scholarly journals Renal cell carcinoma in young FH mutation carriers: case series and review of the literature

2019 ◽  
Vol 19 (1) ◽  
pp. 55-63 ◽  
Author(s):  
J. A. Hol ◽  
M. C. J. Jongmans ◽  
A. S. Littooij ◽  
R. R. de Krijger ◽  
R. P. Kuiper ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Renal Cysts ◽  
Small Data ◽  
Review Of The Literature ◽  
Increased Risk ◽  
Mri Surveillance

AbstractHereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (FH) gene. It is characterized by cutaneous and uterine leiomyomas and an increased risk of developing renal cell carcinoma (RCC), which is usually adult-onset. HLRCC-related RCC tends to be aggressive and can metastasize even when the primary tumor is small. Data on children and adolescents are scarce. Herein, we report two patients from unrelated Dutch families, with HLRCC-related RCC at the ages of 15 and 18 years, and a third patient with an FH mutation and complex renal cysts at the age of 13. Both RCC’s were localized and successfully resected, and careful MRI surveillance was initiated to monitor the renal cysts. One of the patients with RCC subsequently developed an ovarian Leydig cell tumor. A review of the literature identified 10 previously reported cases of HLRCC-related RCC in patients aged younger than 20 years, five of them presenting with metastatic disease. These data emphasize the importance of recognizing HLRCC in young patients to enable early detection of RCC, albeit rare. They support the recommendations from the 2014 consensus guideline, in which genetic testing for FH mutations, and renal MRI surveillance, is advised for HLRCC family members from the age of 8–10 years onwards.

scholarly journals Risk Factors for Renal Cell Cancer in a Japanese Population

2009 ◽  
Vol 3 ◽  
pp. CMO.S2669 ◽  
Author(s):  
Masakazu Washio ◽  
Mitsuru Mori
Keyword(s):  
Risk Factors ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Dietary Habits ◽  
Large Population ◽  
Cell Cancer ◽  
Black Tea ◽  
Increased Risk

The incidence of renal cell cancer has been increasing worldwide. Although the incidence of renal cell cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. In this paper, we would like to introduce the result of our studies, which evaluate the risk factors for renal cell cancer in Japan. Hypertension, diabetes mellitus, kidney diseases, fondness for fatty food and black tea showed an increased risk of renal cell carcinoma while an intake of starchy roots such as taro, sweet potato and potato reduced the risk of renal cell carcinoma. In Japan, however, drinking black tea may be a surrogate for westernized dietary habits while eating starchy roots may be a surrogate for traditional Japanese dietary habits. Further studies may be needed to evaluate risk factors for renal cell cancer because the number of renal cancer cases was small in our studies in spite of a large population-based cohort study.

scholarly journals A Case of Renal Cell Carcinoma and Pheochromocytoma Due to Germline Inactivating Mutation in Fumarate Hydratase (FH)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A986-A986
Author(s):  
Sarah Alicia Reda ◽  
Emily A Japp ◽  
Qiusheng Si ◽  
Ketan Badani ◽  
Alice C Levine
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Adrenal Mass ◽  
Autosomal Dominant ◽  
Fumarate Hydratase ◽  
Low Grade ◽  
Vanillylmandelic Acid ◽  
Increased Risk ◽  
Free Cortisol

Abstract A 60-year-old female with a history of well-controlled hypertension, prediabetes, status post hysterectomy for fibroids, presented for evaluation of hematuria and unintentional weight loss. She denied palpitations, headaches, tremors, and diaphoresis. Initial CT demonstrated a right renal mass suspicious for renal cell carcinoma and an adrenal mass. Magnetic resonance imaging (MRI) confirmed a hypervascular, right adrenal mass (6.7 x 6 x 5 cm) without loss of signal. Laboratory Testing: elevated 24-hour urine vanillylmandelic acid (VMA) 17.5 mg/24 h (<6), and urine normetanephrines 2276 ug/24 h (122-676) with normal urine metanephrines 158 ug/24 h (90-315). 24-hour urine free cortisol was normal. The patient underwent a right adrenalectomy and partial nephrectomy. Pathology confirmed a low-grade renal cell carcinoma (RCC) and a 6.8 cm pheochromocytoma (PCC). Genetic analysis revealed an inherited mutation in the fumarate hydratase (FH) gene, which is diagnostic of hereditary leiomyomatosis and renal cell cancer (HLRCC). Wildtype FH codes for an enzyme that converts fumarate to malate in the mitochondrial Krebs cycle. Inactivating mutations in FH trigger the hypoxia pathway by activating hypoxia-inducible factor (HIF) thereby promoting tumor growth and angiogenesis. In PCC, 30-40% are hereditary and another 40-50% are found to have somatic mutations in 1 of 20 PCC susceptibility genes. Several autosomal dominant heritable syndromes, including Neurofibromatosis type 1 (NF-1), von Hippel-Lindau (VHL), Multiple Endocrine Neoplasia Type 2 (MEN 2), and Paraganglioma Syndromes Types 1–5, have an increased incidence of PCC, most of which modulate hypoxia pathways. FH mutations are similarly inherited in an autosomal dominant fashion and cause HLRCC. HLRCC is associated with 75-80% risk for cutaneous and uterine leiomyomas, and a 10-16% risk for type II papillary renal cell carcinoma. The risk of RCC in patients with FH mutations is much greater than in the general population, where the prevalence is ~2% in those who lack the mutation. In one study, FH deficiencies attribute between 19-41% of all RCC cases. Rare families with PGL/PCC have also been found to carry this germline FH mutation. This FH mutation is associated with increased risk of metastasis in patients with PGL/PCC by a similar mechanism of carcinogenesis via the hypoxia pathway. Currently, there are no strict guidelines for surveillance in individuals with HLRCC, however, patients should have a yearly abdominal MRI, skin examination every 2 years, and an annual gynecological evaluation for leiomyosarcoma. Each first-degree relative should be offered genetic testing of the FH mutation, as 50% of relatives may carry the gene. This case underscores the importance of genetic workups in patients with PCC, especially if associated with other tumors.

scholarly journals A Case of Metastatic Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome-Associated Renal Cell Carcinoma Treated with a Sequence of Axitinib and Nivolumab Following Cytoreductive Nephrectomy

2020 ◽  
Vol 7 (2) ◽  
pp. 6-10
Author(s):  
Ichiro Yonese ◽  
Masaya Ito ◽  
Kosuke Takemura ◽  
Takao Kamai ◽  
Fumitaka Koga
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Cancer Syndrome ◽  
Durable Response ◽  
Pelvic Cancer ◽  
Hereditary Leiomyomatosis

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) associated renal cell carcinoma (RCC) is an aggressive form of type 2 papillary RCC caused by deficiency of the fumarate hydratase gene. For patients with metastatic disease, no standard treatment has been established with dismal prognosis. We report a case of metastatic HLRCC-associated RCC in a 65-year-old Japanese male whose clinical features mimicked advanced renal pelvic cancer. A durable response was achieved with a sequence of axitinib and nivolumab after cytoreductive and diagnostic nephrectomy. Their potential therapeutic roles in the management of metastatic HLRCC-associated RCC have been discussed based on its molecular and biological backgrounds.

scholarly journals Hereditary Leiomyomatosis and Renal Cell Cancer: Recent Insights Into Mechanisms and Systemic Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Congwang Zhang ◽  
Lijun Li ◽  
Yipeng Zhang ◽  
Changchun Zeng
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Cell Cancer ◽  
Fumarate Hydratase ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Underlying Mechanisms ◽  
Hereditary Leiomyomatosis

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare autosomal dominant hereditary cancer syndrome characterized by a predisposition to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). It is known to be caused by germline mutations of the fumarate hydratase (FH) gene, which encodes an enzyme component of the citric acid cycle and catalyzes the conversion of fumarate to L-malate. Currently, there is no standardized treatment for HLRCC, which may be due in part to a lack of understanding of the underlying mechanisms. Here, the underlying molecular mechanisms by which the inactivation of FH causes HLRCC are discussed. Additionally, potential therapeutic pharmacological strategies are also summarized to provide new perspectives for the prevention and treatment of HLRCC.

scholarly journals Renal Cell Carcinoma with Synchronous Metastasis to the Calcaneus and Metachronous Metastases to the Ovary and Gallbladder

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Jasper Decoene ◽  
Filip Ameye ◽  
Evelyne Lerut ◽  
Raymond Oyen ◽  
Hein Van Poppel ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Surgical Treatment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Review Of The Literature ◽  
Synchronous Metastasis ◽  
Renal Cell Carcinomas ◽  
Gallbladder Metastasis ◽  
Metachronous Metastases ◽  
Systemic Therapies

Renal cell carcinomas (RCCs) are known for their unpredictable metastatic pattern. We present the case of a 63-year-old woman who initially presented in 1992 with a metastasis in the left calcaneus that led to the discovery of RCC. In 1998, a new metastasis was found in the ovary. In 2008, the diagnosis of a gallbladder metastasis was made. All metastases were surgically removed; no additional systemic therapies were used. Aggressive surgical treatment can prolong the survival of patients with resectable metastases. Patterns of metastasis are discussed, and a brief review of the literature is given regarding each localization.

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