 |
|
Case Reports Indian Pediatrics 2001; 38: 284-287 |
|||||
|
Burkitts
Lymphoma Developing in a Child with Hyper |
|||||
|
The incidence of lymphoreticular malig-nancies is significantly higher in immuno-deficient patients(1) Hyperimmuno-globulin E syndrome (HIE) does not carry an increased risk for malignancies. Only 3 cases: Burkitt’s lymphoma(2), histiocytic lymphoma of the brain(3) and Hodgkin’s disease(4) have been reported in this condition so far. We report a case of Burkitt’s lymphoma in a girl with HIE.
An 8-years, female, a product of non-consanguineous marriage presented in January 1995, with several episodes of severe infections (pyoderma, otitis, pneumonia, diarrhea, onychia), pruritis, generalized eczema with discharging abscesses, since the age of 8 months, with hospitalization on 4 occasions. She had coarse features, short stature (height 104 cm, <25 percentile) and was under-nourished (weight 17.5 kg). Laboratory data revealed the following: IgE = 44,180 U/dL, IgG = 179 mg/dL, IgM = 210 mg/dL, IgA = 85 mg/dL, WBC = 16,000/cu mm, CD4 = 59%, CD8 = 37%, CD19 = 3% cells, normal C3, C4 levels, ANA absent, absolute eosinophil count = 2,500/cu mm, abnormal chemotaxis (Rebecuck’s window test), absent anti-measles antibodies and negative skin prick tests for recall antigens (PPD, Candida, Aspergillus, Tricophyton Tetanus toxoid). The nitrobluetetrazolium dye reduc-tion test and myeloperoxidase stain for neutro-phils was normal. Skin culture grew methicillin resistant Staph. aureus, Candida albicans and brochoalveolar lavage (BAL) fluid grew Pseudomonas aeruginosa. Diagnosis of HIE was made because of repeated infections, raised IgE levels, abnormal chemotaxis and anergy to common recall antigens. Antibiotics and antifungal agents gave marginal relief. In April 1995 low dose methotrexate (2.5 mg/PO/week) was started. As there was rapid improvement, methotrexate was increased to 7.5 mg/week and continued for 4 months. The urticaria and pyoderma healed completely. In August 1995 she developed Herpes zoster when methotrexate was stopped and 200 mg of acyclovir four times a day for 4 days was given. She was lost to follow up for 2 years. In August 1997 she had severe pyoderma with methicillin resistant Staph. aureus. Intravenous Immunoglobulin G (10 g/day for 5 days) gave her relief only for 2 months. Methotrexate (7.5 mg/week) was restarted in May 1998. The skin was cleared of methicillin resistant Staph. aureus. In August 1998 she developed watery diarrhea not responding to any treatment. Gastro-duodeno-scopy and colonoscopy were normal. Serum methotrexate levels were subnormal (0.01 mmol/L), and methotrexate was continued (5 mg/week). In December 1998 she developed bleeding per rectum, lost weight and became emaciated. Serum SGPT level was normal. Endoscopy revealed several bleeding sites throughout the gastrointestinal tract. The stools did not show strongyloides, isospora, crypto-spora or cytomegalovirus. She revealed malabsorption for fats and carbohydrates. Rectal mucosal biopsy showed shortening and flattening of the villi with eosinophilic infiltration. A diagnosis of mucositis was made. Methotrexate was discontinued on 24/12/98, and a special diet containing medium chain triglycerides was advised. From December 1998, anti-tuberculosis therapy was prescribed by her physician for paratracheal lymph-adenopathy (Mantoux negative, BAL fluid; grew Pseudomonas areuginosa and was AFB negative). In February 1999, she was admitted with severe epistaxis and swelling involving the left cheek, roof of the mouth and nasopharynx. CT showed a mass in the left nasal fossa extending to the left maxillary sinus, eroding its wall, the ethmoid sinus and the floor of the orbit. There was no intra-cranial extension. Biopsy confirmed a high grade non-cleaved, small cell Burkitt’s lymphoma. Bone marrow biopsy showed significant eosinophilia but absent malignant cells. CSF was normal. CT abdomen showed mild hepatomegaly and multiple para-aortic and mesenteric lymph nodes. ELISA for HIV, antibodies to HBV and HCV and Paul Bunnel test were negative. Tumor cells were negative for EBV mRNA on in-situ hybridization. Other investigations revealed: serum LDH = 1809 U/L, SGPT = 237 mg/dL, Uric acid = 8 mg/dL, Serum interleukin 2 receptor = 1643 units/mL (normal range = 200-1000), b2µ globulin level = 1685 ng/ml (normal range = 1010-1730 ng/mL). She was staged as III Burkitt’s lymphoma by St. Jude’s classification(5). BFM95 protocol could not be started because of raised liver enzymes and mucositis. Endoxan (200 mg/m2/day) and Prednisolone (60 mg/m2/day) for 5 days was given in the prephase. In February 1999, 14 fractions of 21 Gy of local irradiation caused substantial reduction in the tumor mass. In June 1999, she developed Pneumocysts carinii pneumonia for which she was treated. In July 1999, she received vincristine and high dose metho-trexate (10 g/m2) with Leukovarum factor (15 mg/m2) at 48, 52 and 54 hours. A second cycle was repeated 3 weeks later after recovery from neutropenia and stomatitis, for which GCSF 5 mg/kg/day was given for 7 days. The disease recurred with bilateral maxillary masses and lymphadenopathy. Radiotherapy was restarted and there was considerable reduction in the tumor masses. In October 1999 the patient died of severe hemoptysis.
Hyperimmunoglobulin E syndrome is a rare immunodeficiency disorder involving both the B and T cells. Unregulated T-helper activity augments IgE production(3). Occurrence of lymphoreticular malignancies in this condition is rare. Burkitt’s lymphoma is a distinct form of non-Hodgkin lymphoma seen predominantly in children between 2-14 years of age. Non- Hodgkin lymphoma constitutes 4% of all pediatric cancers of which Burkitt’s lymphoma comprises 47%(2,4). Polyclonal B cell proli-feration driven by Ebstein Barr virus, HIV or malaria infection in immunodeficient patients could develop into monoclonal malignancy owing to critical cytogenetic errors involving c-myc and Ig loci(6). It is suggested that the normal immune system exerts some form of immuno-surveillance against cancer and its subnormal functioning could cause malignancy in hyperimmunoglobulin E syndrome(7). There are two reports(8) of reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dematomyositis. Both were in elderly women; one had received low dose (10 mg/week intramuscularly reduced to oral 7.5 mg/week) methotrexate for approximately 3 years and the other a high dose (37.5 mg/week intramuscularly which was decreased to 7 mg/week orally following an increase in lactate dehydrogenase levels). It is hard to speculate that in this case methotrexate may have precipitated Burkitt’s lymphoma because tests for EBVmRNA were negative in the tumor tissue, dose of methotrexate was small and not very prolonged, and cell type was different (non-cleaved small cell versus large cell in Hodgkin’s lymphoma). Jaw involvement, as a presenting feature, as in this case is observed in 15-20% of cases. Jaw tumors and central nervous system involvement are the hallmarks of endemic Burkitt’s lymphoma. Abdominal and bone marrow involvement are seen more frequently in the sporadic form. The extremely high growth fraction and cell turnover marks Burkitt’s lymphoma highly sensitive to chemotherapy. Various intensive multi-agent chemotherapy protocols producing a disease free survival rate of 85% to 90% for localized disease and 50% to 75% for dis-seminated disease have been described. The child reported, had a rapid down-hill course probably because of high tumor burden (multiple sites), elevated serum levels of LDH, SIL-2 R, b2µ globulin, uric acid and lactic acid(9). Contributors: AP co-ordinated the study (particularly diagnosis, management) and drafted the paper; she will act as guarantor for the paper. MB and MC helped in day to day follow-up and chemotherapy and AD helped in the study of receptors.
Funding:
None.
|
