This case report describes a patient with multicentric mixed type
Castleman\u2032s disease and concomitant non-Hodgkin\u2032s 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

Venizelos I, Tamiolakis D, Simopoulos C, Nikolaidou S, Barbagadaki S,
Lambropoulou M, Alexiadis G, Boglou P, Papadopoulos Nikolas

Bioline International

Indian Journal of Cancer  |  July - September 2004  |  Volume 41 |  Issue 3 135Multicentric CD is a systemic illness with disseminatedlymphadenopathy; its aggressive and usually fatal courseis associated with infectious complications1-3 and risk formalignant tumors, such as lymphoma or Kaposisarcoma.4-7Case ReportA male aged 73 was admitted to our hospital for thefirst time with the complaint of fever and weakness,which had appeared 15 days previously. On clinicalexamination there was splenomegaly and bilateralcervical and axillary lymphadenopathy. Laboratoryfindings were significant: hemolytic anemia(hemoglobin level 6.3 g/dl, direct Coombs’ testpositive), hypocalcemia and polyclonalhypergammaglobulinemia. Immunophenotypicperipheral blood profile was consistent with viralinfection (CD3: 40%, CD8: 18%, CD4: 22%, NK:40%). Bone marrow aspirate and trephine examinationshowed a normal cell population. Imaging studies,including standard posteroanterior and lateral chest X-ray, abdominal X-ray, whole body computedtomography, and ultrasonography showed evidence ofDiffuse large B-cell lymphoma arising from amulticentric mixed variant of Castleman’sdiseaseVenizelos I, Tamiolakis D1, Simopoulos C2, Nikolaidou S1, Barbagadaki S1,Lambropoulou M3, Alexiadis G3, Boglou P3, Papadopoulos N3Department of Pathology, Ippokration Hospital of Salonica, 1Department of Cytology, General Hospitalof Chania, 2Department of Experimental Surgery, Democritus University of Thrace, 3Department ofHistology - Embryology, Democritus University of Thrace, Greece.CaseReportAbstractThis case report describes a patient with multicentric mixed type Castleman’s disease and concomitant non-Hodgkin’slymphoma of diffuse large B cell type in the neck. Multicentric CD is a systemic illness with disseminatedlymphadenopathy; its aggressive and usually fatal course is associated with infectious complications and risk formalignant tumors, such as lymphoma or Kaposi sarcoma.Key Words: Castleman’s disease; Non-Hodgkin lymphomasupraclavicular and axillary lymphadenopathy andsplenomegaly. Contrast-enhanced CT of the thorax(after bolus injection of contrast medium) showed nocontrast enhancement in supraclavicular and axillarylymphadenopathy. Serological data were positive foranti-Coxsackie IgM antibodies. Immunologic studieswere normal. Fine-needle aspiration biopsy (FNAB) wasindicative of reactive lymphadenopathy. At excisionalcervical lymph-node biopsy a diagnosis of Castleman’sdisease with features of both the hyaline-vascular andplasma-cell variants was established. The patientresponded to corticosteroids (prednisone) but 4 monthslater he was readmitted with edema of the lowerextremities, fever and weakness, hemolytic anemia,splenomegaly, remarkable lymphadenopathy of the chestand retroperitoneum, hypocalcemia, renal failure andnoticeable peripheral blood profile: CD38: 100%, CD3:78%, CD8: 56%, CD4: 22%, NK: 8%. A newexcisional biopsy of a cervical node was performed andthe result was diagnostic of malignant diffuse large B-cell lymphoma. Serology was negative for Kaposisarcoma-associated herpesvirus KSHV/HHV8 and HIV,while the levels of serum C reactive protein, IL-6 andIL-10 were normal as well. The patient was treatedIndian Journal of Cancer  |  July - September 2004  |  Volume 41 |  Issue 3136with CHOP, and passed away 6 months after thediagnosis of lymphoma due to complication withpneumonia and sepsis. No autopsy study wasperformed.The gross examination of the first cervical lymph nodebiopsy specimen showed a fairly well-encapsulated, softtan lesion with a largest dimension of 2.5 cm. Lightmicroscopy, revealed areas of hyaline-vascular CDpattern, in which the majority of the lymphoid follicleshad atrophic or regressive germinal centers oftenpenetrated by capillaries. There was concentric layeringof lymphocytes in an onion-skin appearance and one ormore penetrating blood vessels. The interfollicularstroma was also prominent with numerous hyperplasticvessels of the postcapillary venule type and plumpendothelial lining. In other areas a plasma cell CDpattern was seen with the characteristic monotonoussheets of mature-appearing plasma cells expanding intothe interfollicular zones of the node. The follicularcenters were enlarged and hyperplastic, in contrast tothe atrophic follicular centers of the hyaline-vasculartype. Although most of the plasma cells had abundantcytoplasm and small eccentric nuclei, occasional atypicalforms with enlarged nuclei, irregular nuclear contoursand prominent nucleoli were found.Immunohistochemical study in paraffin sectionsdemonstrated, enlarged follicular dendritic cells(CD21+), decreased follicular center cell proliferation(CD20+, CD10+, CD5-, and negative for surfaceimmunoglobulins), and an aberrant population ofmantle zone lymphocytes (CD20+, CD10- and CD5-).The plasma cell infiltrates in the interfollicular areaswere polyclonal by immunoglobulin light chain staining(positive for both κ and λ light chains). Theimmunohistochemical staining for Bcl-2 oncoproteinwas not expressed in follicular centers of the lymphnode. Small T-lymphocytes and macrophages weredetected in the follicular germinal centers byimmunostaining with antibody to CD45RO and CD68respectively.These findings corresponded to Castleman’s disease ofmixed (transitional) variant (Figure 1).Grossly, the node was enlarged (diameter 3 cm) with adiffuse yellowish color on the cut surface. At lowmagnification, the normal nodal architecture was totallyeffaced and the node was diffusely infiltrated by apopulation of atypical lymphocytes (large cleaved cells,large noncleaved cells, immunoblasts, multilobated cells,and anaplastic cells). Clusters of similar pleomorphiccells were additionally seen in perivascular areas and insinuses, while proliferation of high endothelial venuleswas highlighted. Extensive infiltration of the lymphnode 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-6and p53, and polyclonal antibodies were used todetermine the expression of CD3 antigen and of the Igchains κ, λ, µ, γ, and α. The number of MIB-1 positivecells was determined by counting the number of cellswith clear nuclear positivity per 100 cells in five high-power fields (X40 objective; BX40-Olympus).Immunostaining was carried using appropriate positiveand negative controls.The tumor cells were positive for CD20 (Figure 2),CD79a, CD45, CD10, BCL-2, and BCL-6, withVenizelos et al: Diffuse large B-cell lymphoma arising from a multicentricFigure 1: Hyaline-vascular changes, and solid, confluent sheetsof plasma cells. Cervical node. Multicentric Castleman’s diseaseof mixed type (H & E stain X100).Figure 2: Pleomorphic lymphoid cells. Cervical node. Diffuse largeB cell lymphoma (CD20 immunostain, X200).Indian Journal of Cancer  |  July - September 2004  |  Volume 41 |  Issue 3 137Venizelos et al: Diffuse large B-cell lymphoma arising from a multicentriccombination of mixed type Castleman’s disease anddiffuse B-cell lymphoma arising in the neck. The moststriking points in this case are: 1) the absence ofmalignancy in the first lymph node biopsy as had beendemonstrated using the immunohistochemical analyses,2) the fast evolution of CD to NHL (within 4 months)and 3) the negative serological test for HHV-8 andHIV; the positivity for the last one could explain thefast evolution.References1. Frizzera G. Atypical lymphoproliferative disorders. In: KnowlersDM, ed. Neoplastic Hematopathology. Baltimore, MD: Williams &Wilkins 1992:454-95.2. Marwah N, Sharma R, Marwah S, Singh S, Singh I, Arora B.Castleman’s disease of the retroperitoneum-a case report. In-dian J Pathol Microbio 2002;45:335-6.3. Ascoli V, Signoretti S, Onett-Muda A, Pescarmona E, Della-RocaC, Nardi F, et al. Primary effusion lymphoma in HIV-infected pa-tients with multicentric Castleman’s disease. J Pathol2001;193:200-9.4. Desai SB, Pradhan SA, Chinoy RF. Mediastinal Castleman’s dis-ease complicated by follicular dendritic cell tumour. Indian J Can-cer 2000;37:129-32.5. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D,Babinet P, et al. Kaposi’s sarcoma-associated herpesvirus-likeDNA sequences in multicentric Castleman’s disease. Blood1995;86:1276-80.6. Kojima M, Nakamura S, Shimizu K, Suda Y, Kasuga Y, Sugihara S,et al. Nodal marginal zone B-cell lymphoma resembling plasma-cytoma arising from a plasma cell variant of localized Castleman’disease: A case report. APMIS 2002;110:523-7.7. Akyuz C, Kale G, Emir S, Akcoren Z, Buyukpamukcu M. T-cell lym-phoma in a child with multicentric Castleman’s disease. MedPediatr Oncol 2000;35:133-4.8. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al.A revised European-American classification of lymphoid neo-plasms: A proposal from the International Lymphoma StudyGroup. Blood 1994;84:1361-92.9. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organiza-tion Classification of Tumors. Tumous of Haematopoietic and Lym-phoid Tissues. Pathology and Genetics. Lyon: IARG Press 2001.Figure 3: MIB-1/Ki67 positive lymphoid neoplastic cells. Cervicalnode. Diffuse large B cell lymphoma (Immunostain, X200).absence of staining for CD3, CD5, and CD23. Amonotypical expression of the light chain κ and of theheavy chain IgM was observed. Determination of thegrowth fraction revealed a large number of MIB-1/Ki67-positive cells comprising up to 80% of theneoplastic population (Figure 3). Molecular analysisshowed a Bcl-2 oncogene rearrangement with t(14;18)chromosome translocation, and Bcl-6 oncogenerearrangement with translocation involving chromosome3(3q27). EBV in situ hybridization was negative. Thehistological feature, and the immunohistologicalfindings, led us to diagnose a diffuse large B celllymphoma, according to the REAL/WHO lymphomaclassifications.8-9DiscussionIn this case report, we describe a patient with a

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

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