Hereditary leiomyomatosis and renal cell carcinoma syndrome: a case report and implications of early onset

Abstract Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant manifestation of cutaneous and uterine leiomyomas together with renal cancer due to autosomal dominant germline mutations of fumarate hydratase gene. A twenty-year-old female patient presented with type-II segmental piloleiomyoma and increased menstruation due to uterine leiomyomas, with a history of bilateral nephrectomy performed at 13 and 16 years of age for type 2 papillary renal cell carcinoma. This case represents one of the very early onsets of hereditary leiomyomatosis and renal cell carcinoma syndrome. As genetic anticipation for renal cancer is a well-documented entity for HLRCC syndrome, early recognition is crucial for both the patient and her family in order to provide appropriate counseling and initiation of surveillance.

Leiomioma cutáneo atípico en un paciente con leiomiomatosis cutánea y mutación de la enzima fumarato hidratasa / Atypical leiomyoma in a patient with cutaneous leiomyomatosis and mutation of the enzyme fumarate hydratase

Se presenta un varón de 56 años con un leiomioma atípico en el contexto de una leiomiomatosis cutánea, con antecedentes familiares de miomatosis uterina y con estudio genético que revela una mutación en el gen de la enzima fumarato hidratasa, sin que hasta el momento presente ningún tipo de neoplasia maligna renal. El leiomioma atípico es un tumor poco frecuente, que usualmente ocurre de forma aislada, siendo excepcional la presentación en pacientes con leiomiomatosis cutánea. Es ampliamente conocida la relación de la mutación de la enzima fumarato hidratasa con leiomiomas mútiples, miomas uterinos y el mayor riesgo de desarrollar cáncer renal; sin embargo, el papel de esta mutación en el desarrollo de leiomiomas atípicos es por hoy imposible de esclarecer debido a los escasos casos recogidos en la literatura.

We report the case of a 56 year-old male with an atypical leiomyoma in the context of a cutaneous leiomyomatosis and a family history of uterine leiomyomatosis. The genetic study revealed a mutation in the gene for the enzyme fumarate hydratase, but he has not had any renal malignancy so far. Atypical leiomyoma is a rare tumor that usually presents as a single lesion and is exceptional in patients with cutaneous leiomyomatosis. The relation between fumarate hydratase enzyme mutations with multiple leiomyomas, uterine leiomyomatosis and an increased risk of developing kidney cancer is widely known. However, the role of these mutations in the development of atypical leiomyomas is still impossible to clarify given the few cases reported in the literature.

Cutaneous leiomyomatosis in a mother and daughter / Leiomiomatose cutanea em mae e filha

A 34-year-old woman with no known medical history was evaluated for multiple painful brown nodules and papules on the anterior aspect of the trunk. She mentioned a history of similar cutaneous findings on her mother. Biopsies of three lesions revealed piloleiomyomata. Renal and adrenal ultrasound revealed an isolated simple cortical cyst, and pelvic and endovaginal ultrasound revealed two uterine myomata. The clinical diagnosis of hereditary leiomyomatosis and renal cell cancer was corroborated by the identification of a heterozygous variant on exon 5 of the fumarate hydratase gene (c.578C>T p.T193I). Identification of the tumor piloleiomyoma should alert the dermatologist to this rare genodermatosis, which is associated with an increased risk of renal cell tumors, demanding multidisciplinary follow-up, and personal and family counseling.

Uma mulher de 34 anos sem antecedentes patológicos conhecidos foi avaliada por apresentar múltiplos nódulos e pápulas castanhos, dolorosos, na face anterior do tronco. Referia história de achados cutâneos semelhantes na sua mãe. As biópsias de três lesões revelaram piloleiomiomas. As ecografias renal e suprarenal identificaram apenas cisto renal cortical simples, e as ecografias endovaginal e pélvica, dois miomas uterinos. O diagnóstico clínico de leiomiomatose herediária e câncer de células renais foi corroborado pela identificação de variante heterozigota no exon 5 do gene da Fumarato hidratase (c.578C>T p.T193I). O piloleimomioma é um tumor cuja identificação deve alertar o dermatologista para esta rara genodermatose, associada a um risco aumentado de tumores de células renais, exigindo seguimento multidisciplinar e aconselhamento pessoal e familiar.

Familial leiomyomatosis cutis affecting nine family members in two successive generations including four cases of Reed's syndrome.

Reed's syndrome or familial leiomyomatosis cutis et uteri is an autosomal dominant disorder, characterized by multiple cutaneous and uterine leiomyomas. We report here a case of a 53-year-old woman who presented to us with multiple painful nodules over different parts of her body. Based on the histopathological examination, imaging, and past medical records, a diagnosis of Reed's syndrome was made. Three of her sisters had similar disease. Subsequently, it was found that a total of nine members of their family in two successive generations were affected with cutaneous leiomyomas. The present case series has been reported for its interesting clinical presentations and rarity.

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor.