Cancer Therapy Vol 7, page 109 Cancer Therapy Vol 7, 109-112, 2009
Follicular lymphoma resembling with Hyalinevascular type of Castleman’s disease. The morphological and immunohistochemical findings of two cases Case Report
Masaru Kojima1, Shinji Sakurai2, Atsushi Isoda3, Norihumi Tsukamoto4, Nobuhide Masawa5, Naoya Nakamura6 1
Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, Ohta, Japan Department of Tumor Pathology, Graduate School of Medicine, Gunma University Maebashi, Japan 3 Department of Hematology, National Nishigunma Hospital, Shibukawa, Japan 4 Department of Medicine and Clinical Science, Gunma University School of Medicine, Maebashi, Japan 5 Department of Diagnostic and Anatomic Pathology, Dokkyo Medical University School of Medicine, Mibu, Japan 6 Department of Pathology, Tokai University School of Medicine, Isehara, Japan 2
__________________________________________________________________________________ *Correspondence: Masaru Kojima, M D, Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, 617-1, Takabayashinishi-cho Ohta, 373-8550, Japan; Tel: +81-276-38-0771; Fax:+81-276-38-8386; e-mail:
[email protected] Key words: Follicular lymphoma/Castleman’ disease/hyaline-vascular type/immunohistochemistry Abbreviations: Castleman’s disease, (CD); cyclophosphamide, doxorubicin, vincristine, prednisone, (CHOP); follicular dendritic cells, (FDCs); follicular lymphoma, (FL); hematoxylin-eosin, (HE); hyaline-vascular, (HV); immunoglobulin heavy-chain, (IgH); polymerase chain reaction, (PCR)
Received: 3 December 2008; Revised: 12 February 2009 Accepted: 24 February 2009; electronically published: February 2009
Summary The neoplastic follicles of follicular lymphoma may rarely showed a concentric arrangement and penetration by hyalinized vessels that mimics Castleman’s disease of hyaline-vascular type. We report here two such cases. Majority of the lymphoid follicles had relatively small germinal centers and were occasionally penetrated by small vessels Moreover, few germinal centers had inconspicuous vascularity and were characterized by a predominance of follicular dendritic cells with enlarged nuclei and conspicuous nucleoli and resembling so called “epithelioid germinal centers”. Both lesions demonstrated a germ line bands on polymerase chain reaction assay for the immunoglobulin heavy chain gene. Moreover, the neplastic follicles were bcl-2- in one case. However, the expression of CD10 and Bcl-6 was seen in both the follicular and interfollicular areas in both lesions. Moreover, cytogenetic analyses demonstrated that one contained a characteristic translocation involving in the long arm of chromosomes 14 and 18, t(14;18)(q32;q21) in nine of 20 cells. Immunostaining for CD10 and bcl-6 and cytogenetic study confirmed neoplastic follicular center cell nature of both lesions.
I. Introduction
II. Case report A. Case 1
Morphological spectrum of follicular lymphoma (FL) demonstrated marked morphological varieties. The neoplastic follicles may rarely showed a concentric arrangement and penetration by hyalinized vessels that mimics Castleman’s disease (CD) of hyaline-vascular (HV) type (Keller et al, 1972; Warnke et al, 1995; Nozawa et al, 2002). We report here, two such cases.
A 53-year-old Japanese female presented with a 10-month history of swelling in the left submandibular region. Biopsy of the enlarged lymph nodes showed non-Hodgkin’s lymphoma and staging demonstrated widespread lymphadenopathy (stage IVA). She was administered Rituximab+ CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy and is currently alive without disease 10 month after the onset of disease.
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Kojima et al: Follicular lymphoma
B. Case 2
Cytogenetic analyses demonstrated that Case 1 contained a characteristic translocation involving in the long arm of chromosomes 14 and 18, t(14;18)(q32;q21) in nine of 20 cells. Genotypic studies with IgH probes demonstrated a germ line bands in both cases.
A 75-year-old Japanese female presented with systemic lymphadenopathy. Biopsy of the enlarged lymph nodes showed non-Hodgkin’s lymphoma and staging demonstrated widespread lymphadenopathy (stage IIIA). She was administered Rituximab+CHOP therapy and is currently alive without disease 10 month after the onset of disease.
V. Discussion
III. Material and Methods
An unusual histological variant of follicular lymphoma resembling CD is extremely rare in the previously reported variants (Warnke et al, 1995; Nozawa et al, 2002). Such cases can be distinguished from CD of HV type with a richer B-lymphocytes in the germinal centers, and the presence in other areas of more typical histological findings of follicular lymphoma. In problematic cases, immunohistological and genotypic studies are needed to clarify the diagnosis (Warnke et al, 1995). However, there were monotypic intracytoplasmic immunoglobulins in either lesion. Moreover, the tumor cells from Case 2 was bcl-2-(Wang et al, 1995). Dogan and colleagues reported in 2000 that in follicular lymphoma, the expression of CD10 and Bcl-6 was seen in both the follicular and interfollicular areas, whereas in follicular hyperplasia, CD10 and BCL-6 were expressed almost exclusively by the follicular center cells (Dogan et al, 2000). Immunostaining for CD10 and bcl-6 and cytogenetic study confirmed neoplastic follicular center cell nature of both lesions (Dogan et al, 2000). Interestingly, both lesions contained “epithelioid germinal centers”, which is one of the characteristic findings of multicentric CD (Frizzera et al, 1983, 2000; Weisenberger, 1985). Histologically, a portion of the multicentric CD demonstrated HV type (Weisenberger, 1985). Moreover, both cases showed multicentric lymphadenopathy. However, there was no clinical findings characteristic of multicentric CD, such as systemic symptoms, hepatosplenomegaly, polyclonal hyperimmunoglobulinemia and positivity for autoantibodies (Frizzera et al, 1983, 2000; Weisenberger, 1985). CD23 immunostain demonstrated that FDC networks of some of the neoplastic lymphoid follicles showed a tight/concentric pattern which is characteristic FDC findings of HV CD, as previously reported by Nugyen and colleagues in 1994. Both lesions demonstrated a germ line bands on PCR assay for the IgH gene. It has been said that there is a false negative rate on the PCR technique of 10-40% (Segal, 1996; Chan, 2007). The false negative rate is higher for germinal center and post germinal center B-cell neoplasms (such as follicular lymphoma and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type) because the rearranged immunoglobulin genes somatic hypermutations (Segal, 1996; Chan, 2007). The false negativity of IgH gene rearrangement appears that both lesions are follicular lymphoma.
The tissue specimens were fixed in formalin solution, routinely processed and embedded in paraffin. For light microscopic examination, the sections were stained with hematoxylin-eosin (HE). Immunohistochemical studies were performed using the Ventana automated (BenchMarkTM) stainer according to the manufacturer's instructions. The panel of antibodies included human immunoglobulin light chains (κ and λ) (Novocastra, Newcastle, UK) , PS-1 (CD3; Immunotech, Marseille, France), 4C7 (CD5; Novocastra), 56C6 (CD10; Novocastra), L26 (CD20; Dako A/S, Glostrup, Denmark), 1B12 (CD 23; Novocastra), SP-4 (Cyclin D1; Nichirei Co., Tokyo, Japan), 124 (bcl-2; Dako) and polyclonal bcl-6 (Dako). Sections with known reactivity for the antibodies assayed served as positive controls and the sections treated with normal rabbit- and mouse serum served as negative controls. Paraffin-embedded tissues from the operatively resected specimen were prepared for polymerase chain reaction (PCR), and the rearranged immunoglobulin heavy-chain (IgH) genes were amplified using the seminested PCR method as described by Wan and colleagues in 1990.
IV. Results Both cases showed essentially similar histological findings. The lymphoid follicles were well separated and not closely packed (Figure 1A). They had also well defined mantle zone, but a few tingible body macrophages and mitotic figures. Majority of the lymphoid follicles had relatively small germinal centers and were occasionally penetrated by small vessels (Figure 1B). Moreover, few germinal centers had inconspicuous vascularity and were characterized by a predominance of follicular dendritic cells (FDCs) with enlarged nuclei and conspicuous nucleoli and resembling so called “epithelioid germinal centers” described by Frizzera and colleagues in 1983 (Figure 1C). The germinal center cells composed of small cleaved cells and large non-cleaved cells (Figure 1B, C). The lymphoid follicles were extended into the perinodal tissue in both cases. On HE-stained section, FL resembling CD was suspected. The germinal center cells were CD3-, CD5-, CD10+, CD20+, CD23-, CD43-, Cyclin D1-, bcl-6+(Figure 1D) and intracytoplasmic immunoglobuline-. The germinal center cells expressed bcl-2 in Case 1 (Figure 1E) whereas, the germinal center cells in Case 2 were bcl-2-. However, numerous CD10+, Bcl-6+ medium- to large Bcells were found in both the follicular and interfollicular area (Figure 1D). CD23 immunostain demonstrated that FDC networks showed a tight/concentric pattern in neoplastic follicles resembling HV and epithelioid germinal centers (Figure 1F).
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Figure1. (A) The lymphoid follicles were well separated and not closely packed. Some of the lymphoid follicles had relatively small germinal centers. Case 1. HEx25. (B) Note a small germinal center penetrated by small vessels. The germinal center cells composed of small cleaved cells and large non-cleaved cells. Case1. HEx100. (C) Note a germinal center had inconspicuous vascularity and were characterized by a predominance of follicular dendritic cells with enlarged nuclei and conspicuous nucleoli (arrows). Case 2 HEx100. (D) Numerous bcl-6+ medium- to large lymphoid cells were seen in the interfollicular area as well as in the germinal center. Case 2 x50. (E) The neoplastic germinal center cells were bcl-2+ Case 1x50. (F) CD23 inmmunostain demonstrated a tight/concentric pattern of the follicular dendritic cell network in a epithelioid germinal center. Case 2 x50.
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