Graft-versus-host-disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT), affects the skin, liver and gastrointestinal (GI) tract. There are no plasma biomarkers specific for any acute GVHD target organ. We used a large scale, quantitative proteomic discovery procedure to identify biomarker candidates of skin GVHD and validated the lead candidate, elafin, by ELISA in samples from 492 patients. Elafin was overexpressed in GVHD skin biopsies. Plasma levels of elafin were significantly higher at the onset of skin GVHD, correlated with the eventual maximum grade of GVHD, and were associated with a greater risk of death relative to other known risk factors (hazard ratio of 1.78). We conclude that elafin has significant diagnostic and prognostic value as a biomarker of skin GVHD.
A 66-year-old woman without prior oncologic history initially presented to her primary care physician with postmenopausal spotting. Transabdominal and transvaginal ultrasound at that time demonstrated a small uterine fibroid and an unremarkable left ovary. The right ovary could not be visualized. Laboratory investigations revealed a CA-125 level of 58.7 U/mL (normal range, 0.0 to 35.0 U/mL), which increased to 74.9 U/mL 1 month later. At that time, the patient was also concerned about left neck fullness. Physical examination confirmed left cervical lymphadenopathy with some tenderness. Cervical ultrasound revealed a normalappearing thyroid gland and multiple enlarged cervical lymph nodes, the largest of which was 2 ϫ 1 cm. An excisional biopsy was performed on one of the enlarged lymph nodes. Additional laboratory findings at the time of excisional biopsy included a normal complete blood count with slight absolute basophilia. The red cell distribution width and mean corpuscular volume were within normal limits.Excisional biopsy revealed effacement of normal lymph node architecture by a proliferation of signet ring cells exhibiting a nodular growth pattern. The nodules varied in size and showed confluence and focal extension into the medulla. Well-developed mantles and tingible body macrophages were lacking. The neoplastic cells were predominantly small, cleaved lymphocytes with scattered background large centroblasts. Many of these cells showed distinct cytoplasmic vacuolization that could be appreciated infiltrating in between and within the neoplastic follicles (Fig 1A). Examination under higher power demonstrated signet ring cell morphology and confirmed the intrafollicular as well as interfollicular distribution of these cells (Fig 1B).Immunohistochemical studies were performed using antibodies directed against CD3, CD20, BCL6, CD10, BCL2, pan-cytokeratin (AE1/AE3/CAM5.2), and S-100. The small cleaved cells as well as the large centroblasts in the neoplastic follicles were highlighted by CD20, BCL6, and CD10 with coexpression of BCL2, confirming the histologic impression of follicular lymphoma, grade 1 to 2. Interestingly, these same markers were also positive in the signet ring cells (Fig 2A: CD20; 2B: CD10; 2C: BCL6; 2D: BCL2). S-100 and pan-cytokeratin were both negative. A final diagnosis of follicular lymphoma, lowgrade, signet ring cell variant, was made.
Lymphangiomas are uncommon in the posterior mediastinum. We report a case of a lymphangioma in this location that was diagnosed by computed tomographic-guided fine-needle aspiration biopsy. The cell block of the lesion closely simulated a normal structure immediately adjacent to the target and could have been misdiagnosed as "normal tissue." On-site evaluation of the aspirate by a cytopathologist promoted pathologist-radiologist communication that helped prevent the potential error and facilitated making the correct diagnosis in the case.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.