Multiple Uterine Leiomyomas Research Articles

Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition in which susceptible individuals are at risk for the development of cutaneous leiomyomas, early onset multiple uterine leiomyomas and an aggressive form of type 2 papillary renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene which inactivate the enzyme and alters the function of the tricarboxylic acid (Krebs) cycle. Issues surrounding surveillance and treatment for HLRCC-associated renal cell cancer were considered as part of a recent international symposium on HLRCC. The management protocol proposed in this article is based on a literature review and a consensus meeting. The lifetime renal cancer risk for FH mutation carriers is estimated to be 15 %. In view of the potential for early onset of RCC in HLRCC, periodic renal imaging and, when available, predictive testing for a FH mutation is recommended from 8 to 10 years of age. However, the small risk of renal cell cancer in the 10-20 years age range and the potential drawbacks of screening should be carefully discussed on an individual basis. Surveillance preferably consists of annual abdominal MRI. Treatment of renal tumours should be prompt and generally consist of wide-margin surgical excision and consideration of retroperitoneal lymph node dissection. The choice for systemic 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 of families.

Long-term risk of fibroid recurrence after laparoscopic myomectomy

ObjectiveThe use of laparoscopic myomectomy as a surgical treatment for uterine leiomyoma is associated with low intraoperative morbidity and short hospitalization. Limited data about the long-term outcome of this surgical approach are available. The aims of this study were to estimate the risk of uterine fibroid recurrence after laparoscopic myomectomy and to identify factors contributing to the rate of fibroid relapse. Study designBetween 1996 and 2003, 331 patients underwent laparoscopic myomectomy to treat uterine leiomyoma in our hospital; 224 of these patients consented to participate in our 2009 follow-up survey. Clinical symptomatic uterine leiomyoma recurrence was defined as relapse. Recurrence rates at 24 and 60 months post-operatively were calculated for the study population. Fisher’s exact tests were used to examine the impacts of factors previously linked to an increased risk of fibroid recurrence, including (1) patient age at the time of initial surgery, (2) pre-operative body mass index, (3) number and localization of uterine leiomyoma removed, and (4) pregnancy and (5) delivery after laparoscopic myomectomy on fibroid recurrence in our study cohort. ResultsWe observed 75 recurrences in 224 patients. The cumulative risk of recurrence was 4.9% at 24 months and 21.4% at 60 months post-operatively. An age of 30–40 years and the presence of more than one fibroid at the time of initial laparoscopic myomectomy were identified as factors significantly increasing the risk of symptomatic recurrence after laparoscopic myomectomy (31.25% and 38.71%, respectively; both p<0.01). ConclusionPatients with multiple uterine leiomyoma and those in the third decade of life should be counselled thoroughly about the risk of recurrence prior to laparoscopic myomectomy. The low observed recurrence rate in peri- and postmenopausal patients in our study may support the use of laparoscopic myomectomy as a uterus-preserving surgical alternative beyond the reproductive period.

Selected Case From the Arkadi M. Rywlin International Pathology Slide Series

We present the clinicopathologic features of 3 cases of leiomyomatosis peritonealis disseminata (LPD). The patients were 33, 34, and 41 years old at the time of diagnoses. The 3 women had undergone laparoscopic removal of multiple uterine leiomyomas between 1 and 6 years before the diagnoses of LPD. Laparoscopic uterine leiomyomectomies were performed on 3 occasions in patient 1, and once in patients 2 and 3 by the time a diagnosis of LPD was made. In patients 2 and 3, one of the multiple uterine leiomyomas had been qualified as mitotically active. Patients 1 and 2 received hormonal treatment before LPD was diagnosed. Malignancy was clinically and/or pathologically suspected in all the 3 cases. Patients 1 and 2 were managed conservatively. Patient 3 underwent radical hysterectomy with bilateral adnexectomy and omentectomy. Patients 1 and 2 belong to a rare subset of LPD that have fewer tumor nodules larger (5 to 10 cm) than typically seen. Patient 3 was classic in that she exhibited innumerable nodules measuring between a few millimeters and 1.5 cm, intraoperatively mimicking peritoneal carcinomatosis. Histopathologically, patients 1 and 2 were diagnosed as pure LPD, whereas patient 3 was diagnosed as LPD associated with endometriosis (adenomyosis type). Patients 1 and 3 had incipient foci of leiomyomatous changes in the blood vessel walls, at the site of the LPD tumors, supporting the hypothesis that these are de novo lesions arising locally and not migrated or disseminated from the previously excised or concurrent uterine smooth muscle tumors, usually seen in this context. Conceivably, laparoscopic leiomyomectomy with morcellation may play a role in the pathogenesis of this rare condition, at least in hormonally susceptible patients. Alternatively, LPD may derive from metaplastic submesothelial cells, a condition analogous to gliomatosis peritonei.

Serous Tubal Intraepithelial Carcinoma in a Japanese Woman with a Deleterious BRCA1 Mutation

Risk-reducing salpingo-oophorectomy for reducing future cancer risk in women with hereditary breast and ovarian cancer syndrome is rarely performed in Japan; therefore, the cancer preventive effect of risk-reducing salpingo-oophorectomy for hereditary breast and ovarian cancer syndrome among the Japanese population remains unclear. Here, we report the first case of serous tubal intraepithelial carcinoma identified through a risk-reducing salpingo-oophorectomy in a Japanese woman with hereditary breast and ovarian cancer syndrome and who had a deleterious germline mutation of E1214X in BRCA1, but not a BRCA2 mutation. A pre-operative examination revealed multiple uterine leiomyomas but no adnexal mass. Robotic-assisted bilateral salpingo-oophorectomy together with hysterectomy was performed. A pathological examination identified serous tubal intraepithelial carcinoma in the right fallopian tube with no dissemination. Serous tubal intraepithelial carcinoma is implicated as an origin of invasive cancer of the fallopian tube with peritoneal dissemination; prophylactic salpingo-oophorectomy is currently the only method to identify this occult cancer. Our case demonstrated that risk-reducing salpingo-oophorectomy can detect occult cancers, including serous tubal intraepithelial carcinoma, thereby preventing future cancer development in the Japanese hereditary breast and ovarian cancer syndrome population.

Fumarase Deficiency Associated With Noninflammatory Biliary Atresia

Fumarase Deficiency Associated With Noninflammatory Biliary Atresia

Unusual Calcifying Fibrous Tumor in the Fallopian Tube

Calcifying fibrous tumor (CFT) is a rare benign soft tissue tumor of unknown etiology and extremely rare in female reproductive system. We present a case of unusual CFT in the ampulla of fallopian tube occurring in a middle-aged female patient with multiple uterine leiomyomas. A hysterectomy was performed on a 48-year-old woman for uterine leiomyomas. At surgery, a solitary, well-defined nodule, measuring 1.0 cm in diameter, was incidentally observed on the wall of ampulla of right fallopian tube. The lesion of fallopian tube was resected totally. Histologically, this lesion was unencapsulated and composed of hyalinized collagenous fibrous tissue with psammomatous calcification and focal lymphoplasmacytic infiltrate. Sparsely fibroblast-like spindle cells were scattered in the dense hyalinized background with bland nuclei. By immunohistochemistry, vimentin was diffusely positive in most cells, and a focal reactivity for CD34 was also observed in spindle cells. However, they were negative for cytokeratin (AE1/AE3), S-100 protein, CD117, DOG1, SMA, desmin, and ALK. The Ki-67 labeling index of the lesion was <1%. A diagnosis of primary CFT of fallopian tube was made. To our knowledge, this is the first report of CFT occurring in female reproductive tract. Awareness of CFT and its distinctive features is important to avoid a diagnostic pitfall caused by histologic similarities to other spindle cell or calcifying lesions in unusual locations. Although marginal excision is usually adequate for most of CFT, long-term follow-up is suggested as delayed recurrence might occur infrequently.

Abnormal uterine bleeding as a presenting symptom is related to multiple uterine leiomyoma: an ultrasound-based study

PurposeTo determine the prevalence of uterine leiomyomas, diagnosed by ultrasound, in a private health care setting located in the central eastern region of Portugal, and to explore the demographic and clinical factors related to diagnosis and symptomatology.Patients and methodsThe files of 624 patients attending a private clinic in Covilhã, Portugal, from January 2 to December 31, 2010 were retrieved for evaluation. Pelvic ultrasound record, age, weight, height, age at menarche, number of pregnancies and deliveries, marital status, menstrual cycles characteristic, and contraceptive method at consultation were included in the analysis.ResultsUterine leiomyoma (UL) was diagnosed by ultrasonography in 161 (25.8%) patients. A single UL was diagnosed in 80 (49.7%) patients. In 79 (49.1%) patients, the largest leiomyoma had a dimension <20 mm. Prevalence of UL was age dependent: at 11.0% for women 20–39 years old; 45.4% for those aged 40–59 years; and 19.5% for women 60 years or older. Metrorrhagia was the most distressing presenting symptom. When menorrhagia was the presenting symptom, the probability of having an ultrasound diagnosis of UL was 73.3%. Metrorrhagia or menorrhagia, as presenting symptom, was significantly related to the ultrasound diagnosis of multiple ULs.ConclusionUL was especially prevalent in women aged between 40 and 59 years. Patients with multiple ULs had significantly more abnormal uterine bleeding. In patients with menorrhagia or metrorrhagia, special attention should be taken in searching for the presence of multiple ULs during ultrasound.

Chronic Unilateral Eruption of Painful, Erythematous Papules and Nodules

A72-year-oldwhitewoman of German heritage presentedwith a 30-yearhistoryof several painful lesionson the left sideofherbody. Clinical examination revealednumerous tender, erythematouspapules and nodules over her left chest, flank, and lower extremity (Figure 1). The patient’s medical history was significant for hyperlipidemia, multiple uterine leiomyomas status after hysterectomy in 1972, and severe coronary artery disease status after coronary artery bypass grafting in 2004. The patient emigrated from GermanyshortlyafterWorldWar II; familialmedicalhistorywasnotavailable. Her medications were aspirin, warfarin, duloxetine, pregabalin, and atorvastatin. A shave biopsy was performed from a characteristic papule on the left lower extremity. Routine hematoxylin-eosin–stained sections are shown in Figure 2 and Figure 3. What is your diagnosis?

A 40-Year-Old Woman With Multiple Lung Nodules

A 40-year-old woman was referred to pulmonary clinic for evaluation of multiple lung nodules on chest imaging. Her past medical history was remarkable for end-stage kidney disease on peritoneal dialysis due to chronic hypertension 5 years ago and large uterine leiomyomata that led to total hysterectomy at age 30 years. Pathology diagnosis was compatible with multiple uterine corpus and cervical leiomyoma with no signifi cant atypia and no necrosis. She is a mother of one healthy child and a lifetime nonsmoker. The patient denied cough, shortness of breath, hemoptysis, recent travel, or any other symptoms. On examination, she appeared comfortable, and the dialysis catheter site was clean. The rest of her physical examination was normal. The patient’s medical history, social history, and review of systems were otherwise unremarkable. Blood work revealed the following values: sodium, 139 mmol/L; potassium, 4.9 mmol/L; bicarbonate, 22 mmol/L; BUN, 50 mg/dL; creatinine, 5.2 mg/dL; calcium, 8.7 mg/dL (8.4-10.4 mg/dL); albumin, 3.9 g/dL; phosphorus, 4.8 mg/dL (2.5-4.9 mg/dL); magnesium, 1.9 mg/dL; and hemoglobin, 11 g/dL (mean corpuscular volume, 95%). The patient’s WBC count, serum bilirubin, and transaminases levels were normal. The patient’s posteroanterior and lateral chest radiographs are shown in Figure 1 . CT image of the chest (axial view) is shown in Figure 2 . Fluorodeoxyglucose PET/CT scan showed no hypermetabolic activity. A thoracoscopic lung biopsy of the left lower lobe through video-assisted thoracic surgery was performed. The pleural surface had a nodular protrusion and cut A 40-Year-Old Woman With Multiple Lung Nodules

Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene

Mutations in the FH gene cause the deficiency of the enzyme fumarase (fumarate hydratase, EC 4.2.1.2) which result in autosomal recessive fumaric aciduria in early childhood with failure to thrive, seizures, developmental delay, mental retardation, hypotonia and sometimes with polycythemia, leukopenia, and neutropenia. Many children with fumarate hydratase deficiency do not survive infancy or childhood; those surviving beyond childhood have severe psychomotor retardation. Recently, FH gene was also identified as a “non-classical” tumor suppressor gene and heterozygous mutations were shown to cause multiple cutaneous and uterine leiomyomas as well as hereditary leiomyomatosis and renal cell cancer. A male patient who was referred to investigate the etiology of psychomotor retardation was later diagnosed to have fumaric aciduria due to the combination of a previously known (c.1431_1433dupAAA) and a novel (c.782G>T) mutation. The patient had an unusually mild clinical course without acidotic attacks. Interestingly his father who was heterozygous for the c.1431_1433dupAAA mutation in the FH gene had cutaneous leiomyoma.

Bilateral Ovarian Lymphangioma (Lymphangioleiomyoma)

Lymphangiomas of the ovary are rare and are usually unilateral. We present a 50-yr-old patient who presented with irregular bleeding secondary to multiple uterine leiomyomas who was found to have bilateral ovarian lymphangiomas. There was no evidence of pelvic lymphatic obstruction or of lymphadenopathy, and this appeared to exclude the possibility of acquired lymphangiectasia. The ovarian tumors were associated with a prominent smooth muscle cell component that partly surrounded many of the dilated vascular spaces to the extent that the diagnoses of lymphangioleiomyoma and lymphangioleiomyomatosis were also considered. However, there was no clinical evidence of lymphangioleiomyomatosis in other sites and the smooth muscle cells did not express melanocytic markers immunohistochemically. Lymphangioma and lymphangioleiomyoma should be considered in the differential diagnosis of bilateral, multicystic ovarian neoplasms.

Uterine artery embolization for uterine leiomyomas: a comparison between solitary and multiple uterine leiomyomas

Uterine artery embolization for uterine leiomyomas: a comparison between solitary and multiple uterine leiomyomas

Familial myomatosis cutis et uteri, segmental type 2

Reed's syndrome or familial myomatosis cutis et uteri, an autosomal dominant inherited condition with incomplete penetrance, is characterized by multiple cutaneous and uterine leiomyomas.[1] Uterine leiomyomas usually commence earlier compared to that in the general population and cutaneous leiomyomas may precede, follow or occur concurrently. Few patients may have associated renal cell carcinoma. Herein we report a case of a 50-year-old female with multiple, painful cutaneous leiomyomas and who had undergone hysterectomy owing to large uterine fibroids. Her 18-year-old daughter also has uterine fibroids.

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.

Elective cesarean myomectomy: A report of two cases

Myomectomy at the time of cesarean section has traditionally been discouraged due to the risks of hemorrhage and increased postoperative morbidity. However with the new frontiers in surgical practice, successfully performed cesarean myomectomies in selected patients has continuously been reported. Two cases of multiple uterine leiomyoma coexisting with pregnancy were selected, counseled, and had elective cesarean myomectomy. The first patient was a 38-year-old primigravida with 22 years history of subfertility. Her antenatal period was largely uneventful. Her evaluation revealed a singleton pregnancy coexisting with multiple uterine fibroid. At 38 weeks of gestation, she had cesarean section and myomectomy. Thirty-six seedlings were removed. The largest was 12 Χ 8 cm and she lost 1 L of blood. She was discharged home on the 8 th postoperative day in good condition. The second case was a 33-year-old primigravida who was diagnosed with uterine fibroid in pregnancy. She also had an uneventful antenatal care and at 38 weeks gestational age, she had the removal of a huge intramural leiomyoma from the lower uterine segment (12 Χ 14 cm) during cesarean section to get access to the baby. She lost 1.2 L of blood and was transfused two pints of blood. Her postoperative condition was satisfactory. She was discharged home on the 7 th postoperative day. Cesarean myomectomy can be successfully performed with careful planning, patient selection, and skillful surgery. However, blood transfusion services should be available.

A Rare Case with a Solitary Fibrous Tumour of the Colon and an Epithelioid Angiomyolipoma of the Kidney

Solitary fibrous tumour is a soft tissue tumour composed of a subset of fibroblast-like cells and frequently needs immunohistochemical staining for final diagnosis. Epithelioid angiomyolipoma is a variant of angiomyolipoma but characterized by the absence of both adipocytes and abnormal blood vessels. We introduce a very rare case with the combination of these two tumours. A Japanese female patient without significant symptom was hospitalized and operated due to multiple uterine leiomyomas. During the operation, the surgeons found another tumour attaching to serosa of sigmoid colon. This tumour was resected and interpreted as solitary fibrous tumour, suspicious of malignancy. After 13 months of treatment, she was hospitalized again due to hematuria. The doctors detected a tumour in her right kidney. After consultation, laparoscopic right nephrectomy was done. The pathological result of this tumour was epithelioid angiomyolipoma. This is the first report on this very rare combination of tumours with extensive immunohistochemical demonstration of both tumours. Hereby, we review clinical information and histopathological findings together with discussion on each tumour.

Pulmonary benign metastasizing leiomyoma: a case report and review of the literature

Pulmonary benign metastasizing leiomyoma characterized by the growth of uterine leiomyoma in the lung is a very rare disease. We herein report the case of a 46-year-old asymptomatic woman who underwent a total abdominal hysterectomy for her multiple uterine leiomyomas 5 years ago, with the presence of multiple shadows in her chest roentgenogram during the regular check-up. Chest computerized tomography (CT) showed multiple solitary nodules in both lungs. Video-assisted thoracoscopic surgery with a wedge resection of the lesion was performed. Histopathologically, the pulmonary nodule was composed of benign smooth muscle cells and demonstrated low mitotic activity and absence of necrosis. Immunohistochemical staining for smooth muscle actin (SMA) and Desmin were extremely positive. CD10, CD117 and S-100 were negative in the tumor cells. Positive immunoreactivity for estrogen receptor (ER) and progesterone receptor (PR) were detected. The pathological diagnosis was pulmonary benign metastasizing leiomyoma.

Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and renal cell cancer. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. A Finnish family with nine closely related women with uterine leiomyomas was detected by an alert gynecologist. No cutaneous or renal cell tumors were reported in the family when it was referred to genetic analyses. Samples were available from seven patients, and a novel germline FH mutation was detected in five of them. Mutation carriers were symptomatic, had multiple tumors and were diagnosed at an early age. This study emphasizes the importance of considering FH mutation screening when gynecologists encounter families with multiple severe uterine leiomyoma cases. Due to possibility of phenocopies more than one patient should be tested. Early mutation detection allows regular screening of the mutation carriers and enables early detection of possible highly aggressive renal tumors. It may also affect family planning as multiple myomas at early age may significantly reduce fertility.

Hereditary cutaneous leiomyomatosis

The occurrence of multiple cutaneous leiomyomas can be indicative of hereditary cutaneous leiomyomatosis. This autosomal dominant disorder is due to germline mutations in the fumarate hydratase (FH) gene. Associations with uterine myomas and renal cell carcinomas have been described and are referred to as Multiple Cutaneous and Uterine Leiomyomas (MCUL) or Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), respectively. A 34-year-old man presented with multiple red-brown papules and nodules. After histopathologic confirmation of piloleiomyomas, we made the diagnosis of hereditary cutaneous leiomyomatosis. Taking into consideration the aforementioned complications, close interdisciplinary management of these patients and regular screening examinations within affected families are mandatory.

A CYP17A1 gene polymorphism in association with multiple uterine leimyomas; a meta-analysis

The mutant genotype GG of the CYP17A1 gene polymorphism has been linked to higher levels of serum estradiol and thus might be associated with steroid-hormone dependent tumors. We decided to assess an association of CYP17A1 polymorphism with uterine leiomyomas (ULM) and multiple ULM by conducting a meta-analysis and subgroup analysis. We searched the HuGE Navigator and PubMed databases using the terms "leiomyoma" and "CYP17A1" for articles published by October 1, 2010. Our article in press was added. The selection criteria were (i) cases having ULM, (ii) controls showing no ULM from the same ethnic group, (iii) cases and controls not overlapping. The subgroup analysis included cases having multiple ULM, predisposing black women mostly present with multiple ULM. Pooled risk ratio was calculated using χ<formula> ^{2}</formula> statistic. Five papers fulfilled the selection criteria for meta-analysis and two papers for the subgroup analysis. The meta-analysis revealed no association of CYP17A1 polymorphism with all ULM. A high pooled risk ratio for multiple ULM was associated with the presence of mutant genotype GG (RR 3.25). CYP17A1 polymorphism may be associated with multiple ULM but not with all ULM. The future research might enable us to predict the course of the disease.