December 2015

A 55 Year old male with nausea, vomiting, headaches and difficulty walking

David Cantu, MD and Peter Perrotta, MD

Overview

A 55 year-old man with a past medical history of cerebral palsy, hypertension, and hyperlipidemia presented to the emergency department complaining of nausea, vomiting, headaches and difficulty walking for the past month. A CT scan revealed a suprasellar mass with 4 additional enhancing masses in hypothalamus, pineal gland, trigon of right lateral ventricle and foramen of Magendie.

Gross Description

The patient was taken to the operating room and a biopsy was obtained for intraoperative consultation and permanent sections (Fig 1-7), which included appropriate immunohistochemical stains.

Fig 1. Frozen Section (10 x) showing a hypercellular specimen.
Fig 2. At higher magnification (40x), the cells show a high nuclear/cytoplasmic ratio, pleomorphism and increased mitotic rate.
Fig 3. Permanent section stained with H&E (10x) showing a highly cellular specimen with focal areas of necrosis.
Fig 4. Higher magnification (20x) of the architecture displaying a starry sky pattern.
Fig 5. Photograph taken at 40x to assess cellular features such as mitoses which are abundant in this case.

By immunohistochemistry, the tumor cells were CD20-positive and co-expressed CD10. The cells were negative for bcl2, bcl6, CD3, and CD5. EBER in situ hybridization was also negative.

Fig 6. CD20 showing a membranous staining pattern.
Fig 7. Photograph of malignant cells expressing CD10.

Diagnosis

What chromosomal translocation is characteristic of this patient’s disease ?

Answer

Please select an answer above.

Discussion

C-MYC alteration resulting (8;14)(q24;q32) fusion

Fig 8. MYC BAP Probe 5’ MYC; 5’ MYC ( 8q24) [orange] 3’ MYC (8q24) [green]

Fig 9. D FISH IGH/ MYC Probe; MYC (8q24) [orange]IGH (14q32 [green] Arrow Yellow Fusion Signals

Primary Burkitt lymphoma of the brain

Primary central nervous system lymphoma (PCNSL) is defined as a lymphoma occurring in the CNS without evidence of systemic involvement. The vast majority of CNS lymphomas are due to secondary involvement of the brain, spinal cord or dura by nodal or extranodal lymphomas. PCNSLs represent a small fraction of CNS lymphomas and tend to affect immunosuppressed individuals more commonly. [5] PCNSL is slightly more common in males and the average age at diagnosis is 56 years.   PCNSL represents 3% of all brain tumors and about 2-3% of all cases of Non-Hodgkin Lymphoma. [4] About 25% to 50% of PCNSLs are multifocal and more than 50% occur in immunocompromised patients. The most common location for PCNSLs is the frontal lobe. Up to 40% of PCNSLs invade the leptomeninges. [2] Diffuse large B-cell lymphomas represent up to 90% of all PCNSLs. Other variants include T-cell lymphoma, mucosa associated lymphoid tissue (MALT) lymphoma, Hodgkin lymphoma and Burkitt lymphoma. [3,6]

Burkitt lymphoma (BL) is a high-grade lymphoma with a very short doubling time originating from germinal center or post germinal center B-cells. BL represents up to 50% of all lymphomas in the pediatric population. Three variants have been described: Endemic, Sporadic and Immunodeficiency associated.   The endemic variant represents the most common childhood malignancy in Equatorial Africa and is strongly associated with Epstein-Barr virus (EBV) infection. The sporadic variant is seen throughout the world and represents 1-2% of all lymphomas in the United States and Western Europe. EBV can be detected in up to 30% of sporadic BL. The immunodeficiency-associated variant is mainly seen in patients with HIV infection and it is commonly the first manifestation of AIDS. EBV is present in up to 40% of cases. [1]

Extranodal sites are commonly affected and CNS involvement can be present in all three variants. The tumor cells are medium-sized and have a monomorphic pattern. The nuclei are round with paracentral nucleoli. The cytoplasm is basophilic and has multiple lipid vacuoles. Mitotic figures are abundant. A strong presence of tingible body macrophages gives the typical “starry sky” pattern. Tumor cells express strong levels of membrane IgM with light chain restriction as well as B-cell associated antigens, CD10, BCL6, CD38, CD77 and CD43.   The MYC translocation involving 8q24 and 4q32, or less common, 22q11 is present in the majority of cases. However, up to 10% of cases lack a MYC translocation by FISH. [1] The prognosis of PCNSL is poor and if no treatment is received promptly, rapid progression is the rule. [4]

References

  1. Swerdlow, SH, Campo, E, Harris, NL, et al. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4ed. International Agency for Research on Cancer (IARC). Lyon, France. 262-264
  2. Preyson, RA (2012) Neuropathology 2nd Edition. El Sevier Saunders. Philadelphia , PA. 539-542
  3. Burger, PC, Sheithauer, BW (2007) Tumors of the Central Nervous System. Armed Forces Institute of Pathology. Washington, DC. 411-426
  4. Alabdulsalam, A, Zaidi, SZA, Tailor, I, Orz, Y, Al-Dandan, A (2014) Primary Burkitt Lymphoma of the Fourth Ventricle in an Immunocompetent Young Patient. Case Reports in Pathology. Volume 2014.
  5. Monabati, A, Rakei, SM, Kumar, PV, Taghipoor, M, Rahimi, A (2002) Primary Burkitt lymphoma of the brain in an immunocompetent patient. J Neurosrug 96:1127-1129.
  6. Gu, Y, Hou, Y Zhang, X, Hu, F (2010) Primary central nervous system Burkitt lymphoma as concomitant lesions in the third and left ventricles: a case study and literature review. J Neurooncol 99:277-281