A common tumor in an uncommon site: epithelioid Leiomyoma arising from the seminal vesicle-a case report.

BACKGROUND: Leiomyoma of the seminal vesicle is a rare leiomyoma characterized by the formation of benign leiomyomatous tissue within the seminal vesicle. Although histologically benign, excessive size can lead to urinary system disease if left untreated. Herein, we report a case of a seminal vesicle epithelioid leiomyoma. CASE PRESENTATION: A 36-year-old Chinese man sought medical attention at our hospital for urination pain and hemospermia. CT showed a 5.3 cm × 5.0 cm seminal vesicle mass with a mixed density in the right seminal vesicle. The gross specimen showed light yellow, gray, and white tissues, with softness and hemorrhage in some places. Histologically, it showed classic spindle cell proliferation, with spindle cells arranged in fascicles, and mitosis was rare. Immunohistochemistry showed frequent expression of smooth muscle markers, such as calponin, SMA, and desmin. A diagnosis of epithelioid leiomyoma was proposed according to the immunohistochemical findings and morphology. The patient did not receive adjuvant therapy. There was no evidence of tumor recurrence in the 10 months after surgery. CONCLUSIONS: We report the first case of epithelioid leiomyoma in the seminal vesicle. This disease should be included in the differential diagnostic list of seminal vesicle tumors with epithelioid morphology.

Fertility after uterine artery embolization for symptomatic multiple fibroids with no other infertility factors.

OBJECTIVES: To evaluate the fertility of women eligible for surgical multiple myomectomy, but who carefully elected a fertility-sparing uterine artery embolization (UAE). METHODS: Non-comparative open-label trial, on women ≤40 years, presenting with multiple symptomatic fibroids (at least 3, ≥3 cm), immediate pregnancy wish, and no associated infertility factor. Women had a bilateral limited UAE using tris-acryl gelatin microspheres ≥500 µm. Fertility, ovarian reserve, uterus and fibroid sizes, and quality of life questionnaires (UFS-QoL) were prospectively followed. RESULTS: Fifteen patients, aged 34.8 years (95%CI 32.2-37.5, median 36.0, q1-q3 29.4-39.5) were included from November 2008 to May 2012. During the year following UAE, 9 women actively attempting to conceive experienced 5 live-births (intention-to-treat fertility rate 33.3%, 95%CI 11.8%-61.6%). Markers of ovarian reserve remained stable. The symptoms score was reduced by 66% (95%CI 48%-85%) and the quality of life score was improved by 112% (95%CI 21%-204%). Uterine volume was reduced by 38% (95%CI 24%-52%). Women were followed for 43.1 months (95%CI 32.4-53.9), 10 live-births occurred in 8 patients, and 5 patients required secondary surgeries for fibroids. CONCLUSION: Women without associated infertility factors demonstrated an encouraging capacity to deliver after UAE. Further randomized controlled trials comparing UAE and myomectomy are warranted. KEY POINTS: • Women without infertility factors showed an encouraging delivery rate after UAE. • For women choosing UAE over abdominal myomectomy, childbearing may not be impaired. • Data are insufficient to definitively recommend UAE as comparable to myomectomy. • Further randomized trials comparing fertility after UAE or myomectomy are warranted.

Possible involvement of inflammatory/reparative processes in the development of uterine fibroids.

Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the "usual leiomyoma", characterized by overexpression of ECM proteins, whereas the "cellular type" has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1ß, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the "usual type". Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the "usual type", we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the "cellular type", stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth.

Ligation-assisted endoscopic enucleation for treatment of esophageal subepithelial lesions originating from the muscularis propria: a preliminary study.

An innovative ligation-assisted endoscopic enucleation (EE-L) technique was developed for the diagnosis and treatment of esophageal subepithelial lesions (smaller than 12 mm) originating from muscularis propria by combining endoscopic band ligation and endoscopic enucleation techniques. The aim of the study was to evaluate efficacy and safety of EE-L technique in the treatment of esophageal subepithelial lesions (smaller than 12 mm) originating from muscularis propria. Forty-seven esophageal subepithelial lesions (smaller than 12 mm) originating from the muscularis propria in 44 patients were treated with EE-L between September 2010 and September 2012. The lesion was first aspirated into the transparent cap attached to the tip of endoscope. The elastic band was then released around its base. The purpose of ligation was to force the lesion to assume a polypoid form with a pseudostalk. Endoscopic enucleation was then performed until the tumor was completely enucleated from muscularis propria using a hook knife and forceps. All tumors (median diameter: 8.2 ± 2.3 mm, range: 4-12 mm) were enucleated completely. Histopathology identified 45 tumors (95.7%) as leiomyoma, 2 (4.3%) tumors as gastrointestinal stromal tumor with very low risk. The mean time of the EE-L procedure was 12.5 ± 4.6 minutes (range: 6-23 minutes). Two patients experienced self-limiting, non-life-threatening hemorrhage after EE-L. No perforation and massive hemorrhage requiring further endoscopic or surgical intervention occurred. There were no recurrences during the 6-24 months follow-up period. EE-L offers the option of localized treatment of small esophageal muscularis propria tumors (smaller than 12 mm) with relatively few complications and low mortality, and provides the advantage of allowing a histopathological diagnosis. All the resected lesions in this study had a benign pathology.

Unilateral ovarian agenesis and clear cell type epithelioid leiomyoma of uterus mimicking ovarian malignancy.

A case of unilateral absent ovary together with clear cell type epithelioid leiomyoma of uterus mimicking ovarian malignancy discovered during laparotomy is presented. Unilateral absence of an ovary is an extremely rare finding. Although the exact pathophysiological mechanism is not known, it could result from a defect in embryological development or asymptomatic torsion of ovary. Clear cell type epithelioid leiomyoma of uterus is also a rare variant, composed of round or polygonal 'clear' cells rather than typical spindle-shaped cells and ultra structurally differs from non-uterine counterparts.

Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

Uterine leiomyomata (fibroids) are common and clinically important tumors, but little is known about their etiology and pathogenesis. We previously mapped a gene that predisposes to multiple fibroids, cutaneous leiomyomata and renal cell carcinoma to chromosome 1q42.3-q43 (refs 4-6). Here we show, through a combination of mapping critical recombinants, identifying individuals with germline mutations and screening known and predicted transcripts, that this gene encodes fumarate hydratase, an enzyme of the tricarboxylic acid cycle. Leiomyomatosis-associated mutations are predicted to result in absent or truncated protein, or substitutions or deletions of highly conserved amino acids. Activity of fumarate hydratase is reduced in lymphoblastoid cells from individuals with leiomyomatosis. This enzyme acts as a tumor suppressor in familial leiomyomata, and its measured activity is very low or absent in tumors from individuals with leiomyomatosis. Mutations in FH also occur in the recessive condition fumarate hydratase deficiency, and some parents of people with this condition are susceptible to leiomyomata. Thus, heterozygous and homozygous or compound heterozygous mutants have very different clinical phenotypes. Our results provide clues to the pathogenesis of fibroids and emphasize the importance of mutations of housekeeping and mitochondrial proteins in the pathogenesis of common types of tumor.

Epithelioid cotyledonoid dissecting leiomyoma: a case report and review of the literature.

A 63-year-old mother of two, presented with blood-stained vaginal discharge and right sided lower abdominal pain. A MRI examination confirmed a right parametrial mass, abutting the lateral margin of the uterus and the patient had a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histological examination diagnosed a cotyledonoid leiomyoma, but with a new epithelioid variant. Cotyledonoid leiomyom's usually have a large, fungating appearance and demonstrate apparent widespread infiltrative growth and extension into the pelvic cavity, broad ligament and retroperitoneal space which may raise significant concern about the possibility of a malignant neoplasm. As these tumours are rare and infrequently encountered, it is imperative that clinicians be aware of this entity as they may pose a significant diagnostic and management challenge when encountered. Awareness of this newly described epithelioid cell variant of cotyledonoid dissecting leiomyoma is necessary for an accurate diagnosis and to facilitate appropriate management decisions at the time of surgery. This new variant further emphasizes the need for meticulous histopathological assessment which should be undertaken to circumvent misdiagnosis. This has direct clinical relevance to all operating gynaecologists and may have implications for litigation because patients may be inappropriately and inadvertently over-treated for an essentially benign condition.

Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: a review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy.

Uterine smooth muscle tumors are classified according to their morphologic features that include architecture, growth pattern, cellular characteristics and constituents of the intercellular stroma. While terminologies used for the pathologic diagnosis of various subtypes may be eloquent and histologically accurate, some of these are confusing for the clinician and may also be open to interpretation by different pathologists: the labeling of atypical leiomyomas epitomizes this intricate system. Clinically, it is probably more useful to classify them as either tumors with or tumors without recurrent and/or metastatic potential. The term "atypical leiomyoma" has been used to label tumors that have a low risk of recurrence and is synonymous with benign tumors. The latter are known variously as leiomyoma with bizarre nuclei, symplastic leiomyoma, or pleomorphic leiomyoma. Variants of benign uterine smooth muscle tumors, such as mitotically active leiomyoma, cellular and highly cellular leiomyoma, epithelioid leiomyoma, and myxoid leiomyoma each have distinctive hallmarks that enable subclassification. Nevertheless, they may occasionally possess one or more unusual features that are cause for alarm. Tumors that have a dissecting growth pattern, with or without extrauterine extension, may mimic malignancy both grossly and microscopically. The current review discusses the pathologic diagnosis of and terminology applied to selected variants of uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas with emphasis on unusual reported features that may indicate malignancy. This includes an update on uterine smooth muscle tumor of uncertain malignant potential (STUMP), intravenous leiomyomatosis, benign metastasizing leiomyoma, and diffuse leiomyomatosis. Their clinicopathologic features, differential diagnoses, and management options based on findings in the previously reported cases will also be reviewed.

Multiple epitheloid plexiform tumourlet leiomyoma of the uterus with focal vascular invasion.

We report the first case of multiple plexiform tumourlets showing focal vascular invasion suggesting that, unlike what the common and accepted opinion would advocate, these tumours may have a more aggressive behaviour. However, the prognosis of this variant of epithelioid leiomyoma remains unknown, due to its rarity. The main differential diagnosis of this entity are discussed, including endometrial stromal sarcoma exhibiting epitheloid cytomorphology, intravenous leiomyomatosis of epitheloid variant.

Molecular and cytogenetic characterization of plexiform leiomyomata provide further evidence for genetic heterogeneity underlying uterine fibroids.

The plexiform variant of uterine leiomyomata (UL) is named for its ribbons or nests of smooth muscle cells that have a rounded, epithelioid shape caused by their entrapment in abundant extracellular matrix. Plexiform UL are currently classified as epithelioid smooth muscle tumors alongside the less predictable, "true" epithelioid tumors (ie, leiomyoblastomas). Karyotypes of six plexiform UL cases were studied, and their abnormalities were found to differ from those of leiomyoblastomas. Analyses using real-time polymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization demonstrated elevated mRNA and protein levels of the architectural factor HMGA2 and, in some cases, increased DNA copy number. Four of these plexiform UL were profiled with Affymetrix human U133 plus 2.0 expression arrays. Cluster analysis using genes previously shown to discriminate benign and malignant uterine smooth muscle tissues revealed that the plexiform tumors form an isolated group in the benign branch. This is in contrast to an earlier finding in which another variant, cellular UL characterized by loss of a portion of the short arm of chromosome 1, clustered with malignant leiomyosarcomas. These results provide additional evidence of genetic heterogeneity underlying UL of various histological types. We further suggest that plexiform UL should be classified among tumors with extensive hyalinization rather than with "true" epithelioid smooth muscle neoplasms.

[Epithelioid uterine leiomyoma with giant cystic degeneration. A case report]. / Leiomioma uterino epitelioide con degeneración quística gigante. Reporte de un caso.

At present, show woman 46-years-old, presented hiperpolimenorrea, pelvis ultrasound appearance with cystic giant mass in the uterine corpus; histopathological revealed a epithelioid leiomyoma with giant cystic degeneration. We considered it is the first reported case of this variant of the epithelioid leiomyoma.

Vulvar epithelioid leiomyoma with myxoid change: A case report and literature review.

RATIONALE: Smooth muscle tumors of the vulva are infrequent neoplasms with diverse histologic features and unclear biologic behavior. Herein, we report a very rare case of vulvar epithelioid leiomyoma and review of previous reported cases of these tumors. In addition, we have discussed the representative diagnostic criteria of vulvar smooth muscle tumors and prognostic significance of epithelioid morphology. PATIENT CONCERNS: We recently met a 45-year-old woman with complaint of painful vulvar mass. INTERVENTIONS: Excisional biopsy was performed. DIAGNOSES: Pathologic examination revealed a vulvar epithelioid leiomyoma with multinodular growth pattern. Mitotic activity was rare and cellular atypia was not identified. Based on histology and immunohistochemical staining results, the case was diagnosed as vulvar epithelioid leiomyoma. OUTCOMES: After mass excision, the patient was discharged with no complication and there was no evidence recurrence for 6 months. LESSONS: After reviewing previous papers and diagnostic criterion, we thought that vulvar smooth muscle tumors with predominant epithelioid morphology may be associated with unfavorable prognosis, Therefore, pathologists should examine the epithelioid component in vulvar smooth muscle tumors carefully.

Epithelioid smooth muscle tumors of the uterus do not express CD1a: a potential immunohistochemical adjunct in their distinction from uterine perivascular epithelioid cell tumors.

Uterine epithelioid smooth muscle tumors and uterine perivascular epithelioid cell tumors (PEComas) are known to display such a substantial overlap in morphologic and immunophenotypic characteristics that the existence of the latter as a distinct clinicopathologic entity at this location has been called into question. Recent research suggests that the constituent entities of the PEComa family at all anatomical locations, including lymphangioleiomyomatosis of the uterus, uniformly display immunoreactivity for CD1a. The purpose of this study is to determine the proportion of uterine epithelioid smooth muscle tumors that may similarly be CD1a-positive. Representative sections from 18 archived epithelioid smooth muscle tumors of the uterine corpus (6 epithelioid leiomyosarcomas and 12 epithelioid leiomyomas), diagnosed and classified as such based on World Health Organization criteria, were subjected to immunohistochemical stains for CD1a and HMB-45. The epithelioid component of the tissue sections evaluated ranged from 10% to 100% (mean, 70%). Two cases were composed predominantly of cells with overtly clear cytoplasm. All cases were entirely negative for CD1a. Of 18 cases, 1 (5.5%) (an epithelioid leiomyosarcoma) displayed immunoreactivity for HMB-45 in scattered lesional cells that constituted approximately 5% of the overall tumoral volume for the case. All others were HMB-45-negative. Given their rarity, future studies are required to confirm that all PEComas of the uterus are indeed uniformly positive for CD1a. However, if the latter staining pattern is confirmed, our findings herein suggest that CD1a may be a useful immunohistochemical adjunct in distinguishing uterine epithelioid smooth muscle tumors from uterine PEComas.

Review of the pathophysiology, diagnosis, and therapy of vulvar leiomyoma, a rare gynecological tumor.

The objective of this article is to discuss the pathophysiology, diagnosis, differential diagnosis, and therapy of vulvar leiomyoma. We performed a review of all English-language reports of vulvar leiomyoma published in PubMed from 1978 to 2015 using the following search terms: "vulval leiomyoma," "vulvar leiomyoma," "vulval smooth muscle tumor," and "external genitalia smooth muscle tumor." Vulvar leiomyomas, which are rare benign monoclonal tumors, most commonly occur in the fourth and fifth decades of life. The genetics of vulvar leiomyoma remain undefined. Three principal histological patterns have been identified: spindled, epithelioid, and myxoid. Imaging tests such as ultrasound, endoscopic ultrasound, and magnetic resonance imaging are used in diagnosis. Surgical excision is the only curative treatment for vulvar leiomyomas. Establishment of a full differential diagnosis list and correct final diagnosis before surgery are essential for optimal clinical management. Although recurrence of vulvar leiomyoma is extremely rare, long-term follow-up of all cases is advisable.

Psammomatous melanotic schwannoma presenting as colonic polyps.

Psammomatous melanotic schwannoma is an uncommon neoplasm that usually occurs in the setting of Carney's complex. They can occur in the gastrointestinal tract with preferential location in the stomach. A 43-year-old female presented with two colonic polyps at routine endoscopy. The patient was asymptomatic and did not have features of Carney's complex. Both polyps were composed of melanin-containing epithelioid and spindle cells with several psammoma bodies. There was no evidence of cytological atypia or necrosis. The tumor was diffusely positive for S-100, and focally for HMB-45 and melan-A. The differential diagnosis includes melanoma, GIST, pigmented neuroendocrine tumor, and epithelioid leiomyoma. The lack of malignant features separates this lesion from melanoma while the immunophenotype of the other lesions is characteristic.

Esophageal leiomyosarcoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has proven itself to be a reliable method for the diagnosis of gastrointestinal stromal tumors and other gastrointestinal mesenchymal neoplasms. The diagnosis and distinction of these entities remain important, as these neoplasms have different prognoses and treatment options. We present a case of a 14.5-cm esophageal mass in a 67-yr-old woman sampled by EUS-FNA. Smears showed a cellular, spindle cell lesion with marked cytologic and nuclear pleomorphism. A cell block showed neoplastic cells reacting strongly with antibodies to smooth muscle antigens and not with antibodies to keratin, CD34 and CD117. Resection confirmed the diagnosis of esophageal leiomyosarcoma. To the best of our knowledge, this represents the first reported case of an esophageal leiomyosarcoma diagnosed by EUS-FNA. Clinical, imaging, and cytologic features as well as differential diagnosis are discussed.