Primary cutaneous Burkitt lymphoma C83.7; C91.8

Denis Parsons Burkitt, British tropical physician and surgeon (1911-1993)

Burkitt's lymphoma (BL), is a highly malignant (aggressive) B-cell non-Hodgkin's lymphoma (NHL) with a very high proliferation rate (Crombie J et al. 2021). Although extranodal sites are frequently involved in Burkitt's lymphoma, cutaneous involvement is very rare in this lymphoma species (Berk DR et al 2008). However, cases of cutaneous Burkitt's lymphoma are typically due to tumor seeding after surgical procedures or local invasion of a rapidly enlarging subcutaneous tumor as part of a generalization of the process. Diffuse nodular infiltrates have been demonstrated in HIV-associated Burkitt's lymphoma (de Masson A et al. 2016).

Burkitt's lymphoma is classified as follows:

Endemic Burkitt's lymphoma: Endemic Burkitt's lymphoma occurs particularly in Africa, Brazil and Papua New Guinea and manifests itself mostly in childhood as a mandibular or facial tumor. It can spread to the ovaries, testes, kidneys, mamma, and especially bone marrow and meninges. Endemic African BL is 95% EBV-associated.

Sporadic Burkitt's lymphoma: This occurs worldwide, especially in children and younger adults. It usually manifests abdominally (mainly ileocecal region) with possible involvement of kidneys, testes and/or ovaries. Spread to bone marrow and central nervous system (CNS) is also possible. Sporadic BL is associated with EBV in 20% of cases.

Immunodeficiency-associated Burkitt's lymphoma: Burkitt's lymphoma associated with immunodeficiencies occurs, for example, in association with HIV infection. Nodal involvement and bone marrow involvement are common.

Burkitt's lymphoma affects 1-2% of adults with non-Hodgkin's lymphoma (NHL). In children, BL accounts for approximately 30% of NHL. Cutaneous manifestations are limited to a few published isolated cases.

The causes of Burkitt's lymphoma are still largely unknown. A connection with viral infections (especially Epstein-Barr virus) and chromosomal damage can be assumed. Burkitt's lymphoma is associated with a translocation of MYC on chromosome 8 (gene location 8q24) in more than 95% of cases. Partners of the translocation are:

• IgH (85 %) on chromosome 14: (t8;14)(q24;q32)
• Kappa light chain (IgK) (5%) on chromosome 2: t(2;8)(p11;q24)
• Lambda light chain (IgL) (15%) on chromosome 22: (t8;22)(q24;q11)

However, other genetic alterations are necessary for malignant transformation to Burkitt's lymphoma (e.g. mutations of p53 or retinoblastoma gene).

Common to all BL is the translocation of IG and MYC genes. In this process, the MYC gene moves into the vicinity of immunoglobulin (IG) genes, namely into the region of the immunoglobulin heavy chain on chromosome 14 or the light chains kappa on chromosome 2 or lambda on chromosome 22. The translocation leads to a dysregulation of the MYC gene, which performs a central regulatory function in cell division and influences a large number of other genes. Since the light and heavy chains of immunoglobulins in B cells are read and expressed quasi continuously during antibody production, this also happens for the MYC gene and MYC protein. This results in overexpression of MYC protein and uninhibited cell division. In addition to the dysregulation of the MYC gene, further genetic alterations are necessary for a malignant transformation to a Burkitt lymphoma to occur. Thus, in about 40% of cases of Burkitt's lymphoma, mutations in the p53 gene as well as mutations in the retinoblastoma (Rb) gene (its encoded products are protein 107 (p107) and protein 130 (p130)) are found.

In the endemic form of Burkitt's lymphoma in Africa, infection of B cells by EBV (Epstein-Barr virus) plays an initiating role. This induces polyclonal growth of B lymphocytes. EBV infestation is about 80% of children in certain areas in equatorial Africa.

Infections with malaria are also thought to play a proliferation-promoting role in this context. Malaria infection leads to a disruption of the T-cell population, which has a proliferation-promoting effect on B-cell clones.

In Europe and North America, EBV infection and childhood malaria are much less common. Sporadic BL show association with EBV in less than 20%.

The age of onset is usually < 35 years.

In principle, cutaneous Burkitt's lymphoma can occur in any part of the body. Specific infiltrates have been described, especially on the head and trunk.

S. u. Burkitt's lymphoma

Infiltrate of medium sized cells with round nuclei, multiple nucleoli and a basophilic cytoplasm with vacuoles. The proliferation rate is almost 100 %. Bright macrophages lie between the lymphoid tumor cells, producing the classic "starry sky" pattern. Immunohistochemically, the tumor cells are positive for: CD19, CD20, CD10, BCL6. They are negative for BCL2.

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