Hereditary papillary renal cell carcinoma primarily diagnosed in a cervical lymph node: a case report of a 30-year-old woman with multiple metastases

We describe a case of a 30-year-old woman with hereditary leiomyomatosis and renal cell carcinoma syndrome with extensively metastasized papillary renal cell carcinoma, primarily diagnosed in a cervical lymph node lacking leiomyomas at any site.Papillary renal cell carcinoma in young patients should be further investigated for a hereditary variant like the hereditary leiomyomatosis and renal cell carcinoma even if leiomyomas could not be detected. A detailed histological examination and search for mutations is essential for the survival of patients and relatives.Renal cell carcinoma (RCC) is a rather rare cancer with an incidence of about 71,000 newly diagnosed cases per year in Europe. Approximately 31,000 of these patients die because of RCC [1]. Only a few cases represent hereditary RCCs [2], of which the Von-Hipple-Lindau syndrome (VHL; MIM# 193300) is best known [3]. Furthermore, Birt-Hogg-Dubé syndrome (BHD; MIM# 135150) [4] and tuberous sclerosis (TS1; MIM# 191100 / TS2; MIM# 613254) [5] have been reported to be associated with hereditary RCC mostly of the clear cell or chromophobe subtype. In addition two syndromes associated with hereditary papillary RCC have been described. One is represented by the hereditary papillary renal carcinoma (HPRC; MIM# 605074) usually consisting of papillary RCC type I with a better prognosis [6] showing activating mutations in the met proto-oncogene (MET) on chromosome 7q32 are responsible for HPRC [7]. The other syndrome compromises the hereditary leiomyomatosis and renal cell carcinoma (HLRCC; MIM# 150800), which is characterized by papillary RCC type II with a worse prognosis as well as typically cutaneous and uterine leiomyomas [8]. The HLRCC is caused by heterozygous germline mutations of the fumarate hydratase (FH) gene on chromosome 1q34 [9]. The intracellular hypoxia inducible factor (HIF) is stabilized due to an accumulation of FH based on the mutations in this gene region and is responsible for a pseudohypoxic state