The diagnosis of PTFL depends on a constellation of findings related to its presentation, tissue distribution, histology, and expression of certain proteins and genomic abnormalities. The disease occurs in males (~90% of cases) that are more often children, adolescents, or young adults who have enlargement of lymph nodes located in one or two nearby sites of the head or neck or less commonly, armpit or groin regions. Histopathological examination of the involved lymph nodes reveals medium- to large-sized lymphoblasts mixed with occasional macrophages and rare centrocytes and centroblasts that together form follicular structures that partially or completely replace the nodes' normal structure with irregularly shaped and merged follicles, abnormally attenuated mantle zones, and the presence of helper T-cells that are pushed to the periphery of the follicles. Its histology is most often rated as high grade and by this criterion defines the disease as an aggressive grade III<unk>  (see follicular<unk>  grading). Nonetheless, PTFL almost always behaves as a non-aggressive or minimally aggressive malignancy. Immunohistiochemical analyses of the involved tissues indicates that the malignant cells express CD20, CD10, and BCL6 but not BCL2 or interferon regulatory factor protein. Genomic analyses of these cells indicate that they have a clonal rearrangement in their IgH genes in all cases and in many cases the Ip6 deletion and gene mutations cited in the above pathophysiology section. These cells lack the t(14:18)(q32:q21.3) translocation which is characteristic of malignant cells in follicular<unk>  but in a small percentage of cases still overexpress the TNFRSF14 gene product which is a consequence of this translocation. The exact cause for this overexpression is unclear. Differential diagnosis The following lymphocyte disorders may be confused with but can be distinguished from PTFL based on the following points: * Follicular<unk>  does not have a strong male-predominance; is most common in older adults; is usually associated with the involvement of other tissues (e.g. bone marrow) in addition to lymph nodes; and has a histology that is usually dominated by centrocytes and centorblasts; that in >85-90% of cases have the t(14:18)(q32:q21.3) translocation; and in 10-40% of cases MAP2K1 mutations. * Large B-cell<unk>  with IRF4 rearrangement often occurs in females (male to female ratio 1-1.2 to 1:1.5); has not yet been reported to occur in adults; almost always involves non-nodal tissues in addition to lymph nodes; has a histology in involved tissues that is similar to diffuse large cell<unk> s; and has malignant cells that overexpress interferon regulatory factor protein in almost all cases, frequently express BC10, and in most cases exhibit overt rearrangements of the IRF4 gene. * The<unk>  form of Marginal zone B-cell<unk>  has lymph node lesions consisting of a mixed population of monocyte-like cells, plasma cells, and lymphoblasts; its malignant cells do not to express CD10 and BCL6 and have relatively few genomic abnormalities except for trisomy 18 (up to 20% of cases). * Benign reactive lymph node and follicular hyperplasia's lymph nodes do not exhibit irregularly shaped and merged follicles, abnormally attenuated mantle zones, or the presence of helper T-cells that are pushed to the periphery of the follicles.
Pediatric-type follicular lymphoma
Nodal marginal zone B cell lymphoma
Duodenal-type follicular lymphoma
Marginal zone B-cell lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma
Follicular lymphoma
Indolent lymphoma
AIDS-related lymphoma