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High Grade Lymphomas

COMPARED to diffuse large B-cell lymphomas, high grade lymphomas behave more aggressively, require more intensive chemotherapy and occur more often in children. Because rapidly dividing cells are more sensitive to anti-cancer agents and because the young patients usually lack other health problems, some of these lymphomas show a dramatic response to therapy.
         Lymphomas generally thought of as "high-grade" (it is not a formal WHO classification category) include lymphoblastic lymphomas and Burkitt's lymphomas. Lymphoblastic lymphomas are usually T-cell processes; but in order to compare and contrast them with B-cell lymphomas, they will be covered in this section.

Lymphoblastic Lymphoma
These lymphomas (images) occur mainly in children and adolescents, where they account for about half of pediatric lymphomas. About two-thirds of the patients are males. A second peak is seen again in patients over 40 years of age. The distinction from acute lymphoblastic leukemia is in part arbitrary, based on the degree of marrow involvement. The chief biologic difference is that lymphoblastic leukemias are predominantly B-cell diseases, unlike the extra-medullary, mostly T-cell lymphoblastic lymphomas.
         Lymphoblastic lymphoma usually presents supradiaphragmatically in the cervical, supraclavicular, and axillary regions. Over half the patients have an anterior mediastinal mass, which may cause acute chest symptoms. The marrow is focally involved in about half the cases, and other extranodal sites are common. Spread to the gonads or central nervous system is especially significant because in these "privileged" hideouts the lymphoma finds sanctuary from the usual chemotherapeutic agents.
         Untreated patients do dismally. With intensive chemotherapy, however, long-term disease-free survival may be attained, and the childhood complete remission rate is as high as 96%.
         Lymphoblastic lymphoma cells are larger than benign lymphocytes but smaller than histiocytes. The nuclei are convoluted or regular in contour and contain finely granular, dark chromatin and at most inconspicuous nucleoli. The lymphoma often extends into perinodal soft tissue. It may display the "starry-sky" pattern more usually associated with Burkitt's lymphoma. The cells are called "blasts" because they are the neoplastic counterpart of normal thymic or marrow early lymphoid precursors, which have never seen antigen. Thus they differ from the "centroblasts" and "immunoblasts" of large cell lymphomas, which correspond to normal cells undergoing a second round of proliferation in response to antigen stimulation.
         Lymphoblastic lymphoma cells contain nuclear terminal deoxynucleotidyl transferase (Tdt). This is appropriate for an early lymphoid cell, which requires that enzyme to rearrange its immune genes. About 80% of lymphoblastic lymphomas are T-lineage. These display the earliest T-cell markers CD7 and CD2 in addition to later markers depending on the lymphoma's maturity. B-cell lymphoblastic lymphomas usually express B-cell marker CD19 and most also react for CD10 (called CALLA: common acute lymphoblastic leukemia antigen). They do not express surface immunoglobulin. Testing for Tdt and these other markers is part of working up a new lymphoblastic lymphoma.

Burkitt Lymphoma
Burkitt lymphomas come (images) in at least 3 sorts, all of which are more prevalent in males:

  • Endemic Burkitt lymphoma (a WHO classification subtype): a childhood lymphoma prevalent in equatorial Africa and intimately associated with both Epstein-Barr virus infection and a characteristic translocation of the MYC gene.
  • Sporadic Burkitt lymphoma (a WHO classification subtype): a world-wide lymphoma affecting slightly older patients, also associated with MYC changes but less so with EBV infection.
  • Burkitt-like lymphoma (a WHO classification morphologic variant): a rather different disease affecting an older population and not notably associated with EBV infection.
All 3 kinds have also been called "small non-cleaved cell lymphoma". SNCL
         The morphology of endemic and sporadic Burkitt lymphoma is the same: expansile sheets of monotonous, fiercely mitotic cells with nuclei the size of histiocyte nuclei. The chromatin is coarse, and the multiple nucleoli are prominent. On smears, the amphophilic cytoplasm includes numerous lipid-laden cytoplasmic vacuoles. Scattered tingible-body macrophages (histiocytes with fragments of necrotic lymphoma cell nuclei in their pale cytoplasm) stand out in the midst of the dark lymphoma cells, forming a so-called "starry sky" pattern. In Burkitt-like lymphoma, there is more cytologic variantion in size and shape. Nuclear chromatin tends to be more open, often with single, prominent nucleoli.
         The poor prognosis of endemic Burkitt lymphoma is tied to its occurrence mainly in under-developed countries with less sophisticated medical facilities. Both sporadic Burkitt and Burkitt-like lymphoma behave similarly: untreated they are extremely aggressive. Both diseases, however, may respond well to intensive chemotherapy. Burkitt lymphoma is one of the most common types of lymphoma seen in patients with AIDS.
         The following table compares and contrasts features of these 3 types of Burkitt lymphoma.

  Endemic Burkitt Sporadic Burkitt Burkitt-like
Age 5-10 y/o. Children and adolescents. 30 to 50 years of age.
Site Jaw and abdomen. Also CNS, testis, orbit. Marrow (+) in only 10%. Abdomen, especially ileum and cecum. Jaw usually (-). More often peripheral lymph nodes; less often abdomen.
Histology Expansile sheets of monotonous cells with nuclei the size of histiocyte nuclei. See above for details. Same as endemic Burkitt. More vesicular nuclei with more varied size and shape. Cytoplasm is relatively more abundant.
MYC Gene Status Almost always rearranged: usually t(8;14). Less often t(2;8) or t(8;22). Same as endemic Burkitt. Same as endemic Burkitt.
Epstein-Barr Virus Status EBV genome in almost all lymphomas. EBV genomes in about 20% of lymphomas. EBV genomes only in a subset.

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