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An Unusual Variant of Composite Lymphoma.

A Short Case Report and Review of the Literature

The term composite lymphoma was first proposed by Custer to denote "the occurrence of more than one histological pattern of lymphoma in a single patient."[2] The working formulation of non-Hodgkin lymphoma (NHL) defined composite lymphoma as "two distinctly demarcated types of non-Hodgkin's lymphoma or its rare association with Hodgkin's lymphoma within a single organ or tissue."[3] The incidence of these tumors is low, varying from 1% to 4.7%. We report the unusual case of a 73-year-old man with follicular small cleaved cell lymphoma involving a right groin lymph node 13 years before present admission who had a composite lymphoma, with a combination of nodular sclerosing Hodgkin disease (HD) and follicular small cleaved cell lymphoma. The recognition of these tumors is important to assess the prognosis and outcome of the patient.


The patient is a 73-year-old man with a history of NHL, follicular small cleaved cell type, treated with radiation therapy 13 years before the present admission. He was seen in the hospital with the chief complaints of mass in the right groin, fever, sore throat, and malaise of 3 days' duration. Physical examination revealed a chain of lymph nodes in the right inguinal area. An abdominal computed tomographic scan was negative for lymph-adenopathy and organomegaly. A right inguinal node biopsy was performed.


The biopsy specimen consisted of a 4.5 x 2.5 x 2.0-cm lymph node with a fleshy gray-white nodular cut surface. The tissue was fixed in 10% buffered formalin and B5, paraffin embedded, and stained with hematoxylin-eosin.

Immunohistochemical studies were performed using a biotin-streptavidin detection system (BioGenex, San Ramon, Calif). The tissue was deparaffinized, rehydrated, and protease digested where required. Histologic sections were treated sequentially with various primary antibodies (leukocyte common antigen, Leu-M1, L-26, and [Kappa] and [Lambda] light chains). Staining was done with a mixture of chromogen 3,3-diaminobenzidine tetrahydrochloride and hydrogen peroxide, after rinsing well in tap water. The slides were counterstained with 4% Mayer's hematoxylin for 1 minute, dehydrated, cleared, and mounted on Permount (Fisher Scientific, Fair Town, NJ).


On light microscopy, the nodal architecture was effaced by numerous variably sized follicles with indistinct mantle zones. The follicles were composed of a monotonous population of small cleaved cells similar to the follicular lymphoma diagnosed 13 years previously. In addition, large vaguely nodular areas with characteristic lacunar-type Reed-Sternberg (RS) cells typical of nodular sclerosing HD were identified (Figure 1). Sharp transition between the 2 elements was evident. Immunohistochemical studies revealed [Lambda] light chain restriction in the neoplastic follicles (Figure 2).The large atypical cells in the nodular areas representing the HD component were positive with antibodies to Leu-M1 and CD30, confirming the composite nature of this tumor. Flow analysis revealed clonal population of small lymphoid cells of B [Lambda] type.



Composite lymphomas constitute the presence of 2 different types of NHL or a rare association of NHL and HD in a single organ or tissue. They are uncommon, with an incidence ranging from 1% to 4.7%, depending on the series. The combination of 2 different types of NHL composed of small cleaved cell lymphoma and diffuse large cell lymphoma is the most common variant, accounting for up to 58% of cases.[3] Composite lymphomas, composed of HD and one of the components of NHL, are very rare. Kim[4] described the first reported case of this type in 1974. Traditionally, HD and NHL are considered 2 different entities. However, recent evidence of positive staining of RS cells with antibodies to CD30, CD25, and CDw70 suggest a lymphoid origin of these cells. Interestingly, immunologic studies have demonstrated that the nodular lymphocyte predominant type of Hodgkin lymphoma is characterized by the presence of polyclonal B lymphocytes, in contrast to the T-cell-rich infiltrates of other types of HD.[5] The RS cells in nodular lymphocyte predominance Hodgkin disease (NLPHD) variant stain positive with antibodies to leukocyte common antigen, L26, and pan-B-cell markers in contrast to the RS cells of other variants, which are Leu-M1 positive and nonreactive with pan-B-cell markers. In addition, the RS cells of NLPHD variant are shown to express J chain, which is synthesized only by B cells. These studies favor a B-cell origin for NLPHD, which is the most common variant of HD in association with NHL.

Hodgkin disease has been described to occur with NHL at the same site or simultaneously at different sites in a single patient or sequentially following NHL. Sequential occurrence has been described to occur with increased frequency following treatment.

Krikorian et al[6] reported a sixfold increase in NHL after HD. Travis et al[7] reported a fourfold increase in HD after NHL. However, this incidence is extremely low when compared with the other second tumors following treatment of either HD or NHL. Of the posttreatment NHL and HD composite lymphomas, the combination of NLPHD and HD is the most frequent. Since NLPHD is strongly believed to be a B-cell neoplasm, this type of lymphoma is thought to be a B-cell neoplasm at different stages of evolution. Meittinen et al[8] described this type of association in 10% of patients with HD after treatment. Hansmann et al[9] reported a low incidence of 2.6%. Diffuse large cell lymphoma in this setting is localized, with a good response to therapy as opposed to the diffuse large cell lymphoma that occurs sporadically. The most plausible explanation for these posttherapy composite lymphomas is the prolonged immunodeficiency associated with the primary lymphoma and/or therapy-induced immune suppression.

Composite lymphomas, with HD variants other than NLPHD and NHL, are rare. Jaffe et al[1] reported 13 cases, which included 7 cases of nodular HD followed by 3 cases of mixed cellularity variant. The other 3 cases were reported as "unclassified."

In composite lymphomas of HD and NHL, the least described variant of NHL is follicular small cleaved cell lymphoma. To the best of our knowledge, only one such histologic type has been reported in the literature, by Jaffe et al,[1] and our case constitutes the second (Table).

Nodular Sclerosing Hodgkin Disease (HD) and Follicular Small Cleaved Cell (NHL) Composite Lymphomas
Age/Sex/Source Site Diagnosis Phenotype

66/F/Jaffe et al(1) Lymph node Follicular B cell
 (unspecified small cleaved
 site) type

78/M/present study Lymph node Follicular small B cell
 (inguinal type cleaved
 region type

Age/Sex/Source Diagnosis Phenotype

66/F/Jaffe et al(1) Nodular [CD15.sup.+], [L26.sup.-]

78/M/present study Nodular [CD15.sup.+], [L26.sup.-],
 sclerosis [CD30.sup.+]

Also, HD has been described to occur in patients with chronic lymphocytic leukemia, constituting a variant of Richter syndrome. Richter syndrome is defined as the development of a large cell lymphoma in patients with chronic lymphocytic leukemia, and this transformation is characterized by rapid deterioration in the patient's general condition, lymphadenopathy, and hepatosplenomegaly. The large cell transformation is characterized by biastic appearance of some of the cells of the chronic lymphocytic leukemia component, which demonstrate typical morphologic structure and immunohistochemical characteristics of RS cells, raising the possibility of HD.[8] Harousseau et al[10] reported 2 cases of HD in association with Richter syndrome in the 25 cases they studied. Jaffe et al in 1992 reported coexistent HD and Richter syndrome in 8 patients. The recognition of HD variant of Richter syndrome is important, since the patients with this type of transformation have a better prognosis than those with the NHL variant of Richter syndrome.

Composite lymphomas that consist of 2 different types of T-cell lymphomas are rare. The only entity described is mycosis fungoides, a low-grade cutaneous neoplasm that can progress into a large cell lymphoma. Cerroni et al[11] reported a high incidence (56%) of large cell transformation in the 36 cases they studied.

Composite lymphomas that contain lymphoid cells of both B- and T-cell lineage have also been described. York et al[5] in 1985 reported 3 cases, which were originally diagnosed as follicular center cell lymphomas. After an average interval of 39 months, all 3 patients developed a diffuse large cell lymphoma of T-cell type. Two other cases were reported by Shimizu et al.[12] One possible explanation for this bilineage is the presence of pluripotent lymphoid cells capable of differentiating T- and B-cell lineage.

In summary, we present an unusual variant of composite lymphoma composed of nodular sclerosing HD and follicular small cleaved cell lymphoma in a single lymph node. This occurrence in a patient with a history of follicular small cleaved cell lymphoma 13 years earlier who had undergone radiation therapy may explain the possibility of therapy-induced tumor. Other possible explanations are simultaneous occurrence by chance or some yet unidentified common etiologic agent.


[1.] Jaffe ES, Zarate-Osorno A, Medeiros LJ. The interrelationship of Hodgkin's disease and non-Hodgkin's lymphomas: lessons learned from composite and sequential malignancies. Semin Diagn Pathol. 1992;9:297-303.

[2.] Custer RP. Pitfalls in the diagnosis of lymphoma and leukemia from pathologist's point of view. In: Proceedings of Second National Conference--New York American Cancer Society. 1954:554-557.

[3.] Kim H, Hendrickson MD, Dorfman RF. Composite lymphoma. Cancer. 1977;41:1676-1682.

[4.] Kim H. Composite lymphomas and related tumors. Am J Clin Pathol. 1993; 99:445-451.

[5.] York JC, Cousar JB, Glick AD, Flexner JM, Stein R, Collins RD. Morphologic and immunologic evidence of composite B- and T-cell lymphomas: a report of three cases developing in follicular center cell lymphomas. Am J Clin Pathol. 1985;84:35-43.

[6.] Krikorian JG, Burke JS, Rosenberg SA, Kaplan HS. Occurrence of non-Hodgkin's lymphoma after therapy for Hodgkin's disease. N Engl J Med. 1979;300: 452-458.

[7.] Travis LB, Curtis RE, Boice JD Jr, Hankey BF Fraumeni JF Jr. Second cancers following non-Hodgkin's lymphoma. Cancer. 1991;67:2002-2009.

[8.] Miettinen M, Franssila KO, Saxen E. Hodgkin's disease, lymphocytic predominance nodular: increased risk for subsequent non-Hodgkin's lymphoma. Cancer. 1983;51:2293-2300.

[9.] Hansmann ML, Stein H, Fellbaum C, Hui PK, Parwaresch MR, Lennert K. Nodular paragranuloma can transform into high-grade malignant lymphoma of B type. Hum Pathol. 1989;20:1169-1175.

[10.] Harousseau JL, Flandrin G, Tricot G, Brouet JC, Seligmann M, Bernard J. Malignant lymphoma supervening in chronic lymphocytic leukemia and related disorders, Richter's syndrome, a study of 25 cases. Cancer. 1981;48:1302-1308.

[11.] Cerroni L, Rieger E, Hodl S, Kerl H. Clinicopathologic and immunologic features associated with transformation of mycosis fungoides to large-cell lymphoma. Am J Surg Pathol. 1992;16:543-552.

[12.] Shimizu K, Hirano M, Maruyama F, et al. T-cell malignancy following B-cell lymphoma in remission. Am J Clin Pathol. 1989;92:362-366.

Accepted for publication January 27, 2000.

From the Department of Cytopathology, Lankenau Hospital, Wynnewood, Pa (Dr Thirumala); and Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY (Drs Esposito and Fuchs).

Reprints: Seshadri Thirumala, MD, 1000 Conestoga Rd, Apt C258, Rosemont, PA 19010.
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Author:Thirumala, Seshadri; Esposito, Michael; Fuchs, Alexander
Publication:Archives of Pathology & Laboratory Medicine
Geographic Code:1USA
Date:Sep 1, 2000
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