–Exposure to irradiation: after atomic bomb explosion; after irradiation of thymus

–Drug-induced: after immunosuppressive treatment; after hydantoin treatment

6.4Pathology and Classification

•Heterogeneous group of disorders with variable morphological, cytochemical, immunological, biochemical, and cytogenetic characteristics of lymphoid or monocytic histiocytic cell elements

•In children mainly the diffuse histological form (i.e., lymphoblastic and of T cell lineage)

•Nodular form less than 1%

•The earlier different classification and nomenclature systems are now unified in the WHO classification

WHO classification

6.5Histological, Immunological, and Cytogenetic Characteristics of the Different Forms of NHL

6.5.1Burkitt Lymphoma (BL) and Burkitt Like Lymphoma (BLL)

•About 50% of NHL

•Localization: abdomen, lymphatic tissue of the adenoids and tonsils (Waldeyer’stonsillar ring)

•Morphology: large vacuolated cells with fine nuclear chromatin, two to five nucleoli, basophilic cytoplasm, L3 morphology (see Chap. 2; resembles a starry sky)

•Mainly B-cell NHL with immunoglobulin surface expression (mostly IgM, either of light kappa – or light lambda-chain)

•High Ki-67 value, Mid-1 positivity

•CD19, –20, –22, –77, –79a-positive; sometimes also CD10 and −38-positive; TdT mainly negative

•Eighty percent with translocation t(8;14) or t(8;2) and t(22;8), with c-MYC on chromosome 8q24, which stimulates proliferation

•Forty percent with a p53 mutation

•Burkitt-like lymphoma (BLL): mainly with translocation t(14;18) on BCL6

6.5.2Large B-Cell Lymphoma (LBCL)

•Seven to eight percent of NHL

•Localization: abdomen, peripheral lymph nodes, skin, bone

•Morphology: large cells, frequently with lobulated nucleus and prominent nucleoli (differential diagnosis: Reed–Sternberg cell); sometimes mixture of cells (lymphocytes, macrophages), which makes the exact diagnosis difficult

•Heterogeneous group of B lymphocytes

•CD19, –20, –22, –38, and 79a-positive, occasionally CD10-positive; TdT-negative, surface immunoglobulins negative

•Translocation with BCL2 and BCL6 genes, 5–10% with translocation t(8;14)

6.5.3Lymphoblastic Lymphoma (LL)

•Thirty percent of NHL

•Morphologically indistinguishable from lymphoid leukemic cells of acute lymphoblastic leukemia (ALL)

•Morphology: mostly uniform cell population, high nuclear to cytoplasmic ratio; mostly lobulated nucleus with fine chromatin structure, nucleoli difficult to discern; morphology is similar to L1/L2 cells (see Chap. 2)

•Majority of cells have T-precursor characteristics: CD1, –2, –3, –5, –7, and −8- positive, sometimes also CD4 – or CD8-positive, which indicates a more mature variant; TdT-positive (as precursor cell)

•Occasionally CD10-positive (CALLA) and HLA-DR-positive

•Mediastinal enlargement (thymus) usually present

•T-cell receptors: T™ in immature form, T© or T® detectable in more mature forms

•Ten to fifteen percent with pre-B phenotype: CD10 and −19 as well as HLA-DR positivity; surface immunoglobulins negative

•Various translocations: t(11;14), t(1;14), t(8;14), t(10;14), and others

•Alteration of various proto-oncogenes: TAL1/2, LMO1/2, HOX11/12, NOTCH1,

LCK, FGFR1, CMYC

•Similar to ALL

6.5.4Anaplastic Large Cell Lymphoma (ALCL)

•Seven to eight percent of NHL

•Morphology: predominantly anaplastic cells

•CD30-positive, CD15and −45-positive or – negative; positive for epithelial membrane antigen (EMA)

•Partial T-cell receptor expression (T®, T™)

–Expression of ALK, a tyrosine kinase, in >90%, often translocated t(2;5) to form a fusion protein with nucleophosphim (NPM)