Multiple Cutaneous And Uterine Leiomyomatosis Research Articles

Reed’s syndrome: a combination of a renal cyst with leiomyoma of the skin and uterus (clinical observation)

Multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reeds syndrome, is a rare genodermatosis, with an autosomal dominant pattern of inheritance. It results from a germline heterozygous mutation of fumarate hydratase gene, that is classified as a tumor suppressor gene. Hereditary leiomyomatosis and renal cell cancer is characterized by the association of multiple cutaneous and uterine leiomyomatosis with renal cell carcinoma. The diagnosis of multiple leiomyomas is based on the identification of morphological characteristic rashes (small, oval, red-brown or flesh-colored nodules located around the hair follicles, often painful) and is confirmed by the method of pathomorphological examination. Treatment of leiomyomas depends on their number, size, area of skin lesion and severity of subjective symptoms. With single rashes, surgical excision of the largest and most painful elements is possible, with severe pain syndrome ― calcium channel blockers, alpha-blockers and gabapentin. Cryotherapy, diathermocoagulation, and laser ablation with a carbon dioxide laser are used to destroy the nodes.
 The presence of cutaneous leiomyomas in patients dictates the need for careful collection of anamnesis, including family and obstetric-gynecological, conducting a full-fledged clinical, laboratory and instrumental examination and consulting by related specialists. Annual screening for early detection and therapy of renal cell carcinoma is also mandatory.
 Due to the existing probability of the hereditary nature of Reeds syndrome, a thorough examination of the patients relatives is necessary.
 We report a case of a 58-year-old woman with Reeds syndrome: multiple cutaneous leiomyomas, uterine leiomyoma and renal cysts.

Multiple cutaneous and uterine leiomyomatosis with renal involvement: Report of a rare association

Cutaneous leiomyomas (CLs) are uncommon benign smooth muscle tumours characterised by solitary or multiple painful nodules. Based on origin, three types are recognised, namely piloleiomyoma, dartoic leiomyoma, and angioleiomyoma, with piloleiomyomas being the commonest one. Reed's syndrome also known as multiple cutaneous and uterine leiomyomatosis (MCULs) is characterised by CLs in men and CLs and uterine fibroids in women. Association of Reed's syndrome with renal cell carcinoma is labelled as hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Both MCUL and HLRCC are caused by a heterozygous mutation in the fumarate hydratase gene. Besides renal cell carcinoma, there were extremely rare reports of association of MCUL with benign renal lesions. We report a case of a 55-year-old female with segmental tender papulonodular lesions suggestive of leiomyoma associated with uterine leiomyomas and unilateral renal cyst. The case is reported here for its rarity and uncommon association with asymptomatic benign renal cyst.

Reed's Syndrome.

Multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reed's syndrome, is a rare genodermatosis, with an autosomal dominant pattern of inheritance. It results from a germline heterozygous mutation of fumarate hydratase gene, that is classified as a tumor suppressor gene. Hereditary leiomyomatosis and renal cell cancer is characterized by the association of MCUL with renal cell carcinoma. We report a case of a 57-year-old woman, with multiple cutaneous leiomyomas as the presenting sign of Reed's syndrome.

Successful treatment of multiple cutaneous leiomyomas with carbon dioxide laser ablation.

Successful treatment of multiple cutaneous leiomyomas with carbon dioxide laser ablation.

Gastrointestinal Stromal Tumour in a Patient with Multiple Cutaneous and Uterine Leiomyomatosis- Implications and Anaesthetic Management

Multiple cutaneous leiomyomatosis have been associated with uterine leiomyomatosis and known as Reed's syndrome or Multiple Cutaneous and Uterine Leiomyomatosis (MCUL). Gastrointestinal Stromal Tumours (GIST) have been reported to be associated with this syndrome only once previously in literature to the best of our knowledge. Here we report a rare case of GIST and multiple uterine leiomyomatosis in a middle aged patient with longstanding cutaneous leiomyomatosis who underwent GIST excision and hysterectomy. A 35year old female patient with multiple cutaneous leiomyomatosis for the past 20years was diagnosed to have gastrointestinal stromal tumour and multiple uterine leiomyomatosis for which she underwent laparotomy for GIST excision and hysterectomy. In the report we have elaborated the clinical and pathological observations as well as the anaesthetic management. This case report further substantiates the association of GIST with multiple cutaneous and uterine leiomyomatosis and also reminds us that cutaneous lesions can be clues to the diagnosis of underlying malignancy.

Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.

Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH-deficiency. We have tested 42 smooth muscle neoplasms, 13 lesions of patients with suspicious or confirmed HLRCC, 20 sporadic piloleiomyomas, two angioleiomyomas and 7 leiomyosarcomas. FH staining grades from 1 to 3. Ten of the 13 lesions from the patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented grade 3 FH staining although five cases presented grade 1 FH staining. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. This staining could indicate a high risk of HLRCC in most of the confirmed cases but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. HLRCC syndrome should be rule out in FH negative piloleiomyomas after complete anamnesis if multiple lesions or positive familiar history is found.

Gastric Leiomyoma and Hyperplastic Polyposis Coli in a Patient with Multiple Cutaneous and Uterine Leiomyomatosis

Cutaneous leiomyomatosis has been associated with multiple uterine myomas and, more recently, with germline heterozygous mutations of the FH gene and certain types of renal cancer. Despite the growing amount of knowledge concerning this genodermatosis, its clinical spectrum remains incompletely characterized. We report the observation of a patient with multiple cutaneous and uterine leiomyomatosis (MCUL) with unusual gastrointestinal manifestations. A gastric leiomyoma was diagnosed on a 38-year-old female MCUL patient on endoscopy performed because of mild dyspepsia. Furthermore, routine colonoscopy disclosed hyperplastic polyposis. Genetic testing revealed a previously not reported mutation of the FH gene. Gastrointestinal lesions such as the present ones are frequently asymptomatic and probably underdiagnosed. As the phenotypical spectrum associated with mutations of the FH gene keeps expanding, clinicians should keep in mind that, besides renal cancer, other unexpected tumors could also arise in this setting.

NovelFHmutation in a patient with cutaneous leiomyomatosis associated with cutis verticis gyrata, eruptive collagenoma and Charcot-Marie-Tooth disease

Multiple cutaneous and uterine leiomyomatosis (MCUL)/hereditary leiomyomatosis and renal cell cancer (HLRCC) (OMIM 150800/OMIM 605839) is a rare hereditary disorder leading to the development of benign cutaneous and uterine smooth muscle tumours in young adults.(1,2) This disease is characterized by an increased risk of developing renal cell carcinomas.(3) It results from dominantly inherited autosomal mutations in the fumarate hydratase (FH) gene.(4) This gene encodes a Krebs cycle enzyme, present in both cytosolic and mitochondrial compartments, and probably acts as a tumour suppressor gene. We report a 22-year-old man affected by cutaneous leiomyomatosis associated with cutis verticis gyrata, disseminated collagenoma and Charcot-Marie-Tooth disease, who was harbouring the novel FH gene mutation c.821C > T, p.Ala274Val.

Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer

Germline heterozygous loss-of-function mutations of fumarate hydratase (FH) predispose to the autosomal dominant syndrome of multiple cutaneous and uterine leiomyomatosis (MCUL). Forty-five distinct FH mutations have been identified in 76 of 89 (85%) reported probands with skin leiomyomas. This suggests that MCUL is a genetically homogeneous condition and that most patients presenting with skin leiomyomas will have underlying FH mutations. FH mutations identified include 26/45 (58%) missense; 12/45 (27%) frameshift, 4/45 (9%) nonsense changes and 3/45 (7%) different whole gene deletions. In MCUL kindreds, the majority of females with FH mutations have both skin and uterine leiomyomas. A proportion of individuals with FH mutations have associated renal cancer, a variant known as hereditary leiomyomatosis and renal cell cancer (HLRCC). If selection bias is removed, the prevalence of renal cancer in MCUL lies between one of 46 (2%) families who were not radiologically screened, and two of 32 (6%) families who were radiologically screened. Truncating, particularly frameshift, mutations appear to be significantly associated with renal cancer (P = 0.003), suggesting a possible basis for selective screening. There may also be a significantly increased rate of renal cancer in females (P = 0.004), suggesting a possible role for hormonal factors. Review of the literature suggests that, unlike most individuals presenting with skin leiomyomas, the majority of patients presenting with uterine leiomyomas or renal cancer will not have underlying FH mutations.

Clinical Features of Multiple Cutaneous and Uterine Leiomyomatosis

To investigate the clinical features of the multiple cutaneous and uterine leiomyomatosis (MCUL) syndrome, including the hereditary leiomyomatosis and renal cell cancer syndrome. A case series of patients with multiple skin leiomyomas solicited via a circular letter to dermatologists. Research institute. A total of 108 affected individuals, including 46 probands and 62 affected relatives. The proportion of probands with underlying fumarate hydratase (FH) mutations, the penetrance of FH mutations, and clinicopathologic features of MCUL. Forty-one (89%) of 46 probands with multiple skin leiomyomas had evidence of germline FH mutations, which were highly penetrant. All 26 male mutation carriers had skin leiomyomas. Of 67 women with FH mutations, 46 (69%) had both skin and uterine leiomyomas; 10 (15%) had only skin leiomyomas; 5 (7%) had only uterine leiomyomas; and 6 (9%) were clinically unaffected. Patients presented with skin leiomyomas at a mean age of 24 years and had a mean of 25 lesions. Forty-one individuals (89%) reported painful lesions, particularly in response to cold or trauma. Fibroids were histologically unremarkable, highly symptomatic, and associated with a high risk of early hysterectomy. One individual had a very aggressive collecting duct renal cancer. The G354R FH mutation predisposed patients to uterine fibroids without skin leiomyomas (P = .03). Many patients with skin leiomyomas had not previously presented for medical attention. Fibroids were rarely recognized as cases of MCUL. Highly penetrant FH mutations underlie MCUL. Increased clinical awareness is important because of the associated risk of severe uterine fibroids and, in some cases, aggressive renal cancer.

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.