Hereditary Leiomyomatosis and Renal Cell Cancer

Abstract

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited tumour predisposition syndrome. Around 75% of individuals with HLRCC develop cutaneous leiomyomas, which are skin tumours that can cause pain and itching. Most women with HLRCC develop uterine leiomyomas that often cause gynecological symptoms and typically require surgery. Around 20% develop renal cell carcinoma. HLRCCassociated renal cell carcinomas are aggressive tumours with a high potential to metastasize. Individuals with features suggestive of HLRCC and at-risk family members should undergo genetic testing. Individuals harbouring a pathogenic mutation should be offered lifelong surveillance so renal neoplasms are detected and treated in time. Hereditary leiomyomatosis and renal cell cancer is a genodermatosis with an autosomal dominant inheritance pattern. It is a tumour predisposition syndrome characterized by cutaneous and uterine leiomyomas, and increased susceptibility to develop renal cell carcinoma. There are 200-300 families with hereditary leiomyomatosis and renal cell carcinoma reported worldwide, but the syndrome is believed to be underdiagnosed. Cutaneous leiomyomas are small smooth muscle tumours that tend to grow over time. Larger lesions, in particular, can cause pain or itching. Uterine leiomyomas have a high penetrance in women with hereditary leiomyomatosis and renal cell cancer. They frequently cause symptoms, and surgical intervention is often necessary. Hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas have a high potential to metastasize. Patients are diag nosed by genetic testing if a pathogenic mutation is demonstrated in the gene encoding fumarate hydratase. Immunohistochemistry may be a useful diagnostic approach in patients without a detectable pathogenic mutation. Diagnosed patients should be monitored for renal tumours in a lifelong surveillance programme.

Hereditary leiomyomatosis and acute lymphoblastic leukemia: A link through fumarate dyshydratase mutation?

“…Total nephrectomy is recommended for patients with a renal mass due to the high aggressiveness of renal cancers associated with Reed's syndrome [22,24,26,27]. The prognosis primarily relies on the early detection of HL-associated renal cancers in order to treat them as soon as possible [28]. Following diagnosis, the management should include annual screening for renal cell carcinomas using contrast-enhanced magnetic resonance imaging (IRM) starting in infancy [17,24,28].…”

“…The prognosis primarily relies on the early detection of HL-associated renal cancers in order to treat them as soon as possible [28]. Following diagnosis, the management should include annual screening for renal cell carcinomas using contrast-enhanced magnetic resonance imaging (IRM) starting in infancy [17,24,28]. Ultrasound could assist MRI in the screening program although some discrepancy exists among authors [28].…”

Hereditary renal cell tumors: Clinicopathologic importance

“…HLRCC is caused by a germline mutation in the fumarate hydratase (FH) gene located on chromosome 1q42. FH encodes an enzyme responsible for catalyzing the conversion of fumarate to malate in the Krebs cycle [25][26][27][28]. This mutation subsequently leads to an accumulation of intracellular fumarate, which mediates various proteomic and epigenetic events, ultimately resulting in activation of HIF-1.…”

“…Approximately 71-100% of families with features suggestive of HLRCC demonstrate pathogenic variants [25,26,29]. Extrarenal manifestations include multiple cutaneous leiomyomas and early onset uterine leiomyomas and leiomyosarcomas.…”

Hereditary leiomyomatosis and renal cell cancer: a case report

“…Вместе с тем высказывают предположение о недиагностированной доле случаев HLRCC в популяции, как и о неточной оценке частоты развития РП при HLRCC [5]. Опубликованные в 2021 г. данные свидетельствуют о том, что риск РП на протяжении жизни у больных HLRCC превышает 20 % [6,7]. В качестве минимальных диагностических критериев, позволяющих поставить предварительный диагноз HLRCC, рассматривают множественные лейомиомы кожи и матки (у женщин) и семейную историю заболевания, а также сочетание лейомиом и РП [8].…”