thirteencases of malignant tumors with the histologicpattern of Burkitt's lymphoma, found in thefiles of the Department of Pathology of theWashington University School of Medicine[10] . Since then two additional reports [11,12]have appeared in which cases resembling

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Burkitt's lymphoma are described in NorthAmerican children .

REFERENCES

1 . BURRITT, D . Sarcoma involving jaws in Africanchildren . Brit . J. Surg., 46 : 218, 1958.

2. BURKITT, D . and O'CONNOR, G. T . Malignant lym-phoma in African children . L A clinical syn-drome . Cancer, 14 : 258, 1961 .

3. O'CONOR, G. T. Malignant lymphoma in Africanchildren. u. A pathological entity . Cancer, 14 : 270,1961 .

4. BURKITT, D . Observations on the geography ofmalignant lymphoma . East African M. J., 38 :511 7 1961 .

5. BTREJTT, D . A children cancer dependent on cli-matic factors . Nature, 194 : 232, 1962 .

6 . CLIFT, R. A . . WRIGHT, D. H. and CLIFFORD, P .Leukemia in Burkitt's lymphoma . Blood, 22, 243,1963 .

7 . Rowe, N. H. and JOHNSON, C . M. A search for theBurkitt's lymphoma in tropical central America .Brit. J. Cancer, 18 : 228, 1964 .

8. DORN, H. F. and CUTLER, S. J . Morbidity fromCancer in the United States . Public HealthMonograph No . 56 . Washington, D. C., 1959 .U. S . Government Printing Office.

9. CORREA, P . and LLANOS, G. Cancer morbidity inCali, Colombia . To be published .

10. Clinicopathologic Conference . Lymphosarcoma in aSt. Louis girl clinically and histologically resem-bling Burkitt's African lymphomas . Am . J. Med.,38 : 96, 1965 .

11. O'CONOR, G. T., RAPPAPORT, H . and SMITH, E . B.Childhood lymphoma resembling Burkitt's tumorin the United States. Cancer, 18 : 411, 1965 .

12. DORFMAN, R . F. Childhood lymphosarcoma in St .Louis, Missouri, clinically and histologically re-sembling Burkitt's tumor. Cancer, 18 : 418, 1965 .

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