The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Hematologic Neoplasms 407
The differences between these two entities involve the clinical features and behavior of the disease
and is based largely on the types and proportions of noncancerous cells.
Some of the common findings in both types of HL include the following:
• The disease usually arises in a lymph node, virtually in the cellular-rich region, and involves
contiguous rather than disseminated nodes.
• The majority of deaths occur in young adults.
• Neoplastic tissues usually contain a small number of scattered large mononuclear and multinucleated
tumor cells known as Hodgkin’s Reed–Sternberg (H-RS) cells. HL is a unique form of cancer,
as affected nodes generally contain a few cancer (H-RS) cells surrounded by many more
noncancerous cells. This ratio might be as high as 1000 to 1.
• T-lymphocytes usually ring the tumor cells in a rosette like manner.
Nodular Lymphocyte Predominant Hodgkin Lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of
all Hodgkin lymphomas. It is a B-cell neoplasm with monoclonal proliferation and is characterized
by a nodular or a nodular and diffuse polymorphous proliferation of scattered, large, neoplastic cells
known as popcorn cells or lymphocytic and/or histiocytic (L&H) Reed–Sternberg cell variants. The
usual sites of involvement at the time of presentation are cervical, axillary, or inguinal lymph nodes.
Patients typically present with a localized proliferative lymphadenopathy.
With morphological exam, lymph node architecture is totally or partially replaced by a nodular or
nodular end diffused infiltrate, predominately consisting of small lymphocytes, histiocytes, epithelioid
cells, and intermingled L&H cells. Notably, neutrophils and eosinophils are absent in both nodular and
diffuse regions. With immunophenotyping, L&H cells are positive for CD20, CD79a, BCL6, and CD45
in nearly all cases (245–247). In most instances, they are also Ig J chain and CD75 positive (255).
Organic cation transported 2 (OCT2) is a transcription factor that induces immunoglobulin synthesis
by activating the promoter of immunoglobulin genes. Immunolabeling for OCT2 selectively
highlights L&H cells and might become a useful means of identifying them (248) and in differenting
between NLPHL and classical Hodgkin lymphoma (249).
The L&H cells, in any given case, have identical monoclonally rearranged immunoglobulin genes
(250–252). These rearrangements are usually not detectable in whole-tissue DNA, but only in the
DNA of an isolated single islet. The variable region of the Ig heavy chain shows a significantly high
rate of somatic mutations and also shows evidence of ongoing mutations. Germinal center B-cells
might be at the blastic stage and are possible cells of disease origin. The prognosis of patients with
early-stage disease is very good, with 10-year survival in more than 80% of cases (253).
Classical Hodgkin Lymphoma
Classical Hodgkin lymphoma (CHL) is defined as a monoclonal B-cell neoplasm. The cell morphology
is defined as the presence of mononuclear and multinucleated Hodgkin’s Reed–Sternberg
cells in an infiltrate containing a variable mixture of non-neoplastic small lymphocytes, eosinophils,
neutrophils, histiocytes, plasma cells, fibroblasts, and collagen fibers. The immunophenotypic and
genetic features of the mononuclear and multinucleated cells are indistinguishable, but the clinical
features and association with EBV show differences (254).
Classical Hodgkin lymphoma accounts for the majority (95%) of all HLs and shows a bimodal age
group peak at 15 and 35 years of age. Primary involvement in this lymphoma is extranodal. At initial
presentation, about half of the patients have stage I or stage II (localized) disease. The introduction of
modern radiation and chemotherapy has made CHL curable in the majority of cases.
Approximately 60% of patients, the majority of them with the nodular sclerosing subtype, usually
have mediastinal infiltrations. Lymph node architecture is replaced by a variable number of H-RS
cells mixed with an inflammatory background. Classical diagnostic Reed–Sternberg cells are large,