GUEST EDITORS

Syed Ali Abutalib, MD

L. Jeffrey Medeiros, MD

Dr. Abutalib is Associate Director of the Hematology and Cellular Therapy Program and Director of the Clinical Apheresis Program of the Cancer Treatment Centers of America, Zion, Illinois; Associate Professor at Rosalind Franklin University of Medicine and Science; and Founder and Co-Editor-in-Chief of Advances in Cell & Gene Therapy. Dr. Medeiros is Professor and Chair of the Department of Hematopathology at The University of Texas MD Anderson Cancer Center, Houston.

The ASCO Post is pleased to present Hematology Expert Review, an ongoing feature that occasionally quizzes readers on issues in hematology. In this first-part of a two-part installment, Drs. Abutalib and Medeiros highlight the histologically rare lymphocyte-rich type of classic Hodgkin lymphoma, which accounts for about 5% of all classic Hodgkin lymphomas. See the second part that follows this one on mixed-cellularity classic Hodgkin lymphoma. For each quiz question that follows, select the one best answer. The correct answers and accompanying discussions follow.

Question 1

Which of the following statements about lymphocyte-rich classic Hodgkin lymphoma is correct?

A. This neoplasm has a female predominance.

B. This neoplasm usually presents with early-stage disease.

C. This neoplasm is usually observed in patients with HIV infection.

D. This neoplasm is the most common type of classic Hodgkin lymphoma.

Question 2

Which of the following statements about morphology in lymphocyte-rich classic Hodgkin lymphoma is correct?

A. This neoplasm is characterized by scattered Hodgkin/Reed-Sternberg cells in a cellular background of small lymphocytes and commonly has a nodular pattern.

B. This neoplasm is characterized by Hodgkin/Reed-Sternberg cells with lacunar-type morphology.

C. This neoplasm is characterized by scattered Hodgkin/Reed-Sternberg cells in a cellular background comprising neutrophils and eosinophils and commonly has a diffuse pattern.

D. All of the above

Question 3

Which of the following statements about immune histology in lymphocyte-rich classic Hodgkin lymphoma is correct?

A. CD30 is absent in 10% of cases.

B. Rosettes with a T follicular helper cell immunophenotype surrounding the neoplastic cells are present in all cases.

C. The background lymphocytes are mostly of T-cell lineage with a predominance of CD4-positive cells.

D. The background lymphocytes in the nodules have an immunophenotype similar to that of mantle zones.

Answers to Hematology Expert Review Questions

Question 1

Which of the following statements about lymphocyte-rich classic Hodgkin lymphoma is correct?

Correct answer: B. This neoplasm usually presents with early-stage disease.

Expert Perspective

Classic Hodgkin lymphoma is a monoclonal lymphoid neoplasm derived from B cells and composed of mononuclear Hodgkin cells and multinucleated Reed-Sternberg cells in a background containing a variable mixture of non-neoplastic reactive immune cells, including small lymphocytes, eosinophils, histiocytes, and plasma cells.^1,2 Approximately 90% of cases are classic Hodgkin lymphoma, and approximately 10% of cases are nodular lymphocyte-predominant Hodgkin lymphoma. There are four histologic types of classic Hodgkin lymphoma: nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. There is a male predominance for most classic Hodgkin lymphoma types (including lymphocyte-rich), with the exception being nodular sclerosis type, in which the incidence is approximately equal in men and women.

Mixed cellularity, not lymphocyte-rich, classic Hodgkin lymphoma is more frequent in patients with HIV infection and in developing nations. Nodular sclerosis accounts for most (approximately 70%) cases of classic Hodgkin lymphoma cases in Europe and in the United States.^1,2 Lymphocyte-rich classic Hodgkin lymphoma accounts for approximately 5% of classic Hodgkin lymphomas, occurring at a frequency slightly less than that of nodular lymphocyte-predominant Hodgkin lymphoma. Compared with other histologic types, patients with lymphocyte-rich classic Hodgkin lymphoma are, on average, older and usually present with early stages of disease.³

Question 2

Which of the following statements about morphology in lymphocyte-rich classic Hodgkin lymphoma is correct?

Correct answer: A. This neoplasm is characterized by scattered Hodgkin/Reed-Sternberg cells in a cellular background of small lymphocytes and commonly has a nodular pattern.

Expert Perspective

Lymphocyte-rich classic Hodgkin lymphoma is characterized by scattered Hodgkin/Reed-Sternberg cells in a background of small lymphocytes that usually has a nodular pattern (Figure 1A) but uncommonly can have a diffuse pattern.² The nodules can contain small reactive germinal centers, with the neoplastic Hodgkin/Reed-Sternberg cells in a mantle-zone like distribution (Figure 1B). The T zones of the lymph node are attenuated. Nodular sclerosis is characterized by collagen bands that surround at least one nodule and by Hodgkin/Reed-Sternberg cells with lacunar-type morphology.¹ The background cells in nodular sclerosis include many granulocytes.

Lymphocyte-rich classic Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma are both nodular and have a background of small lymphocytes. However, the cells of the lymphocyte-rich type have a classic immunophenotype, and the neoplastic lymphocyte-predominant cells of nodular lymphocyte-predominant Hodgkin lymphoma are B cells positive for CD20 and CD45/LCA.

Question 3

Which of the following statements about immune histology in lymphocyte-rich classic Hodgkin lymphoma is correct?

Correct answer: D. The background lymphocytes in the nodules have an immunophenotype similar to mantle zones.

Expert Perspective

CD30 is expressed by the neoplastic cells in virtually all cases of classic Hodgkin lymphoma, including all cases of the lymphocyte-rich variant (Figure 1C). The neoplastic cells also commonly express CD15. Rosettes with a T follicular helper cell (TFH) immunophenotype (PD1/CD279+, CD57-/+) surrounding the neoplastic cells are present in as many as 50% of cases. The background lymphocytes in lymphocyte-rich classic Hodgkin lymphoma are mostly B cells positive for CD20, PAX-5, IgM, and IgD and are negative for CD10 and BCL-6, similar to mantle zone lymphocytes (See Table 1 for a brief overview of lymphocyte-rich classic Hodgkin lymphoma.) 

DISCLOSURE: Dr. Abutalib is an advisor for AstraZeneca. Dr. Medeiros reported no conflicts of interest.

REFERENCES

1. Stein H, Pileri SA, Weiss LM, et al: Hodgkin lymphomas: Introduction, in Swerdlow SH, Campo E, Harris NL, et al (eds.): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, pp 424-430. Lyon, France, International Agency for Research in Cancer, 2017.

2. Anagnostopoulos I, Piris MA, Isaacson PG, et al: Classic Hodgkin lymphoma, in Swerdlow SH, Campo E, Harris NL, et al (eds.): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, pp 438-440. Lyon, France, International Agency for Research in Cancer, 2017.

3. Shimabukuro-Vornhagen A, Haverkamp H, Engert A, et al: Lymphocyte-rich classical Hodgkin’s lymphoma: Clinical presentation and treatment outcome in 100 patients treated within German Hodgkin’s Study Group trials. J Clin Oncol 23:5739-5745, 2005.