Annals ofthe Rheumatic Diseases 1990; 49: 407-409

Primary Sjogren's syndrome presenting as a case ofsarcoidosis and a suspected pancreatic tumour

P P Koopmans, C Bodeutsch, P C M de Wilde, A M Th Boerbooms

AbstractA 45 year old man, previously diagnosed as

having sarcoid, presented with signs andsymptoms of a pancreatic malignancy. Anexplorative laparotomy, however, showed onlychronic pancreatitis. He was found to have a

raised erythrocyte sedimentation rate, normo-

cytic normochromic anaemia, renal insuf-ficiency, hypergammaglobulinaemia, and astrongly positive rheumatoid factor and anti-nuclear antibody titre. Bilateral hilar lymphnode enlargement was noted on chest x ray.

Subsequently, the patient complained of xero-stomia and keratoconjunctivitis sicca. Largelymphocytic infiltrates and a shift in therelative number of IgA bearing plasma cells infavour of IgG and IgM bearing plasma cellswere seen in tissue obtained by sublabialsalivary gland biopsy. A transbronchial lungbiopsy and review of the biopsies of thepancreas, the lung, liver, and a lymph node allfailed to show granulomatous disease. Thesefindings strongly suggested a diagnosis ofSjogren's syndrome instead of sarcoidosis.This case shows the difficulty sometimesencountered in differentiating betweensarcoid and systemic Sjogren's syndrome, andthe value of a sublabial salivary gland biopsy.

Department of Medicine,Division of GeneralInternal Medicine,University HospitalNijmegen, PO Box 9101,The NetherlandsP P KoopmansDepartment ofPathologic Anatomy,University HospitalNijmegen, PO Box 9101,The NetherlandsC BodeutschP C M de WildeDivision ofRheumatology,University HospitalNijmegen, PO Box 9101,The NetherlandsA M Th BoerboomsCorrespondence to:Dr Koopmans.Accepted for publication4 August 1989

Primary Sjogren s syndrome is a chronic inflam-matory autoimmune disorder, which may

present as the sicca complex only, but may alsoaffect many organs. Sarcoidosis can mimic theclinical symptoms of Sjogren's syndrome anddifferential diagnosis between these disordersclinically and histologically may be difficult.'Recently, Melsom et al reported a patientpresenting with clinical and histological featuresof Sjogren's syndrome, who seemed to havesarcoidosis.2We present a patient with sarcoidosis, who

underwent an exploratory laparotomy for a

suspected pancreatic malignancy. Microscopicexamination of biopsy specimens of the lung,liver, pancreas, and sublabial salivary glandshowed no granuloma formation. The findingsin the sublabial salivary gland strongly supporteda diagnosis of Siogren's syndrome.

Case reportIn July 1986 a 45 year old man was referred to

the department of general internal medicine bythe department of surgery. He had undergone a

diagnostic laparatomy because of a suspectedpancreatic malignancy. An enlargement of thepancreatic head was found. Microscopic

examination of the pancreas showed onlfy exten-sive fibrosis and a diffuse mononuclear infiltrate,compatible with a diagnosis of chronic pan-creatitis. There were no signs of a malignancy inthe pancreas or the associated lymph node.The patient complained of extreme tiredness,

a dry mouth, and dysphagia and difficulty inchewing. The submandibulary salivary glandsseemed to be enlarged, and six monthspreviously he had consulted an ophthalmologistfor dry eyes. There was no arthralgia, anorexia,or weight loss. He had had Raynaud's pheno-menonOne year previously he had attended his local

hospital because of tiredness. An x ray of thechest had shown bilateral hilar lymph nodeenlargement and as sarcoidosis was suspected atransbronchial lung biopsy had been performed.Microscopic examination of these biopsy speci-mens had shown epitheloid cells and a fewgranulomatous structures. Therefore it wasconcluded that the patient had sarcoidosis. Afew months later he again attended his localhospital because of pain in the right upperabdominal quadrant. Biochemical examinationshowed raised values for alkaline phosphatase390 U/l (normal <125), y-glutamyltransferase519 U/l (normal <30), S-alanine aminotrans-ferase (91 U/1) (normal <25), and S-aspartateaminotransferase 262 U/l (normal <25). A liverbiopsy specimen showed small infiltrates ofgranulocytes and lymphocytes but no evidenceof granulomatous disease. An endoscopic retro-grade cholangiopancreatography was performed,showing narrowing of the pancreatic and thecommon bile duct, raising suspicions of atumour of the pancreas. Computed tomographyshowed an enlarged pancreatic head. At thispoint the patient was referred for explorativelaparotomy.

Physical examination at the department ofgeneral internal medicine showed a patient wholooked anaemic with slightly enlarged, tendersubmandibulary glands, and a dry oral mucosa;otherwise the findings were unremarkable.There was no hepatomegaly, splenomegaly, orlymph node enlargement.

Laboratory investigations showed raisederythrocyte sedimentation rate (ESR) (112mm/h), a normochromic, normocytic anaemiawith a haemoglobin 106 g/l (normal 130-160).The other haematological indices were normal.The gammaglobulins were 25 g/l (normal 7-15).Serum immunoelectrophoresis showed a hyper-gammaglobulinaemia and no paraprotein. Nocryoglobulins were found. Serological tests forrheumatoid factor, the antinuclear antibodytest, and circulating immune complexes were

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Koopmans, Bodeutsch, de Wilde, Boerbooms

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Figure 1: Part ofthe second lung biopsy specimen withfibrosis and some mononuclear

inflammatory cells. No evidence ofnon-caseating granulomatous process. (Haematoxylin andeosin.) :~~~~~~~~~~A~~~ ~ ~

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Figure 2: Sublabial salivary gland biopsy specimen with large confluent lymphocytic foci anddestruction ofparenchyma. (Haematoxylin and eosin.)

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Figure 3: Part ofthefirst lung biopsy specimen with fibrosis and diffuse infiltration withmononuclear inflammatory cells. No evidence ofnon-caseating granulomatous process.(Haematoxylin and eosin.)

strongly positive. SS-A and SS-B were notdetected. Serum creatinine was slightly raised(166 ,umol/1) (normal 60-100) and there was aproteinuria of 0-82 g/l. Tests for liver function,serum amylase, and calcium were normal.Angiotensin converting enzyme concentrationwas increased 20-2 mE/ml (normal 12-15). ASchirmer test (right 6 mm, left 8 mm) showeddiminished tear production. Rose bengal stain-ing of the conjunctiva was positive. Routinechest x rays showed diffuse fibrotic lesions andbilateral hilar enlargement, the latter confirmedby tomography. Submandibulary gland sialo-graphy was performed, showing diffuse narrow-ing and widening of the ducts, suggestingchronic inflammation.As clinically the differential diagnosis lay

between sarcoidosis or Sjogren's syndrome,fibreoptic bronchoscopy and a sublabial salivarygland biopsy were carried out. Fibrosis and aninfiltration of histiocytes and lymphocytes wasfound in the lung biopsy specimen (fig 1) but nogranulomata, multinucleate giant cells, orepithelioid cells were seen. Microscopy of thesublabial salivary gland biopsy specimen (fig 2)showed large focal lymphocytic infiltrations(focus score 215 with confluent foci) and ductalhyperplasia. No granulomata or multinucleategiant cells were found. Immunohistochemicalstaining showed a polyclonal plasmacytic infil-trate and a shift in the relative number of IgAbearing plasma cells in favour of IgG and IgMbearing plasma cells. The plasmacytic infiltrateconsisted of 40 1% IgA bearing cells (normal(SD) 919 (8 6)%, 47-1% IgG bearing cells(normal 3-4 (4 8)%), and 12-8% IgM bearingplasma cells (normal 4-8 (4-8)%). Both thehistological and immunohistochemical findingsin the sublabial salivary gland biopsy specimenwere strongly suggestive of Sjogren's syndrome.When revision of the early lung biopsy wasperformed a non-specific fibrosing inflammatoryprocess was found. Some structures were sug-gestive of sarcoidosis, but no granulomata,epitheloid cells, or multinucleate giant cellscould be shown (fig 3).

DiscussionPrimary Sjogren's syndrome is a chronicinflammatory disorder characterised bylymphoid cell infitration and destruction ofsalivary and lachrymal glands, resulting inkeratoconjunctivitis sicca and xerostomia.Sarcoidosis may present with keratoconjuncti-vitis and sialoadenitis resembling Sjogren's syn-drome.4 In addition, the pulmonary manifesta-tions of Sjogren's syndrome may resemble thoseof sarcoidosis.5 6 Bilateral hilar lymph nodeenlargement strongly suggested sarcoidosis inour patient, and this diagnosis was supported bythe general symptoms and the raised angiotensinconverting enzyme concentration in plasma.The clinical diagnosis of primary Sjogren's

syndrome was supported by the typical ocularand salivary symptoms, the sialoadenitis seen onsialography, and the biochemical indices, in-cluding raised ESR, gammaglobulin value, andthe positive rheumatoid factor and antinuclearantibody test.7 Antibodies to SS-A and SS-B

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Primary Sjogren's syndrome presenting as pancreatic malignancy

were negative, but although often found inSjogren's syndrome, they are not always pre-sent.8 Furthermore, the patient had chronicpancreatitis, proteinuria, and raised serumcreatinine, which have been reported in primarySjogren's syndrome.7 91o Thus as none of thesefindings is specific a diagnosis on clinicalgrounds was not possible.

Therefore, a sublabial salivary gland biopsyand a second lung biopsy were carried out todifferentiate between sarcoidosis and Sjogren'ssyndrome. Furthermore, when the previoustransbronchial lung biopsy specimen wasreviewed, no definite granulomata, multi-nucleate giant cells, or epitheloid cells could beshown, but fibrosis and infiltrations of histio-cytes and lymphocytes were present. The firstbiopsy specimen did, however, show somestructures faintly resembling granulomata suchas may be found in sarcoidosis.The histological and immunohistological

findings in the sublabial salivary gland biopsyspecimen strongly indicated Sjogren's syn-drome.' 1 1 The absence of granulomata wasalso against a diagnosis of sarcoidosis.

Non-specific infiltrations by mononuclearcells and fibrosis in the biopsy specimens of theliver, lymph node, and pancreas as seen in thiscase have been often reported in primarySj6gren's syndrome,7 and as no granulomatacould be shown in these biopsy specimens thediagnosis of primary Sj6gren's syndrome wassupported indirectly.

In conclusion, this case report shows (a) thesevere systemic manifestations, includinginvolvement of the lung, pancreas, and (prob-

ably) the kidney, which may occur in primarySjogren's syndrome; (b) how difficult differen-tial diagnosis from sarcoidosis can be; and (c)that a sublabial salivary gland biopsy may behelpful for the diagnosis.

1 De Wilde P C M, Slootweg P J, Hene R J, Baak J P A, KaterL. Multinucleate giant cells in sublabial salivary gland tissuein Siogren's syndrome. A diagnostic pitfall. Virchows Arch[A] 1984; 403: 247-56.

2 Melsom R D, Speight P M, Ryan J, Perry J D. Sarcoidosis ina patient presenting with clinical and histological features ofprimary Siogren's syndrome. Ann Rheum Dis 1988; 47:166-8.

3 De Wilde P C M, Kater L, Baak J P A, Van HouwelingenJ C, Hene R J, Slootweg P J. A new and highly sensitiveimmunohistological diagnostic criterion for Siogren's syn-drome. Arthritis Rheum (in press).

4 Nessan V J, Jacoway J R. Biopsy of minor salivary glandbiopsy in the diagnosis of sarcoidosis. N Engl J Med 1979;301: 922-4.

5 Strimlan V C, Rosenow E C, Divertie M B, Harrison E G Jr.Pulmonary manifestations of Sjogren's syndrome. Chest1976; 70: 354-61.

6 Constantopoulos S H, Papadimitriou C S, MoutsopoulosH M. Respiratory manifestations in primary Sjogren'ssyndrome. Chest 1985; 88: 226-9.

7 Talal N, Moutsopoulos H M, Kassan S S. Sjogren's syndrome.Berlin, Heidelberg: Springer, 1987.

8 Smeenk R, Westgeest T, Swaak T. Antinuclear antibodydetermination: the present state of diagnostic and clinicalrelevance. ScandJa Rheumatol [Suppl] 1985; 56: S78-92.

9 Montefusco P P, Geiss A C, Bronzo R L, Randall S, KahnE, McKinley M J. Sclerosing cholangitis, chronic pan-creatitis, and Siogren's syndrome: a syndrome complex. AmJ Surg 1984; 147: 822-6.

10 Versapuech J M, Labayle D, Grange D, Fischer D, KemenyF, D'Hubert E. Cholangite sclerosante, pancreatite chroni-que et syndrome de Sjogren. Ann Med Interne (Paris) 1986;137: 147-54.

11 Lane H C, Callihan T R, Jaffe E S, Fauci A S, MoutsopoulosH M. Presence of intra-cytoplasmic IgG in the lymphocyticinfiltrates of the minor salivary glands of patients withprimary Sjogren's syndrome. Clin Exp Rheumatol 1983; 1:237-9.

12 Greenspan J S, Daniels T E, Talal N, Sylvester R A. Thehistopathology of Siogren's syndrome in labial salivarygland biopsies. Oral Surg Oral Med Oral Pathol 1974; 37:217-29.

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