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Lymphocytic Hypophysitis Associated with Dacryoadenitis an Autoimmunologically Mediated Syndrome

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Lymphocytic Hypophysitis Associated with Dacryoadenitis an Autoimmunologically Mediated Syndrome CLINICOPATHOLOGIC REPORT Lymphocytic Hypophysitis Associated With Dacryoadenitis An Autoimmunologically Mediated Syndrome Antonia M. Joussen, MD; Clemens Sommer, MD; Christa Flechtenmacher, MD; Hans E. Voelcker, MD e report a rare case of lymphocytic hypophysitis followed by dacryoadenitis. Lympho- cytic hypophysitis is a rare disease that can easily be mistaken for neoplastic prolif- W eration. Because combination with rheumatoid arthritis, thyroiditis, or pernicious ane- mia is frequent, an immunological pathogenesis is likely. Arch Ophthalmol. 1999;117:959-962 To our knowledge, this is the first descrip- complex are still unknown. In this study tion of lymphocytic hypophysitis in asso- we describe the histological and immu- ciation with dacryoadenitis. Histologi- nocytochemical findings in the symptom cally, both hypophysitis and dacryoadenitis complex of lymphocytic hypophysitis and demonstrate a lymphocytic infiltrate con- dacryoadenitis. sisting of CD3+ T cells and CD20+ B cells. Lymphoproliferative diseases, infectious REPORT OF A CASE diseases, and vasculitis should be in- cluded in the differential diagnosis. HISTORY Swelling of the lacrimal gland can be caused by infectious dacryoadenitis, which A 22-year-old woman was first seen at our in turn often results from obstruction of the clinic in August 1996 with a swelling of nasolacrimal duct or changes in the cana- the left lacrimal gland that persisted for 3 liculi. Secondary acute dacryoadenitis is weeks. She reported that swelling and pain usually caused by systemic infection, such did not respond to 1 week of systemic an- as endemic parotiditis, herpes zoster oph- tibiotic treatment with 300 mg of clinda- thalmicus, or infectious mononucleosis. In- mycin. She was also using steroid eye drops flammatory changes of the lacrimal gland and topical ointment at night. Ibuprofen are seen in association with Graves dis- (600 mg) was being taken orally to re- ease, granulomatous diseases such as sar- lieve pain. The patient was receiving a hor- coidosis, or Sjo¨gren syndrome.1 A unilat- mone substitution therapy owing to in- eral infiltration of the lacrimal gland without sufficiency of the hypophysis after systemic disease is rare. transsphenoidal hypophysectomy. This About 100 cases of lymphocytic hy- had been performed in March 1995 for a pophysitis have been reported in the lit- suspected hypophysal tumor. Prior to the erature. Like lymphocytic dacryoadeni- operation the patient had had amenor- tis, hypophysitis is often seen in patients rhea, but did not suffer from visual dis- with autoimmune disorders like adrenal- turbances. Eighteen months after sur- itis, gastritis type A, or Hashimoto thy- gery, her medication regimen consisted of roiditis.2,3 However, there is, to our knowl- 37.5 mg of prednisolone, estrogen and ge- edge, no report of an association of stagen, and somatropin. lymphocytic hypophysitis with dacryoad- enitis. Although knowledge about immu- CLINICAL APPEARANCE AND nological diseases is growing, the origin LABORATORY TEST RESULTS and pathophysiology of this symptom The patient had a painful, tender swell- From the Departments of Ophthalmology (Drs Joussen and Voelcker), Neuropathology ing of the lacrimal gland with a section- (Dr Sommer), and General Pathology (Dr Flechtenmacher), University of Heidelberg, mark–shaped upper eyelid (Figure 1) Heidelberg, Germany. without inflammatory signs. On ophthal- ARCH OPHTHALMOL / VOL 117, JULY 1999 959 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 lacrimal gland, most likely due to dacryoadenitis and compression of the chiasma, which could be grow- ing residual pituitary tissue (as indicated by the history of partial hypophysectomy). THERAPY After the possibility of infectious dis- ease was ruled out, systemic antibi- otic treatment was stopped. A bi- opsy specimen was obtained to exclude a lymphoblastomatous in- filtration of the lacrimal gland. Be- cause of the possible immunologi- cal cause of the disease, the patient was treated with high-dose steroids Figure 1. Clinical appearance of the dacryoadenitis. (prednisolone, 100 mg/d intrave- nously, in addition to her hormone substitution therapy). A few days af- ter initiation of the steroid therapy, regression of the periorbital and lac- rimal gland swelling was observed. The associated pain also vanished during treatment. Steroid therapy was slowly tapered and the appearance of the orbit returned to normal. Two years later, the patient has not experienced any recurrence. Medication was stopped except for hormone substitution therapy. HISTOLOGICAL FINDINGS Specimensofboththehypophysisand lacrimal gland were fixed in 4% for- maldehyde,embeddedinparaffin,and Figure 2. Lacrimal gland with lymphocytic infiltrate in between the acini (hematoxylin-eosin, original cut into 4- to 6-µm sections. Sections magnification 3400). were stained with hematoxylin-eosin and periodic acid–Schiff. Immunocy- mic examination there was full vi- disease. There was no vitamin B12 de- tochemistry was performed by an sual acuity for both eyes and no signs ficiency. indirect method using antibodies. of inflammation of the anterior seg- Serologically there were no ti- Sections were examined and the ment. The fundus and optic nerve ters for human immunodeficiency vi- number and distribution of cells were showed no pathological changes. rus, herpes simplex virus, varicella assessed. Perimetry confirmed normal outer zoster virus, or Epstein-Barr virus in- Both specimens of the hypophy- visual field borders for both eyes. fection. Gonorrhea, samonellosis, sis and the lacrimal gland showed Findings from physical exami- borrelliosis, yersiniosis, syphillis, and lymphocytic infiltrates (Figure 2 nation revealed no signs of sys- mycoplasmosis had also been ex- and Figure 3). Both hypophysis and temic rheumatoid or lymphatic dis- cluded. There was no evidence for vi- lacrimal gland tissue showed a nor- ease. There was no sign of peripheral ral or bacterial infection in the lacri- mal glandular and acinar pattern. lymphadenopathy. Abdominal and mal fluid. Parasitological screening There was no evidence of caseous ne- thyroid ultrasonographic tests for toxoplasmosis and Toxocara ca- crosis, epitheloid granulomas, or ab- yielded normal results, as did the nis and screening of the stool for scesses within the infiltrates. chest x-ray film. worm infection were negative. The medium-dense infiltrate of All hematological parameters Thyroid hormone screening lymphocytes in the specimen of the were within normal limits, as were showed all parameters within nor- anterior pituitary gland spread protein electrophoresis and immu- mal limits. Computed tomography among the interstitium and partly noglobulin fractions. Rheumatologi- and magnetic resonance imaging of into the alveoli. The structure of the cal screening did not indicate a sys- the orbits and neurocranium showed remaining anterior lobe was nor- temic collagenous or rheumatological a significant enlargement of the left mal. There was fibrosis, which led ARCH OPHTHALMOL / VOL 117, JULY 1999 960 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 to broadening of the septa. The re- sidual adenohypophysal cells com- prised different cell types. Immuno- cytochemistry showed multiple growth hormone– and prolactin- reactive cells (Figure 4). Thyroid- stimulating hormone immunoreac- tive cells were only occasionally observed. There were a few cortico- tropin-positive cells. The biopsy specimen of the lac- rimal gland showed a well-differen- tiated lacrimal gland parenchyma. The interstitial septae were broadened and infiltrated by lymphocytes. In small areas the periductal infiltrate invaded the acini and the excretory ducts. A few excretory ducts showed Figure 3. Hypophysis anterior lobe tissue with lymphocytic infiltrates (hematoxylin-eosin, original signs of obstruction with granulo- magnification 3240). cytes. Immunoglobulin staining of the specimen showed a low expres- sion of l as well as k light chains. There were IgG- and IgM-positive plasma cells (Figure 5). Immunostaining of the infil- trate of both specimens showed a mixed population of CD3+ T cells and CD20+ B cells. Common leuko- cytic antigen was expressed in the infiltrates. In neither specimen were there signs of a lymphoblastoma- tous infiltrate. The similarity of the infiltration of the pituitary and lac- rimal glands indicated an autoim- munological process. COMMENT We report the symptom complex of lymphocytic hypophysitis followed Figure 4. Lacrimal gland tissue: anti-IgG immunohistochemistry (original magnification 3400). by lymphocytic dacryoadenitis in a healthy young woman. If systemic disorders are apparent, lacrimal glands are usually bilaterally af- fected and the disease is chronic. Our patient had an acute onset of dacryo- adenitis, which remained unilat- eral. A lymphoblastomatous cause of the infiltration was excluded by im- munohistochemistry. In the literature, there is evi- dence that lymphocytic hypophy- sitis has an autoimmunopathic cause. However, we did not find any association with other autoimmu- nological diseases such as rheuma- toid arthritis, thyroiditis, or perni- cious anemia. Although there was no systemic correlation, another type of glandular tissue (the lacrimal gland) was affected. This association has not Figure 5. Pituitary tissue: antiprolactin immunohistochemistry (original magnification 3400). been reported before. ARCH
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