Burkitt's lymphoma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor-in-Chief: Soumya Sachdeva, Sowminya Arikapudi, M.B,B.S. [2], Kamal Akbar, M.D.[3]

Overview

Burkitt's lymphoma must be differentiated from other diseases such as Hodgkin's lymphoma, diffuse large B cell lymphoma, follicular lymphoma, Mucosa-Associated Lymphatic Tissue lymphoma (MALT), small cell lymphocytic lymphoma, and mantle cell lymphoma (MCL).

Differentiating Burkitt's lymphoma from other Diseases

Burkitt's lymphoma must be differentiated from other diseases such as:[1]

Differential Diagnosis of Sporadic Burkitt's Lymphoma

S.No. Disease Symptoms Signs Diagnosis Comments
Abdominal Pain Hematuria Headache Abdominal mass Abdominal tenderness Ultrasonography CT scan Histology
1. Wilms tumor + + - + +
  • Wilms tumor has a triphasic appearance.
  • It is comprised of 3 types of cells:
  • All the 3 types are not required for the diagnosis of Wilms tumor.
  • Primitive tubules and glomeruli are often seen comprised of neoplastic cells.
  • Beckwith and Palmer reported in NWTS the different histopathologic types of Wilms tumor to categorize them based on prognosis.[5]
2. Renal cell carcinoma + + +/- + -
  • Ultrasound (US) may be helpful when CT scan results are equivocal. It is noteworthy to mention that not all renal cell carcinomas are detectable on ultrasound.
Both CT and MRI may be used to detect neoplastic masses that may define renal cell carcinoma or metastasis of the primary cancer. CT scan and use of intravenous (IV) contrast is generally used for work-up and follow-up of patients with renal cell carcinoma. The histological pattern of renal cell carcinoma depends whether it is papillary, chromophobe or collecting duct renal cell carcinoma.
3. Rhabdoid kidney disease + + - + -
  • CT scan may be diagnostic of malignant rhabdoid tumor. Findings on CT scan suggestive of malignant rhabdoid tumor include a large, heterogenous, centrally located mass, which is lobulated with individual lobules separated by intervening areas of decreased attenuation, relating to either previous hemorrhage or necrosis. Enhancement is similarly heterogeneous. Calcification is relatively common, observed in 20-50% of cases and is typically linear and tends to outline tumor lobules.
  • Malignant rhabdoid tumor is characterized by the round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures.
4. Polycystic kidney disease + + + (from hypertension) + -

Ultrasound may be helpful in the diagnosis of polycystic kidney disease. Findings on an ultrasound diagnostic of polycystic kidney disease include:[6][7]

  • At least three unilateral or bilateral cysts in patients 15 - 39 years old
  • Atleast two cysts in each kidney in patients 40 - 59 years old
  • Atleast four cysts in each kidney in patients 60 years of age or older

Renal CT scan may be helpful in the diagnosis of polycystic kidney disease. Findings on CT scan diagnostic of ADPKD include:

  • Numerous renal cysts of varying size and shape with little intervening parenchyma with water attenuation and very thin wall.
  • Reduction in sinus fat due to expansion of the cortex
  • Occasional complex cysts with hyperdense appearance, with possible septations or calcifications
  • Multiple homogeneous and hypoattenuating cystic lesions in the liver in patients with liver involvement
  • On microscopic histopathological analysis, interstitial fibrosis, tubular atrophy, thickening and lamellation of tubular basement membranes, microcysts and negative immunofluorescence for complement and immunoglobulin are characteristic findings of ADPKD.[8][9][10][11]
5. Pheochromocytoma - - + (as a part of the hypertension paroxysm) - -
  • CT is the preferred imaging modality for the diagnosis of pheochromocytoma.
The following findings may be observed on CT scan:[12]
  • On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma.
6. Burkitt lymphoma +/- (in non-endemic or sporadic form of the disease) - - - -
  • Chest, abdomen, and pelvis CT scan may be helpful in the diagnosis of Burkitt's lymphoma but it is not done routinely.[16]
  • On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:[17]
  • Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells)
  • Round nucleus
  • Small nucleoli
  • Relatively abundant cytoplasm (basophilic)
  • Brisk mitotic rate and apoptotic activity
  • Cellular outline usually appears squared off
  • "Starry-sky pattern":
  • The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells.
  • The tumour cells are the sky
7. Intussusception + - - +/- +
  • Ultrasound is the gold standard imaging modality used to diagnose intussusception[18]
    • Target or doughnut sign[19]
      • Edematous intussuscipien forms an external ring around the centrally located intussusceptum
      • Target sign is usually seen in right lower quadrant
    • Layers of intussusception forms pseudo-kidney appearance on the transverse view
  • CT scan may be helpful in the diagnosis of intussusception. CT scan maybe used when other image modalities like x-ray and ultrasound have not given positive results but suspicion of intussusception is high.
  • Intussusception occurs if there is an imbalance between the longitudinal and radial smooth muscle forces of intestine that maintain its normal structure. This imbalance leads to a segment of intestine to invaginate into another segment and cause entero-enteral intussusception. Etiology of intussusception is either idiopathic or pathologic (lead point). 
8. Hydronephrosis + +/- - - + (CVA tenderness in case of pyelonephritis)
  • In the case of renal colic (one sided loin pain usually accompanied by a trace of blood in the urine) the initial investigation is usually an intravenous urogram. This has the advantage of showing whether there is any obstruction of flow of urine causing hydronephrosis as well as demonstrating the function of the other kidney. Many stones are not visible on plain x ray or IVU but 99% of stones are visible on CT and therefore CT is becoming a common choice of initial investigation.
  • The kidney undergoes extensive dilation with atrophy and thinning of the renal cortex.
9. Dysplastic kidney N/A N/A N/A N/A N/A

MCDK is usually diagnosed by ultrasound examination before birth.

  • Mass of non-communicating cysts of variable size.
  • Unlike severe hydronephrosis, in which the largest cystic structure (the renal pelvis) lies in a central location and is surrounded by dilated calices, in multicystic dysplastic kidney the cyst distribution shows no recognizable pattern.
  • Dysplastic, echogenic parenchyma may be visible between the cysts, but no normal renal parenchyma is seen.
  • MCKD can be discovered accidentally on CT scan.
  • CT scan shows myltiple cysts with absence of renal parenchyma.
  • MCKD is the result of abnormal differentiation of the renal parenchyma.
10. Pediatric Neuroblastoma + - - +/- +/-
  • CT scan is the investigation of choice for the diagnosis of neuroblastoma.[21]
  • On CT scan, neuroblastoma is characterized by:[22]
  • On microscopic histopathological analysis the presence of round blue cells separated by thin fibrous septa are characteristic findings of neuroblastoma.
  • Other findings of neuroblastoma on light microscopy may include:[23]
  • Homer-Wright rosettes (rosettes with a small meshwork of fibers at the center)
  • Neuropil-like stroma (paucicellular stroma with a cotton candy-like appearance)
11. Pediatric Rhabdomyosarcoma + +/- +/- - +/- On CT scan, rhabdomyosarocma is characterized by:
  • Soft tissue density
  • Some enhancement with contrast
  • Adjacent bony destruction (over 20% of cases)
12. Mesoblastic nephroma + + - + -
  • Ultrasound may be helpful in the diagnosis of mesoblastic nephroma.
  • Mesoblastic nephroma may presents as a well-defined mass with low-level homogeneous echoes.[24]
  • The presence of concentric echogenic and hypoechoic rings can be a helpful diagnostic feature of mesoblastic nephroma.
  • CT scan may be helpful in the diagnosis of mesoblastic nephroma.
  • Findings on CT scan suggestive of mesoblastic nephroma include:
  • Solid hypoattenuating renal lesion
  • Variable contrast enhancement
  • No calcification

Classic mesoblastic nephroma

Cellular mesoblastic nephroma

  • Plump cells with vesicular nuclei
  • Well-defined border
  • Mitotically active

Mixed mesoblastic nephroma

  • Both classic pattern and cellular pattern areas are present
Most common renal tumor that occurs in 1st month of life

Differential Diagnosis of Endemic Burkitt's Lymphoma

Endemic Burkitt's lymphoma typically presents as a cervico-facial mass and must be differentiated from other diseases that may present as a cervico-facial mass such as salivary glands tumors, sialolithiasis, human immunodeficiency virus, radiation, and systemic diseases such as, sarcoidosis, and sjögren's syndrome.[25][26][27][28][29][30][31][32]

Diseases Symptoms and sign Laboratory Findings Other Findings
Onset Unilateral/Bilateral Pain Swelling Tenderness Purulent discharge Common site of involvement ESR Leukocytosis
Sialolithiasis Acute Unilateral + + + - Submandibular gland ↑/NL ↑/NL Radio-opaque in X-ray
Acute bacterial sialadenitis Acute Unilateral + + + + Parotid Other sign of infection may be present
Chronic bacterial sialadenitis Chronic Unilateral + + - +/- Parotid Other sign of infection may be present
Viral sialadenitis Acute Bilateral + + + - Parotid Coryza symptoms
Human immunodeficiency virus Acute Bilateral + + - - Parotid NL NL Other systemic findings of HIV/ check ELISA
 Radiation sialadenitis Acute Unilateral + + + - Depends on the treatment field NL NL History of radiation in the salivary gland site
Salivary gland tumors Subacute Unilateral - + - - Parotid ↑/NL ↑/NL Advance age
Sarcoidosis Gradual Bilateral - + - - Parotid Systemic findings in other organs
Sjögren's syndrome Gradual Bilateral +/- + - - Parotid or submandibular glands ↑/NL ↑/NL Dry eye/dry mouth
Malnutrition Gradual Bilateral +/- + - - Parotid NL NL Systemic findings in other organs

Differentials Based on Cell Surface Markers

Based on the expression of cell surface markers, the table below differentiates Burkitt's lymphoma from other diseases that cause similar clinical presentations:[33]

Differential Diagnosis Surface Immunoglobulin CD5 CD22/FMC7 CD23 CD79b CD103

Chronic lymphocytic leukemia

Weakly positive

Positive

Negative

Positive

Negative

Positive/Negative

Prolymphocytic leukemia

Strongly positive

Negative

Positive

Negative

Positive

Negative

Hairy cell leukemia

Strongly positive

Negative

Positive

Negative

Positive/Negative

Positive

Mantle cell lymphoma

Positive

Positive

Strongly positive

Negative

Strongly positive

Negative

Follicular lymphoma

Strongly positive

Negative

Positive

Negative

Strongly positive

Negative

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