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Indian Journal of Cancer
Medknow Publications on behalf of Indian Cancer Society
ISSN: 0019-509X EISSN: 1998-4774
Vol. 41, Num. 3, 2004, pp. 135-137

Indian Journal of Cancer, Vol. 41, No. 3, July-September, 2004, pp. 135-137

Case Report

Diffuse large B-cell lymphoma arising from a multicentric mixed variant of Castleman's disease

Department of Histology - Embryology, Democritus University of Thrace
Correspondence Address:Department of Histology - Embryology, Democritus University of Thrace

Code Number: cn04026


This case report describes a patient with multicentric mixed type Castleman's disease and concomitant non-Hodgkin's lymphoma of diffuse large B cell type in the neck. Multicentric CD is a systemic illness with disseminated lymphadenopathy; its aggressive and usually fatal course is associated with infectious complications and risk for malignant tumors, such as lymphoma or Kaposi sarcoma.

Multicentric CD is a systemic illness with disseminated lymphadenopathy; its aggressive and usually fatal course is associated with infectious complications[1],[2],[3] and risk for malignant tumors, such as lymphoma or Kaposi sarcoma.[4],[5],[6],[7]

Key Words: Castleman’s disease; Non-Hodgkin lymphoma

Case Report

A male aged 73 was admitted to our hospital for the first time with the complaint of fever and weakness, which had appeared 15 days previously. On clinical examination there was splenomegaly and bilateral cervical and axillary lymphadenopathy. Laboratory findings were significant: hemolytic anemia (hemoglobin level 6.3 g/dl, direct Coombs′ test positive), hypocalcemia and polyclonal hypergammaglobulinemia. Immunophenotypic peripheral blood profile was consistent with viral infection (CD3: 40%, CD8: 18%, CD4: 22%, NK: 40%). Bone marrow aspirate and trephine examination showed a normal cell population. Imaging studies, including standard posteroanterior and lateral chest X-ray, abdominal X-ray, whole body computed tomography, and ultrasonography showed evidence of supraclavicular and axillary lymphadenopathy and splenomegaly. Contrast-enhanced CT of the thorax (after bolus injection of contrast medium) showed no contrast enhancement in supraclavicular and axillary lymphadenopathy. Serological data were positive for anti-Coxsackie IgM antibodies. Immunologic studies were normal. Fine-needle aspiration biopsy (FNAB) was indicative of reactive lymphadenopathy. At excisional cervical lymph-node biopsy a diagnosis of Castleman′s disease with features of both the hyaline-vascular and plasma-cell variants was established. The patient responded to corticosteroids (prednisone) but 4 months later he was readmitted with edema of the lower extremities, fever and weakness, hemolytic anemia, splenomegaly, remarkable lymphadenopathy of the chest and retroperitoneum, hypocalcemia, renal failure and noticeable peripheral blood profile: CD38: 100%, CD3: 78%, CD8: 56%, CD4: 22%, NK: 8%. A new excisional biopsy of a cervical node was performed and the result was diagnostic of malignant diffuse large B-cell lymphoma. Serology was negative for Kaposi sarcoma-associated herpesvirus KSHV/HHV8 and HIV, while the levels of serum C reactive protein, IL-6 and IL-10 were normal as well. The patient was treated with CHOP, and passed away 6 months after the diagnosis of lymphoma due to complication with pneumonia and sepsis. No autopsy study was performed.

The gross examination of the first cervical lymph node biopsy specimen showed a fairly well-encapsulated, soft tan lesion with a largest dimension of 2.5 cm. Light microscopy, revealed areas of hyaline-vascular CD pattern, in which the majority of the lymphoid follicles had atrophic or regressive germinal centers often penetrated by capillaries. There was concentric layering of lymphocytes in an onion-skin appearance and one or more penetrating blood vessels. The interfollicular stroma was also prominent with numerous hyperplastic vessels of the postcapillary venule type and plump endothelial lining. In other areas a plasma cell CD pattern was seen with the characteristic monotonous sheets of mature-appearing plasma cells expanding into the interfollicular zones of the node. The follicular centers were enlarged and hyperplastic, in contrast to the atrophic follicular centers of the hyaline-vascular type. Although most of the plasma cells had abundant cytoplasm and small eccentric nuclei, occasional atypical forms with enlarged nuclei, irregular nuclear contours and prominent nucleoli were found. Immunohistochemical study in paraffin sections demonstrated, enlarged follicular dendritic cells (CD21+), decreased follicular center cell proliferation (CD20+, CD10+, CD5-, and negative for surface immunoglobulins), and an aberrant population of mantle zone lymphocytes (CD20+, CD10- and CD5-). The plasma cell infiltrates in the interfollicular areas were polyclonal by immunoglobulin light chain staining (positive for both k and l light chains). The immunohistochemical staining for Bcl-2 oncoprotein was not expressed in follicular centers of the lymph node. Small T-lymphocytes and macrophages were detected in the follicular germinal centers by immunostaining with antibody to CD45RO and CD68 respectively.

These findings corresponded to Castleman′s disease of mixed (transitional) variant [Figure - 1].

Grossly, the node was enlarged (diameter 3 cm) with a diffuse yellowish color on the cut surface. At low magnification, the normal nodal architecture was totally effaced and the node was diffusely infiltrated by a population of atypical lymphocytes (large cleaved cells, large noncleaved cells, immunoblasts, multilobated cells, and anaplastic cells). Clusters of similar pleomorphic cells were additionally seen in perivascular areas and in sinuses, while proliferation of high endothelial venules was highlighted. Extensive infiltration of the lymph node capsule and surrounding fat was observed as well.

Slides were stained with CD45, CD79a, CD20, CD5, CD43, CD23, CD10, CD21, MIB-1, BCL-2, BCL-6 and p53, and polyclonal antibodies were used to determine the expression of CD3 antigen and of the Ig chains k, l, µ, g, and a. The number of MIB-1 positive cells was determined by counting the number of cells with clear nuclear positivity per 100 cells in five high-power fields (X40 objective; BX40-Olympus). Immunostaining was carried using appropriate positive and negative controls.

The tumor cells were positive for CD20 [Figure - 2], CD79a, CD45, CD10, BCL-2, and BCL-6, with absence of staining for CD3, CD5, and CD23. A monotypical expression of the light chain k and of the heavy chain IgM was observed. Determination of the growth fraction revealed a large number of MIB-1/Ki67-positive cells comprising up to 80% of the neoplastic population [Figure - 3]. Molecular analysis showed a Bcl-2 oncogene rearrangement with t(14;18) chromosome translocation, and Bcl-6 oncogene rearrangement with translocation involving chromosome 3(3q27). EBV in situ hybridization was negative. The histological feature, and the immunohistological findings, led us to diagnose a diffuse large B cell lymphoma, according to the REAL/WHO lymphoma classifications.[8],[9]


In this case report, we describe a patient with a combination of mixed type Castleman′s disease and diffuse B-cell lymphoma arising in the neck. The most striking points in this case are: 1) the absence of malignancy in the first lymph node biopsy as had been demonstrated using the immunohistochemical analyses, 2) the fast evolution of CD to NHL (within 4 months) and 3) the negative serological test for HHV-8 and HIV; the positivity for the last one could explain the fast evolution.


1.Frizzera G. Atypical lymphoproliferative disorders. In: Knowlers DM, ed. Neoplastic Hematopathology. Baltimore, MD: Williams & Wilkins 1992:454-95.  Back to cited text no. 1    
2.Marwah N, Sharma R, Marwah S, Singh S, Singh I, Arora B. Castleman's disease of the retroperitoneum-a case report. Indian J Pathol Microbio 2002;45:335-6.  Back to cited text no. 2    
3.Ascoli V, Signoretti S, Onett-Muda A, Pescarmona E, Della-Roca C, Nardi F, et al. Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease. J Pathol 2001;193:200-9.  Back to cited text no. 3    
4.Desai SB, Pradhan SA, Chinoy RF. Mediastinal Castleman's disease complicated by follicular dendritic cell tumour. Indian J Cancer 2000;37:129-32.  Back to cited text no. 4    
5.Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, et al. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 1995;86:1276-80.  Back to cited text no. 5    
6.Kojima M, Nakamura S, Shimizu K, Suda Y, Kasuga Y, Sugihara S, et al. Nodal marginal zone B-cell lymphoma resembling plasmacytoma arising from a plasma cell variant of localized Castleman' disease: A case report. APMIS 2002;110:523-7.  Back to cited text no. 6    
7.Akyuz C, Kale G, Emir S, Akcoren Z, Buyukpamukcu M. T-cell lymphoma in a child with multicentric Castleman's disease. Med Pediatr Oncol 2000;35:133-4.  Back to cited text no. 7    
8.Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 1994;84:1361-92.  Back to cited text no. 8    
9.Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of Tumors. Tumous of Haematopoietic and Lymphoid Tissues. Pathology and Genetics. Lyon: IARG Press 2001.  Back to cited text no. 9    

Copyright 2004 - Indian Journal of Cancer

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