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Male, 61 years, B-cell chronic lymphocytic leukemia

Lymphoma

Lymphomas comprise a heterogeneous group of solid tumors that are composed of neoplastic lymphoid cells. Furthermore, lymphoid tumors with involvement of the bone marrow, are closely related to leukemia which is typically characterized by spread of tumor cells in peripheral blood. Multiple myeloma, a malignant tumor representing plasma cell differentiation, is moreover also related to the group of tumors derived from immune and blood cells.

Lymphoma can develop in any organ where lymphoid tissue is present. Commonly lymphomas present with enlarged lymph nodes, spleen or tonsil, but lymphomas can also arise in for example the gut or skin. Lymphoma can be classified as low-grade and clinically indolent or high-grade and clinically aggressive. Lymphoma is further categorized into B-cell, T-cell and Hodgkin lymphoma.

Classical Hodgkin lymphomas are mainly B-cell tumors and can be sub-classified into four different subtypes dependent on morphological features, the dominant admixture of various other cell types and the composition of the stroma component. Classical Hodgkin lymphomas have in common the presence of characteristic tumor cells named Hodgkin cells and Reed-Sternberg cells. In addition, there is a fifth type of nodular lymphocyte rich Hodgkin lymphoma which lack these characteristic cells.

B-cell lymphoma is the most common form and can be sub-classified according to morphology, protein expression patterns and genetic alterations. The most frequent variants of B-cell lymphomas include small lymphocytic lymphoma, (closely related to chronic lymphocytic leukemia (CLL) both morphologically and immunophenotypically), follicular lymphoma and diffuse large B-cell lymphoma. The distinction between these entities, and the over 40 additional variants of lymphoma that are well defined, is based on microscopical examination using morphology and immunohistochemistry to determine what cell types are present and the stage of differentiation of the tumor cells.

In brief, small lymphocytic lymphoma is an indolent lymphoma that is characterized by a monotomous population of small lymphocytes replacing the normal architecture of a lymph node. Mitotic figures are uncommon and necrosis is typically not a feature. Approximately one third of all patients with small lymphocytic lymphoma develop lymphocytosis and a clinical picture that is indistinguishable from chronic lymphocytic leukemia (CLL). Follicular lymphoma is also a B-cell lymphoma and can be of low or intermediate grade. The tumor is characterized by a follicular growth pattern that in part mimics that of the normal lymph node architecture (germinal center with surrounding lymphoid cells in a lymph follicle). Diffuse large B-cell lymphoma is characterized by a diffuse infiltration of atypical lymphoid cells. Tumor cell nuclei are large and irregular with coarsely reticulated chromatin and one or several nucleoli apposed to the nuclear membrane. Mitotic figures are common and can be atypical.

T-cell lymphoma accounts for approximately 15 % of lymphomas of non-Hodgkin type. Peripheral T-cell lymphoma is the most common form of T-cell lymphoma. One of the more common forms of peripheral T-cell lymphoma is cutaneous lymphoma arising in the skin.

Immunohistochemistry has played a vital role for the understanding and classification of lymphoma and several of the well-known CD markers are used for differential diagnostics. Additionally, defined chromosomal translocations and genetic mutations provide a basis for adequate classification of lymphoma which is necessary for optimized treatment regimens.

Normal tissue: Lymph node

Examples

Lymphoma 1, B-CLL
Lymphoma 2, Follicular lymphoma
Lymphoma 3, DLBCL
Lymphoma 4, Hodgkin
Lymphoma 5, Hodgkin