Sequential treatments in Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC). Case report and review of the literature.

Abstract

The overall survival for patients with advanced papillary renal carcinoma (RCC) is still limited. Although multikinase inhibitors have recently been developed for clear cell carcinoma, response rates in other histology non-clear cell RCC are poor and patients often face dose-limiting toxicities which lead to a reduction in prognosis and treatment success. We present a patient with hereditary leiomyomatosis and RCC (HLRCC), showing a sustained response for more than 12 months to gemcitabine-bevacizumab therapy after failure tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) therapies.

Molecular Dissection of Complete Response to Receptor Tyrosine Kinase Inhibition in Type II Papillary Renal Cell Carcinoma

“…[24][25][26][27] Responses to therapy in HLRCC patients with FH-deficient metastatic pRCC appear equally short-lived. 28,29 Fumarate accumulation in FH-deficient tumors drives a pseudohypoxia response characterized by increased transcription of HIF1A targets critical for aerobic glycolysis, including VEGF and PDGF. 3 Binding of these angiogenic growth factors to RTKs in endothelial cells stimulates a downstream signaling cascade ultimately leading to increased vascularity.…”

Review of hereditary leiomyomatosis renal cell carcinoma with focus on clinical and pathobiological aspects of renal tumors

“…Microscopically, the tumor is composed of neoplastic cells with various morphological architectures such as papillary, tubulopapillary, solid, cystic tubulocystic, vacuolated/cribriform or mixed pattern [8,15,16,22,40]. Regarding the histological subtype, papillary RCC, type 2 is most frequent, but collecting duct carcinoma may be seen [3,7,9,11,17,18,22,35,36,37,41,42,43,44,45,46,47,48,49,50]. Clear cell RCC, unclassified RCC, oncocytic tumor, cystic tumor, angiomyolipoma or Wilms tumor has been described [7,37,39,49,50,51,52,53].…”

“…HLRCC renal cancer, particularly papillary RCC, type 2 and CDC behave in an aggressive fashion and most cases generally die of disease within 5 years since the initial diagnosis [8,11,13,15,16,17,18,20,25,27,28,35,38,41,45,46,47,48,49,50,62,64,75,76]. Approximately two thirds of patients show stage III/IV at the diagnosis [7].…”

“…The most frequent metastatic site is regional lymph node, but the metastasis to distant lymph node can occur [15,16,35,36]. Furthermore, distant metastasis to lung, bone and liver has been reported [15,16,35,36,48]. Dissemination to peritoneum, pleura and meninges can occur [15,25,48].…”

“…Furthermore, distant metastasis to lung, bone and liver has been reported [15,16,35,36,48]. Dissemination to peritoneum, pleura and meninges can occur [15,25,48].…”