Placental Alkaline Phosphatase (PLAP) and Podoplanin (D2-40) Define Two Subtypes of Cells in Lymphangioleimyomatosis
S Mandal, E Hyjek, A Husain, L Schuger. University of Chicago, Chicago, IL
Background: Lymphangioleiomyomatosis (LAM) is a poorly understood rare fatal lung disease of premenopausal women. LAM lesions show infiltrating smooth muscle (SM)-like cells causing cystic destruction of lungs, eventually mandating lung transplant. LAM cells often metastasize to regional lymph nodes, circulate in blood, and occasionally produce distal metastases, including, to transplanted lungs. Occasionally LAM occurs in association with tuberous sclerosis disease and tsc2 mutations were found in a few sporadic LAM cases. Since we noticed that vascular SM immunoreact for PLAP (Placental Alkaline Phosphatase) we evaluated LAM lesions for its expression. Moreover, since PLAP circulates patients with PLAP-positive tumors, we sought to evaluate the integrity of the vasculo-lympatic channels in/around LAM lesions.
Design: Serial sections of FFPE lung tissue sampled from 21 patients with LAM were immunostained for LAM markers SM α actin (SMA) and HMB45, PLAP, vascular endothelial marker CD31 and lymphatic endothelial marker D2-40 (podoplanin).
Results: SMA was detected in most LAM cells followed in frequency by D2-40. PLAP and HMB45 were detected in a lower number of cells. Predominantly D2-40-positive lesions also had abundant HMB45-positive cells, but only rare PLAP-positive cells. Predominantly PLAP-positive lesions were negative or occasionally weakly positive for D2-40 and had a few HMB45-positive cells. Furthermore, cells that expressed PLAP did not express D2-40 or HMB45. Blood vessels stained weakly for PLAP but were negative for D2-40 or HMB45. D2-40 stained only lymphatic channels in normal or other disease lung controls. CD31 stained most of the epitheloid cells lining the LAM cysts.
Conclusions: - PLAP is a novel marker for a subpopulation of LAM cells, immunoreacting significantly stronger than vascular or airway SM cells. - Since PLAP, a GPI-anchored membrane protein is extruded on exosomes and circulating LAM cells can also carry PLAP, it should be cleaved from both by serum Phosphatidyl Inositol Phospholipase D (PIPLD). In such a case serum PLAP level could potentially be a surveillance marker for LAM patients. - Podoplanin (D2-40) is a novel marker for a large subpopulation of LAM cells. Since a larger number of LAM cells stain for D2-40 than HMB45, the former may be a better diagnostic marker for LAM. - Since podoplanin is involved in cell invasion, its presence in LAM lesions may have functional implications in progression of the disease. - There are either PLAP-predominant or podoplanin-predominant LAM lesions/cases.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 239, Monday Morning