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ChaPTEr 79 Lymphomas 1075

HODGKIN LYMPHOMAS Survival for localized cases with or without treatment is long.
However, cases with variant histology are more likely to have
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HL and non-HL have long been regarded as distinct disease advanced stage disease with a higher relapse rate. Moreover,
entities on the basis of their differences in pathology, phenotype, patients with advanced-stage disease respond poorly to HL
clinical features, and response to therapy. It is now accepted that regimens, such as adriamycin, bleomycin, vinblastine, dacarbazine
the malignant cell of HL is an altered B cell. Therefore it is not (ABVD), and benefit from treatment for aggressive B-cell
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surprising that biological and clinical overlap occurs between lymphoma. Although considered two separate entities with
these two lymphoma groups, as also shown by GEP in PMBCL major differences, NLPHL shares immunomorphological similari-
and classic Hodgkin cell lines. In spite of the close histogenetic ties with THRLBCL; these similarities have also been shown by
relationship (hence the name Hodgkin lymphoma), these disorders GEP and array comparative genomic hybridization. Two forms
are still treated with different modalities. of histological progression can be seen, either to DLBCL or to
The diagnosis of classic HL (CHL) depends on the identifica- a process resembling THRLBCL.
tion of Hodgkin/Reed–Sternberg (HRS) cells in an appropriate
inflammatory background composed of small T lymphocytes, Classic Hodgkin Lymphoma, Nodular Sclerosis
plasma cells, histiocytes, and granulocytes (often eosinophils). This variant of HL, classic Hodgkin lymphoma, nodular sclerosis
All cases of CHL share certain immunophenotypic and genotypic (CHLNS) is most commonly seen in adolescents and young
+/−
+
−
−
features. The phenotype is CD30 , CD15 , CD45 , and EMA . adults but can occur at any age. Female cases equal or exceed
Expression of B cell–associated antigens is seen in up to 75% of those in males. The mediastinum is commonly involved; stage
cases; however, when present, CD20 staining is usually weaker and bulk of disease have prognostic importance.
or more variable than that seen in normal B cells. CD79a is The tumor has at least a partially nodular pattern, with fibrous
usually negative. Ig and TCR genes are usually germline because bands separating the nodules in most cases. Diffuse areas with
of the paucity of tumor cells in the inflammatory background; necrosis may be present. The characteristic cell is the “lacunar-
however, microdissection can enable amplification for clonal type” Reed-Sternberg (RS) cell, which may be very numerous.
rearrangement of the Ig genes by polymerase chain reaction Diagnostic RS cells are usually also present. The background
(PCR). In addition, the presence of somatic mutations indicates contains lymphocytes, histiocytes, plasma cells, eosinophils, and
transit through the germinal center. neutrophils. Grading (I and II) is based on the proportion of
Sufficient evidence has emerged in recent years to warrant the tumor cells and the presence of necrosis but is considered
the recognition of nodular lymphocyte-predominant HL as a optional. The immunophenotype and genotype are characteristic
distinct entity. Although it resembles other types of HL in having of CHL. However, EBV is infrequently positive— less than 15%
a minority of putative neoplastic cells in a background of benign of cases.
inflammatory cells, it differs morphologically, immunophenotypi- CHLNS is often curable; however, in long-term survivors,
cally, and clinically from CHL. The preferred term Hodgkin the risk of secondary malignancies is increased, especially in
lymphoma, versus Hodgkin disease, reflects current knowledge those receiving both chemotherapy and radiation. CHLNS of
concerning the nature of the neoplastic cell as a lymphocyte. the mediastinum is thought to be closely related to PMBCL, and
both types of tumors can be seen in the same patient, either as
Nodular Lymphocyte-Predominant Hodgkin Lymphoma composite malignancy or sequentially.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)
occurs at all ages but is more common in adult males. It usually Classic Hodgkin Lymphoma, Mixed Cellularity
involves peripheral lymph nodes with sparing of the mediastinum Classic Hodgkin lymphoma, mixed cellularity (CHLMC) is
and is localized at diagnosis, although rarely it may be predominantly seen in male adults. A bimodal age distribution,
disseminated. NLPHL usually has a nodular growth pattern, with peaks in young children and later in older adults can
with or without diffuse areas. The number of infiltrating reactive be present. Both CHLMC and the lymphocyte-depleted form
T cells is variable, and various patterns have been described on (see below) can be associated with underlying HIV infection.
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the basis of the cellular composition and growth pattern. The The infiltrate is diffuse without band-forming sclerosis, although
atypical cells have vesicular, polylobated nuclei and small fine interstitial fibrosis may be present (Fig. 79.4). HRS
nucleoli. These had been called lymphocytic and/or histiocytic cells are of the classic type. It is often EBV-positive, seen in up
(L&H) cells, or “popcorn” cells, but the term lymphocyte- to 75% of cases. The stage is often advanced at diagnosis.
predominant (LP) cell is now preferred. LP cells differ from classic The clinical course is moderately aggressive, but is often
HRS cells. The background is composed predominantly of curable.
lymphocytes with or without clusters of epithelioid histiocytes.
Plasma cells are infrequent; eosinophils and neutrophils are also Classic Hodgkin Lymphoma, Lymphocyte Depletion
+
rare. The atypical cells are CD45 , positive for B cell–associated Classic Hodgkin lymphoma, lymphocyte depletion (CHLLD) is
+
−
+/−
antigens (CD19, CD20, CD22, CD79a), CDw75 , EMA CD15 , the least common variant of CHL and is most common in older
−/+
−
CD30 and usually sIg , as shown by routine techniques. Small people, in HIV-positive individuals, and in populations of
lymphocytes in the nodules are predominantly B cells with a nonindustrialized countries. It frequently presents with abdominal
mantle zone phenotype. However, numerous T cells are present, lymphadenopathy, and spleen, liver, and bone marrow involve-
+
with CD279 T cells “rosetting” the LP cells. The proportion of ment, but without peripheral adenopathy. The infiltrate is diffuse
T cells tends to increase over time in sequential biopsies. A and often appears hypocellular because of the presence of diffuse
prominent follicular DC meshwork is present within the nodules. fibrosis and necrosis. A large number of HRS cells and occasional
LP cells, when microdissected, have shown to have clonally bizarre “sarcomatous” variants are seen relative to the fewer
rearranged immunoglobulin genes with evidence of somatic number of normal lymphocytes and scarce other inflammatory
hypermutation. cells. The immunophenotype is characteristic of CHL. Since the