Hereditary leiomyomatosis and renal cell cancer syndrome – case report and review of the literature

Abstract

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is an exceptionally rare autosomal dominant condition caused by a germline heterozygous mutation of the fumarate hydratase gene. It manifests as multiple piloleiomyomas, associated with numerous, early-onset uterine leiomyomas in female patients, as well as a highly increased risk of renal cell carcinoma (RCC), most often type 2 papillary RCC. HLRCC has been described in association with adrenal cortical hyperplasia, pheochromocytoma, adrenal cortical carcinoma, and other solid tumors, but the exact relationship between these disorders has not yet been clarified. We present a case of HLRCC associated with bilateral adrenal cortical hyperplasia and discuss the pathogenesis, clinical and paraclinical features of HLRCC, as well as the adequate management of these patients.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome in a young patient presenting with a large uterus: A case report and review of the literature

“…A total of 5 cases with HLRCC were found in the literature and these are summarized in Table 1 , which gives the patients' chief complaint, timing of hysterectomy or myomectomy, the clinical manifestation of HLRCC and the methods to confirm HLRCC. The first four patients (cases 1–4) underwent either hysterectomy or myomectomy and HLRCC was confirmed later by genetic testing [ 1 , 3 , 4 , 11 ]. These patients came back months or years later with other clinical manifestations of HLRCC and further workup helped confirmed the condition by histopathology and genetics.…”

“…Only one patient (case 5) had genetic testing before surgery since she presented with all the telltale signs of HLRCC and had a family history of the condition [ 12 ]. In most reports, the authors suggested using cutaneous leiomyomas as the primary indicator of HLRCC [ 1 , 3 , 4 , 12 ]. However, no case used uterine myomas as the only indicator in a young woman with suspected HLRCC after hysterectomy or myomectomy.…”

“…[ 11 ] 42-year-old female with abdominal pain Myomectomy at 32-years-old due to pain and anemia Renal cyst-tumor Multiple uterine myomas Genetics of FH locus after open nephrectomy confirming type 2 papillary RCC and total hysterectomy 2020, Popa L. & al. [ 1 ] 62-year-old female with multiple cutaneous coloured and nodular lesions Multiple myomectomies before 30-years-old and total hysterectomy (not specified) Cutaneous leiomyomas Renal cyst Histopathology from skin biopsy with personal and family history 2018, Natalia F & al. [ 4 ] 27-year-old female with hematuria, right flank pain, menorrhagia and dysmenorrhea Open myomectomy performed few months after nephrectomy Solid mass in right kidney Multiple uterine leiomyomas Cutaneous leiomyomas Genetics not conclusive for FH mutation Dermatologic examination (not specified) 2016, Tulandi T & Foulkes WD [ 12 ] 30-year-old female with swelling and pain in her abdomen with painful-coloured cutaneous nodules Myomectomy at the time of chief complaint Cutaneous leiomyomas Uterine leiomyomas Right renal cyst Genetics of FH gene Histopathology from skin biopsy and uterine myomectomy …”

“…Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited autosomal-dominant condition with a variable or de novo penetrance [ 1 , 2 ]. HLRCC is caused by a heterozygous germline mutation in the fumarate hydratase (FH) gene, which is involved in the tricarboxylic acid (TCA) cycle or Krebs cycle which transforms fumarate to malate [ [1] , [2] , [3] , [4] , [5] , [6] , [7] ]. The most serious manifestation of genetic condition is renal cell carcinoma (RCC).…”

Ferroptosis: a promising target for fumarate hydratase-deficient tumor therapeutics literature review

“…They are light brown protuberant nodules that measure approximately 1 cm. Although the symptoms are not obvious, these nodules on the skin can be painful under harsh environments, such as emotional stress and cold temperatures ( 110 - 112 ).…”