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Year : 2011  |  Volume : 54  |  Issue : 2  |  Page : 430-431
Sjogren's syndrome complicated by non-Hodgkin's lymphoma: Spectrum of lymphoid proliferations and associated hepatitis C virus infection

1 Department of Hematology, SGPGIMS, Lucknow, India
2 Department of Pathology, SGPGIMS, Lucknow, India

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Date of Web Publication27-May-2011

How to cite this article:
Awasthi NP, Kashyap R, Kumari N, Krishnani N. Sjogren's syndrome complicated by non-Hodgkin's lymphoma: Spectrum of lymphoid proliferations and associated hepatitis C virus infection. Indian J Pathol Microbiol 2011;54:430-1

How to cite this URL:
Awasthi NP, Kashyap R, Kumari N, Krishnani N. Sjogren's syndrome complicated by non-Hodgkin's lymphoma: Spectrum of lymphoid proliferations and associated hepatitis C virus infection. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Jul 12];54:430-1. Available from: http://www.ijpmonline.org/text.asp?2011/54/2/430/81621

Presentation at a meeting: Presented as Poster at APCON 2009, Kolkata.


Sjogren's syndrome (SS) is an autoimmune epithelitis characterized by lymphocytic infiltration of exocrine glands together with polyclonal B-cell activation. SS may be primary or secondary. Risk of non-Hodgkin's lymphoma (NHL) has been estimated to be 44 times greater in SS patients than in normal population. [1] NHL has 4.3% prevalence in patients with SS. [1] Among autoimmune diseases, SS is most commonly associated with Hepatitis C Virus (HCV), which may in fact be implicated in the development of SS in specific subsets of patients. [2]

With this background we report two cases of SS, one primary and the other secondary who developed low-grade and high-grade NHL, respectively. Both the cases were diagnosed as Sjogren's syndrome based on the revised International classification criteria for SS. [3]

A 67-year-old woman presented with bilateral parotid, submandibular, and lacrimal swelling along with dryness of mouth and eyes for one year. Cheek biopsy was suggestive of SS [Figure 1]. Schirmer's test was positive. Wedge biopsy of liver [Figure 2] and submandibular lymph node revealed low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. All three biopsies were performed simultaneously. Serologically she was negative for anti-SS-A/Ro, anti-SS-B/La, rheumatoid factor (RF), HCV, and antinuclear antibody (ANA). She was diagnosed as primary SS with MALT NHL stage IIIA. She received six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and is in remission now.
Figure 1: Minor salivary gland showing aggregates of lymphocytes with lymphoepithelial lesion (H and E, ×200)

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Figure 2: Liver biopsy showing infiltration by neoplastic lymphoid cells (H and E, ×200). Inset shows CD20 positive lymphoid cells (immunohistochemistry, ×200)

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A 40-year-old woman presented with a history of xerophthalmia and xerostomia for 17 years followed by symmetric polyarthritis for 15 years. She now presented with bilateral parotid gland enlargement, cervical and axillary lymphadenopathy, and splenomegaly. Parotid gland biopsy was suggestive of SS [Figure 3]. Lymph node biopsy revealed diffuse large B-cell lymphoma (DLBCL) [Figure 4]. Serology was positive for SSA, SSB, RF, ANA, and HCV. She was diagnosed as secondary SS with DLBCL stage IIIB. The patient has been given two cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and is responding well.
Figure 3: Parotid gland biopsy showing lymphoepithelial lesion and aggregates of lymphocytes (H and E, ×400)

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Figure 4: Lymph node biopsy showing lymphomatous transformation (H and E, ×400). Inset shows CD20 positive lymphoid cells (IHC, x200)

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According to the present classification criteria, secondary SS is designated for all cases concomitantly presenting with another connective tissue disorder, even in cases in which SS was present years before the "primary" disorder. [4] This implies that SS component would be of minor importance with regard to patient outcome as most often seen with rheumatoid arthritis (RA). [4] RA is frequently associated with both sicca symptoms and true secondary SS. [4] The occurrence of secondary SS was mainly predicted by the presence of high titers of RF as in the second case. SS is one of the most closely associated autoimmune diseases with HCV. [2] HCV infects and replicates in the epithelial cells of salivary glands in patients with SS or chronic sialadenitis. HCV is considered a virus with triple tissue tropism (hepatotropism, lymphotropism, and sialotropism) and this may explain the higher prevalence of sicca syndrome, cryoglobulinemia, and lymphoproliferative disorder in patients with chronic HCV infection. [2] There is also a higher prevalence of liver involvement and neoplasia (predominantly MALT) in SS-HCV. [2] Standardized incidence risk (SIR) for lymphoma development in SS is 18.9 (in contrast to 7.52 for SLE and 3.25 for RA). [1] MALT lymphoma is by far the most common type followed by DLBCL. There is 28-fold risk for marginal zone B-cell lymphoma (including MALT) development and 11-fold risk for DLBCL development in patients who had SS. [1] Lymphoepithelial sialdenitis is a morphologic feature of SS but may also be found in patients without SS and may lead to the development of primary lymphoma in the salivary gland. [5] Clinical and serologic predictors of lymphoma development in SS are splenomegaly, persistent enlargement of parotid glands, serum or urine monoclonal bands, lymphadenopathy, palpable purpura, leg ulcers, peripheral neuropathy, low levels of C4, high serum β2-microglobulin, CD4 lymphopenia, and mixed monoclonal cryoglobulinemia. [1] Salivary MALT lymphomas have indolent course with long time to progression. Transformation of MALT to DLBCL is characterized by worse outcome. The present two cases represent variable expression and association of SS to RA and HCV complicated by NHL. Patients who have SS and have high risk factors should be monitored more closely than others for lymphoma development. Triple association between HCV, B-cell lymphoma, and systemic autoimmune disease suggest an important role of associated autoimmune and/or chronic viral infection in the pathogenesis of B-cell lymphoproliferative disorder and reinforces the hypothesis of link between autoimmune disease, infection, and cancer. We recommend careful evaluation of B-cell NHL patients to detect silent autoimmune disease or chronic viral disease.

   References Top

1.Voulgarelis M, Moutsopoulos HM. Mucosa-associated lymphoid tissue lymphoma in Sjogren's syndrome: Risks, management and prognosis. Rheum Dis Clin N Am 2008;34:921-33.   Back to cited text no. 1
2.Ramos-Casals M, Munoz S. Hepatitis C virus and Sjogren's syndrome: Trigger or mimic? Rheum Dis Clin N Am 2008;34:869-84.  Back to cited text no. 2
3.Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren's syndrome: A revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61:554-8.  Back to cited text no. 3
4.Theander E, Jacobsson LTH. Relationship of Sjogren's syndrome to other connective tissue and autoimmune disorders. Rheum Dis Clin N Am 2008;34:935-47.  Back to cited text no. 4
5.Agale S V, D'Costa GF, Hastak MS, Shedge RK. Primary non-Hodgkin's lymphoma of the salivary gland: A spectrum of lymphoepithelial sialadenitis, low grade B-cell lymphoma of mucosa-associated lymphoid tissue with transformation to high-grade lymphoma. Indian J Pathol Microbiol 2010;53:364-7.  Back to cited text no. 5
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Correspondence Address:
Namrata P Awasthi
HIG 48, Sector E, Aliganj, Lucknow-226 024, UP
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.81621

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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