Benign Uterine Leiomyoma Research Articles

Spontaneously Occurring Fibroid Tumors of the Laying Hen Oviduct

Spontaneously occurring benign uterine leiomyomas (fibroids) are the most common tumors of reproductive-age women. It is estimated that more than 70% of all women will develop uterine fibroids, and the presence of these tumors is a primary cause of hysterectomies. Research into the causes and treatment of uterine fibroids is hampered by a lack of reliable animal models for the disease. Leiomyomas that appear to be outwardly similar to human uterine fibroid tumors are known to occur on the oviducts of laying hens over 2 yr of age. The objective of this study was to characterize these tumors and compare them to human uterine fibroids to determine the suitability of the aging hen as a model system for the study of the disease. In this study, hens at 5 yr of age were examined for the presence of oviduct-associated fibroid tumors. Tumors were found attached to the internal surface of the oviduct, embedded in the oviduct wall, or attached to the exterior of the magnum and isthmus. Tumor and normal oviduct samples were frozen or fixed in formalin for histological analyses or immunohistochemistry for estrogen and progesterone receptors, proliferating cell nuclear antigen and Bcl-2 protein expression. Human uterine fibroid samples were acquired and evaluated compared with hen oviduct fibroids. The results indicate that laying hen fibroid tumors are similar to human fibroid tumors with respect to estrogen and progesterone receptors, localized cellular proliferation, and expression of the Bcl-2 protein.

A Case of Benign Metastasizing Leiomyoma with Multiple Metastasis to the Soft Tissue, Skeletal Muscle, Lung and Breast

Benign metastasizing leiomyoma (BML) is composed of well-differentiated smooth muscle cells and dense connective tissue. BML affects middle-aged women who have had previous hysterectomies due to a histologically benign-appearing uterine leiomyoma. We report here on a case of BML from the uterine leiomyoma in a 39-year-old woman that involved the soft tissues, skeletal muscles, lungs and breasts. She underwent a hysterectomy for the uterine leiomyoma, double oophorectomy for hormonal ablation and lung wedge resection to confirm the diagnosis. The microscopic findings of the breast and lung tumor were similar to those of the benign uterine leiomyoma. Therefore, we consider that these lesions were breast and pulmonary metastases of the uterine leiomyoma. We report here on a rare case of benign metastasizing uterine leiomyoma that involved the soft tissue, skeletal muscles, lungs and breasts, and we include a review of the relevant literature.

Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

Benign metastasizing leiomyoma is a rare condition affecting women with a history of uterine leiomyomata and is characterized by multiple histologically benign pulmonary smooth muscle tumors. Speculations on its pathogenesis include a benign uterine leiomyoma colonizing the lung, a metastatic low-grade uterine leiomyosarcoma, and primary pulmonary leiomyomatosis. To elucidate its pathogenesis, we analyzed the clinical, pathological and immunohistochemical features, clonality, and telomere length of multiple lung and uterine tumors in three patients with benign metastasizing leiomyoma. In all cases, pulmonary tumors had benign histology and immunohistochemical profiles (estrogen receptor positive, progesterone receptor positive, and very low proliferative index) identical to uterine leiomyoma. In eight tumors from three patients, clonality was assessed by analyzing the variable length of the polymorphic CAG repeat sequence within the human androgen receptor gene. In the two informative patients pulmonary and uterine tumors showed identical patterns of androgen receptor allelic inactivation, indicating that they were clonal. The telomere length measured by fluorescence in situ hybridization in pulmonary leiomyomas of all three patients were either long or very long and were identical to the uterine counterparts, indicating significant telomere shortening is not a crucial step for developing metastases. Our evidence supports the notion that benign metastasizing leiomyoma is clonally derived from benign-appearing uterine leiomyomas.

The Eker Rat: Establishing a Genetic Paradigm Linking Renal Cell Carcinoma and Uterine Leiomyoma

Renal Cell Carcinoma (RCC) and uterine leiomyoma (often referred to as fibroids) are tumors arising from tubular epithelium and myometrial compartments of the kidney and uterus, respectively. These tumors have a very different clinical presentation, with RCC being one of the less common cancers, having a very poor prognosis, and occurring predominantly in men, whereas uterine leiomyoma are the most common tumor of women and are benign. Although they are distinct histologically, with RCC arising from epithelial cells and leiomyoma arising from smooth muscle cells, they share a common embryological origin. Renal tubular epithelial cells arise during nephrogenesis as a result of the mesenchymal-epithelial transition of condensed mesenchyme induced by the developing ureteric bud, and have a shared mesenchymal lineage with smooth muscle cells of the uterus. In addition to a common embryological origin, RCC and leiomyoma have been demonstrated to share a common genetic etiology. The Eker rat model was the first demonstration of a specific genetic linkage between RCC and uterine leiomyoma. Eker rats carry a germline defect in the rat homologue of the tuberous sclerosis complex 2 (TSC-2) tumor suppressor gene and develop spontaneous RCC and uterine leiomyoma with a high frequency. TSC patients are also at risk for RCC, and sporadic human uterine leiomyomas exhibit loss of function of the TSC-2 gene product, tuberin. Individuals with the inherited cancer syndrome hereditary leiomyomatosis and renal cell cancer (HLRCC) that have germline defects in the fumarate hydratase (FH) gene develop papillary RCC and uterine and skin leiomyomas. Benign cutaneous lesions and uterine leiomyoma also arise in German Shepherd dogs with germline mutations in the Birt-Hogg-Dube (BHD) gene, and these animals develop RCC and uterine leiomyoma with a high frequency. Identification of the tumor suppressor genes involved in these diseases, TSC, FH and BHD, and the elucidation of the function of their protein products, tuberin, fumarate hydratase and folliculin, respectively, opens new avenues for understanding the pathogenesis of both RCC and uterine leiomyoma.

Smooth muscle tumors of uncertain malignant potential and leiomyosarcomas of the uterus: MR findings

To study the MR characteristics of nonbenign uterine smooth muscle tumors. Nine patients with pathologically proven leiomyosarcomas, and three patients with smooth muscle tumors of uncertain malignant potential (SMTUMP) were included in this study. Twelve cases of benign uterine leiomyomas and variants, in which gynecologists suspected leiomyosarcomas, were also analyzed. In each case we studied the size, location, signal intensity, and contrast enhancement of the tumors. Nine of the 12 nonbenign characters had more than 50% of high-intensity areas on T2-weighted images (T2WI), and some hyperintense foci on T1-weighted images (T1WI). In the contrast study, nine of 12 nonbenign characters had well-demarcated unenhanced areas. On the other hand, only two of 12 benign characters showed such a signal intensity pattern, and none of them had a pocket-like unenhanced area. Although there were some exceptions, more than 50% of high signal on T2WI, and the presence of any small high-signal areas on T1WI with unenhanced pockets were considered MR-suggestive for SMTUMPs and leiomyosarcomas.

Benign metastasizing leiomyoma to skull base and spine: a report of two cases

Objective and importance: We report two patients with benign uterine leiomyoma metastasizing to the nervous system, respectively, to the skull base and to the spine. Although primary cranial and metastatic spinal leiomyomas have been rarely described, to our knowledge no case of benign leiomyoma metastasizing to the skull base has been reported before. Clinical presentation: Two female patients with history of hysterectomy for benign leiomyoma, subsequently metastasizing to the lungs and smooth muscles of the skin, presented with a focal neurologic deficit. Magnetic resonance imaging revealed a sacral mass in one case and a skull base tumor in the other. Intervention: Both patients underwent surgery for resection of the lesions. Good postoperative results were obtained. Histologic examination of the surgical specimen revealed a benign metastasizing leiomyoma. Conclusion: Benign metastasizing leiomyoma should be considered in the differential diagnosis of mass lesions in the sacral spine and skull base in patients who have a history of uterine leiomyoma or benign metastases of the same disease in organs outside the nervous system.

Submucosal Leiomyoma of the Uterus Incorporated into the Fetal Membranes and Mimicking a Placental Neoplasm: A Case Report

Leiomyoma of the placenta is uncommon. We present a leiomyoma of the fetal membranes that was incidentally discovered on examination of a spontaneously expulsed placenta following Caesarean section. Although it is an uncommon entity, it is known that leiomyomas may arise from the vasculature nourishing the fetal membranes. The baby was male and genetic studies were performed to detect Y chromosome in tumoral tissue. Polymerase chain reaction technique demonstrated Y chromosome in placental tissue but not in tumour tissue. Thus the tumour was finally diagnosed as incorporated benign uterine leiomyoma.

Cotyledonoid leiomyoma: a benign uterine tumor with alarming gross appearance.

Cotyledonoid leiomyoma or grapelike leiomyoma is a very rare tumor among the ever-expanding repertoire of growth variants described in benign uterine leiomyoma. We report a case of cotyledonoid leiomyoma in a 55-year-old woman who presented with menorrhagia and uterine prolapse. A large multinodular fungating tumor adhering to the right posterolateral wall of the uterus and extending to the broad ligament was discovered at vaginal hysterectomy. With a provisional diagnosis of sarcoma, total hysterectomy and bilateral salpingo-oophorectomy were performed. Postoperatively, the patient was well with no evidence of recurrence at 14 months. Pathologic examination revealed a 10-cm, red-brown tumor that comprised multiple bulbous processes protruding over the uterine surface, in continuity with a dissecting intramyometrial component. It was composed of fascicles and nodules of bland-looking smooth muscle cells with prominent perinodular hydropic degeneration. Coagulative necrosis, mitoses, and nuclear atypia were absent. Cotyledonoid leiomyoma apparently results from a combination of several uncommon growth patterns operating together, including subserosal growth, dissecting growth, and perinodular hydropic degeneration. Increased awareness of this grossly alarming variant of benign uterine leiomyoma can help avoid overtreatment.

Applications of the Telomerase Assay in Peritoneal Washing Fluids

Objective. The aim of this study was to detect telomerase activity in peritoneal ascites and to assess whether it can be used as an assistant tool for the early detection of ovarian cancer.Methods. Telomerase activity was measured by TRAP assay in 47 patients with ovarian malignancies and 50 patients with benign uterine leiomyomas (control group).Results. All 26 peritoneal washing cytology positive cases were telomerase positive. Of the 21 peritoneal washing cytology negative cases, 3 were telomerase positive. When these 3 were reevaluated for peritoneal cytology, malignant ascitis was identified in 1. All telomerase negative cases were negative for peritoneal washing cytology. The sensitivity and specificity of peritoneal cytology and telomerase testing in correlation with true malignant cells were 96 (26/27) and 100% (20/20) versus 100 (27/27) and 90% (18/20), respectively. The false negative rate of peritoneal cytology was 4.7% (1/21). The false positive rate of the telomerase test in relation to malignant ascites was 6.9% (2/29).Conclusion. Our preliminary results reveal a high sensitivity and specificity of both telomerase testing and conventional cytology in peritoneal fluids. Our data suggest that the telomerase test in peritoneal fluids can be used as an adjuvant to cytopathological methods in the diagnosis of malignant peritoneal ascites, particularly in cases of negative cytology. In these cases, a review of peritoneal histocytology is advised.

Elevation of insulin-like growth factor-binding protein-1 mRNA expression following hormone replacement therapy.

The purpose of this study was to investigate the possible regulatory roles of insulin-like growth factors (IGF) and IGF binding protein-1 (IGFBP-1) on postmenopausal endometrium in women undergoing hormone replacement therapy (HRT). Endometrial tissues and blood samples were collected from 25 postmenopausal women with abnormal uterine bleeding before and after HRT. As a control, blood and endometrial samples were also obtained at mid-luteal phase (days 18-23 of the menstrual cycle) from 10 women with benign uterine leiomyoma during surgical intervention. Expression of mRNA for IGF-I, IGF-II, type 1-IGF receptor, IGFBP-1, oestrogen receptor (ER) and progesterone receptor (PR) in the endometrium was explored by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Serum concentrations of IGFBP-1, oestradiol, progesterone, follicle stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were also determined. In the endometrium obtained from postmenopausal women with abnormal uterine bleeding (before HRT), expression of IGFBP-1 was undetectable, whereas PR expression was abundant. HRT significantly up-regulated expression of IGFBP-1 but down-regulated PR. Moderate expression of IGF-I, IGF-II, type 1-IGF receptor and ER was identified in the postmenopausal endometrium before HRT. HRT significantly down-regulated IGF-I, up-regulated IGF-II, but had no effects on expression of type 1-IGF receptor and ER. In conclusion, up-regulation of IGFBP-1 collaboratively with down-regulation of IGF-I may account for the protective effect of progesterone in HRT on the endometrium.

Metastasizing Uterine Leiomyoma: A Case with Cardiac and Pulmonary Metastasis

A case of histologically benign cardiac and pulmonary metastases from a uterine leiomyoma in a 45-year-old woman is reported. The solitary cardiac tumor consisted of five lobules with a stalk attached to the anterior papillary muscle of the right ventricle, which occupied the right ventricular cavity and almost completely obstructed the pulmonary main trunk in the systolic cycle. Multiple small nodules were found throughout both lungs. The cardiac tumor was resected at open heart surgery and open lung biopsy of the pulmonary lesion was simultaneously performed. Both of them were histologically identical to the apparently histologically benign uterine leiomyoma which had been resected five years previously. Based on the clinical and laboratory findings, it is postulated that antegrade metastases via the venous system resulted in the cardiac metastasis from the uterine leiomyoma and the secondary pulmonary metastasis from the cardiac tumor. In contrast to the light microscopic findings, ultrastructural examination suggested the possibility of malignancy associated with the presence of immature smooth muscle cells. This is the first reported case of a so-called benign metastasizing leiomyoma occurring in the heart.

Uterine Leiomyomas: Cytogenetic and Histologic Profile

The main purpose of this study was to determine whether there is any correlation between the cytogenetic abnormalities and histology in uterine leiomyomas.A total of 93 benign uterine leiomyomas were included in the study. The majority (88 of 93) were classified as typical benign leiomyomas, four as cellular, and one as atypical symplastic.A normal chromosome complement (46,XX) was observed in approximately 50% of the cases (41 of 93). Seventeen leiomyomas did not grow sufficiently in culture to yield cells for chromosome analyses. Of the 35 cases with clonal abnormalities, 28 could be divided into four major subgroups, each representing one of the most common abnormalities observed, such as those of chromosomes 1, 7, and 13, and t(12;14).Our findings indicate that approximately 50% of leiomyomas show clonal abnormalities, which can be subdivided into four different major categories; four of five (80%) of the atypical leiomyomas showed clonal chromosome abnormalities, which in one case were complex. The results indicate that different specific chromosome abnormalities may characterize the same tumor type.

Subgroups of uterine leiomyomas based on cytogenetic analysis

Chromosomes from 39 cases of benign uterine leiomyomas were studied. Consistent chromosomal abnormalities were detected in 15 cases (38.5%). Abnormalities involving chromosomes 12 and 14 with or without additional chromosomal changes were found in five cases (12.8%). Deletion of chromosome 7 was detected in five cases; in three cases (7.6%), this was the only abnormality present. Complex translocations involving X, 5, and 14 as well as X, 3, and 14 were observed in one case each. Insertion of a portion of chromosome 4 to chromosome 1, deletion involving chromosome 3, and nonreciprocal translocation between chromosomes 14 and 15 were observed in one case each. Monosomy 22, with a derived chromosome 14, was observed in one case. Trisomy 7 was also identified in one case. The structural and numeric abnormalities involved chromosomes X, 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 14, 15, and 22. A normal 46,XX stem line with one or two abnormal cells was observed in 20 cases. Only normal karyotypes were obtained in the remaining four cases. A review of the literature and the results of our study indicate that uterine leiomyomas may be divided into eight groups based on cytogenetic analysis.

Low-grade stromal sarcoma: a benign appearing malignant uterine tumour; a review of current literature. Differential diagnostic problems illustrated by four cases

Clinicopathological features of four cases of low-grade stromal sarcoma (LGSS) are presented. Established diagnostic criteria have been followed. Differential diagnoses are discussed with emphasis on the difficulties in separating LGSS from the very common benign uterine leiomyomas. The finding of infiltrating cells, morphologically similar to the cells of the proliferating endometrium, has been decisive for our diagnoses. Prognosis and treatment are discussed on the basis of a compilation of data collected from 31 Clinicopathological studies. Of 91 patients with initial disease confined to the uterus, 37 (41%) developed recurrence within 10 years. In contrast to most other uterine sarcomas LGSS is amenable to surgery. We recommend total abdominal hysterectomy with bilateral salpingo-oophorectomy in cases of initial disease confined to the uterus, and radical or palliative surgery in cases of extra-uterine involvement. Long-term follow-up with surgical intervention in cases of recurrence or metastases is advocated.

Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas

The incidence of leiomyosarcoma in uterine leiomyomas is estimated to be between 0.13 to 0.29%. However, the exact incidence of leiomyosarcoma in uteri removed with a preoperative diagnosis of benign uterine leiomyomas has not been previously reported. Between 1983 and 1988, a total of 1432 patients in Women's Hospital, a self-referred indigent population, had a hysterectomy planned because of abnormal uterine bleeding or abdominal pain associated with the presence of uterine leiomyomas, or because of a pelvic mass thought to be uterine leiomyoma of sufficient size or character to warrant surgical exploration. The ages of these women ranged from 36 to 62 years and the presence of leiomyosarcoma in the hysterectomy specimens increased steadily from the fourth to seventh decades of age (0.2%, 0.9%, 1.4%, and 1.7%, respectively). Preoperative histologic examination of the endometrium was performed in eight patients. Three of the eight patients had a preoperative tissue diagnosis of leiomyosarcoma that was clinically confined to the uterus. After the hysterectomy in the 1429 patients with presumed benign disease, histologic diagnosis of leiomyosarcoma was made in seven (0.49%). There was no evidence of malignancy in the endometrial sampling of any of these seven patients and the diagnosis was suspected intraoperatively in only three. Preoperative uterine size ranged from 8 to 20 weeks' gestational size and postoperative uterine weight ranged from 120 to 1100 gm. Seven of the 10 patients had symptoms of abnormal uterine bleeding. Between the ages of 40 and 60 years, 1% (8 of 817) of women with presumed uterine leiomyomas producing symptoms that necessitated hysterectomy in this series had leiomyosarcoma diagnosis postoperatively. Such treatments as gonadotropin-releasing hormone agonists, endometrial ablation, myomectomy by hysteroscopy or laparotomy instead of hysterectomy in such women could delay the diagnosis and definitive treatment of leiomyosarcoma.

Intravenous Leiomyomatosis of the Uterus

We describe 16 cases of intravenous leiomyomatosis of the uterus with unusual histologic features. Most of the patients, who ranged in age from 28 to 76 years (median, 42 years), presented with abnormal uterine bleeding or pelvic pain. On pelvic examination, they had an enlarged uterus. Extension of tumor into the broad ligament was noted at operation in six patients; it was documented on pathologic examination in an additional three cases. Gross examination disclosed enlargement of the uterus by solitary or multiple masses; wormlike plugs of tumor within myometrial veins were noted on initial examination in only five cases. Histologic examination in each case revealed proliferations of benign-appearing smooth muscle within myometrial vessels, at least some of which were large veins. The tumors differed from typical intravenous leiomyomatosis (IVL). They were classified as cellular IVL (six cases), epithelioid IVL (four cases), IVL with bizarre nuclei (two cases), intravenous lipoleiomyomatosis (two cases), myxoid IVL (one case), and IVL with an endometrial component (one case). Of 13 patients with follow-up information, 11 are alive with no evidence of disease or have died of unrelated causes at postoperative intervals of 0.5 to 19 years. One patient underwent resection of pelvic recurrent tumor 2 years postoperatively and was alive with no evidence of disease 2 years later. Another patient had pulmonary metastases 9 years postoperatively, but was alive with stable disease after an additional 6 years. This analysis indicates that most of the histologic variants of benign uterine leiomyoma can exhibit the intravascular growth pattern of IVL. These variants of IVL, except for their cellular composition, resemble typical IVL in both their clinical and pathological features. They should be distinguished from other tumors, particularly endometrial stromal sarcoma and leiomyosarcoma, which differ in their behavior and management.

Association of breakpoint 14q23 with uterine leiomyoma

A chromosomal study of short-term cultured tumor cells from a benign uterine leiomyoma showed a clonal insertion, dir ins(14;6)(q23;p23p25) as a unique change. This finding supports the hypothesis of a specific association of the breakpoint 14q23 with uterine leiomyoma.

Chronic Consumptive Coagulopathy With A Uterine Leiomyoma

Summary: A case of benign uterine leiomyoma presenting as chronic consumptive coagulopathy and microangiopathic haemolytic anaemia (MAHA) is reported. Resection of the tumour was followed by recovery of normal haemostatic function. The histological finding of extensive thrombosis of sinusoidal blood vessels within the large tumour suggested interesting pathogenetic relationships.

Uterine Fibroleiomyomata with Aortic Lymph Node Metastases

This is a report of extensive metastases of histologically benign uterine leiomyomas to para-aortic lymph nodes in a 32-year-old woman. The pathologic features and clinical characteristics are described, and the previously recorded experience with this rare entity is reviewed.

Benign uterine leiomyoma with vascular involvement: Report of 3 cases

Three cases of intravascular extension of leiomyomatous tumor tissue have been presented. Prominent symptoms in these patients were abdominal pain and enlargement and menometrorrhagia. No malignant features other than the aforementioned extensions were noted, and all of the tumors were histologically benign. The tumors can be distinguished from stromal endometriosis by microscopic examination.