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□ CASE REPORT □

Plasma Cell Granuloma of the Sigmoid Colon Associatedwith Diverticular Disease and Accompanying IgM-Type

Monoclonal Gammopathy

Yuichi Nakamura 1,2, Hidekazu Kayano 3, Tsuneyuki Shimada 1,Yoshihiro Ito 1 and Masami Bessho 1

Abstract

Plasma cell granuloma is a pseudoneoplastic lesion composed of reactive plasma cells of a polyclonal na-ture and must be distinguished from plasmacytoma. We report a case of plasma cell granuloma in the sig-moid colon associated with diverticulosis. In this case, the lesion consisted of multiple submucosal tumorswith prominent infiltration of polyclonal plasma cells. Although the patient exhibited IgM-type monoclonalgammopathy, the expression of a monoclonal immunoglobulin was not detected in the sigmoid colonic le-sion, but in the bone marrow cells. Plasma cell granuloma in the lower alimentary tract has been rarely re-ported. Recurrent inflammatory process with diverticular disease was considered as a pathogenesis of thepseudoneoplasm and a possible cause of monoclonal proliferation of IgM-producing lymphoid cells in thiscase.

Key words: plasma cell granuloma, sigmoid colon, monoclonal gammopathy

(Inter Med 49: 227-230, 2010)(DOI: 10.2169/internalmedicine.49.2240)

Introduction

Plasma cell granuloma is a non-malignant lesion com-posed of reactive plasma cells with a polyclonal nature andmust be distinguished from plasmacytoma, which presents amonoclonal proliferation of plasma cells (1). The lesion ismost frequently reported in the lung and bronchus, and theoccurrence in the lower gastrointestinal tract is rare. Herein,we report a case of plasma cell granuloma involving the sig-moid colon associated with diverticular disease. As the pa-tient also presented a monoclonal gammopathy, the clonalitywas analyzed in the sigmoid colonic lesion and the bonemarrow cells.

Case Report

An 82-year-old woman was admitted because of lowerabdominal pain and melena. She had a ten-year history of

colonic diverticular disease with recurrent diverticulitis aswell as hypertension, diabetes mellitus, bronchial asthmaand old tuberculosis. Routine laboratory test presented noremarkable abnormalities except for slight anemia (hemoglo-bin 11.1 g/dL) and hypoalbuminemia (albumin 3.2 g/dL).Blood examination showed slight elevation of serum IgM(645 mg/dL) without decrease of immunoglobulin level ofthe other classes. Serum electrophoresis presented an M-peak, which was ascertained as IgM-kappa type monoclonalprotein by immunofixation study (Fig. 1). A radiological ex-amination revealed the tumor lesions in the sigmoid colonand the fistula formation in the descending colon, in addi-tion to the multiple diverticular formations (Fig. 2). Com-puted tomography (CT) scan revealed the thickness of thesigmoid colonic wall, but no abnormalities or mass lesionsin other sites were identified.Colonoscopy showed the multiple submucosal tumors inthe sigmoid colon (Fig. 3). Pathological examination of en-doscopic biopsied specimen from a tumor in the sigmoid co-

１Department of Hematology, Saitama Medical University, Saitama, ２Research Center for Genomic Medicine, Saitama Medical University, Sai-tama and ３Department of Pathology, Saitama Medical University, SaitamaReceived for publication March 8, 2009; Accepted for publication September 28, 2009Correspondence to Dr. Yuichi Nakamura, ynakam@saitama-med.ac.jp

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Figure 1. Detection of the monoclonal immunoglobulin. A) Serum electrophoresis. The arrow shows the M-peak. B) Se-rum immunofixation. The arrow indicates the M-band by the IgM-kappa M-protein.

Figure 2. Radiological examination using diatrizoate meglumine and diatrizoate sodium (Gastrografin®, Bracco Diagnostics, Inc., Princeton, NJ) showing diverticular disease and a stricture involving the sigmoid colon.

Figure 3. Colonoscopy showing multiple submucosal tumor lesions in the sigmoid colon.

lon presented the marked proliferation of mature plasmacells in an edematous and highly vascular granulomatousmatrix (Fig. 4A). The plasma cell nature of the cellular infil-trate was confirmed immunohistochemically by CD138 posi-tivity (Fig. 4B). These plasma cells were considered to be ofpolyclonal nature, as there was no restriction for IgG, IgAand IgM heavy chains and kappa and lambda chains by in-tracellular immunostaining (Figs. 4C, 4D). A diagnosis ofplasma cell granuloma was made based on these histologicaland immunohistochemical findings.Bone marrow aspirate presented a normal number of

plasma cells (1.0%) and no infiltration of lymphoplasma-cytic or lymphoma cells. After informed consent, RNA was

extracted from cells in the sigmoid colonic lesion and bonemarrow mononuclear cells and was subjected to reverse-transcription polymerase chain reaction (RT-PCR) analysisfor the expression of the rearranged immunoglobulin (Ig)heavy chain gene. As shown in Fig. 5, a monoclonal bandwas detected in the bone marrow, but not in the sigmoidcolonic lesion, using primers amplifying the third comple-mentarity determining region (CDR3) (2). Thus, it was con-firmed that the sigmoid colonic lesion was not a producingsite of the monoclonal Ig. As no tumors other than thecolonic lesion or symptoms attributable to M-protein wereidentified, a diagnosis of IgM monoclonal gammopathy ofundetermined significance (MGUS) was made according tothe criteria (3).Surgical resection of the lesion was not performed as herpulmonary function was reduced because of old tuberculosisand bronchial asthma. The patient is doing well for 2 yearsafter the diagnosis except for two episodes of melena whichrecovered by conservative treatment. Follow-up CT scanshowed slight improvement of the thickness of the sigmoidcolonic wall. Serum IgM level was not significantly changedto date.

Discussion

Plasma cell granuloma, also called inflammatory pseudo-tumor or inflammatory myofibroblastic tumor, is a rare non-neoplastic lesion characterized by a proliferation of inflam-matory cells with a predominance of mature polyclonalplasma cells in a fibrovascular background (1). This lesionmay mimic true neoplasm and should be distinguished fromthe malignant plasma cell tumor, plasmacytoma, which pre-sents as a monoclonal plasma cell proliferation. Immunohis-tochemical study staining intracellular Igs, especially kappaand lambda light chains, is necessary to confirm the poly-clonal nature of plasma cells.Plasma cell granuloma is most frequently reported in thelung and bronchus, but rarely found in extrapulmonary sites.To our knowledge, fourteen cases with plasma cell granu-

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Figure 4. Histology of the sigmoid colonic lesion. A: Prominent infiltration of mature plasma cells (Hematoxylin and Eosin staining: ×400). B-D: Immunohistochemical staining showing a posi-tive reaction for CD138 (B), kappa (C) and lambda (D) chains (×400).

Figure 5. Reverse-transcription polymerase chain reaction (RT-PCR) analysis. RNA was extracted from sigmoid colonic lesion and bone marrow mononuclear cells in this case and re-verse transcribed. cDNA was amplified using the VH-consen-sus primer (5́-CTGTCGACACGGCCGTGTATTACTGTG-3́) corresponding to 3́ end of FR3 of VH and the JH-consen-sus primer (5́-AACTCAGAGGAGACGGTGACC-3́) and electrophoresed through 4.0% agarose gel. These primers were designed to amplify CDR3 of the rearranged IgH ac-cording to the previous report (2) with slight modifications. cDNA was also amplified using GAPDH primers. RNA from CD138-positive bone marrow plasma cells in a patient with multiple myeloma was similarly analyzed. Monoclonal bands (indicated by arrow) were detected in the myeloma cells (lane 1), and in the patient’s bone marrow cells (lane 3), but not in the sigmoid colonic lesion (lane 2).

loma, inflammatory pseudotumor or inflammatory myofibro-blastic tumor presenting involvement in the large intestinehave been reported to date in the English language litera-ture (4-14). The clinical behaviors in these cases were vari-ous (Table 1). In six adult cases, four presented intraluminalpolypoid or spherical tumors, two of which caused thecolonic obstruction. In the present case, the lesion did notpresent a solitary mass, but multiple submucosal tumors in asegment of diverticular disease with stricture formation ac-companying bleeding.Although the exact pathogenesis of plasma cell granulomaremains uncertain, it is considered to be inflammatory in na-ture. In this case, chronic inflammatory stimulation by diver-ticulitis would lead to the formation of the lesion. Two caseswith inflammatory pseudotumor in the urinary bladder asso-ciated with sigmoid colonic diverticulitis were re-ported (8, 15). Formation of invasive pseudotumors inducedby chronic inflammation should be recognized as a compli-cation with diverticular disease in the high prevalence of thedisease in the population.In the present case, plasmacytoma was initially suspectedbased on the predominant plasma cell infiltration and thepresence of monoclonal gammopathy. However, the immu-nohistochemical study showed the polyclonal nature of theinfiltrating plasma cells and the RT-PCR analysis confirmedthat the monoclonal Ig was expressed in the bone marrowcells, but not in the sigmoid colonic lesion. In addition tothe serum monoclonal IgM concentration, the absence ofsymptoms attributable to tumor infiltration or monoclonalprotein led us to the diagnosis of IgM MGUS (3). Produc-

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Table 1. Clinicopathologic Features of the Reported Plasma Cell Granuloma (PCG), Inflammatory Pseudotumor (IPT), or Inflammatory Myofibroblastic Tumor (IMT) Cases in the Large Intestin

tion of a high volume of inflammatory cytokines such as in-terleukin (IL)-1 beta and IL-6 have been demonstrated in acase with plasma cell granuloma in the lung with systemicsymptoms (16). In the present case, the persistent productionof cytokines by inflammatory stimulation associated with di-verticular disease might have induced the systemic monoclo-nal proliferation of IgM-producing B-lymphoid cells as wellas the reactive infiltration of polyclonal plasma cells in the

lesion, although no treatment for monoclonal gammopathywas necessary. This case emphasized the significance ofclonality analysis of the plasma cell proliferative lesion toattain an accurate diagnosis and avoid unnecessary radio-therapy or chemotherapy.

AcknowledgementWe thank Mrs. Emi Kakegawa for her technical assistance.

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