Does GVHD Involve the Gyn Tract? Immunohistochemical Expression of Elafin as a Marker of Graft-Versus-Host Disease in Gynecological Biopsies
Gabriela S Gomez-Macias, Pamela Stratton, Beatriz A Walter Rodriguez, Maria J Merino. NCI, NIH, Bethesda; NICHD, NIH, Bethesda
Background: Graft-versus-Host Disease (GVHD) is a common complication of allogenic bone marrow transplant affecting frequently skin, liver and gastrointestinal tract. Involvement of the gyn tract, particularly vulva and vagina has not been well characterized, and the diagnosis depends on clinical criteria that is sometimes unspecific. Recently, Elafin, an elastase inhibitor secreted in response to cytokines (IL-1 and TNF alpha) has been proposed as a good biomarker to recognize GVHD in skin biopsies. In this study, we describe the morphological findings of 16 patients with GVHD and gynecologic lesions and the use of IHC for Elafin in patients with GVHD.
Design: 30 biopsies (vulva (11), cervix (7), vagina (5), endometrium (3), endocervix(2); 1 areola and 1 perianal region were obtained from 16 patients with lesions suspicious of GVHD, reviewed and stained by IHC with the Elafin antibody. Ten skin biopsies with known GVHD were used as control. A positive Elafin expression was defined as a staining that extend to a depth of >50% of the mucosa or epidermis.
Results: Patients mean age was 35.8 y. Most frequent symptoms included vaginal dryness and discharge, dyspareunia, vulvar discomfort and vaginal scarring. Nine cases had GVHD in the eye, skin, mouth, GI, lung and liver. Morphologically, the vulvar biopsies showed changes similar to GVHD in the skin with occasional ulceration, apoptotic bodies in the basal layer of the epidermis, and chronic inflammatory cells predominantly lymphocytes. The vaginal biopsies showed increased fibrosis, inflammation and variable degrees of VIN and condyloma. Rare apoptotic bodies were also seen. The cervical biopsies had marked acute and chronic cervicitis. One case was involved by leukemia and in another an abnormal lymphoid infiltrate was present. The mucosa had occasional apoptotic bodies. Rare apoptotic bodies were also found in the endometrial glands. HPV was identified in 8 patients. For the Elafin marker, 11 biopsies were interpreted as positive. These biopsies corresponded to those highly suspected of GVHD. Patients received treatment with topical steroids, topical estrogens and dilators.
Conclusions: Our results suggest that the gynecologic tract is affected by GVHD with vulva and vagina being the areas more frequently affected. Morphologic changes are similar to those occurring in the skin and other organs. Elafin over expression was found in cases with histological changes of GVHD and suggest its potential usefulness to diagnosis GVHD in patients that are clinically suspicious.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 2:15 PM
Platform Session: Section B, Tuesday Afternoon