ASH Image Bank (2002); doi:10.1182/ashimagebank-2002-100525
Copyright © 2002 by the American Society of Hematology.
Lymphocyte-rich Classical Hodgkin Lymphoma
Marshall Kadin, MD
Beth Israel Deaconess/Harvard
Parul Bhargava
Robin Joyce
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Figure 8. L&H variants are surrounded by a rosette of CD3+ T cells in CD20+ B-cell rich nodules. L&H cells express nuclear transcription factor bcl-6 and are negative for fascin
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Figure 9. HRS cells express CD30 and are negative for LCA and CD20. In this case, they are also negative for CD15, in contrast to most cases of classical HL in which they are CD15+.
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Figure 11. Fascin is a 55 kDa actin-bundling protein expressed by Epstein-Barr–transformed B lymphocytes and dendritic cells. Transfection of epithelial cells with fascin results in disrupted cell adhesion and increased motility.
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Clinical Summary
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The patient is a 74 year old white American female who was evaluated for a left-sided breast mass. Following a car accident in December, 2001, she had a persistent left-sided ecchymosis and in early 2002, she noticed a left-sided breast lump. In August 2002, she underwent a core biopsy followed by biopsy of a left axillary lymph node.
PMH: In 1996, biopsy of a previous "lump in the right breast" revealed a lymph node with follicular hyperplasia and a single progressively transformed germinal center.
Physical examination: Afebrile. A 2cm lump was found in the tail of the left breast. No other adenopathy or organomegaly was detected.
Lab: WBC: 13,000 with 76.2% neutrophiles. No other abnormality.
Imaging: CT scans of chest, abdomen and pelvis all normal except for the site of breast biopsy. SPECT images of chest, abdomen and pelvis show no abnormal uptake.
Lymph node biopsy (2002) (Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figures 6A and 6B, Figure 7, Figure 8, Figure 9, Figure 10)
Lymph node affected by LRCHL with coexistent PTGC. Immunoperoxidase stains demonstrate the presence of both classical Reed-Sternberg cells and L&H or "popcorn" variants .
Sex
Female
Age
74
Ethnicity
White
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Diagnosis
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Lymphocyte-rich classical Hodgkin lymphoma, with progressively transformed germinal centers
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Discussion
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The large majority of Hodgkin lymphomas (HLs) are derived from germinal center B cells that fail to undergo apoptosis. HL is separated into nodular lymphocyte predominant type (NLPHL), which represents about 5% of all HL, and classical HL which is further divided into 4 histologic subtypes (nodular sclerosis, mixed cellularity, lymphocyte depleted and lymphocyte rich) based on the character of the inflammatory infiltrate and presence or absence of fibrosis.
Recently, approximately 30% of cases initially classified as NLPHL were reclassified as lymphocyte-rich classical HL (LRCHL). As in this case, patients with NLPHL and LRCHL usually present with stage I or II disease and absence of systemic B symptoms. Patients with NLPHL have a higher frequency of relapse. Patients with LRCHL are significantly older and have a worse prognosis after relapse that could be partly explained by their older average age.
A nodular growth pattern is characteristic of both NLPHL and LRCHL. Progressively transformed germinal centers (PTGCs) appear to be a precursor to NLPHL in some patients, although most patients with PTGC will never develop HL. In NLPHL, L&H or popcorn variants of HRS cells are found within nodules rich in B lymphocytes. In LRCHL, HRS cells which may resemble L&H cells or lacunar variants of HRS cells are found within expanded mantle zones, as in this case. The HRS cells in LRCHL and NLPHL can be distinguished by immunophenotype (Table 1, Figure 11). HRS cells with distinct immunophenotypes were found in intrafollicular and mantle regions of the lymph node.
Recent studies show that L&H cells lack fascin, an actin bundling protein, found in HRS cells in classical HL, in T-zone reticulum cells, and in Epstein-Barr virus transformed B lymphocytes (Table 2- Figure 12 ). In this case, intrafollicular H/RS cells resembling L&H cells did not express fascin whereas those within lacunar spaces in mantle zones did express fascin.
The differential diagnosis of NLPHL and CLRHL can be difficult as demonstrated in this case. Features favoring NLPHL are the coexistence of PTGC and the presence of L&H cells with a B-cell phenotype, lacking CD15, CD30, and fascin. Features favoring CLRHL are lacunar variants of HRS cells with a classical HL phenotype (CD30+, CD15+/–, fascin+, LCA–, CD20–/+). The older age of the patient in this case is more typical of LRCHL.
This case raises the possibility that there is a transition from PTGC to NLPHL to CLRHL. A molecular analysis of HRS cells of the different immunophenotypes may shed light on this question. L&H cells in NLPHL frequently have ongoing somatic hypermutations of Ig genes with intraclonal sequence diversity whereas HRS cells in classical HL have crippled or silenced mutations and lack intraclonal diversity.
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Chapter 12: Lymphoproliferative disorders
Copyright © 2002 by the American Society of Hematology.
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