Are Cysts the Precancerous Lesion in HLRCC? The Morphologic Spectrum of Premalignant Lesions and Associated Molecular Changes in Hereditary Renal Cell Carcinoma: Their Clinical Significance
Arunima Ghosh, Maria J Merino, Marston W Linehan. Laboratory of Pathology, National Cancer Institute/National Institutes of Health, Bethesda, MD; NCI, NIH, Bethesda, MD
Background: Renal cell carcinoma (RCC) accounts for more than 13,000 deaths per year. Most of the tumors occur sporadically, but about 5-7% happen in association with hereditary syndromes (HS). Our understanding of renal cancer has improved significantly, and many of the genes associated with specific tumors have been discovered. In the renal parenchyma of patients with HS and renal tumors, premalignant changes may occur, that may progress to invasive carcinoma.
Design: We studied the adjacent renal parenchyma of kidneys with RCCs developed in the HS (VHL, BHD, HPRC1, HLRCC,) and here describe the premalignant conditions associated with each syndrome. The molecular changes were compared with the known genetic alterations of the cancers. IHC for CD10, CK7, MiB1 CD117 and p53 was performed. LOH was investigated for 3p, 17p, 1q. Trisomies for chromosomes 7 and 17 were evaluated by either CISH or FISH.
Results: In VHL, the early lesions are predominantly cysts lined by clear cells in different stages of proliferation that are papillary or solid. Small solid clusters of clear cells were also seen. LOH showed losses in 3p (VHL gene). BHD is characterized by the presence of multiple hybrid tumors. Poorly circumscribed microscopic lesions consistent with renal oncocytosis, composed of cells with clear or eosinophilic cytoplasm were noted in the grossly normal renal cortex enpanding into adjacent tubules. LOH showed losses in Chromosome 17p. HPRC1: in normal renal parenchyma papillary renal adenomas <0.5 cm in size can be detected, ranging from one to fifteen. Lesions stain positive for CK7 and show trisomies in chromosome 7. HLRCC can show single cysts that appear early or during the course of the disease. They are either lined by single cells with prominent nuclei or have papillary formation in which cells show the characteristic nucleoli. Cysts may show malignant transformation with invasion into the adjacent parenchyma. Areas of renal epithelial neoplasia (RIN) may be seen in the medullary ducts. The cells of these cysts show LOH in 1q.
Conclusions: Premalignant lesions are a common finding in the adjacent “normal” parenchyma of patients with kidney cancer and HS, and the immunohistochemical and molecular profiles are identical to the primary tumor. Preneoplastic lesions may be present in the remaining parenchyma of patients treated by partial nephrectomy and may be the source of local recurrences.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 8:45 AM
Proffered Papers: Section A, Monday Morning