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Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, to identify robust epigenomic differences among tissue types, differentiation states, and disease subtypes. Applying DeCET to our own data from 21 uterine benign tumor (leiomyoma) patients identifies distinct epigenomic features discriminating normal myometrium and leiomyoma subtypes. Leiomyomas possess preponderant alterations in distal enhancers and long-range histone modifications confined to chromatin contact domains that constrain the evolution of pathological epigenomes. Moreover, we demonstrate the power and advantage of DeCET on multiple publicly available epigenomic datasets representing different cancers and cellular states. Epigenomic features extracted by DeCET can thus help improve our understanding of disease states, cellular development, and differentiation, thereby facilitating future therapeutic, diagnostic, and prognostic strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the differences in leiomyoma pathophysiology by patient age at the time of surgery and the possible significance of postmenopausal uterine leiomyomas, particularly variants., Methods: We retrospectively reviewed data from 471 patients who underwent surgery for uterine leiomyomas and evaluated their clinical data., Results: Overall, 441 (93.4%) women were premenopausal and 30 (6.4%) were postmenopausal. There were no differences in the frequency of the coexistence of ovarian steroid-dependent diseases among age groups. Common histopathological features were observed in most cases despite menopausal status; however, the incidence of variants among postmenopausal patients was high compared to that among premenopausal women (23.3% [7/30] vs 3.2% [14/441], respectively). Among the variant leiomyomas in postmenopausal patients, lipoleiomyomas comprised six., Conclusion: Although progesterone is known to play a vital role in promoting leiomyoma growth, it reportedly performs dual actions and does not always stimulate leiomyoma growth. Our study may support the idea that the dual action of progesterone is the primary reason for the surgical treatment required for uterine leiomyomas in the postmenopausal period. We also found that lipoleiomyoma might be the most common uterine leiomyoma variant requiring surgical treatment among postmenopausal women. Thus, we must consider the diagnosis of uterine lipoleiomyoma in postmenopausal women with uterine leiomyomas., (© 2018 Japan Society of Obstetrics and Gynecology.)

The diagnosis of a uterine myoma size and location can be very precise when a 3D sonograph and knowledge are available. The majority of fibroids are asymptomatic, and expectant management is recommended. In young patients, fibroids cause infertility and in middle-aged women, abnormal uterine bleedings. Laparoscopic myomectomy is the preferred way of surgery for IM and SS fibroids, versus hysteroscopy for SM fibroids. In both cases, the size, number of fibroids and the surgeon's experience determine the limitations of the MIGS. Medical treatments provide only temporary tumor reduction and symptom alleviation. Leiomyosarcoma risk is higher in older women usually carrying fibroids larger than 8 cm. There are no other pathognomonic parameters ruling out a sarcoma. In case of suspected fibroid malignancy, the best treatment option is laparotomy and total hysterectomy. Myomectomy complications can be reduced when MIGS is performed by a surgeon with proper training and experience., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: To comparatively evaluate the role of magnetic resonance (MR) T1 perfusion-based time-signal intensity (SI) curves of fibroid tissue and the myometrium in classification of fibroids for predicting treatment outcomes of high-intensity focused ultrasound (HIFU) treatment., Methods: The fibroids of 74 women who underwent MR-HIFU treatment were classified into group A (time-SI curve of fibroid lower than that of the myometrium) and group B (time-SI curve of fibroid equal to or higher than that of the myometrium). Non-perfused volume (NPV) ratios immediately after treatment and fibroid volume reduction ratios and symptom severity scores (SSS) at the 6-month follow-up were retrospectively assessed., Results: The immediate NPV ratios in groups A and B were 95.3 ± 6.3% (n = 62) and 63.8 ± 11% (n = 12), respectively. At the 6-month follow-up, the fibroid volume reduction ratios in groups A and B were 0.52 ± 0.14 (n = 50) and 0.07 ± 0.14 (n = 11), with the corresponding improvement in mean transformed SSS being 0.86 ± 0.14 and 0.19 ± 0.3, respectively. No serious adverse effects were reported., Conclusions: Our novel classification method could play an important role in classifying fibroids for predicting the immediate outcomes of HIFU treatment., Key Points: • MRI is an important modality for outcome prediction in HIFU treatment • Patient selection is a significant factor for achieving high NPV ratio • NPV ratio is very strongly correlated with T1 perfusion-based classification • T1 perfusion-based classification is a strong predictor of treatment outcome.

Objective: To determine the reproducibility of classifying uterine fibroids using the 2011 International Federation of Gynecology and Obstetrics (FIGO) staging system., Methods: The present retrospective cohort study included patients presenting for the treatment of symptomatic uterine fibroids at the Gynecology Fibroid Clinic at Mayo Clinic, Rochester, USA, between April 1, 2013 and April 1, 2014. Magnetic resonance imaging of fibroid uteri was performed and the images were independently reviewed by two academic gynecologists and two radiologists specializing in fibroid care. Fibroid classifications assigned by each physician were compared and the significance of the variations was graded by whether they would affect surgical planning., Results: There were 42 fibroids from 23 patients; only 6 (14%) fibroids had unanimous classification agreement. The majority (36 [86%]) had at least two unique answers and 4 (10%) fibroids had four unique classifications. Variations in classification were not associated with physician specialty. More than one-third of the classification discrepancies would have impacted surgical planning., Conclusion: FIGO fibroid classification was not consistent among four fibroid specialists. The variation was clinically significant for 36% of the fibroids. Additional validation of the FIGO fibroid classification system is needed., (© 2017 International Federation of Gynecology and Obstetrics.)

Objective: Laparoscopic approaches are the gold standard surgical treatment for intramural and subserous fibroids, whereas submucosal myomas can be treated via hysteroscopy. Removal of intramural myomas often requires a subsequent reconstruction of the uterine wall that ranges from single- to multiple-layer sutures to complex reconstructions. Several classification systems are currently used to characterize uterine fibroids, all of which focus on the assessment of submucosal fibroids during hysteroscopic myomectomy. There are no classification systems for the comprehensive localization of fibroids or for uterine reconstruction after myomectomy. Therefore, the aim of this study was to validate a new scoring system developed by our group to classify uterine leiomyoma as well as a standardized assessment scoring system for uterine reconstruction after surgical myomectomy., Methods/patients: To validate the uterine fibroid and uterine reconstruction classification systems, a retrospective review of 136 patients undergoing surgical myomectomy and uterine reconstruction at a single tertiary institution was performed. The age of the patient, duration of surgery, number, size, and location of excised fibroids, number of uterine incisions, level of uterine reconstruction, desire for future pregnancies, pre- and postoperative hemoglobin concentrations, duration of postoperative hospitalization, and operating surgeon were obtained by medical chart review. For each patient, a specific fibroid score and the level of uterine reconstruction were determined according to the classification systems. Correlations between the uterine fibroid and reconstruction scores, as well as between the classification scores and perioperative parameters, were analyzed., Results: The newly developed classification system for uterine fibroids incorporates the number, location, and size of myomas, as well as the number of uterine incisions required for myomectomy. The uterine reconstruction scoring system comprises four levels of reconstruction, ranging from no reconstruction to advanced reconstruction. Outcomes from 136 patients showed a correlation between uterine fibroid and uterine reconstructive scores. High fibroid scores were correlated with higher levels of reconstruction. Both scoring systems showed associations with the duration of surgery, intraoperative blood loss, and days of hospitalization., Conclusions: This study presents the first scoring system for uterine fibroids that incorporates all possible fibroid locations and a standardized assessment of uterine reconstruction. Scoring systems were validated in a large cohort, and a correlation was identified between uterine fibroid and uterine reconstruction scores. In daily clinical practice, this scoring system allows a better planning of surgery, specifically of the estimated duration of surgery, blood loss, and time of hospitalization.

Purpose of Investigation: This study aimed to estimate the effectiveness of hysteroscopic myomectomy for symptomatic submucous uterine fibroids and to identify prognostic factors for persistent or recurrent symptoms., Materials and Methods: A total of 237 patients who underwent hysteroscopic myomectomy were divided into three groups according to the classification of the European Society for Gynaecological Endoscopy: Type 0 (n=116), Type I (n=97), and Type II (n=24). Medical records and videotape records of all patients were retrospectively reviewed., Results: Improvement of symptoms was achieved in 100% of Types 0 and I, and 66.7% of Type II. The five-year cumulative symptom-free rates after hysteroscopic myomectomy were 96.7% ± 1.9%, 87.8% 6.7%, and 44.5% ± 12.7% in Types 0, I, and II, respectively. The mean symptom-free periods were 46.2 ± 2.6, 47.7 ± 2.7, and 24.7 ± 6.3 months in Types 0, I, and II, respectively. Logistic regression analysis showed that co-existence of other myomas and Type II were independent prognostic factors for recurrence of symptoms., Conclusion: Type I fibroids are a good indication for hysteroscopic myomectomy. In Type II, some patients feel that their symptoms improve, but this curative effect could be temporary.

Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Myofibroblastoma belongs to a family of CD34-positive tumors with similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. A subset of these tumors demonstrates distinct smooth muscle differentiation. We aimed to characterize 4 cases of the leiomyomatous variant of myofibroblastoma arising in the breast by clinicopathological, immunohistochemical, and molecular means. All 4 examples arose in women aged 41 to 62 years (median, 46.5 years). Tumors ranged in size from 1.7 to 2.5 cm (median, 2.2 cm). Morphologically, all tumors were characterized by bundles of smooth muscle cells with elongated cigar-shaped nuclei and eosinophilic cytoplasm. All 4 tumors showed diffuse positive staining with desmin, caldesmon, smooth muscle actin, estrogen receptor, and Bcl-2. CD34 staining was diffusely positive in 2 cases, was weak and patchy in 1 case, and was negative in 1 case. Two (50%) of 4 tumors showed deletion of RB1 by fluorescence in situ hybridization. Loss of Rb staining was seen in 1 tumor with RB1 deletion by fluorescence in situ hybridization, whereas intact Rb staining was observed in 1 nondeleted case studied. In conclusion, this rare variant of myofibroblastoma is a distinct subgroup of tumors among an already uncommon category of (smooth muscle) breast tumors. Some reported examples of "parenchymal leiomyoma" may represent the leiomyomatous variant of myofibroblastoma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

While clear cell, papillary and chromophobic renal cell carinoma (RCC) represent the most common malignant renal neoplasms, the evaluation and classification of rare renal carcinomas has currently come into focus. One of these is the leiomyomatous RCC, which shows morphologic similarities to clear cell RCCs, however exhibiting additional, atypical smooth muscle differentiation. We report the clinical case of a patient simultaneously presenting with leiomyomatous and papillary RCC and discuss new tumor entities of RCC.

Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women's health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among leiomyomas harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen, type IV, alpha 5 and collagen, type IV, alpha 6 (COL4A5-COL4A6) deletions. We also explored the transcriptional consequences of 7q22, 22q, and 1p deletions, aiming to identify possible target genes. We investigated 94 leiomyomas and 60 corresponding myometrial tissues using exon arrays, whole genome sequencing, and SNP arrays. This integrative approach revealed subtype-specific expression changes in key driver pathways, including Wnt/β-catenin, Prolactin, and insulin-like growth factor (IGF)1 signaling. Leiomyomas with HMGA2 aberrations displayed highly significant up-regulation of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1), suggesting that HMGA2 promotes tumorigenesis through PLAG1 activation. This was supported by the identification of genetic PLAG1 alterations resulting in expression signatures as seen in leiomyomas with HMGA2 aberrations. RAD51 paralog B (RAD51B), the preferential translocation partner of HMGA2, was up-regulated in MED12 mutant lesions, suggesting a role for this gene in the genesis of leiomyomas. FH-deficient leiomyomas were uniquely characterized by activation of nuclear factor erythroid 2-related factor 2 (NRF2) target genes, supporting the hypothesis that accumulation of fumarate leads to activation of the oncogenic transcription factor NRF2. This study emphasizes the need for molecular stratification in leiomyoma research and possibly in clinical practice as well. Further research is needed to determine whether the candidate biomarkers presented herein can provide guidance for managing the millions of patients affected by these lesions.

A case of multiple benign leiomyomas in the right ventricle of a 47-year-old woman is presented. Multiple lesions were revealed at different locations in the right ventricle; 1 lesion extended into the right pulmonary artery. Histologic examination showed benign leiomyomas arising from the tunica media of the intramyocardial vessels. Also, the primary origin of the cardiac tumors is demonstrated by the evidence that no leiomyoma was found in the genital system 30 months after the cardiac operation. To our knowledge, this is the first case report of multiple primary cardiac leiomyomas in a premenopausal woman. The midterm prognosis after complete resection is good., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The oncogenic phosphatidylinositol 3-kinase-AKT-mammlian target of rapamycin pathway (PI3K-AKT-mTOR) pathway is known to be activated in uterine smooth muscle tumors, and Stathmin 1 (STMN1) expression has been identified as a marker of PI3K-AKT-mTOR pathway activation. We hypothesized that STMN1 may have some diagnostic utility and explored how well STMN1 expression correlated with histologic classifications of uterine smooth muscle tumors into benign and malignant groupings. 84 smooth muscle tumors were assessed for STMN1 expression by immunohistochemistry. These included spindle cell leiomyosarcoma (n=32), conventional spindle cell leiomyomas (n=30), atypical (symplastic) leiomyoma (n=5), cellular leiomyoma (n=7), smooth muscle tumor of uncertain malignant potential (n=4), mitotically active leiomyomas (n=2), benign metastasizing leiomyoma (n=3), and cotyledonoid dissecting leiomyoma (n=1). All spindle cell leiomyosarcomas were positive (32/32 positive; 100%) as compared with conventional leiomyomata (11/30; 37%) (P<0.0001). The average immunohistochemical score (0-12+, reflective of intensity and extent) for leiomyosarcomas was 8.7 (±1.43) whereas the conventional leiomyomata average score was 1.6 (±1.07) (P<0.0001). This difference in scores was reflected in the patterns of expression: leiomyosarcomas were predominantly strongly and diffusely positive whereas leiomyomata were predominantly weakly, albeit diffusely positive when expression was present. The sensitivity of STMN1 expression for leiomyosarcomas was 100%. However, the specificity was found to be only 55% (CI=43-68%). The negative and positive predictive values for leiomyosarcomas were 100% and 52% respectively. The odds ratio (OR) for any STMN1 expression in predicting a spindle cell leiomyosarcoma diagnosis from this dataset was highly significant (OR=144, P=0.0006). Thirteen non-smooth muscle tumors that involved the uterus all showed at least focal STMN1 immunoreactivity. In summary, STMN1 is a highly sensitive marker for leiomyosarcoma but is suboptimally specific for diagnostic purposes. The 100% negative predictive value for leiomyosarcoma may offer some diagnostic utility in a small sample, since the absence of STMN1 immunoreactivity in a putative leiomyosarcoma is a strong argument against this diagnostic possibility.

Renal leiomyoma is an exceptionally rare benign mesenchymal tumor of the kidney predominantly arising in proximity of the renal capsule or pelvis. Its rarity and nonspecific clinical and imaging features may lead to radical or partial nephrectomy on the basis of preoperative suspicion of renal cell carcinoma. The diagnosis of renal leiomyoma is challenging because of the histologic overlap with lipid-poor angiomyolipoma (AML). We conducted a multi-institution study to characterize renal leiomyoma in greater detail. We collected and reviewed 24 cases diagnosed initially as renal leiomyoma in 10 institutions from North America, Canada, and Europe. Immunohistochemical expression of desmin, HMB-45, estrogen receptor (ER), progesterone receptor (PR), and cathepsin K was evaluated. Upon central review, 9 tumors were classified as renal leiomyoma, whereas the remaining were reclassified as AML (n=13), myolipoma (n=1), and medullary fibroma (n=1). All renal leiomyomas were solitary and occurred in female patients (mean age 63 y; range, 44 to 74 y). Tumor size ranged from 0.6 to 7.0 cm (mean 2.9 cm); 7 originated from the renal capsule or the subcapsular area and 1 from a large vessel in the renal sinus. All leiomyomas were diffusely positive for desmin and negative for HMB-45 and cathepsin K; 6/9 (67%) showed diffuse ER and PR expression, and 1 case showed focal ER positivity only. Renal leiomyoma should be included in the histologic differential diagnosis of solid renal masses, particularly in perimenopausal women. The main differential diagnosis is with lipid-poor AML, and cathepsin K plays a key role in distinguishing these 2 lesions.

Leiomyoma is the most frequent benign monoclonal tumor (cells behave identically in culture) of the female reproductive system. It affected almost 50% of childbearing age women, deteriorating the quality of life and may cause infertility. The unique features of this pathology is the absence of detailed understanding of pathogenic mechanisms and continuous morbidity among any age groups. Despite the huge amount of articles and studies related to leiomyoma, review pretend to depict herein actual and non-trivial information. This review assemble a versatile description of medical and biological aspects of leiomyomas. Explanation of genetic, molecular, pathophysiological mechanisms of uterine fibroid growing predetermine marked clinical symptoms of pathology. Mentioned model systems show multivariation of leiomyomas in human and animals. Review gives an opportunity analyze separate facets and collect it in one deep understanding of leiomyomas.

Leiomyoma with bizarre nuclei (LM-BN) is an uncommon tumor with histologic features (mononucleated or multinucleated bizarre cells that may have a diffuse distribution, prominent nucleoli, and karyorrhectic nuclei that may mimic atypical mitoses) that often causes confusion with leiomyosarcoma. Fifty-nine LM-BNs were collected from our consultation files over the years 2000 to 2011. Features recorded included patient age, therapy, tumor size, border, gross appearance, density and distribution of BN, mitotic count, karyorrhectic nuclei, prominent nucleoli, cells with conspicuous dense eosinophilic cytoplasm (rhabdoid-like), vascular changes and type of vasculature, and presence of necrosis and its nature. Follow-up information was obtained for all patients. Patients ranged in age from 25 to 75 (average 45) years (11 patients between 25 and 35 y, 20 between 36 and 45 y, 22 between 46 and 55 y, and 6 between 56 and 75 y). Forty-two underwent hysterectomy and 17 myomectomy. For 51 tumors gross findings were known. Forty (78%) had a solid white and whorled cut surface and 11 (22%) a yellow appearance. Five (10%) neoplasms showed prominent cystic degeneration, and hemorrhage and/or necrosis was seen in 9 (18%). Forty-five LM-BNs had a pushing margin with the surrounding myometrium, whereas 1 showed irregular borders. Margins could not be ascertained in the slides available in 13 cases. Twenty-eight (48%), 19 (32%), and 12 (20%) LM-BN showed low, intermediate, and high BN density. Eighteen (30%) tumors showed diffuse, 26 (44%) showed multifocal, and 15 (26%) had focal BN distribution. Mitotic counts ranged from 0 to 7/10 high-power fields (HPF) (average 1 to 2/10 HPF). Thirty-seven (63%) had <2/10 HPF, 19 (32%) had 2 to 5 mitoses/10 HPF, and in 3 tumors (5%) mitotic counts were 6, 7, and 7/10 HPF (2 with focal and 1 with diffuse BN). All but 4 LM-BNs showed karyorrhectic nuclei, striking in 12 neoplasms, mimicking atypical mitoses. Nineteen (32%) LMs had prominent eosinophilic nucleoli surrounded by a clear halo. Ischemic necrosis was detected in 21 (36%) LM-BN. Rhabdoid-like cells were noted in 24 (41%) tumors. All patients had no evidence of recurrence, ranging from 1 to 13 years (overall average 6 y; in patients with myomectomy 6.3 y with a range of 2.6 to 11 y). Our results corroborate that LM-BN is associated with a favorable outcome even in those patients only treated by myomectomy and highlights that a conservative approach can be undertaken in these patients, as many of them are of reproductive age. Because of the favorable outcome, the term LM-BN is preferable to alternative terminology including "atypical leiomyoma."

Uterine leiomyoma (UL), the most common benign tumour found in females, is associated with many recurrent genetic aberrations, such as translocations, interstitial deletions and specific germline mutations. Among these, mutations affecting exon 2 of the mediator complex subunit 12 (MED12) gene are commonly detected in the majority of ULs. Mutational analysis of the MED12 gene, performed on 36 UL samples, revealed that 12 leiomyomas (33.4%) exhibited heterozygous missense mutations in codon 44 of exon 2 of the MED12 gene, four leiomyomas (11.1%) showed internal in-frame deletions, and two leiomyomas (5.5%) exhibited deletions involving intron 1-exon 2 junction, which caused a predicted loss of the splice acceptor. No mutations were detected in uterine myometrium (UM) and pseudocapsule (PC) samples, including those from women with a MED12 mutation in UL. These data showed that the PC is a healthy tissue that surrounds the UL to maintain UM integrity. Analysis of insulin-like growth factor 2 (IGF-2) and collagen type IV alpha 2 (COL4A2) mRNA expression levels in the same set of ULs revealed that only those with MED12 missense mutations expressed significantly higher levels of IGF-2 mRNA. In contrast, MED12 gene status does not appear to affect mRNA expression levels of the COL4A2 gene. On the basis of this finding, we suggest that the MED12 status stratifies the ULs into two mutually exclusive pathways of leiomyoma genesis, one with IGF-2 overexpression and the other with no IGF-2 activation. The occurrence of IGF-2 overexpression could be therapeutically targeted for the non-surgical treatment of leiomyomas., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Uterine leiomyomas are benign smooth-muscle tumors of extremely low malignant potential. Early work utilizing classical cytogenetics revealed that a subset of uterine leiomyomas harbor recurrent chromosomal rearrangements, such as translocations affecting the HMGA2 gene. Our understanding of the genetics of many tumor types has deepened remarkably with the emergence of next-generation sequencing technologies. Exome sequencing identified that the majority of leiomyomas display highly specific MED12 mutations. Further studies suggest that these MED12 hotspot mutations are also frequent in breast fibroadenomas, but not in other human tumors. Whole-genome sequencing showed that a subset of leiomyomas display complex chromosomal rearrangements resembling chromothripsis. These were formed in a single event of chromosomal breakage and random reassembly involving one or a limited number of chromosomes. Although most leiomyomas have been shown to arise independently, these studies also revealed that distinct nodules within a uterus may display identical genetic changes indicating a common clonal origin. A minority of leiomyomas were also found to display deletions within the COL4A5-COL4A6 genes, leading to upregulation of the adjacent gene IRS4. The findings derived from high-throughput sequencing combined with previous knowledge have led to an emerging molecular classification of leiomyomas, suggesting that there are several distinct pathogenic pathways involved in leiomyoma formation. The evidence points to at least 4 molecular subclasses: leiomyomas with MED12 mutation, FH inactivation, HMGA2 overexpression, and COL4A6-COL4A5 deletion. Elucidating the molecular pathogenesis of leiomyomas should be relevant for developing treatments for this very common disease., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The uterine fibroid is a benign tumour. The prevalence, in all the population, is 50% for european women and 80% for black women. 30% of fibroids are symptomatic. The new FIGO classification gives 7 positions (0 to 7), submuccus (0, 1, 2), interstitial (3, 4, 5), subserous (6, 7). Diagnosis is performed by 2D and 3D ultrasound which could be associated by hysterosonography. Hysteroscopy and MRI could be proposed. Hysterectomy is the main treatment, if possible by vaginal or laparoscopic way. Conservative treatment (myomectomy) could be realized by hysteroscopic, laparoscopic way or laparotomy for patients who desire to preserve fertility. Arteries embolisation is an alternative to hysterectomy or myomectomy for patients without desire of pregnancy. Preoperative treatments by GnRH agonist or SPRM like ulipristal acetate treat anaemia, decrease the myoma volume and could modify the therapeutic strategy.

Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed leiomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation 'smooth muscle tumor of uncertain biologic potential' is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution ('dedifferentiation'). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBV-associated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing 'chaotic' karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.

Uterine fibroids (UFs) affect 77 % of women by menopause and account for $9.4 billion in yearly healthcare costs. We recently replicated findings from the first UF genome-wide association study (GWAS), conducted in the Japanese. Here we tested these GWAS-discovered SNPs for association with UF characteristics to further assess whether risk varies by sub-phenotypes of UFs. Women were enrolled in Right from the Start (RFTS) and the BioVU DNA repository (BioVU). UF status was determined by pelvic imaging. We tested the top GWAS-associated SNPs for association with UF characteristics (RFTS: type, number, volume; BioVU: type) using covariate adjusted logistic and linear regression. We also combined association results of UF type using meta-analysis. 456 European American (EA) cases and 1,549 controls were examined. Trinucleotide repeat containing 6B (TNRC6B) rs12484776 associated with volume in RFTS (β = 0.40, 95 % CI 0.05-0.75, p = 0.024). RFTS analyses evaluating stratified quartiles of volume showed the strongest OR at rs12484776 for the largest volume (16.6-179.1 cc, odds ratio (OR) = 2.19, 95 % confidence interval (CI) 1.07-4.46, p = 0.031). Meta-analysis showed a strong association at blocked early in transport 1 homolog (BET1L) rs2280543 for intramural UFs (meta-OR = 0.51, standard error (SE) = 0.14, Q = 0.590, I = 0, p = 2.48 × 10(-6)), which is stronger than the overall association with UF risk. This study is the first to evaluate these SNPs for association with UF characteristics and suggests these genes associate with increasing UF volume and protection from intramural UF in EAs.

Objective: We describe a case of complete enucleation of a Type II leiomyoma using the TRUCLEAR™ (Smith & Nephew Endoscopy, Andover, MA) hysteroscopic morcellator (THM) and demonstrate appropriate preoperative assessment and intraoperative surgical principles during this case. Complete hysteroscopic enucleation of Type II leiomyomas is also systematically reviewed., Materials and Methods: In this case report and review, performed in a tertiary-care university setting, the THM was used for hysteroscopic resection of two submucosal leiomyomas., Results: A 41-year-old gravida 1 para 0010 presented with infertility and symptomatic leiomyomas. Preoperative assessment included a hysterosalpingogram, magnetic resonance imaging, and sonohysterography demonstrating several extrinsic impressions on the uterine cavity and two submucosal leiomyomas (Type I and Type II). Diagnostic hysteroscopy confirmed findings. As the THM blade started resecting the Type II leiomyoma, it began to separate from the underlying myometrium. Attempts to release the edge of the leiomyoma, including reverse rotation of the blade, completely enucleated the leiomyoma, which was subsequently removed from the cavity with the THM. Minimal bleeding was encountered; intraoperative ultrasound confirmed normal overlying myometrium. Postoperatively, sonohysterography showed complete closure of the dead space with only a slightly distorted endometrial cavity., Conclusions: Hysteroscopic uterine leiomyoma enucleation should only be performed in experienced hands. Inadvertent enucleation of a Type II leiomyoma with a THM device is described, with review of key surgical principles that guided safe resection.

Smooth muscle tumors rather benign or malignant can arise wherever the muscular tissue presents but cutaneous leiomyoma is one of the rare benign tumors of the which even the diagnostic criteria from the malignant type of the tumor is still in doubt. This study was aimed to compare the subtypes of cutaneous leiomyoma from different histologic aspects in order to find unique criteria for better classification and diagnosis. The six year data base of our center was reviewed and 25 patients with cutaneous leiomyoma were included in this study. Of 25 patients, 5 were female and 20 were male. 5 patients had angioleiomyoma (ALM) and 20 had pilar leiomyoma (PLM). ALM had following characteristics: dilated vascular canals intermingled with compact smooth muscle bundles; well circumscribe counter and myxoid and hyaline changes through the tumor. In contrast, PLMs had following histologic features: poor defined outline, entrapped hair follicles and eccrine glands, acanthosis and elongated rete ridges with hyperpigmentation and smooth muscle bundles which are interdigitated with elongated rete ridges. Here we introduced some distinct histological features for each subtype of the cutaneous leiomyoma which can lead to create novel criteria for classification and diagnosis of the lesion., (© 2013 Tehran University of Medical Sciences. All rights reserved.)

In November 2010, the International Federation of Gynecology and Obstetrics formally accepted a new classification system for causes of abnormal uterine bleeding in the reproductive years. The system, based on the acronym PALM-COEIN (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy, ovulatory disorders, endometrial causes, iatrogenic, not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation that relates to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding and the various symptoms that comprise abnormal bleeding has also been included. This article describes the rationale, the structured methods that involved stakeholders worldwide, and the suggested use of the International Federation of Gynecology and Obstetrics system for research, education, and clinical care. Investigators in the field are encouraged to use the system in the design of their abnormal uterine bleeding-related research because it is an approach that should improve our understanding and management of this often perplexing clinical condition., (Copyright © 2012. Published by Mosby, Inc.)

Objective: To evaluate 2 different predicting scores of submucous myoma removal, fluid balance, and operative time in woman undergoing hysteroscopic myomectomy., Design: A multicenter and prospective study (Canadian Task Force classification II-2)., Setting: Six hysteroscopy centers in Brazil., Patients: A total of 191 women who underwent hysteroscopic resection of 205 submucous myomas., Intervention: Resection of submucous myomas (hysteroscopic myomectomy). Myomas were scored according to the European Society for Gynaecological Endoscopy (ESGE) and STEPW (size, topography, extension, penetration, and wall) classifications. The validation of the 2 classifications was assessed with sensitivity and specificity of each classification, with their best cutoff point., Main Outcome Measures: To correlate ESGE and STEPW classifications with complete or incomplete removal of submucous myoma, length of surgery, surgical complications, and fluid balance., Results: Removal of the myoma was complete in 190 (92.7%) of 205 myomectomies, and incomplete in 15 (7.3%). All 140 (100%) of 140 myomas with a score ≤ 4 in the STEPW classification were completely removed, and 50 (76.9%) of 65 myomas with a score >4 were removed. All 15 (100%) cases of incomplete hysteroscopic myomectomy had a STEPW score >4. With the ESGE classification, 156/164 (95.1%) cases of type 0 and type 1 myomas, and 34/41 (82.9%) of type 2 were completely resected. STEPW scores >4 were statistically associated with longer duration of surgery, surgical complications, higher levels of fluid balance, and use of gonadotropin releasing hormone analogue if compared with lower scores. The ESGE scores were not associated with any of these variables., Conclusion: Classifying submucous myomas with the STEPW classification allows better prediction of myoma removal, fluid balance, length of surgery and surgical complications in hysteroscopic myomectomy than ESGE classification., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

Submucous leiomyomas or myomas are commonly encountered by gynecologists and specialists in reproductive endocrinology and infertility with patients presenting with 1 or a combination of symptoms that include heavy menstrual bleeding, infertility, and recurrent pregnancy loss. There exists a variety of interventions that include those performed under hysteroscopic, laparoscopic and laparotomic direction; an evolving spectrum of image guided procedures, and an expanding number of pharmaceutical agents, each of which has value for the appropriately selected and counseled patient. Identification of the ideal approach requires the clinician to be intimately familiar with a given patient's history, including her desires with respect to fertility, as well as an appropriately detailed evaluation of the uterus with any one or a combination of a number of imaging techniques, including hysteroscopy. This guideline has been developed following a systematic review of the evidence, to provide guidance to the clinician caring for such patients, and to assist the clinical investigator in determining potential areas of research. Where high level evidence was lacking, but where a majority of opinion or consensus could be reached, the guideline development committee provided consensus recommendations as well., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

Four myxoid variant of uterine mesenchymal tumors are reported. One was a low grade stromal sarcoma with infiltrative margins and the others were well circumscribed tumors corresponding to an endometrial stromal nodule and two leiomyomas. They were hypocellular neoplasms composed of stellated cells with an abundant Alcian Blue positive myxoid matrix. The myxoid nature of the neoplasms obscured their cellular nature and made the distinction between smooth muscle and endometrial stromal tumors difficult. Endometrial stromal tumors, showed very focal areas of small basophilic cells, characteristic of endometrial stroma. The diagnosis was based on the presence of a spiral arteriolar network, a CD10 positivity as well as the absence of h-caldesmon and desmin expression. The two myxoid leiomyomas showed more spindle cells and a desmin expression while h-caldesmon was negative and CD10 focally positive in both cases. Myxoid variant of endometrial stromal tumors does not necessarily exhibit the typical morphology of endometrial stroma. They may demonstrate morphological features of smooth muscle tumors in the uterus. Also, myxoid changes in uterin smooth muscle tumors may modify the classical immunoreactivity of smooth muscle markers in these tumors and make it difficult to distinguish between benign and malignant neoplasms. An immunohistochemical panel of antibodies including CD10, h-caldesmon and desmin may help in establishing the correct diagnosis., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the performance of the STEPW (size, topography, extension, penetration, wall) classification system in predicting partial or complete fibroid removal on hysteroscopic myomectomy., Design: Multicenter, prospective study (Canadian Task Force classification II-2)., Setting: Four hysteroscopy centers in Brazil, China, Italy, and the United States., Patient(s): Four hundred forty-nine women who underwent hysteroscopic resection of 465 submucous fibroids., Intervention(s): Resection of the submucous fibroids (hysteroscopic myomectomy). Fibroids were scored according to the European Society for Gynaecological Endoscopy (ESGE) and STEPW classifications. The validation of the two classifications was assessed using sensitivity and specificity of each classification, with their best cutoff point. A test of equality of the two areas under the receiver operating characteristic curves was performed for correlated samples., Main Outcome Measure(s): Correlation of ESGE and STEPW classifications with complete or incomplete removal of submucous fibroid., Result(s): Removal of the myoma was complete in 432 (92.9%) of 465 myomectomies and incomplete in 33 (7.1%). All 320 fibroids (100%) with a score≤4 in the STEPW classification were completely removed, and 112 of 145 fibroids (77.2%) with a score>4 were removed. All 33 cases of incomplete hysteroscopic myomectomy (100%) had a STEPW score>4. Using the ESGE classification, 85 of 86 cases (98.9%) of type 0 fibroids, 278 of 298 (93.3%) of type 1, and 69 of 81 (85.2%) of type 2 were completely resected., Conclusion(s): Classifying submucous fibroids using the STEPW classification permits greater correlation with complete or incomplete removal of the myoma by hysteroscopic myomectomy., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare potential risk factors for uterine leiomyomata (UL) subtypes among premenopausal African American and Caucasian women., Methods: This cross-sectional study included 986 premenopausal women, aged 35 to 49 years old, from the National Institute of Environmental Health Sciences (NIEHS) Uterine Fibroid Study (UFS). Uterine leiomyomata were subtyped as submucosal, intramural/subserosal, and diffuse, based on ultrasound examinations., Results: For both ethnic groups, age, age at menarche, body mass index, and current physical activity had similar associations across the 3 UL subtypes. Inverse associations with pregnancies after age 24 appeared to be stronger for the submucosal subtype. Current smoking was associated only with diffuse UL (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.11, 3.51 in African Americans, aOR = 3.00, 95% CI: 1.07, 8.38 in Caucasians)., Conclusions: Although the 2 focal UL subtypes had similar risk factor profiles, the diffuse UL subtype appeared to have a distinctive risk profile with regard to current smoking. Further study of the diffuse heterogeneity seen with uterine ultrasound is needed.

Objective: To investigate whether polymorphism in CYP17A1 gene is associated with uterine leiomyomas (ULM) and to evaluate differences in epidemiologic and genetic factors among solitary and multiple leiomyomas., Design: Prospective case control study., Setting: Tertiary gynecology department., Patient(s): One hundred eighty-one women with clinically and surgically diagnosed ULM, 41 healthy control subjects, and 92 population control subjects., Intervention(s): Completing the questionnaires, peripheral venous puncture., Main Outcome Measure(s): Polymerase chain reaction and restriction-fragment-length polymorphism analyses were performed to genotype women regarding the CYP17A1 -34 A/G (rs743572) gene polymorphisms. Epidemiologic data was collected by questionnaire and compared between women with ULM and healthy control subjects., Result(s): Women with multiple ULM had higher prevalence of positive family history, lower age at menarche, lower parity, higher percentage of smoking, younger age at first sexual intercourse, lower prevalence of CYP17A1 AA genotype and lower CYP17A1 A allele frequency than healthy control subjects. These trends were not apparent among women with solitary ULM., Conclusion(s): Carriage of CYP17A1 AA is protective for developing ULM in our population. Women with solitary ULM mostly resembled healthy control subjects, whereas women with multiple ULM differed in CYP17A1 AA genotype and external stimuli., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Uterine leiomyomas (fibroids, myomas) are a common benign disease of the uterus with a prevalence of 8-18%. Prevalence rates vary with race, and fibroids are most common in African American women. Uterine leiomyomas can also be present during pregnancy, which may occur more frequently than previously suspected, with prevalence rates reported of up to 10%. Recent evidence has emerged to clarify the relationship of uterine fibroids on fertility and obstetrical outcomes. In this paper we review evidence that uterine fibroids, specifically submucosal and intramural myomas, negatively impact fertility and are associated with adverse obstetrical outcomes such as: pain, preterm labor, placental abruption, malpresentation, postpartum hemorrhage, and cesarean section. Myomectomy performed for submucosal and intramural fibroids significantly improves fertility outcome, and current evidence suggests myomectomy is the treatment of choice in women desiring to conceive. For women that do not desire surgery, medical management of myomas is available. Treatment with GnRH agonists may be considered, however newer medications with fewer side effects give practitioners and patients more options. Progesterone antagonists, selective progesterone receptor modulators, and aromatase inhibitors have all shown promise as effective therapies. Non-pharmacologic treatments such as uterine artery embolization and MRI-guided ultrasound have also emerged as effective treatments for uterine fibroids. With such a wide range of new and emerging treatment options, it is important for providers to understand which fibroids are likely to respond optimally to a specific treatment, in order to individualize appropriate and effective management for patients.

Hysteroscopic myomectomy currently represents the standard minimally invasive surgical procedure for treating submucous fibroids, with abnormal uterine bleeding and reproductive issues being the most common indications. While hysteroscopic myomectomy has been shown to be safe and effective in the control of menstrual disorders, its effects on infertility remain unclear. The review provides a comprehensive survey of all hysteroscopic techniques used to treat fibroids found completely within the uterine cavity (G0) and those with intramural development (G1 and G2). MEDLINE and EMBASE searches identified published papers from 1970. The choice of the technique mostly depends on the intramural extension of the fibroid, as well as on personal experience and available equipment. 'Resectoscopic slicing' still represents the 'gold standard' technique for treating fibroids G0, even if several other effective techniques including ablation by neodymium-yttrium-aluminum-garnet laser, morcellation and office myomectomy have been proposed. On the other hand, the present review clearly indicates that there is still no single technique proven to be unequivocally superior for treating fibroids G1 and G2. Most techniques aim at the transformation of an intramural fibroid into a totally intracavitary lesion, thus avoiding a deep cut into the myometrium. At present, the 'cold loop' technique seems to represent the best option as it allows a safe and complete removal of such fibroids in just one surgical procedure, while respecting the surrounding healthy myometrium.

Objective: To value a new presurgical classification system of submucous myomas for predicting the difficulty and the safety of hysteroscopic myomectomy., Methods: The clinical data of 491 patients who underwent hysteroscopic resection of submucous myomas were analyzed. The myomas were classified according to the Classification of the European Society for Gynaecological Endoscopy (ESGE) and our group's new classification, which consists of five parameters. The possibility of total resection of submucous myoma, the operating time and the frequency of any complications were considered., Results: The ESGE classification showed significant differences between the level 0 and level I or II (both P < 0.01). Hysteroscopic myomectomy was considered incomplete in 9 patients with myomas. The numbers of complete surgeries of level II was significant lower compared to level 0 or level I (P < 0.01). Using our new classification, the differences of both operating times and the numbers of complete surgeries between group B and A was significant (P < 0.01)., Conclusion: The new classification gives more clues as to the difficulties of hysteroscopic myomectomy than the standard ESGE classification. Although a larger number of patients need to be evaluated by this classification.

Background: Uterine smooth muscle tumors can usually be divided histologically into leiomyoma (L) and leiomyosarcoma (LMS). Occasionally, the histologic features are indeterminate and classified as smooth muscle tumor of uncertain malignant potential (STUMP). Recent gene expression studies have found p16 overexpressed in LMS when compared with normal myometrium. This study evaluated the protein expression of p16 by immunohistochemistry in LMS, L, and normal myometrium. Additionally, 8 tumors originally classified as STUMP were evaluated for p16 expression and correlated to their clinical outcome., Methods: A tissue microarray was constructed and composed of 15 LMS, 8 STUMPs, 22 L, and 10 samples of normal myometrium. p16 expression was correlated with clinical outcome and histologic features., Results: Twelve of the 15 LMS strongly and diffusely expressed p16, 3 of the L had focal p16 staining, and none of the normal myometria were p16 positive. Three of the tumors originally classified as STUMP developed metastatic disease and 2 of these tumors had strong, diffuse p16 positivity. Histologically, these 2 cases were characterized by coagulative tumor cell necrosis and only mild cytologic atypia., Conclusions: p16 is preferentially expressed in LMS with only rare L showing positivity. Histologically, tumors with coagulative tumor cell necrosis alone were clinically LMS. In those cases in which the type of necrosis is uncertain (coagulative tumor cell vs. hyalinized), the addition of p16 may aid in discerning a subset of STUMP that should be classified as LMS.

Objective: To determine the prognostic accuracy of current diagnostic criteria for uterine smooth muscle tumors., Study Design: Cases of uterine leiomyosarcoma (LMS) treated from 1976 to 1999 were analyzed retrospectively. Uterine LMS specimens were reevaluated using current criteria by a pathologist specializing in gynecologic diseases. Kaplan-Meier survival curves were evaluated., Results: Specimens were available from 67 patients diagnosed with uterine LMS. On rereview, only 47 specimens were thought to represent uterine LMS. The 20 other patients were deemed to have leiomyomas or leiomyoma variants, including 13 cellular leiomyomas, 5 atypical leiomyomas and 2 leiomyomas. Median survival for patients with uterine LMS was 2.1 years. (Ninety-seven percent of disease-specific deaths occurred within 6 years after the diagnosis.) With leiomyoma variants, median survival was > 25 years. Among these 18 women were 3 disease-specific deaths (all > 6 years after diagnosis)., Conclusion: Diagnostic criteria for uterine smooth muscle tumors require continued refinement. A small but significant number of patients diagnosed with leiomyoma variants will die of the disease. In contrast to the aggressive behavior of uterine LMS, disease-specific deaths attributed to leiomyoma variants occurred later. With this potential for delayed recurrence, these patients warrant close clinical surveillance.

We report 3 cases of a distinctive uterine leiomyoma containing numerous thick-walled vascular channels, which we term angioleiomyoma. The leiomyomas occurred in women aged 33, 44, and 49 and ranged from 1.5 to 6.0 cm. They were composed of bland, spindle-shaped cells with numerous evenly distributed, arteriole-like vessels with thick muscular walls throughout. The spindle cells often swirled around the vessels. In 1 case, fibrin was present within vessel walls. The spindle cells were positive with smooth-muscle markers and negative with HMB45. We believe angioleiomyoma should be recognized as a distinct entity and included in the World Health Organization classification of tumors of the female genital tract as a benign leiomyoma variant, similar to cellular and atypical leiomyoma. Uterine angioleiomyoma has a close morphological resemblance to the similarly named skin tumor. We review uterine smooth-muscle and other mesenchymal neoplasms in which prominent vascular channels are a feature.

Unlabelled: Mesenchymal tumors of the digestive tract are rare and display variable morphological appearances. Thanks to immunohistochemistry and molecular biology, these tumors are now better classified and dominated by stromal tumors., Aims: the aim of this article is to study morphological characteristics of mesenchymal tumors of the digestive tract and to insist on immunohistochemistry contribution to diagnosis, especially the c-Kit., Materials and Methods: this is a retrospective study of 40 mesenchymal tumors of the digestive tract diagnosed before the event of c-Kit, from 1985 to 1999 in the pathology laboratory of F. Hached hospital in Sousse. Immunohistochemical studies were performed on these tumors with the following antibodies: c-Kit, CD34, smooth muscle actin and S-100 protein., Results: after immunostaining, the tumors were reclassified as the following: 33 stromal tumors, 4 leiomyosarcomas, 1 leiomyoma, 1 schwannoma and 1 desmoid tumor., Conclusion: mesenchymal tumors of the digestive tract are dominated by stromal tumors. The latter are defined usually by a spindle cell proliferation, often expressing the c-Kit protein which must be used in all mesenchymal tumors of the digestive tract.

Purpose: We examined the relationship between tumor size and pathological findings in a contemporary series of surgical renal lesions and we characterized the relationship of incidental and symptomatic tumors to pathological findings., Materials and Methods: We retrospectively reviewed the records of patients treated surgically for renal lesions suspicious for malignancy between March 2000 and May 2005. Specimens were examined for a gross and microscopic description. Statistical analysis was used to determine the correlation of size and symptomatology., Results: A total of 349 renal masses from 331 patients were identified. Of the 349 renal masses 56 (16.0%) were benign, 289 (82.8%) were renal cell carcinoma and 4 (1.1%) were other malignancies. The percent of malignant tumors increased from 72.1% for those less than 2 cm to 93.7% for those greater than 7 cm (OR 1.39, 95% CI 1.17 to 1.65). Of the 349 renal masses 258 (73.9%) were discovered incidentally and 91 (26.1%) were symptomatic. Mean size of incidental and symptomatic tumors was 3.7 and 6.2 cm, respectively (p < 0.001). When comparing T1 incidental and symptomatic tumors, there was no significant difference in the overall frequency of malignancy. When comparing T2 incidental and symptomatic tumors, the groups had similar malignancy rates (90.9% and 100%, respectively, p = 0.16). However, symptomatic lesions showed an increased incidence of high grade malignancy (78.4% vs 40.9%, p = 0.012)., Conclusions: Smaller renal tumors are more likely to be benign or be a lower grade of malignancy. T1 renal tumors are more likely to be detected incidentally than T2 tumors. When T1 incidental and symptomatic tumors were compared, there was no difference between the malignancy rates. However, when T2 incidental and symptomatic tumors were compared, symptomatic tumors were more likely to be high grade malignancy.

The fibrohistiocytic tumors of the skin are a heterogeneous group of dermal/subcutaneous mesenchymal neoplasms which show fibroblastic, myofibroblastic and histiocytic (macrophage-like) differentiation, often one beside the other in the same tumor. "Fibrohistiocytic" means in this context the morphologic similarity of the cells with fibroblasts and histiocytes. The WHO classification of 2005 includes the following entities as fibrohistiocytic tumors of the skin: BENIGN: 1. Fibrous histiocytoma (FH)/(synonymous: Dermatofibroma. Variants of FH: 1a. cellular fibrous histiocytoma, 1b. atypical (pseudosarcomatous) fibrous histiocytoma, 1c. aneurysmatic fibrous histiocytoma, 1d. epithelioid fibrous histiocytoma; 2. dermatomyofibroma; 3. (juvenile) xanthogranuloma. INTERMEDIATE: 4. plexiform fibrohistiocytic tumor; 5. dermatofibrosarcoma protuberans; 6. atypical Fibroxanthoma. MALIGNANT: 7. malignant fibrous histiocytoma. All these entities are reviewed in this paper with particular attention devoted to differential diagnostic considerations.

Study Objective: To develop a new preoperative classification of submucous myomas for evaluating the viability and the degree of difficulty of hysteroscopic myomectomy., Design: Retrospective study (Canadian Task Force classification II-3), Setting: University teaching hospitals., Patients: Fifty-five patients who underwent hysteroscopic resection of submucous myomas., Intervention: The possibility of total resection of the myoma, the operating time, the fluid deficit, and the frequency of any complications were considered. The myomas were classified according to the Classification of the European Society for Gynaecological Endoscopy (ESGE) and by our group's new classification (NC), which considers not only the degree of penetration of the myoma into the myometrium, but also adds in such parameters as the distance of the base of the myoma from the uterine wall, the size of the nodule (cm), and the topography of the uterine cavity. The Fisher's exact test, the Student's t test, and the analysis of variance test were used in the statistical analysis. A p value less than .05 in the two-tailed test was considered significant., Measurements and Main Results: In 57 myomas, hysteroscopic surgery was considered complete. There was no significant difference among the three ESGE levels (0, 1, and 2). Using the NC, the difference between the numbers of complete surgeries was significant (p <.001) for the two levels (groups I and II). The difference between the operating times was significant for the two classifications. With respect to the fluid deficit, only the NC showed significant differences between the levels (p = .02)., Conclusions: We believe that the NC gives more clues as to the difficulties of a hysteroscopic myomectomy than the standard ESGE classification. It should be stressed that the number of hysteroscopic myomectomies used in this analysis was low, and it would be interesting to evaluate the performance of the classification in a larger number of patients.

Ordinary and cellular leiomyomas of 147 patients (age 23 - 65 years) were studied histologically and immunomorphologically. Five females with rapidly growing tumors were operated after therapy with gonadotropines blockers. Variants with weak and pronounced proliferative activity of neoplastic myocytes and various activity of neoangiogenesis were distinguished. The latter may be either phases of development or different tumour types. Use of gonadotropine blockers inhibits myocyte proliferation and activates formation of stroma.

Background: The purpose of this study was to compare three-dimensional saline infusion sonohysterography (3D SIS) and diagnostic hysteroscopy for the diagnosis and classification of submucous uterine fibroids., Methods: This was a prospective double-blind study of 49 women who presented with a history of menorrhagia, diagnosed on non-enhanced two-dimensional ultrasonography with submucous fibroids. Fibroids were classified on 3D SIS according to the proportion of fibroid contained within the endometrial cavity, using the European Society of Hysteroscopy Classification of Submucous Fibroids. These results were then compared with the findings at diagnostic hysteroscopy., Results: A total of 61 submucous fibroids was identified in 49 symptomatic women. Diagnostic hysteroscopy confirmed these findings in all cases. There was agreement between the two methods in 11/12 cases of Type 0 fibroids (92%), 34/37 (92%) of Type I fibroids and 9/12 (75%) of Type II fibroids. The overall level of agreement was good with a kappa value of 0.80., Conclusions: There is a good overall agreement between 3D SIS and diagnostic hysteroscopy in classification of submucous fibroids. Agreement is better in cases where a greater proportion of the fibroid is contained within the uterine cavity.

Recently, patent foramen ovale(PFO) has been highlighted as an important risk factor of cerebral infarctions in young adults. We report a patient of multiple cerebral embolism associated with PFO and deep venous thrombosis caused by a uterine myoma. A 40-year-old woman suddenly suffered from right hemiparesis with motor aphasia. Brain angiography showed an occlusion of M2 portion of the left middle cerebral artery, but atherosclerotic changes were not seen. She developed left facial paresis 23 days later and admitted to our hospital. Brain MRI revealed multiple cerebral infarcts in the left insular cortex, the deep white matter of the right frontal lobe, and bilateral thalamus. Hypoxia with the perfusion defects of S1 and S2 sections of the right lung demonstrated by scintigraphy suggested pulmonary embolism. Transesophageal echocardiography showed a PFO with spontaneous left-to-right shunt and right-to-left shunt evoked by the Valsalva maneuver. Although venography could not detect thrombi, it revealed severe compression of the right external iliac vein by a uterine myoma. These findings suggested thrombi in the right external iliac vein were the embolic source when combined with elevated coagulation markers. An uterine myoma should be considered as an important risk factor for an embolic source in case of cerebral embolism with PFO.

The infrequent exposure of pathologists to soft tissue spindle cell neoplasms coupled with overlapping histologic patterns can often make diagnosis challenging. We reviewed all nonodontogenic spindle cell neoplasms seen between 1982 and 2002 (86,162 total accessions). Diagnoses were reclassified according to current standards supplemented with immunohistochemistry. Of the 307 neoplasms reviewed (0.36% of total accessions), neural tumors were the most common benign entities, accounting for 21% of total cases. Kaposi's sarcoma was the most common malignancy, accounting for 67% of all cases. Diagnoses were revised for 57 cases. Schwannoma and neurofibroma were most commonly revised to palisaded encapsulated neuroma. There were 8 myofibromas and 1 inflammatory myofibroblastic tumor. There were no oral leiomyomas; that is, all 4 originally reported cases were reclassified as myofibroma, palisaded encapsulated neuroma, and solitary fibrous tumor. With the exception of Kaposi's sarcoma, oral soft tissue sarcomas were rare; most benign lesions were neural in origin. The relatively high prevalence of some tumors, such as myofibroma, likely reflects the use of immunohistochemistry in the diagnosis of spindle cell tumors.

A retrospective study to determine the incidence, clinical presentation and management of uterine fibromyoma at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. Five hundred and sixty-nine consecutive cases of histologically confirmed uterine fibroid over a ten-year period were reviewed. Uterine fibromyoma constituted 13.4% of gynaecological admission and was responsible for 26.2% of major gynaecological surgery. Majority of the patients (78.4%) were aged between 30 and 44 years and 60.8% were of low parity (0-2). The common presentations were menstrual disorders (64.3%), infertility (56.2%) and lower abdominal swelling (35.5%). Hypertension was present in 26.5% and 42% were obese. Pelvic adhesion was noted in 58.9% of patients. Total abdominal hysterectomy was the surgical procedure in 52% of cases. Pyrexia (32.5%), Anaemia (29.3%), Prolonged hospital stay (24.1%) and Wound infection (20.2%) were the common postoperative morbidities. Fibromyoma at the University of Ilorin Teaching Hospital follows a pattern similar to other parts of the world. It is responsible for a number of gynaecological complaints. Surgery still remains the main mode of treatment.

There is a prevailing view that leiomyomas of deep soft tissue are rare or nonexistent, but there are limited data on this subject in the form of large clinical studies with long follow-up information. We reviewed 36 consultation cases that had been diagnosed as leiomyoma or probable leiomyoma based on absence of nuclear atypia, necrosis, and no/minimal mitotic activity. Follow-up information was obtained to determine whether these stringent histologic criteria could identify a biologically benign group of smooth muscle tumors of deep soft tissue. The tumors occurred in two distinct locations. The first (n = 13) occurred in deep somatic soft tissue of the lower extremity (7), upper extremity (2), trunk (2), axilla (1), and back (1) and affected the sexes equally (7 male, 6 female). Composed of a circumscribed mass of mature smooth muscle cells, they were frequently calcified with a mean mitotic activity of <1 mitosis/50 high power fields (HPF) (range 1-4 mitoses/50 HPF). Estrogen receptor and progesterone receptor proteins were negative in the three cases tested. No tumors recurred or metastasized (mean follow-up 58.7 months, range 5-97 months). The second group (n = 23) occurred within the retroperitoneum (20) or abdominal cavity (3) of women (1 male, 22 female). Resembling uterine leiomyomas, they were always distinct from the uterus, occasionally multiple (n = 4), and sometimes occurred up to years after hysterectomy (n = 3). Four cases occurred with synchronous uterine leiomyomas. In the six cases tested, five of six were positive for the estrogen receptor protein and all were positive for progesterone receptor protein. Mean mitotic activity was 1 mitosis/50 HPF (range <1-10 mitoses/50 HPF). None developed metastasis within the follow-up period (mean 42.5 months, range 6-120 months); one tumor with a positive margin recurred at 10 months. We conclude that clinically benign smooth muscle tumors of deep soft tissue are rare but can be identified using stringent histologic criteria. They comprise two distinct subtypes: leiomyomas of somatic soft tissue and retroperitoneal-abdominal leiomyomas. The latter probably arise from hormonally sensitive smooth muscle. Although similar to uterine leiomyomas, they are located at sites removed from the uterus and are likely independent soft tissue primaries rather than parasitic leiomyomas of the uterus. We suggest that these two groups of smooth muscle tumors be diagnostically approached in a site-specific fashion.