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【Objective】 To summarize and analyze the clinical data of fumarate hydrase-deficient renal cell carcinoma (FH-RCC), so as to improve the understanding of the disease. 【Methods】 General clinical data of 12 FH-RCC patients treated during Mar.2019 and Dec.2021 were retrospectively analyzed, including the imaging, pathological, genetic testing, surgical and adjuvant therapy, and follow-up results. 【Results】 All cases were confirmed with pathology or genetic tests, including 1 case complicated with uterine fibroids, 3 cases with renal cysts, 4 with family history of uterine fibroids and 2 with family history of renal carcinoma. Cysticular irregular density shadows with an enhancement of 25.8 Hu were detected in 4 cases. Of the 7 cases undergoing genetic testing, 2 had embryo and system mutation, 1 had germ line mutation, 1 had system mutation, and 3 had no germ line or system mutation. Radical nephrotomy was performed in 9 cases. The average operation time was 3.8 h, and the average amount of blood loss was 625 mL. Immunotherapy with targeted therapy was conducted in 10 cases, surgery with postoperative adjuvant therapy in 7 cases, and tyrosine kinase inhibitor with immune checkpoint inhibitor (TKI/ICI) in 1 case. All 12 cases were followed up, 3 died of tumor, 1 had no recurrence, 8 showed progress on imaging. 【Conclusion】 FH-RCC is a rare and highly malignancy prone to metastasis. Imaging shows cystic solid space occupying lesions. FH immunohistochemical staining is negative. Genetic testing is needed to confirm the diagnosis. TKI/ICI combination therapy has a good survival benefit.
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Objective:To Explore the diagnosis, treatment and prognosis of FH-deficient renal cell carcinoma (FH-deficient RCC) with tumor thrombus, and share surgical experience.Methods:From August 2019 to October 2022, 6 cases of FH-deficient RCC with tumor thrombus were diagnosed and treated in our center, including 4 males and 2 females. The patients were aged 22 to 57 years, with 2 cases younger than 40 years, icluding 5 cases on the left and 1 case on the right. The median maximum diameter of the tumor is 8 (4.8, 14.0) cm. Operations were performed after complete examination (enhanced CT and other related examinations). One case underwent open surgery and palliative resection of the left kidney was performed because of severe adhesion of the inferior vena cava. Among the remaining 5 cases, 1 case underwent retroperitoneal laparoscopic right radical nephrectomy with inferior vena cava thrombectomy, 1 case underwent transabdominal laparoscopic left radical nephrectomy with inferior vena cava thrombectomy, and 3 cases underwent robot assisted laparoscopic left radical nephrectomy with inferior vena cava thrombectomy.Results:The median surgical time was 293 (185, 366) min, with blockage of the vena cava for 13 min and 28 min in 2 of 6 cases, respectively. The pathological report of renal tumor and tumor thrombus was FH-deficient renal carcinoma. The pathological features were as follows: the gross section of the specimen was gray yellow solid, often accompanied by necrosis, and the cystic cavity could be seen locally. Microscopically, the tumor extensively involved the renal parenchyma, with papillary, cribriform and tubular cystic structures. Immunohistochemistry showed FH (-), 2SC (+ ). The median postoperative hospital stay was 8 (4, 15) days. The median follow-up time was 13 (4, 27) months. One patient undergoing palliative resection of the left kidney underwent targeted therapy and radiotherapy after surgery (died 15 months after surgery due to gastrointestinal perforation). During the follow-up process, 4 cases experienced metastasis and received systematic treatment, with 1 death 27 months after surgery. Uterine leiomyomas were found in the remaining 1 case during follow-up.Conclusions:FH-deficient RCC with tumor thrombus is very rare. This disease is highly invasive, difficult to be diagnosed preoperatively and poor clinically prognostic. Operation combined with systemic therapy is an effective way to treat FH-deficient RCC with tumor thrombus.
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Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.
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Objective:To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma.Methods:The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD 10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results:(1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD 10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions:FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.
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Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a rare hereditary disease and characterized by cutaneous leiomyoma, uterine leiomyoma and/or renal cell carcinoma, but rarely associated with vena cava embolism. We treated 1 case of HLRCC syndrome patients with inferior vena cava tumor emboli (Mayo grade Ⅳ), confirmed after genetic testing, the patient and her family refused further treatment. The patient died after two months of follow-up after discharge.
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OBJECTIVE@#To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC).@*METHODS@#Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed.@*RESULTS@#There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic.@*CONCLUSION@#Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Biomarkers, Tumor , Carcinoma, Renal Cell/genetics , Fumarate Hydratase/genetics , In Situ Hybridization, Fluorescence , Kidney Neoplasms/genetics , PrognosisABSTRACT
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant syndrome wherein affected individuals are at risk for the development of cutaneous leiomyomas, early-onset multiple uterine leiomyomas, and an aggressive subtype of renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene, which inactivates the enzyme and alters the function of the tricarboxylic acid/Krebs cycle. This article reviews the hitherto described morphologic features of HLRCC-associated renal cell carcinoma (RCC) and outlines the differential diagnosis and ancillary use of immunohistochemistry and molecular diagnostics for these tumors. The morphologic spectrum of HLRCC-associated RCC is wide and histologic features, including tumor cells with prominent nucleoli, perinucleolar halos, and multiple architectural patterns within the same tumor, which are suggestive of this diagnosis. FH immunohistochemistry in conjunction with genetic counseling and germline FH testing are the important parameters for detection of this entity. These kidney tumors warrant prompt treatment as even smaller sized lesions can demonstrate aggressive behavior and systemic oncologic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts.
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Objective@#To investigate the clinicopathologic characteristics, molecular and genetic features, differential diagnoses and prognosis of fumarate hydratase-deficient renal cell carcinoma (FH-RCC).@*Methods@#The immunohistochemical (IHC) expression of FH in 391 renal neoplasms in tissue chips collected from the Affiliated Hospital of Qingdao University and 971 Hospital of PLA Navy from January 2011 to December 2017 was evaluated. The clinicopathologic data of eight FH negative cases were collected.Polymerase chain reaction (PCR) and sequencing were used to detect the changes in FH gene in three cases. Interphase FISH with a dual color and break-apart probe was applied to detect the TFE3 gene alteration in the cases showing TFE3 protein expression.@*Results@#Among the eight patients, seven were male and one was female, and age ranged from 28 to 50 years (mean 39 years). Tumor size ranged from 3.5 cm to 12.0 cm (mean 7.9 cm). Renal pelvis invasion was identified in six cases, and the tumor emboli in renal vein and inferior vena cava were found in four patients. The cut surface of most tumors was solid, colorful, grayish white or yellow with no clear border showing invasive growth pattern. Microscopically, the tumors showed different proportions of papillary, tubular cystic, cribriform and solid structures. The tumor cells were rounded or polygonal with eosinophilic or amphotropic cytoplasm, round or oval nuclei, and focal large and prominent nucleoli (WHO/ISUP grade 3-4). Two cases had sarcomatoid or rhabdoid components. Intravascular tumor emboli were found in five cases. IHC staining showed most tumors expressed PAX8(7/8), CK19(7/8), vimentin (6/8) and P504s(8/8). However, other immunomarkers including CK7, CD10, CD117, RCC, 34βE12, HMB45 and Melan A were all negative. Sequencing showed all three cases had FH gene mutations in exon 1. FISH revealed no TFE3 gene translocation or amplification in the two cases with TFE3 IHC expression. Follow-up data were available in seven patients with the follow-up period from 11 to 66 months. Among them, five patients died between 11 to 31 months after the surgery because of extensive distant metastases of the tumor to the lung, liver and lymph nodes. The other two patients were alive at the 36th and 66th month after the surgery.@*Conclusions@#Morphologically, FH-RCC overlaps with papillary RCC, collecting duct carcinoma and tubular-cystic RCC, showing a mixture of papillary, tubular cystic, cribriform or tubular papillary structures with at least focal large and prominent nucleoli. The negative expression of FH and the detection of FH gene mutation could facilitate the diagnosis of the tumor. FH-RCC is a high aggressive tumor, prone to metastasize, and is associated with poor prognosis. The timely diagnosis of FH-RCC could benefit the patients and their relatives as well.
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PURPOSE: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC. MATERIALS AND METHODS: We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULT: We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding. CONCLUSION: This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.
Subject(s)
Humans , Bevacizumab , Carcinoma, Renal Cell , Diagnosis , Disease-Free Survival , Erlotinib Hydrochloride , Fumarate Hydratase , Germ-Line Mutation , Hemorrhage , Leiomyomatosis , Retrospective StudiesABSTRACT
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.
Subject(s)
Humans , Female , Young Adult , Skin Neoplasms/pathology , Uterine Neoplasms/pathology , Neoplastic Syndromes, Hereditary/pathology , Leiomyomatosis/pathology , Skin/pathology , Skin Neoplasms/genetics , Uterine Neoplasms/genetics , Biopsy , Neoplastic Syndromes, Hereditary/genetics , Immunohistochemistry , Smooth Muscle Tumor/pathology , Leiomyomatosis/genetics , Age of Onset , Fumarate Hydratase/geneticsABSTRACT
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.
Subject(s)
Humans , Male , Middle Aged , Skin Neoplasms/genetics , Leiomyomatosis/genetics , Fumarate Hydratase/genetics , Mutation , Skin Neoplasms/enzymology , Skin Neoplasms/pathology , Leiomyomatosis/enzymology , Leiomyomatosis/pathology , Leiomyoma/enzymology , Leiomyoma/genetics , Leiomyoma/pathologyABSTRACT
Objective To establish the enzyme-linked immunosorbent assay (ELISA) for detecting human serum fumarate hydratase (FH) antibody and evaluate its role in the diagnosis of autoantigen in autoimmune hepatitis (AIH).Methods The indirect ELISA was established using FH protein,and the reaction conditions were determined.Then,the anti-FH antibody were detected in the serum of 88 AIH patients,56 primary biliary cirrhosis (PBC) patients,50 chronic hepatitis B (HBV) patients,36 chronic hepatitis C (HCV) patients and 98 healthy controls(HC).The results were analyzed with chi-quare and Kruskal-Wallis H methods.Results The ELISA for detecting human anti-FH antibody was established successfully and the optimal reaction conditions were defined.The positive rate of anti-FH antibody in the AIH group (40％) was significantly higher than HC (3％,x2=38.44,P＜0.01),PBC group (7％,x2=18.45,P＜0.01),CHB group (2％,x2=23.59,P＜0.01) and CHC group (6％,x2=14.29,P＜0.01).Anti-FH antibody which was used to diagnose AIH revealed a sensitivity of 40％ and specificity of 94％.Conclusion We have established the ELISA,which is used to detect human anti-FH antibody.It can be detected predominantly in AIH,and this implies that anti-FH antibody may be useful in improving the diagnosis of AIH.
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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.
Subject(s)
Adult , Female , Humans , Middle Aged , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Leiomyomatosis/pathology , Skin Neoplasms/pathology , Skin/pathology , Uterine Neoplasms/pathology , Biopsy , Carcinoma, Renal Cell/genetics , Fumarate Hydratase/genetics , Genetic Predisposition to Disease , Kidney Neoplasms/genetics , Leiomyomatosis/genetics , Skin Neoplasms/genetics , Uterine Neoplasms/geneticsABSTRACT
PURPOSE: Multiple skin leiomyoma and uterine myoma bearing autosomal dominant traits are benign smooth muscle tumors which originate in skin or female uterus. Skin leiomyoma occurs after gene mutation originating from arrector pili muscle of hair follicle where its clinical manifestations vary significantly from person to person. Our department hereby reports the histological findings and genetic evaluations of this very rare disease. METHODS: A 57-year-old woman presented in our institute with multiple tumors in the left and central parts of her back that started to appear since 19 years ago. The patient was diagnosed as having uterine myoma 15 years ago and underwent hysterectomy. Biopsy has been done on the specimen, and genomic DNA was separated from Fumarate hydratase gene for it to go through PCR amplification. The results of PCR amplification were aligned by sequencer. RESULTS: According to the results of biopsy, tumor cells were spindle-shaped and were aligned in a bundle where there was no dysplasia or mitosis. Moreover, these cells had abundant eosinophilic cytoplasm with elongated nucleus, and benign leiomyoma that showed positive reactions to SMA stain were found. In genetic examination, mutations such as heterozygous single nucleotide substitutions were found in alignments of amplified DNA. CONCLUSION: Multiple skin leiomyoma and uterine myoma are relatively uncommon diseases that are transmitted through autosomally dominant traits from genetic mutations. When a patient's chief complaint lies upon skin-colored or brown masses that occur in multiples appearing in the trunk or extremities with characteristic clinical symptoms and histological findings, and when the patient's family history is acknowledged such as skin or uterine leiomyoma or renal tumor, necessary genetic examination on multiple skin leiomyoma and uterine myoma could be done, and thereby precise diagnosis could also be made.