History

Fact Explanation
Fever [1] Patients develop fever secondary to opportunistic infections. Chemotherapy can lead to neutropenia which further increases the risk and severity of opportunistic infections including neutropenic sepsis. However some patients may not manifest fever even in the presence of an infection because of the impaired immune response. [2,4,5]
Night sweats [1] Night sweats is also another possible presentation of Burkitt lymphoma (BL). This is commonly associated with opportunistic infections like tuberculosis. [3]
Loss of weight [1] Patient with BL complain of significant loss of weight, due to poor nutrition and recurrent infections. [3]
Bone pain [1] BL is a highly aggressive tumor in which disseminated disease occurs early. Secondary deposits in the spine cause intractable back pain.
Abdominal pain Patients with extranodal involvement can have intra-abdominal mass. Symptoms of intestinal obstruction (nausea, vomiting, colicky abdominal pain and absolute constipation), intussusception (severe colicky abdominal pain, vomiting, red currant jelly stools and drawing up legs during crying) and appendicitis (periumbilical abdominal pain which later radiates to the right iliac fossa, nausea and vomiting) can be the presenting complaints of intra-abdominal disease. [5,6]
Intra-oral lesions Although rare, some patients' initial presentation of BL can be intra-oral mass, which is preceded by toothache and loosening of tooth. [8]
Symptoms of orbital mass BL can present with painless ptosis, orbital mass and chemosis. [8]
Symptoms of central nervous system involvement Acute paraplegia, urinary and fecal incontinence are symptoms due to spinal cord compression. Intra-cranial lesions cause early morning headache, nausea and vomiting. [9]
Risk factors of HIV Patients who had unsafe sex with multiple sexual partners are at risk of acquiring HIV. Certain professions like nurses and doctors are at risk of needlestick injuries thereby at risk of acquiring HIV infection from infected persons. Patients who had HIV infection for a long time are at higher risk of Burkitt lymphoma. [1,7]
References
  1. STROUP JEFFREY S., BRANSTEITTER BRIDGET A., STEPHENS JOHNNY R., HENDRICKSON SCOTT E.. Burkitt Lymphoma in an Adult HIV-Positive Patient. Infectious Diseases in Clinical Practice [online] 2007 March, 15(2):116-118 [viewed 27 July 2014] Available from: doi:10.1097/01.idc.0000230540.02089.c5
  2. SAPLE DG, SHAH I, SURJUSHE AU, MURTHY A, CHUDGAR P, GOTE PD. Lymphoma in HIV patients: Varied presentations Indian J Med Paediatr Oncol [online] 2010, 31(1):39-42 [viewed 28 July 2014] Available from: doi:10.4103/0971-5851.68854
  3. FINCH DAVID A., WILSON MALCOLM S., O'DWYER SARAH T.. Successful Management of Jejunal Perforation in Burkitt’s Lymphoma: A Case Report. Case Reports in Surgery [online] 2012 December, 2012:1-3 [viewed 28 July 2014] Available from: doi:10.1155/2012/230538
  4. FINCH DAVID A., WILSON MALCOLM S., O'DWYER SARAH T.. Successful Management of Jejunal Perforation in Burkitt’s Lymphoma: A Case Report. Case Reports in Surgery [online] 2012 December, 2012:1-3 [viewed 28 July 2014] Available from: doi:10.1155/2012/230538
  5. WELEDJI EP, NGOWE MN, ABBA JS. Burkitt's lymphoma masquerading as appendicitis - two case reports and review of the literature World J Surg Oncol [online] :187 [viewed 28 July 2014] Available from: doi:10.1186/1477-7819-12-187
  6. PUNNOOSE ANN R., KASTURIA SUMAN, GOLUB ROBERT M.. Intussusception. JAMA [online] 2012 February [viewed 28 July 2014] Available from: doi:10.1001/jama.2012.45
  7. KOMATSU N, KAWASE-KOGA Y, MORI Y, KAMIKUBO Y, KUROKAWA M, TAKATO T. HIV-associated Burkitt lymphoma in a Japanese patient with early submandibular swelling BMC Res Notes [online] :557 [viewed 28 July 2014] Available from: doi:10.1186/1756-0500-6-557
  8. AJILA V, GOPAKUMAR R, HEGDE S, BABU SG. Intraoral Burkitt's lymphoma in an HIV positive patient Indian J Sex Transm Dis [online] 2012, 33(2):118-120 [viewed 28 July 2014] Available from: doi:10.4103/0253-7184.102126
  9. HOYOUX C., FORGET P., PIETTE C., DRESSE M. F., FLORKIN B., RAUSIN L., THIRY A.. Paravertebral Burkitt's Lymphoma in a Child: An Unusual Presentation. Case Reports in Medicine [online] 2012 December, 2012:1-4 [viewed 28 July 2014] Available from: doi:10.1155/2012/891714

Examination

Fact Explanation
Cachexia Patients with HIV-AIDS are cachectic. [1]
Lymphadenopathy Patients with BL can have multiple palpable lymph nodes. [2,3]
Mandibular mass Mandibular involvement of BL can result in mandibular mass. [4]
Signs of orbital involvement [4] Orbital involvement of the BL can cause ptosis and chemosis of the affected eye. Orbital mass can also be detected in some patients.
Maxillary mass Although rare some patients with BL have maxillary masses. These may protrude from the jaw and appear black in color. [4]
Abdominal examination Intra-abdominal masses can be palpated in patients with extra-nodal BL. Renal mass can be palpated in renal involvement. [5]
Examination of the central nervous system Flaccid paraplegia are absent deep tendon reflexes are signs of spinal cord involvement. Intracranial space occupying lesions cause papilledema and focal neurological signs. [6]
References
  1. MANGILI A., MURMAN D. H., ZAMPINI A. M., WANKE C. A., MAYER K. H.. Nutrition and HIV Infection: Review of Weight Loss and Wasting in the Era of Highly Active Antiretroviral Therapy from the Nutrition for Healthy Living Cohort. Clinical Infectious Diseases [online] 2006 March, 42(6):836-842 [viewed 28 July 2014] Available from: doi:10.1086/500398
  2. PINTO ANDRE, IKPATT OFFIONG FRANCIS, CHAPMAN-FREDERICKS JENNIFER. Burkitt Lymphoma Presenting as Unilateral Deafness in an Immunocompetent Patient. Case Reports in Medicine [online] 2012 December, 2012:1-5 [viewed 28 July 2014] Available from: doi:10.1155/2012/369264
  3. KOMATSU N, KAWASE-KOGA Y, MORI Y, KAMIKUBO Y, KUROKAWA M, TAKATO T. HIV-associated Burkitt lymphoma in a Japanese patient with early submandibular swelling BMC Res Notes [online] :557 [viewed 28 July 2014] Available from: doi:10.1186/1756-0500-6-557
  4. AJILA V, GOPAKUMAR R, HEGDE S, BABU SG. Intraoral Burkitt's lymphoma in an HIV positive patient Indian J Sex Transm Dis [online] 2012, 33(2):118-120 [viewed 28 July 2014] Available from: doi:10.4103/0253-7184.102126
  5. MOODLEY HALVANI, MAHOMED NASREEN, ANDRONIKOU SAVVAS. Abdominal Burkitt’s lymphoma with renal involvement. S Afr J CH [online] 2013 May [viewed 28 July 2014] Available from: doi:10.7196/SAJCH.548
  6. HOYOUX C., FORGET P., PIETTE C., DRESSE M. F., FLORKIN B., RAUSIN L., THIRY A.. Paravertebral Burkitt's Lymphoma in a Child: An Unusual Presentation. Case Reports in Medicine [online] 2012 December, 2012:1-4 [viewed 28 July 2014] Available from: doi:10.1155/2012/891714

Differential Diagnoses

Fact Explanation
Toxoplasmosis Both patient groups can present with symptoms of central nervous system involvement. The CT scan appearance of both toxoplasmosis and Burkitt lymphoma is a space occupying lesions with ring enhancement. However Toxoplasmosis have more lesions than Burkitt lymphoma. [1]
Other lymphomas associated with HIV These include primary CNS lymphoma, primary effusion lymphomas (plasmablastic lymphoma and classic Hodgkin lymphoma), follicular lymphoma and peripheral T-cell lymphoma. [2]
Catscratch disease After a catscratch or bite patients develop lymphadenopathy, prolonged fever, endocarditis, and atypical pneumonitis. This is common in children and in young adults. [3,4]
References
  1. STROUP JEFFREY S., BRANSTEITTER BRIDGET A., STEPHENS JOHNNY R., HENDRICKSON SCOTT E.. Burkitt Lymphoma in an Adult HIV-Positive Patient. Infectious Diseases in Clinical Practice [online] 2007 March, 15(2):116-118 [viewed 27 July 2014] Available from: doi:10.1097/01.idc.0000230540.02089.c5
  2. DUNLEAVY K., WILSON W. H.. How I treat HIV-associated lymphoma. Blood [online] December, 119(14):3245-3255 [viewed 27 July 2014] Available from: doi:10.1182/blood-2011-08-373738
  3. DžELALIJA BORIS, PETROVEC MIRO, AVšIč‐ŽUPANC TATJANA. Probable Atypical Cat Scratch Disease Presenting as Isolated Posterior Pancreatic Duodenal Lymphadenitis and Abdominal Pain. CLIN INFECT DIS [online] 2001 September, 33(6):912-914 [viewed 28 July 2014] Available from: doi:10.1086/322692
  4. WILLIAMS A.. Lesson of the week: Cat scratch disease. [online] 2002 May, 324(7347):1199-1200 [viewed 28 July 2014] Available from: doi:10.1136/bmj.324.7347.1199

Investigations - for Diagnosis

Fact Explanation
Biopsy Biopsy is essential for the diagnosis. Excisional biopsies and or fine needle aspiration cytology will aid in diagnosis. Microscopic examination detects abnormal B cells with high nuclear-to-cytoplasmic ratio, high mitotic index, basophilic cytoplasm with lipid-filled vesicles, multiple and small-to-intermediate size nucleoli. Increased number of apoptotic cells create a starry-sky appearance. [1,2,3]
Full blood count [2] Patients with HIV have decreased CD4 lymphocyte counts. However BL can occur even before the HIV is diagnosed by low CD4 cell counts. [6]
Blood picture Although rare involvement of peripheral circulation in extra-nodal BL blood picture shows the presence of neoplastic cells. [4]
Serum lactate dehydrogenase (LDH) [2,7] Serum LDH levels are usually increased due to the high cell turnover rate. Serum LDH can be normal in patients with low mitotic index.
Serum uric acid levels [2,7] Serum uric acid levels are also elevated due to increased cell turnover rate.
Bone marrow aspirate and biopsy [2] Bone marrow aspirate and biopsy is useful in detecting the involvement of bone marrow in BL. Patients with bone marrow invasion have malignant cells in the bone marrow as well.
Analysis of cerebrospinal fluid In severe disease lumbar puncture will aid in detection of leptomeningeal lymphoma. Flow cytometry and cytology is done. [2]
Florescent insity hybridization (FISH) FISH can detect the Epstein–Barr virus (EBV) ‐encoded RNA (EBER) in about 30% of the affected patients. [4]
Antibodies against EBV Assessment of antibodies against EBV helps to identify possible EBV infection in patients. Repetitive EBV infection is associated with increased risk of development of BL in patients with HIV infection. [5]
Antibodies against HIV HIV is diagnosed by the presence of circulating antibodies against HIV. [5]
References
  1. PERKINS A. S., FRIEDBERG J. W.. Burkitt Lymphoma in Adults. Hematology [online] 2008 January, 2008(1):341-348 [viewed 27 July 2014] Available from: doi:10.1182/asheducation-2008.1.341
  2. DUNLEAVY K., WILSON W. H.. How I treat HIV-associated lymphoma. Blood [online] December, 119(14):3245-3255 [viewed 27 July 2014] Available from: doi:10.1182/blood-2011-08-373738
  3. FINCH DAVID A., WILSON MALCOLM S., O'DWYER SARAH T.. Successful Management of Jejunal Perforation in Burkitt’s Lymphoma: A Case Report. Case Reports in Surgery [online] 2012 December, 2012:1-3 [viewed 28 July 2014] Available from: doi:10.1155/2012/230538
  4. GROGG KL, MILLER RF, DOGAN A. HIV infection and lymphoma J Clin Pathol [online] 2007 Dec, 60(12):1365-1372 [viewed 28 July 2014] Available from: doi:10.1136/jcp.2007.051953
  5. KOMATSU N, KAWASE-KOGA Y, MORI Y, KAMIKUBO Y, KUROKAWA M, TAKATO T. HIV-associated Burkitt lymphoma in a Japanese patient with early submandibular swelling BMC Res Notes [online] :557 [viewed 28 July 2014] Available from: doi:10.1186/1756-0500-6-557
  6. GUECH-ONGEY M, SIMARD EP, ANDERSON WF, ENGELS EA, BHATIA K, DEVESA SS, MBULAITEYE SM. AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology? Blood [online] 2010 Dec 16, 116(25):5600-5604 [viewed 28 July 2014] Available from: doi:10.1182/blood-2010-03-275917
  7. DUNLEAVY K., WILSON W. H.. How I treat HIV-associated lymphoma. Blood [online] December, 119(14):3245-3255 [viewed 28 July 2014] Available from: doi:10.1182/blood-2011-08-373738

Investigations - Fitness for Management

Fact Explanation
Full blood count Reduced CD4 count can be observed in patients with HIV. [2]
Serum creatinine and electrolytes Assessment of renal function is necessary before prescribing chemotherapy as most of the drugs are metabolized and excreted from the kidneys.
Blood culture Patients are at risk of opportunistic infections and sepsis, especially severe infections with atypical organisms like mycoplasma, candida and tunerculosis. [1]
References
  1. FINCH DAVID A., WILSON MALCOLM S., O'DWYER SARAH T.. Successful Management of Jejunal Perforation in Burkitt’s Lymphoma: A Case Report. Case Reports in Surgery [online] 2012 December, 2012:1-3 [viewed 28 July 2014] Available from: doi:10.1155/2012/230538
  2. GUECH-ONGEY M, SIMARD EP, ANDERSON WF, ENGELS EA, BHATIA K, DEVESA SS, MBULAITEYE SM. AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology? Blood [online] 2010 Dec 16, 116(25):5600-5604 [viewed 28 July 2014] Available from: doi:10.1182/blood-2010-03-275917

Investigations - Followup

Fact Explanation
Full blood count Full blood count should be regularly done in patients with HIV infection to monitor the disease progression. Chemotherapy can cause neutropenia which increases the risk of acquiring opportunistic infections. Both CD4 cell counts and neutrophil counts should be monitored and treatment regime should be altered whenever necessary. [1]
References
  1. SCHREIBMAN TANYA, FRIEDLAND GERALD. Use of Total Lymphocyte Count for Monitoring Response to Antiretroviral Therapy. CLIN INFECT DIS [online] 2004 January, 38(2):257-262 [viewed 28 July 2014] Available from: doi:10.1086/380792

Investigations - Screening/Staging

Fact Explanation
Ultrasound scan of the abdomen BL metastasize to the intra-abdominal organs. Ultrasound scan is useful in detecting intra-abdominal deposits and organ metastases of BL. [1]
CT scan Contrast enhanced CT scan of the thorax, abdomen and pelvis is useful in detecting the thoracic, intra-abdominal and pelvic organ involvement in BL. [1,2]
PET scan PET scan can also diagnose the tumor deposits in the thorax, abdomen and in the pelvis. [1,2]
MRI scan MRI scan is useful in detecting the extranodal involvement of the disease. [3]
References
  1. WELEDJI EP, NGOWE MN, ABBA JS. Burkitt's lymphoma masquerading as appendicitis - two case reports and review of the literature World J Surg Oncol [online] :187 [viewed 28 July 2014] Available from: doi:10.1186/1477-7819-12-187
  2. PETRICH ADAM M., SPARANO JOSEPH A., PAREKH SAMIR. Paradigms and Controversies in the Treatment of HIV-Related Burkitt Lymphoma. Advances in Hematology [online] 2012 December, 2012:1-8 [viewed 28 July 2014] Available from: doi:10.1155/2012/403648
  3. MOODLEY HALVANI, MAHOMED NASREEN, ANDRONIKOU SAVVAS. Abdominal Burkitt’s lymphoma with renal involvement. S Afr J CH [online] 2013 May [viewed 28 July 2014] Available from: doi:10.7196/SAJCH.548

Management - General Measures

Fact Explanation
Health education People who are having unsafe sexual relationships should be advised to use barrier method of contraception. Intravenous drug users should be rehabilitated and advised not to share needles. Nurses, doctors and other health care providers should use personal protective equipment when handling blood and other body fluids.
Prevention of infections Patients should be advised to avoid crowded areas and to use masks for prevention against respiratory tract infections. CD4 cell counts should be monitored regularly and once low antibiotic prophylaxis should be started against opportunistic infections. [1]
References
  1. SCHREIBMAN TANYA, FRIEDLAND GERALD. Use of Total Lymphocyte Count for Monitoring Response to Antiretroviral Therapy. CLIN INFECT DIS [online] 2004 January, 38(2):257-262 [viewed 28 July 2014] Available from: doi:10.1086/380792

Management - Specific Treatments

Fact Explanation
Chemotherapy Early commencement of chemotherapy is vital in the management as BL is a highly aggressive tumor. [5] Therapeutic combinations are being used for the treatment of HIV related Burkitt lymphoma. “m-BACOD” (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) and “CHOP” (cyclophosphamide, doxorubicin, vincristine, and prednisone) are two such regimes used. Intrathecal administration of chemotherapeutic agents is effective in treating and preventing the disease relapse in central nervous system involvement. [1,3]
Highly active antiretroviral therapy (HAART) HAART helps to prevent CD4 cell loss which occurs as a side effect of chemotherapy. This protects the patient from opportunistic infections. [2,4]
Radiotherapy Radiotherapy is effective in achieving local control of the disease like in spinal metastases, superior vena caval obstruction, and in disease recurrences. [5]
References
  1. WANG EUNICE S., STRAUS DAVID J., TERUYA-FELDSTEIN JULIE, QIN JING, PORTLOCK CAROL, MOSKOWITZ CRAIG, GOY ANDRE, HEDRICK ERIC, ZELENETZ ANDREW D., NOY ARIELA. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer [online] December, 98(6):1196-1205 [viewed 27 July 2014] Available from: doi:10.1002/cncr.11628
  2. SPINA M.. HIV-related non-Hodgkin's lymphoma (HIV-NHL) in the era of highly active antiretroviral therapy (HAART): some still unanswered questions for clinical management. Annals of Oncology [online] 2004 July, 15(7):993-995 [viewed 27 July 2014] Available from: doi:10.1093/annonc/mdh281
  3. STROUP JEFFREY S., BRANSTEITTER BRIDGET A., STEPHENS JOHNNY R., HENDRICKSON SCOTT E.. Burkitt Lymphoma in an Adult HIV-Positive Patient. Infectious Diseases in Clinical Practice [online] 2007 March, 15(2):116-118 [viewed 27 July 2014] Available from: doi:10.1097/01.idc.0000230540.02089.c5
  4. RODRIGO J. A., HICKS L. K., CHEUNG M. C., SONG K. W., EZZAT H., LEGER C. S., BORO J., MONTANER J. S. G., HARRIS M., LEITCH H. A.. HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era. Advances in Hematology [online] 2012 December, 2012:1-9 [viewed 28 July 2014] Available from: doi:10.1155/2012/735392
  5. FINCH DAVID A., WILSON MALCOLM S., O'DWYER SARAH T.. Successful Management of Jejunal Perforation in Burkitt’s Lymphoma: A Case Report. Case Reports in Surgery [online] 2012 December, 2012:1-3 [viewed 28 July 2014] Available from: doi:10.1155/2012/230538
  6. WELEDJI EP, NGOWE MN, ABBA JS. Burkitt's lymphoma masquerading as appendicitis - two case reports and review of the literature World J Surg Oncol [online] :187 [viewed 28 July 2014] Available from: doi:10.1186/1477-7819-12-187