Immunohistochemical Markers Indicate Transdifferentiation of Tubular Epithelial Cells into Histiocytic Cells in the Presence of Monoclonal Casts/Crystals and Myoglobin
Margaret Ryan, Jessica Hemminger, Gyongyi Nadasdy, Xiang Ao, Craig Hofmeister, Ed Calomeni, Anjali Satoskar, Sergey Brodsky, Tibor Nadasdy. Ohio State University Wexner Medical Center, Columbus, OH
Background: We recently described a case of possible histiocytic differentiation of tubular epithelial cells in association with amyloidogenic monoclonal light chains accumulated in the tubular epithelium (Hemminger et al. Am J Surg Pathol 36:1253, 2012). We found that tubular cells carrying the amyloid were positive for both histiocytic and tubular epithelial markers. We seek to further characterize and expand our studies to include other reactive tubular changes, including myeloma cast nephropathy, crystalline tubulopathy, and myoglobin cast nephropathy.
Design: From our archives, we selected a subset of cases (3 myeloma cast nephropathy, 1 monoclonal crystalline tubulopathy, 2 myoglobin cast nephropathy) based on the overall slide quality, biopsy size and quality of the casts and associated inflammatory cell reaction. Serial sections were performed and four separate immunohistochemical stains were applied to each case: CK18 and AE1/3 to highlight tubular epithelium and CD68 and CD163 to highlight monocytes and macrophages. After determining that many tubular cells associated with the casts/crystals were positive for both epithelial and monocytic stains, we proceeded to perform the following double stains to simultaneously highlight the tubular epithelium and monocytes/macrophages: CK18 with CD163; CK18 with CD68; AE1/3 with CD163; AE1/3 with CD68. The monocyte markers were stained red and the epithelial markers brown.
Results: Numerous interstitial cells were positive with CD68 and CD163, highlighting the interstitial macrophages. Interestingly, in myeloma cast nephropathy, the tubular luminal cells surrounding cast material were mostly histiocytic; however, several showed staining with both epithelial and histiocytic markers. In contrast, the myoglobin casts were surrounded by cells positive mostly for epithelial markers; only a few double-stained cells were noted. In the crystalline tubulopathy case, several cells containing crystals were positive with both markers. Ultrastructural examination confirmed the cells associated with the cast material and tubular crystals to have both histiocytic (lysosomes, Golgi) and epithelial (cell junctions, microvilli) differentiation.
Conclusions: Our findings lend further support to the hypothesis that tubular epithelial cells are capable of transdifferentiating into histiocytic cells when in the presence of cast material representing an inflammatory stimulus.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 257, Monday Afternoon