Alleviation of Symptoms and Improvement of Endometrial Receptivity Following Laparoscopic Adenomyoma Excision and Secondary Therapy with the Levonorgestrel-releasing Intrauterine System.

To assess the treatment efficacy of adenomyoma and improvement in implantation receptivity associated with the levonorgestrel-releasing intrauterine system (LNG-IUS) combined with adenomyoma resection. Fifty subjects (control group) underwent laparoscopic adenomyoma excision and received gonadotropin-releasing hormone (GnRH) agonists, and 201 subjects (experimental group) underwent laparoscopic adenomyoma resection and received GnRH agonists combined with the LNG-IUS. Pipelle endometrial biopsies were obtained in the mid-luteal phase, before the operation, and 19 months after the operation. Menstrual blood loss was measured using a pictorial blood loss assessment chart. Pain intensity during menstruation was evaluated on a 10-point visual analog scale (VAS). The volume of uterus was measured through ultrasound. Quantification of HOXA10 promoter methylation was performed through bisulfite sequencing polymerase chain reaction (BSP). Real-time polymerase chain reaction analyzed the expression levels of endometrial HOXA10-mRNA and leukemia inhibitory factor (LIF)-mRNA. After surgery, the scores for dysmenorrhea and menorrhagia were significantly improved, and the volume of the uterus was obviously reduced (all p < 0.01). The mean number of methylated CpG sites, level of endometrial HOXA10-mRNA, and level of endometrial LIF-mRNA were 5.6 ± 1.7 versus 3.9 ± 1.3, 0.8 ± 0.2 versus 0.9 ± 0.3, and 0.8 ± 0.2 versus 1.0 ± 0.2, respectively, in the control group versus the experimental group at 19 months after surgery, and significant improvements were observed in the experimental group (p < 0.001, p = 0.034, p < 0.001). Laparoscopic adenomyoma excision and GnRH agonists can alleviate the symptoms, reduce the number of methylated CpG sites in HOXA10, and improve endometrial HOXA10-mRNA and endometrial LIF-mRNA levels. When combined with subsequent use of the LNG-IUS, better efficacy can be achieved.

Immunophenotype of Atypical Polypoid Adenomyoma of the Uterus: Diagnostic Value and Insight on Pathogenesis.

Atypical polypoid adenomyoma (APA) is a rare uterine lesion constituted by atypical endometrioid glands, squamous morules, and myofibromatous stroma. We aimed to assess the immunophenotype of the 3 components of APA, with regard to its pathogenesis and its differential diagnosis. A systematic review was performed by searching electronic databases from their inception to January 2019 for immunohistochemical studies of APA. Thirteen studies with 145 APA cases were included. APA glands appeared analogous to atypical endometrial hyperplasia (endometrioid cytokeratins pattern, Ki67≤50%, common PTEN loss, and occasional mismatch repair deficiency); the prominent expression of hormone receptors and nuclear ß-catenin suggest that APA may be a precursor of "copy number-low," CTNNB1-mutant endometrial cancers. Morules appeared as a peculiar type of hyperdifferentiation (low KI67, nuclear ß-catenin+, CD10+, CDX2+, SATB2+, p63-, and p40-), analogous to morular metaplasia in other lesions and distinguishable immunohistochemically from both conventional squamous metaplasia and solid cancer growth. Stroma immunphenotype (low Ki67, α-smooth-muscle-actin+, h-caldesmon-, CD10-, or weak and patchy) suggested a derivation from a metaplasia of normal endometrial stroma. It was similar to that of nonatypical adenomyoma, and different from adenosarcoma (Ki67 increase and CD10+ in periglandular stroma) and myoinvasive endometrioid carcinoma (h-caldesmon+ in myometrium and periglandular fringe-like CD10 pattern).

Stromal p16 Expression Helps Distinguish Atypical Polypoid Adenomyoma From Myoinvasive Endometrioid Carcinoma of the Uterus.

Atypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear ß-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions.

Atypical polypoid adenomyoma of the uterus: A reappraisal of the clinicopathological and immunohistochemical features.

Atypical polypoid adenomyoma (APAM) is an uncommon uterine mixed epithelial and mesenchymal tumor. The discrimination from endometrial carcinoma remains to be clarified. In this study, we compared the clinicopathological and immunohistochemical features between 36 APAMs and 48 endometrial carcinomas. APAM with a highly complex structure (n = 13) coexisted with atypical hyperplasia (n = 5) and endometrial carcinoma (n = 1). Two patients had endometrial carcinomas at 1 and 102 months. Four patients recurred at 1-57 months but none died of disease. The fibromuscular stroma demonstrated 3 uncharacterized features: a broad bundle (10/36), a lobular structure separated by the stromal branches (26/36), and the extension of fibromuscular stroma underneath the surface epithelium (31/36). However, these features were not seen in endometrial carcinomas except the vaguely lobular pattern. Both APAM and endometrial carcinoma showed a similar immunostaining pattern except high Ki67 index in endometrial carcinomas (p < 0.05). Our study suggests that the distinct features of the fibromuscular stroma can aid in the differential diagnosis between APAM and endometrial carcinoma.

Frequent ß-catenin gene mutations in atypical polypoid adenomyoma of the uterus.

Atypical polypoid adenomyoma (APA) is an uncommon polypoid lesion of the uterus. To clarify the mechanism of its histogenesis, we examined the functional role of ß-catenin, with reference to expression of p21(waf1), cyclin D1, cyclin E, CD10, and α-smooth muscle actin (SMA), as well as cell proliferation, in 7 lesions. In the epithelial components, expression of nuclear ß-catenin, p21(waf1), and cyclin D1 was increased in a stepwise fashion from normal tissue through complex atypical hyperplasia and adenomyoma to APA lesions, particularly in squamous morular areas, whereas cell proliferation, as well as cyclin E expression, was significantly decreased in the latter. Similar findings were evident in the stromal lesions, with the exception of a case of nuclear ß-catenin. In addition, coexpression of CD10 and α-SMA markers was observed in the stromal components in 3 APA cases, in line with the results of normal secretory endometrial and adenomyoma samples, suggesting that cells progress to myofibromatous cells in response to differentiation-promoting events. Finally, ß-catenin gene (CTNNB1) mutations were detected in all APA cases, the single nucleotide substitutions being in the epithelial but not the stromal components. These findings suggest that activation of ß-catenin signaling, probably secondary to the gene abnormalities, plays an important role in the formation of the complex epithelial architecture in APAs, leading to inhibition of cell proliferation through overexpression of p21(waf1). In contrast, changes in the stromal cell phenotype may occur through a shift from CD10 to α-SMA immunopositivity, independent of CTNNB1 status.

[Adenomyomatosis of the gall bladder in rabbits].

Possibility of the adenomiomatosis development of the gallbladder in rabbits of different age is studied. Adenomiomatosis appeared in one of 10 animals of older age animal group. The role of serotonin in the development of adenomiomatosis is discussed.

Infantile adenomyoma subclinically excreted into the patient's diaper.

Adenomyoma is a rare condition of the gastrointestinal tract, consisting of glandular structures lined by columnar or cuboidal epithelium and surrounded by smooth muscle bundles. The vast majority of adenomyomas of gastrointestinal tract have been reported to be located at the propyloric segment of the stomach and their localization in the bowel of infantile patients is considered rare. A review of the literature showed that 13 cases of infantile adenomyoma in the bowel have been reported. In the previous cases, intussusception was the most common complication of adenomyoma in the bowel and all cases underwent laparotomy. Here we describe an extremely rare case of infantile adenomyoma subclinically eliminated in the diaper. In addition, we performed immunohistochemical analysis to speculate on the origin of the adenomyoma.

[Plexiform angiomyxoid myofibroblastic tumor of stomach].

OBJECTIVE: To study the clinicopathologic features, immunophenotype and differential diagnosis of plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach. METHODS: The clinical and pathologic findings of 3 cases of PAMT in the gastric antrum were retrospectively analyzed. Immunohistochemical study was carried out and the literature was reviewed. RESULTS: The age of patients ranged from 31 to 47 years. The male-to-female ratio was 1:2. The clinical presentation included epigastric pain and distension. Endoscopically, the tumor mass protruded into the gastric cavity at the antrum and ranged from 4.5 cm to 8.0 cm in greatest dimension. One of the tumors studied was associated with surface ulceration. Histologically, the tumors were located in the gastric wall. They were composed of bland spindle cells and small vessels arranged in a plexiform or nodular pattern within a myxoid stroma. Immunohistochemical study showed that the spindle cells were consistently positive for smooth muscle actin and muscle-specific actin. There was focal staining for h-caldesmon, desmin in case 3 and focal positive for epithelial membrane antigen, CAM5.2 in case 1. Further, CD10 and progesterone receptor were positive in case 3. CONCLUSIONS: PAMT represents a rare novel mesenchymal tumor of the stomach, with a propensity of gastric antral involvement. The distinctive pathologic features help to differentiate this entity from other benign and malignant tumors.

Atypical polypoid adenomyoma of the uterus: an immunohistochemical study on 5 cases.

Immunohistochemical studies of atypical polypoid adenomyoma (APA) of the uterus are very rare. Five cases of APA were retrieved from the surgical cases of our laboratory. The ages were 38, 41, 54, 65, and 77 years (mean ± SD, 55 ± 14.6 years). The diameters of APA were 1.2, 1.9, 2.3, 3.2, and 7.0 cm (mean ± SD, 3.12 ± 2.00 cm). Histologically, APA consisted of complex glandular element and mesenchymal fibromuscular element. No endometrial stroma was present. Mucins were found in the glands but not in the mesenchyma. The glands were consistently positive for pancytokeratin (AE1/3, CAM5.2), cytokeratin (CK) 7, CK8, CK18, CK19, vimentin, CA125, estrogen receptor, progesterone receptor, MUC1, and MUC6. The glands were consistently negative for CK14, CK20, CEA, epithelial membrane antigen, S100 protein, p53, CD10, MUC2, and MUC5AC. Some cases were positive for CK34ßE12 (4/5), CK5/6 (4/5), and CA19-9 (4/5). The Ki-67 labeling ranged from 3% to 10%. The mesenchymal element was consistently positive for vimentin, α-smooth muscle actin, estrogen receptor, progesterone receptor, and CD10, while consistently negative for pancytokeratin (AE1/3, CAM5.2), CK34ßE12, CK5/6, CK7, CK8, CK14, CK18, CK19, CK20, CEA, epithelial membrane antigen, S100 protein, CA125, CA19-9, p53, MUC1, MUC2, MUC5AC, and MUC6. Some cases were positive for desmin (2/5). Ki-67 labeling ranged from 1% to 8%. In conclusion, the immunoprofile of APA was reported. The findings provide basic knowledge of APA of the uterus.

Immunohistochemical characteristics of atypical polypoid adenomyoma with special reference to h-caldesmon.

Atypical polypoid adenomyoma (APA) is a relatively rare benign uterine tumor, histologically characterized by proliferation of irregular endometrioid glands accompanied by stromal cells of smooth muscle origin. As the epithelial components of APA usually show cytological atypia, a differential diagnosis between this tumor and endometrioid carcinoma invading myometrium is often difficult, especially in curettage material. This distinction is clinically very important to avoid unnecessary hysterectomy. However, only a few immunohistochemical studies of APA that differentiate it from malignancy have been published. Therefore, we have investigated the expression of several antigens in APA and compared them with those present in myoinvasive carcinoma. Six specimens of APA were studied, along with controls of endometrioid carcinoma invading myometrium. Antibodies to p53, Ki-67, CD10, and h-caldesmon reacted positively using immunohistochemistry. Variable positive expressions of p53 and Ki-67 were observed in both epithelial and stromal components of APA, and in myoinvasive endometrioid carcinoma. CD10 was negative or partially and weakly positive whereas h-caldesmon was completely negative in the stromal cells of all 6 specimens of APA. However, in the myometrium in which endometrioid carcinoma invaded, a fringe-like positive staining pattern was occasionally observed for CD10, whereas a diffuse positive signal was obtained for h-caldesmon. The results of this study indicate that immunohistochemically, p53, and Ki-67 are not reliable markers but that h-caldesmon is useful in distinguishing APA from myoinvasive endometrioid carcinoma. Further, our data suggest that the stromal cells of APA are mainly immature smooth muscle cells, and thus APA may be a mixed tumor.

Collagenous spherulosis associated with adenomyoepithelioma of the breast: a case report.

BACKGROUND: Collagenous spherulosis (CS) associated with an adenomyoepithelioma (AME) of the breast is rare. This report describes a case of CS associated with an AME of the right breast, including the cytologic and histopathologic findings. CASE: A 51-year-old female presented with a slow-growing left breast mass that had been present for 5 months. A preoperative core needle biopsy showed the presence of layers or sheaths of myoepithelial cells around epithelial-lined spaces. Imprint cytology of the surgical material showed the presence of bundles of spindle cells with an admixture of epithelial cells. Spherical structures were also found. They were translucent or slightly light green with Papanicolaou staining and metachromatic with Giemsa staining. Grossly, the 1.5-cm lesion was solid and embedded within the breast parenchyma. Microscopically, it was composed of spindle or polygonal cells with eosinophilic cytoplasm and an epithelium lining spaces with many spherical structures. The spindle or polygonal cells were positive for myoepithelial markers and the epithelium was positive for epithelial markers by immunohistochemistry. CONCLUSION: There is no previous report describing the cytologic findings of CS associated with an AME of the breast. AMEs should therefore be considered an underlying pathology of CS of the breast.

Immunohistochemical study of mucin expression in periampullary adenomyoma.

BACKGROUND/PURPOSE: Benign tumors and tumor-like conditions in the ampullary area are uncommon, and there are extremely rare cases of adenomyoma (AM) and adenomyomatous hyperplasia (AMH). Surgical treatment is necessary if these lesions cause biliary obstruction. In addition, the differential diagnosis of AM and AMH from carcinoma is often difficult by standard endoscopic biopsy and cytopathological analysis that may show differential findings, resulting in unnecessary surgeries sometimes being performed. METHODS: Immunohistochemical (IHC) analysis of periampullary AM and AMH was performed. RESULTS: For both types of lesions, epithelial glandular cells (EGCs) showed diffuse expression of MUC6 and focal expression of HIK1083, mainly in the inner region, and focal expression of MUC5AC, mainly at the surface. The EGCs showed no expression of MUC1 or MUC4, both of which were identified as malignant tumor markers in our previous series of mucin expression studies in pancreatobiliary tumors. The expression of CK7, which was diffusely positive in normal periampullary mucosa, was decreased in the EGCs of AM and AMH. CONCLUSIONS: A combined evaluation of IHC findings may be effective in the detection of AM and AMH, and also in distinguishing benign periampullary lesions, such as AM and AMH, from ampulla of Vater adenocarcinoma, thus avoiding excessive surgery.

Adenomyoma of the jejunum.

Adenomyoma of the small intestine is an extremely rare condition characterized by abnormal glandular structures surrounded by smooth muscle. We report a case of adenomyoma of the jejunum. The patient was a 61-year-old female with cancer of the sigmoid colon and multiple liver cysts, who was sent to the operation room for exploratory laparotomy and sigmoidectomy. At surgery, a polypoid lesion was incidentally found in the lower jejunum, which was resected. On histologic examination, the morphologic features were typical of adenomyoma. However, new histopathological and immunohistochemistry features are described here, providing evidence that adenomyoma of the jejunum is a form of intestinal epithelial hamartoma.

Extrauterine adenomyoma with atypical (symplastic) smooth muscle cells: a report of 2 cases.

Adenomyomas are circumscribed tumorlike masses most often involving the uterus and consisting of endometrioid glands, stroma, and smooth muscle tissue. They are uncommon in extrauterine sites and in this situation it may be unclear whether such lesions represent foci of endometriosis with marked smooth muscle hyperplasia/metaplasia, uteruslike mass lesions, or leiomyomas with entrapped endometriotic glandular and stromal elements. In this report 2 cases of extrauterine adenomyoma are presented in which the smooth muscle component showed focal atypical (symplastic) cytologic appearances.

Elastin distribution in the normal uterus, uterine leiomyomas, adenomyosis and adenomyomas: a comparison.

OBJECTIVE: To describe the histologic distribution of elastin in the nonpregnant human uterus, uterine leiomyomas, adenomyosis and adenomyomas. STUDY DESIGN: Uteri were obtained from women undergoing hysterectomy for benign conditions, including 26 cases of uterine leiomyomas, 24 cases of adenomyosis, 18 adenomyomas and 6 cases of autopsy specimens. Specific histochemical staining techniques were employed in order to demonstrate the distribution of elastin. RESULTS: The distribution of elastin components in the uterus was markedly uneven and showed a decreasing gradient from outer to inner myometrium. No elastin was present within leiomyomas, adenomyomas or adenomyosis. CONCLUSION: The distribution of elastin may help explain the normal function of the myometrium in labor. It implies that the uneven distribution of elastin components and absence of elastin within leiomyomas, adenomyomas and adenomyosis could be of some clinical significance. The altered elastin distribution in disease states may help explain such symptoms as dysmenorrhea in uterine endometriosis.

Adenomyoepithelioma: clinical, histologic, and immunohistologic evaluation of a series of related lesions.

Adenomyoepithelioma, strictly defined, is a proliferation of both epithelial and myoepithelial elements. The broad range of lesions that may fall under this umbrella, however, may be quite diverse. The diagnostic confusion surrounding this entity and its prognostic implications have led to a diagnosis by default as malignant and to overtreatment of some patients. We evaluated available material from a series of 35 women whose slides were seen in consultation and who were diagnosed with adenomyoepithelioma or a closely related lesion. This comprehensive review of the varied histology of adenomyoepithelioma and similar lesions and their immunohistochemical properties will assist general pathologists in evaluating these sometimes difficult lesions. Follow-up and treatment information demonstrates their benignity. Architecture and histologic features should be combined with immunohistochemistry when determining categorization.

Expression of apoptosis-related proteins in adenomyotic uteri treated with danazol and GnRH agonists.

The biologic properties of adenomyosis and the effects of therapeutic agents on adenomyosis were evaluated with immunohistochemistry, terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method, transmission electron microscopy, and analysis of genomic abnormality. In the adenomyotic endometrium, estrogen receptor (ER) expression was more intense than in the eutopic endometrium during the secretory phase, and bcl-2 was constantly expressed throughout the menstrual cycle. The expression of ER and bcl-2 was weaker in the adenomyotic endometrium treated with danazol than in that treated with gonadotro-pin-releasing hormone agonist (GnRHa), whereas bcl-2 phosphorylated on serine-87 was more intensely expressed in danazol-treated adenomyotic endometrium than in the GnRHa-treated one. The number of TUNEL-positive cells increased in the adenomyotic endometrium treated with danazol or GnRHa. Ultrastructurally, most of the adenomyotic endometrial cells treated with danazol underwent postapoptotic necrosis and formed a cluster of dead cells. In contrast, cells treated with GnRHa underwent typical apoptosis and were sparsely distributed in the adenomyotic endometrium. Analysis of several cancer-related genes showed no microsatellite instability or loss of heterozygosity in adenomyotic tissues. Therefore, we conclude that the occurrence of adenomyosis is correlated to bcl-2 expression regulated by estrogen and ER rather than genetic mutation.

A clinicopathological study of the relationship between adenomyosis and other hormone-dependent uterine lesions.

AIM: The aim of this study was to investigate the relationship between adenomyosis, endometrial adenocarcinoma, hyperplasia and uterine leiomyomas. MATERIAL AND METHODS: 135 consecutive hysterectomy specimens showing adenomyosis and 82 consecutive cases of endometrial adenocarcinoma were studied in our laboratory in the last 5-year period. The histological sections of all cases were reviewed and in the cases with adenocarcinoma, the type of cancer, the degree of differentiation and the depth of myometrial invasion were recorded. In the adenomyosis group the presence of any other lesions, the extension of adenomyosis and the morphology of the adenomyotic glands were recorded. In ten random cases of adenomyosis, the presence of estrogens and progesterone receptors was investigated by an immunohistochemical method of peroxidase-antiperoxidase and DAB chromogen. In ten cases of this group the expression of E-cadherin was studied immunohistochemocally by an avidin-viotin method and DAB chromogen. RESULTS: In 47/135 cases of adenomyosis adenomatous hyperplasia coexisted (34.8%) and in 86/135 cases of leiomyomas (63.7%). In 31/82 cases of adenocarcinoma there was adenomyosis as well (37.8%), in 4/82 cases malignant changes in foci of adenomyosis were observed and in 1/82 cases the malignancy arose in a focus of adenomyosis. Immunohistochemical studies showed the presence of progesterone receptors in the glandular cells of adenomyosis in 9/10 cases and of estrogen receptors in 2/10 cases. In all study cases (10/10) a positive membrane immunoreaction was observed; focal (6/10) and extensive (4/10). CONCLUSION: The high frequency of coexistence between adenomyosis and other hormone-dependent uterine lesions is indicative of the presence of a hormonal factor in the pathogenesis of adenomyosis.