PATHOLOGY

Phenotypic, molecular and ultrastructural studies of a novel low grade renal epithelial neoplasm possibly related to the loop of Henle
Srigley J, Kapusta L, Reuter V, Amin M, Grignon D, Eble J, Weber A, Moch H
McMaster University, Hamilton ON, Memorial Sloan-Kettering Cancer Centre, New York, NY, Emory University Hospital, Atlanta, GE, Wayne State University, Detroit, MI, University of Indiana, IN, USA, and University of Basel, Switzerland
Mod Pathol. 2002; 15:182A

• Purpose: To study a novel renal epithelial neoplasm with tubular, spindled and mucinous morphology. This tumor has a female predominance and displays a low grade biologic behavior. The origin of this tumor and its relation to other types of renal carcinoma is poorly understood.
• Material and Methods: 20 examples of this light microscopically neoplasm were studied using immunohistochemical (20 cases), molecular (10 cases) and ultrastructural (5 cases) techniques.
• Results: The 20 tumors from patients’ age 17-82 (mean 53 years) included 16 females and 4 males. The tumors consistently stained for cytokeratins (CAM 5.2, CK7, CK8 and CK 18), EMA, Ulex, peanut and soya bean agglutins. They displayed consistent negativity for CK20, CD10, villin and Tamm-Horsfall protein. 16 cases showed positivity for RCC, a proximal nephron marker. CGH revealed chromosomal alterations detected on 11q, 12q, 16q, 17 and 20q. FISH showed no evidence of VHL deletions and confirmed chromosomal monosomies in a subset of tumors. EM studies showed tightly packed, often elongated tubules composed in part of slender attenuated cells similar to those described in normal loop of Henle.
• Conclusions: This novel renal neoplasm displays immunohistochemical heterogeneity with expression of proximal and distal nephronic markers. Molecular analysis allows separation of this tumor entity from common renal epithelial tumors of proximal nephron origin because the latter tumors frequently show 3p deletions (clear cell RCC) or chromosomal 7 gains (papillary RCC). While the immunohistochemical and molecular studies show considerable heterogeneity, the light and electron microscopic studies show a distinct morphologic pattern suggesting a possible histogenetic relationship to the loop of Henle.
  
  
• Editorial Comment
  This is a new comer to the classification of malignant renal cell tumors. Probably this neoplasia was classified by pathologists either as papillary renal cell carcinoma, or placed in the group of the unclassified tumors according to the Heidelberg (J Pathol. 1997; 183:131) or Rochester (Cancer 1997; 80:987) classifications. This tumor has a female predominance and displays a low grade biologic behavior. Pathologists must become aware of its existence. Its morphology is quite distinctive. This paper emphasizes that the histochemical and molecular studies show considerable heterogeneity, but light and electron microscopic studies show a distinct morphologic pattern, suggesting a possible histogenetic relationship to the loop of Henle. A postgraduate student collected 12 tumors of this kind for her doctoral thesis, all from female patients. We had the opportunity to analyze the electron microscopy from 7 of these cases. In all cases, we found discontinuation of the tubular basement membranes. This finding may be a distinct morphologic lesion in this tumor.

Dr. Athanase Billis
Chair, Department of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil