Follow us:

Journal of dentistry oral health and preventive measures (JDOHPM)

Articles in Press

Go Back to Articles in Press

Case Report

Burkitt’s lymphoma in Two Siblings

Corresponding author:
Dr. Cornelius Iyogun*,  Department of Oral & Maxillofacial Pathology, University of Port Harcourt, Nigeria, Email: iyoguncornelius@yahoo.com

Article Information

Article Type: Case Report

Received : September 02, 2019; 
Accepted : September 15, 2019;
Published : October 15, 2019.

Abstract

SUMMARY

Two brothers (same father and same mother) were admitted at different times, diagnosed and treated independently as cases of Burkitt’s lymphoma at the Nigerian Army Reference Hospital Kaduna.One of the siblings was 17-year old male and the other, an 8-year old male. The two were brought up in two different environments making it highly suggestive of a genetic pattern. Since no previous genetic pattern has been recorded in this environment, this case is being reported to update the literature.

Article

INTRODUCTION:

Burkitt’s lymphoma was originally reported as malignant jaw lesion in African Children in regions with holoendemic malaria and high humidity by Dennis P. Burkitt in 1958[1] .

Since that initial report, numerous reports have appeared in the literature with confirmation of its B-cell origin by immunologic method. Also early studies showed that it was confined to certain altitude where humidity is very high and presence of endemic malaria [2-4]. It has, however, been found in many other countries including the United States with slight variations in pattern of presentation (early abdominal and bone marrow feature in the American type as against early jaw presentation in the African type [5]. It is the fastest growing tumor in man. Since its first description by Denies Burkitt, it has undergone various classification changes from Burkitt’s lymphoma to small non-cleaved cell lymphoma to undifferentiated lymphoma in various classifications of lymphomas and leukemia’s. Recently it been changed to its old name of Burkitt’s lymphoma [6]. 
[7] Identified in culture a virus later called the Epstein-Barr virus (EBV). Titers of EBV are very high in the endemic African cases [8-11].
In the endemic type it is almost exclusively confined to children in the age group 2 – 14yrs [12, 13] with peak at 8 to 10 yrs. It is also primarily extra nodal in contrast to other non Hodgkin’s’ Lymphomas. The non-endemic form has older age peak (10 – 12). The non-endemic type is less associated with Epstein-Barr virus.

This tumor starts as a rapidly growing jaw tumor with a doubly time of 24 hours and frequently involving all quadrants of the jaws [9] but destroys the bone with loosening of the teeth in the affected region due to destruction of the lamina Dura (Cortical bone surrounding individual teeth). It spreads to all sinuses, the orbit, and the viscera and eventually to the bone marrow, gastrointestinal tract, ovaries, breast, spinal cord and the brain.
Hardly is there any presentation without prior jaw involvement which is in contradistinction with the non-endemic type which has visceral involvement often without jaw involvement [5].
Recently, a new form of the disease has been recognized; the immunodeficiency associated forms particularly those associated HIV immunodeficiency [14, 15].
Radiological, loss of lamina Dura is a good pointer to diagnosis of Burkitts’ lymphoma. [16] Studied 51 cases of Burkitts’ lymphoma radiological and found that 91% of those cases confined to the jaws had loss of lamina Dura while those confined to the abdomen had 72.7% involvement of the lamina Dura of the teeth. Inference of genetic involvement was recorded with evidence of gene translocation in some patients [17, 18]. However, direct relative susceptibility is hardly reported. 

The only report in Nigeria is an unpublished case of simultaneous affection of two siblings from Abeokuta seen at the UCH, Ibadan. Histological, Burkitt’s lymphoma is said to consist of proliferations of a monotonous monomorphic lymph reticular cells predominantly small lymphocytes with numerous mitosis interspersed by non-neoplastic macrophages containing cellular debris giving a characteristics starry-sky appearance. Not all cases present this peculiar feature.

Treatment is by use of cytotoxic drugs usually cyclophosphamide with metothrexate. Prognosis depends on (1) initial response, (2) extent of lesion and (3) presence of high quantity of antibody to EBV – antigen. Those with low EBV antibody titer have poorer prognosis. 

We are presenting these two cases of this disease its rarity in the literature and because of the probable genetic origin.

REPORT OF CASES

Case 1: 

Master I.A.P. is a 17-yr old Negroid and son of an Army corporal in Kaduna, Nigeria. He was referred for diagnosis and treatment from ABUTH Kaduna whose staff was on industrial strike action during that period. 
The presentation was that of pain and swelling in the jaws and forehead of two weeks duration. Patients also complained of pain and swelling of both extremities for two weeks.
HPC: Patient was said to have been well until two weeks ago when he presented at ABUTH with a history of pain and swelling of the jaws, head and upper and lower limbs.
Pain was severe, throbbing and aggravated by mastication. Pain also radiated to the ear and caused headaches. Patient denied ever being treated or admitted for any other illness previously except this occasion when he was taken to ABUTH and subsequently referred here.
Patient is first child in a family of four (4). Patient’s father then informed us that one of the patient’s younger siblings was being managed in this hospital for the same disease. It was discovered that a previous biopsy was read for the man for another child who was then being managed by the pediatrics team.
On examination patient was obviously very distressed and dysphonic. He was pale, cachetic with facial asymmetry with swelling on the (R) jaw and forehead over the eyebrow. 
Swelling was tender and firm. There were bilateral submandibular lymphadenopathies. Both limbs were very tender to palpation. Oral hygiene was poor with calculus deposits and plaque of high degree. Teeth were mobile and floating. Teeth present were (8-1:1-8)/(8-1:1-8)  and those mobile were (8-6:6-8)/(8-6:6-8)  . No carious lesions and no missing teeth.

Impression was that of Burkitts’ lymphoma or leukemia. Investigations requested for were:

(a) Hb and Pcv
(b) Full blood count. 
(c) Radiographs

(i) PA Skull
(ii) Oblique lateral of the jaws (R) x (L) And
(iii) Chest X-ray. 

(d) Incistonal biopsy. 
(e) Electrolyte and Urea
(f) LFT (Liver function test)

Patient was admitted for the investigations and the following initial palliative treatment was instituted: 

  • Tabs Flagyl 200mg tds x 3/7
  • Caps Ampiclox 500mg 6hrdy x 5/7
  • Tabs Vit Bco 1 bd x 2/52
  • Tabs Paracetamol ii prn/6hrly x 1/52

Warm salt water mouth rinses was also encouraged. 
A biopsy (incision) was also taken for histopathology diagnosis.
Biopsy result confirmed that the case was Burkitt’s lymphoma. X-rays show that were floating with loss of lamina Dura. 8-4 4-8
There was also radiolucency around the roots of teeth appearing clinically normal.
Patient was managed with standard cytotoxic drugs for Burkitt’s lymphoma.
The patient was scheduled to undergo five courses at 14 days interval per course.
At the end of the 3rd course the patient showed marked improvement with all pains disappearing. However, after these three courses the father could not cope with the purchase of drugs at regular intervals. Patient was said to have died 3 weeks after discharge from the hospital. Autopsy was not done as body was not brought to the Hospital.

Case 2:
J.B.P. was an 8-yr old male Negroid who was admitted to this hospital with history of inability to chew and associated pain in the mouth for over a month.
There was also swelling of the jaws and difficulty in breathing since two weeks previously.
HPC: Patient was said to be well until about one and half months ago when he started complaining of toothache and inability to chew properly with associated bleeding from the gums.
Swelling of the jaw was noticed two weeks previously and had been increasing progressively and it was more from the (R) quadrants. Patient afterwards started experiencing difficulty in breathing particularly at night. 
There was no chest pain and no cough, though patient sweats profusely at night. No associated fever, no vomiting, no diarrhea, no constipation and no dysuria.
FSH: He is the 4th in a family of four. All other children were said to be well. Mother was said to be a psychiatric case. 
*(P.S.: - This patient had almost completed his treatment before his elder brother was brought in for same condition. 
O/e Acutely ill-looking child in obvious respiratory distress with flaring of ala nasi. 
RR – 18/min, breathing through the mouth with difficulty (snoring sound).
Not pale. Not jaundiced. Not cyanosed and well hydrated.
Bilateral submandibular lymphadenopathy. 
No pitting pedal edema.
There was marked (R) jaw swelling with moderate swelling of the (L) jaw. 
Teeth were loose with bleeding gums.
Patient was unable to close the mouth. 
PR – 120/min – full and regular
HS. 1 x 11 only. No murmurs.
Chest was clinically clear.
No ascites.
Normal bowel sounds
Patient is conscious. No signs of meningeal irritation.
Provisional Diagnosis
Burkitts’ lymphoma 
R/O TB adenitis

Investigations requested for included: 

  1. RBC, PCV, ESR, Genotype
  2. Biopsy
  3. X-rays – PA view jaws

 (R) X (L) Oblique lateral of the jaws.
      4.         LFT (Liver Function on Test). 

Incision biopsy confirmed a diagnosis of Burkitt’s lymphoma. 
Patient was then started on cytotoxic drugs after 2 units of screened blood were given and also 24hrs after allopurinol was started. The patient was managed as in the first case. 
The patient responded to chemotherapy and was discharged home after the sixth course. No recurrence for 2 yrs of follow-up. 

DISCUSSION:

Burkitt’s lymphoma is said to be the commonest malignant jaw tumor in tropical environment except a few countries like Sudan [19]. Since the original report of Burkitt’s lymphoma by Dennis Burkitt in 1958 [1] numerous other reports have appeared in the literature (including the American type) with more abdominal and bone marrow presentation as early features.
Both altitude and humidity are considered major factors in the development of this tumor [1, 20]. These factors are very prevalent in our environment and that occasioned the numerous reports from this region.
The average age is lowest where Burkitt’s lymphoma is common and highest where it is uncommon [21]. One of the siblings in this report is 17yrs old and the other 8yrs old. This age incidence coincides with the views above. The mean age, however in most cases is 7 – 8yrs of age which is lower than the American type (10 – 12yrs).
The endemic cases in African children usually begin as a rapidly growing mass of the jaw usually starting from one quadrant of the jaws but very often extending to the four guardant. In the two cases the jaws were the initial areas of affection with pain. Loosening of teeth and rapidly growing mass as initial indication of disease which is consistent with original description by Burkitt [1].
The 17yrs old boy had involvement of the central nervous system and bone marrow with paresis, pain and inability to move the   extremities. This is due to late presentation due to the fact that this child was living with an aged grandmother in another locality. Both CNS and Bone marrow involvement of the extremities are known late complications of Burkitt’s lymphoma [21, 22] and also resulted in poorer prognosis. 
In many recent studies it has been confirmed that antibody titers to EBV are high in endemic form of Burkitt’s lymphoma [7] this virus has proved to be an important human pathogen in many lymph proliferative diseases [23] . Antibody to EBV was not done as facilities for this was not available. The histological findings in both cases were consistent with classical description of Burkitt’s lymphoma. 
Treatment of both patients was by combination chemotherapy using cyclophosphamide, vincristine, and methotrexate (including intrathecal methotrexate, prednisolone and allopurinol to prevent the formation of uric acid crystals. This method was used because of its advantage over single chemotherapy [24]. All hematological indices were investigated before and after each course including the liver function test.
But it would be observed that older siblings succumb after the 3rd course of chemotherapy. This was expected due to (1) inability to regularly purchase the required cytotoxic drugs and (2) the known facts that those cases which present with CNS involvement usually have poorer prognosis [23, 25, 8] .
That these two siblings were treated in the same Hospital was a mere coincidence as they were initially handled by two different depts. (Dental and Pediatrics) before the Hematology Unit. The only known case of two siblings with Burkitt’s lymphoma seen in UCH in 1979 was an unpublished data. Therefore, this is the first known case of two direct relative being reported in this country with Burkitt’s lymphoma. Both could be genetic or environmental. Both live in the Northern part of the country but in different states.
Since both siblings are of the same parent (paternal and maternal), live in different state, it is possible that genetic factors may have been responsible. [18, 26, 19], observed chromosomal abnormalities of EBV nuclear antigen also in the cell culture. All cell exhibited B-cell phenotype in the same culture [27-30]. These cases could not be investigated genetically as facilities for this was not available. 

 

References

References   

(1)   Burkitt D.P (1958): A sarcoma involving he jaws in African children. British J Surgery; 46:218-235.
(2)   Kafuko GW, Burkitt D (1970) Burkitt’s lymphoma and Malaria. International Journal of Cancer 6: 1–9.
(3)   Haddow AJ (1970) Epidemiological evidence suggesting an infective element in the etiology. In: Burkitt PDenis, Wright DH, eds (1970) Burkitt’s Lymphoma. Edinburgh: E.S. Livingstone. pp 198–209.
(4)   Morrow RH, Gutensohn N, Smith PG (1976) Epstein-Barr virus-Malaria interaction models for Burkitt’s lymphoma: Implications for preventive trials. Cancer Research 36: 667–669
(5)   Levine, P.H, Kamaraju, L.S., Connelly R.R., (1982): The American Burkitt’s lymphoma Registry; eight years experiences: Cancer, 49: 1016-1022
(6)   Ferry JA (2006):Burkitt’s lymphoma; Histopathological features and differential diagnosis, The Oncologist 2006; 11: 375-383 
(7)   Epstein MA, Achoney BG and Barri YM (1964): Viral particles in cultured lymphoblasts from Burkitt’s lymphoma; Cancer 2 :702-716
(8)   Olweny LMC, Atine I, Kaddu-Mukasa A, Ower R, Anderson-Anvret M, et al.(1977) Epstein-Barr Virus genome studies in Burkitt’s and non-Burkitt’s Lymphomas in Uganda. Journal of the National cancer Institute 58: 1191–1196.
(9)   Biggar RJ, Nkrumah KF (1979) Burkitt’s Lymphoma in Ghana: Urban-Rural distribution, time-space clustering and seasonality. International Journal of Cancer 23: 330–336.
(10) Shiramizu B, Barriga F, Neequaye J, Jafri A, Dalla-Favera R, et al. (1991) Patterns of chromosomal breakpoint locations in Burkitt’s lymphoma: relevance to geography and Epstein-Barr virus association. Blood 77: 1516–1526.
(11) Carpenter L, Newton R, Casabonne D, Ziegler J, Mbulaiteye S, et al. (2008) Antibodies against malaria and Epstein Barr Virus in childhood Burkitt lymphoma: a case-control study in Uganda. International Journal 122: 1319–1323.
(12) Shafer WG, Hine MK and Levy BN (1993), A Textbook of Oral Pathology 4th Edition WB Saunders Company, Philadephia, pp188-189
(13) Dzamalala C, Mdokwe C, Mkula C, Liomba N (2005) The Cancer Epidemic in Malawi: 2001–2003. Blantyre: Malawi Cancer Registry, Ministry of Health.
(14) Doll DC and List AF (1982) Burkitt’s lymphoma in a homosexual, lancet ;1:1027-1027.
(15) Ziegler JL, Drew WL, Miner RC et al (1982); outbreak of burkitt’s-like lymphoma in homosexual men. Lancet 2: 631-633.
(16) Nzeh, D.A. (1987): Importance of the jaw radiographs in diagnosis of Burkitt’s lymphoma; Clinical Radiology; Sept: 38 (5): 519 – 522.
(17) Miyoshi I. (1985): Burkitt’s lymphoma in Japan IARC science Publication 60:135 – 147.
(18) Joshyi S.S., Deboer J.M.: Strandjord S.J et al; (199) Characterization  of a newly established human Burkitt’s Lyphoma cell line. In J. Cancer; March 12; 47 (5) 643-648.
(19) yagi KI, Rahman ES, Abbas KE and Prabhu SR (1983):Burkitt’s lymphoma n Sudan. Int J Oral Surgery Dec. 13 (6):517-527.
(20) Burkitt, D. and O’conor G.T. (1961):Maligant lymphoma in African children. 1. A clinical syndrome; cancer; 14:258 – 282.
(21) Burkitt D.P and wright D.H.  (1970): Burkitt’s lymphoma: Edinburgh and London E and S Living stone. Cavdar; A.O,: Gozdesoglu; S., Yaruz, G. et al (1993): Burkitt’s lymphoma between African and American Types in Turkish Children Clinical, Viral; (EBV)and molecular Studies; Med. Pediatric-oncology: 21(1):36-42.
(22) Burkitt DP and Wright DH (1970): Burkitt’s lymphoma; Edinburgh and London and S Livingstonz
(23) Magrath, I.T., (1991): African Burkitt’s lymphoma; History, Biology, Clinical features and Treatment: American J. pediatric, Hemathology and oncology 13 (2): 222 – 246.
(24) Cadvar AO, Gozdesoglu S, Yaruz G et al (1993):Burkitt’s lymphoma between African and American types in Turkish children Clinical, Viral  Molecular studies;
(25) Patten, L.L, memillan, C.W., Webster WP (1990):American Burkitt’s Lymphoma; A 10-year review and case study;Oral Surgery, Oral Medicine, Oral Pathology, March, 69  (3) 307-316.
(26) Okano, M, Kikuta; H, Abo, W. et al (1992): FrequentAssociation of Epstein – Barr Virus in Japanese patients with Burkitt’s lymphoma: Japanese J. Clinical oncology; Oct. 22 (5) 320 – 324.
(27) Geser A, de The´ G, Lenoir G, Day NE, Williams EH (1982) Final case reporting from the Ugandan prospective study of the relationship between EBV and Burkitt’s Lymphoma. International Journal of Cancer 29: 397–400.
(28) Henle G, Henle W, Clifford P, Diehl V, Kafuko G, et al. (1969) Antibodies to Epstein-Barr virus in Burkitt’s lymphoma and control groups. J Natl Cancer Inst 43: 1147–1157.
(29) de The´ G, Geser A, Day NE, Tukei PM, Williams EH, et a   l. (1978) Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt’s lymphoma from Ugandan prospective study. Nature 274: 756–761.
(30) Dalldorf G, Linsell C, Barnhart F, Martyn R (1964) An epidemiologic approach to the lymphomas of African children and Burkitt’s lymphoma. Perspect Biol Med 36: 435–449.

 

Address
  • 27 Old Gloucester street,
    London United kindom,WCIN3AX.
Contact Us
License
Creative Commons Licence
This work is licensed under a Creative Commons Attribution 4.0 International License.
© 2018. Vagus Inprosys All right reserved.