SATB2 is Consistently Expressed in Squamous Morules Associated With Endometrioid Proliferative Lesions and in the Stroma of Atypical Polypoid Adenomyoma.

So-called squamous morules are closely associated with endometrioid proliferative lesions, in the endometrium and the ovary. Morules have an unusual immunophenoptype, typically exhibiting nuclear staining with ß-catenin, positivity with CDX2, CD10, and p16 and are negative with hormone receptors and p63. We report the previously undescribed occurrence of consistent SATB2 nuclear positivity within morules. Nuclear positivity was present in 38/43 (88%) cases of morules (24 focal; 14 diffuse) while all cases of nonmorular squamous metaplasia in endometrioid proliferative lesions (n=13) were SATB2 negative, except for occasional positive nuclei in 1 case. We also observed that the stromal cells of atypical polypoid adenomyoma typically exhibited diffuse nuclear immunoreactivity with SATB2 while the stromal cells of other endometrial polypoid lesions (endometrial polyp, adenomyoma, adenosarcoma) were usually negative, although there was focal weak staining in occasional cases. Pathologists should be aware of this previously undescribed phenomenon which represents a further example of the unusual immunophenotype of so-called squamous morules. The reasons underlying SATB2 nuclear positivity in squamous morules and the stroma of atypical polypoid adenomyoma are unknown.

Atypical Polypoid Adenomyoma of the Uterus: An Immunohistochemical and Molecular Study of 21 Cases.

Atypical polypoid adenomyoma (APA) is an uncommon uterine lesion that commonly recurs after local excision and is occasionally associated with or precedes the development of atypical hyperplasia or endometrioid adenocarcinoma. Despite the fact that about 230 cases have been reported in the literature, only 2 studies of 6 and of 7 cases have investigated the molecular aspects; as such, molecular alterations that occur in APA remain largely unknown. We undertook a comprehensive immunohistochemical and molecular analysis of 21 cases of APA in 17 patients (including 4 recurrent/persistent lesions). The analyzed genes were PTEN and TP53 (by fluorescence in situ hybridization) and KRAS, BRAF, EGFR, and NRAS (all by polymerase chain reaction). Immunohistochemical staining was performed for PTEN, p53, mTOR, ß-catenin, HNF-1ß, and GLUT1 and for the mismatch-repair proteins MLH-1, MSH-2, MSH-6, and PMS-2. In most cases, there was nuclear expression of ß-catenin in squamous morules and expression of HNF-1ß, mTOR, and GLUT1 in the glandular component. All cases exhibited "wild-type" expression of p53. A common finding was loss of PTEN expression (6/19 cases). In 1 of these cases, loss of PTEN expression was accompanied by PTEN deletion. Mutation of the KRAS gene was found in 5/19 cases. Intact mismatch-repair protein expression was present in all cases, and TP53 abnormalities or mutations of EGFR, NRAS, or BRAF genes were not found. Given the association with atypical hyperplasia and endometrioid adenocarcinoma and the shared immunohistochemical and molecular features, we feel that, conceptually, APA is best regarded as analogous to a localized form of atypical hyperplasia.

Extrauterine adenomyoma of the liver with a focally cellular smooth muscle component occurring in a patient with a history of myomectomy: case report and review of the literature.

Since first reported in 1986, 14 cases of extrauterine adenomyoma have been reported in the English literature, most often occurring in the ovaries. In this report, we present the first case of extrauterine adenomyoma involving the liver in a 29-year-old woman who presented with a 2-year history of low back pain with recent worsening and a history of laparoscopic myomectomy 5 years previously. Gross inspection of the specimen revealed a subcapsular mass that had a well-circumscribed margin with the adjacent liver tissue. By histopathologic examination, the multilobular mass was composed of a smooth muscle component and benign endometrioid glands and stroma. The smooth muscle component was focally cellular, and the endometrioid glands had secretory features. Both the smooth muscle component and endometrioid tissue were positive for ER and PR. The smooth muscle component was also positive for desmin and SMA, while the endometrioid stroma was positive for CD10. Other extrauterine lesions composed of a mixture of smooth muscle tissue and heterotopic endometrioid tissue, including endometriosis with a smooth muscle component, leiomyomatosis/leiomyomas associated with endometriosis and uterus-like masses, should be included in differential diagnoses. The patient was free from recurrence 5 months after liver tumor resection. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1327125766102291.

CD10 immunostaining distinguishes atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) from endometrial carcinoma invading the myometrium.

The major differential diagnostic problem presented by atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) (APA), which usually affects young women, is the exclusion of well-differentiated endometrial carcinoma invading the myometrium. This distinction, however, is of great clinical importance from the standpoint of treatment because reproductive conservation is feasible for patients with APA. Recently, CD10, known to be a marker of endometrial stromal cells, was reported to be also expressed in cells immediately surrounding the neoplastic glands invading the myometrium [Am J Surg Pathol 27 (2003) 786-789; Mod Pathol 16(1) (2003) 22-27]. However, CD10 expression in the myofibromatous component of APA has not been previously examined in the literature. We therefore decided to examine whether the CD10-immunostaining pattern in APA is different from that in myoinvasive carcinoma. Furthermore, we also attempted to obtain any histopathologic findings that may offer some insight regarding the histogenesis of APA. Seven cases of APA were immunostained for CD10 using curettage or polypectomy specimens, in addition to hysterectomy specimens in 1 case. Areas with more fibrotic rather than muscular stroma were focally observed in 4 cases. The pattern of staining was compared with hysterectomy specimens taken from 19 cases in which well- to moderately differentiated endometrioid adenocarcinoma had deeply invaded the myometrium (outer two thirds of the myometrium) but was not associated with adenomyosis. In 6 of 7 cases of APA, CD10 was never expressed in the myofibromatous stromal components. In 1 case of APA, the fascicles of fibrotic and muscular mesenchymal cells in the interglandular areas were focally and weakly positive for CD10. All 19 myoinvasive carcinomas expressed CD10 to some extent in cells immediately surrounding the neoplastic myoinvasive glands (fringe-like staining pattern). The proportion of the myoinvasive nests immediately surrounded by CD10-positive mesenchymal cells was as follows: mean, 74%; median, 80%; minimum, 5%; maximum, 100%. The fringe-like CD10-staining pattern was not observed in APA. Furthermore, we identified a gradual transformation from preexisting endometrial stromal cells (CD10 positive) into the typical myofibromatous stromal component (CD10 negative) of APA in 1 case. In conclusion, this study demonstrated differences in the CD10 immunoreactivity or immunostaining pattern between the stromal components of APA and myoinvasive endometrial carcinoma. This difference should lead to a more accurate diagnosis of APA (pseudo-myoinvasive lesion). Furthermore, the histogenesis of APA may perhaps be explained by "myofibromatous metaplasia" of the endometrial stromal cells.

Adenomyoma with goblet and Paneth cells of the ileum.

A case of ileal adenomyoma with goblet and Paneth cells is reported. A 75-year-old man died of ruptured hepatocellular carcinoma. As an incidental finding at autopsy, a 9 x 7 x 6 mm(3)-sized nodule was found in the ileal wall. Histologically, the lesion occupied the submucosa and muscularis propria, and consisted of glandular structures of various sizes and interlacing smooth muscle bundles surrounding the glandular elements. Goblet cells and Paneth cells were interspersed in the glandular element. Immunohistochemically, the glandular element was positive for cytokeratin (CK) 7 and negative for CK 20. This is the first reported case of adenomyoma of the gastrointestinal tract that contained Paneth cells. The result of the immunohistochemical staining favored the heterotopic pancreas theory concerning its pathogenesis. The appearance of goblet and Paneth cells might be the result of metaplasia.

Cutaneous melanoma metastatic to uterine adenomyoma: report of a case.

Rare cases of metastasis to uterine polyps have been reported in English literature but not, to the best of our knowledge, to uterine adenomyomas. All these cases are represented by breast cancer, most of them involving tamoxifen-associated polyps. We first report a case of cutaneous malignant melanoma metastatic to uterine adenomyoma. A computed tomography scan did not reveal any further evidence of disease, suggesting that this metastatic localization may represent something more than a fortuitous case. Based on these observations it is suggested that a subset of malignant melanoma and breast cancer cells share a sort of "homing'' phenomenon to polypoid lesions of uterus, due probably to the presence of some chemokines and their specific receptors. Pathologists should be aware of this possibility in order to look carefully for metastatic implants in similar lesions. It is proposed that chemokine profile of neoplastic cells can be a useful tool in predicting metastatic targets.

Polypoid leiomyosarcoma of the gallbladder: study of a case associated with adenomyomatous hyperplasia.

A case of polypoid leiomyosarcoma of the gallbladder arising in association with pre-existing adenomyomatous hyperplasia is described. The patient, a 34-year-old woman with symptoms of cholelithiasis, underwent a cholecystectomy for gallstones. The resected specimen showed, in addition to multiple stones, a large, rubbery, broad-based polypoid mass in the fundus. Histologic examination showed a malignant spindle cell proliferation with immunophenotypic features of smooth muscle differentiation. The base of the lesion showed features of adenomyomatous hyperplasia. The possible relationships of this lesion with adenomyomatous hyperplasia and other stromal lesions of the gallbladder are reviewed.

Müllerian tumor (atypical polypoid adenomyoma) with sex-cord differentiation arising from the oviduct in an adolescent cynomolgus monkey (Macaca fascicularis).

In a 6.5-year-old cynomolgus monkey (Macaca fascicularis), a tumor mass was macroscopically located near the right ovary, connected to the oviduct, and completely separated from the uterus. The mass was an elongated spherical shape with a smooth surface and milky-white color. It was approximately 3.5 cm across its major axis, and the sagittal section was composed of cystic walls and a multi-lobular luminal nodule. Light-microscopically, the polypoid mass consisted of admixtures of neoplastic mesenchymal and epithelial elements. Lipid-rich foamy cells scattered within the tumor mass formed nest-like/aggregated populations. Immunohistochemically, mesenchymal tumor cells stained diffusely positive for vimentin, desmin, and alpha (alpha)-smooth muscle actin, demonstrating a smooth muscle origin. Mesenchymal tumor cells contained mitotic figures, and tumor elements including mesenchymal, epithelial, and lipid-rich foamy cells stained strongly positive for proliferating cell nuclear antigen (PCNA). Moreover, lipid-rich foamy cells elicited positive reactions for testosterone, suggesting sex-cord element differentiation. Electron-microscopically, actin filaments, basement membranes, and electron-dense cytoplasmic bodies were noted in the spindle cells, and invaginated nuclei were observed in adenomatous cells. In contrast, foamy cells contained numerous lipid vacuoles in the cytoplasm. From these findings, the tumor was diagnosed as an atypical polypoid adenomyoma (benign mixed müllerian tumor) with sex-cord differentiation arising from the oviduct. This tumor was considered to be an exceedingly rare finding in the adolescent cynomolgus monkey.

Uterine adenomyoma with uterus-like features: a report of two cases.

Two uterine adenomyomas with unusual features are presented. Case 1 was a 43-year-old woman who had a 1-year history of menorrhagia and dysmenorrhea. The uterus showed a 3-cm-sized mass attached to the posterior wall of the lower uterine segment. On section, there was a well-circumscribed, submucosal cystic mass with a thick muscular wall. Histologically, the cavities were lined by well-developed secretory-phase endometrium and surrounded by smooth muscle, like a small uterus. Case 2 was a 52-year-old woman who visited the hospital because of itching sensation on the vulva. On physical examination, the mass was found on the left side of the pelvis. The enlarged uterus had an 8-cm-sized protruding mass from the left side of the lower uterine segment. On section, the mass was cystic and solid. Histologically, the cysts were lined by thin basalis-type endometrial glands and stroma, and the solid portion was composed of smooth muscle and fat cells.

Endocervical adenomyoma. A case report with histochemical and immunohistochemical studies.

We report a case of adenomyoma of endocervical type arising in a 44-year-old female. Grossly, a well-circumscribed tumor protruding from the right side of the uterine cervix was seen which was assumed to be an ovarian tumor by imaging studies carried out preoperatively. The tumor was composed of a mixture of proliferating glands of endocervical type and fascicles of smooth muscle cells. There was no distinct nuclear anaplasia in the proliferating glands, there were no architectural abnormalities, and there was no evidence of destructive stromal invasion such as desmoplasia. Minimal deviation adenocarcinoma, which shows a gastric phenotype with immunoreactivity for M-GGMC-1 and predominantly PAS-positive neutral mucin, was a serious diagnostic possibility, but the lesion was well-circumscribed, cytologic and architectural abnormalities were absent, and staining for M-GGMC-1 was negative, which suggested a diagnosis of endocervical adenomyoma. An increased Ki-67 labeling index by up to 20%, the presence of predominantly PAS-positive neutral mucin, and membranous immunoreactivity for CEA in limited areas were diagnostic pitfalls, which could lead to an erroneous diagnosis of minimal deviation adenocarcinoma of the uterine cervix. Therefore, the results of these ancillary techniques should be interpreted with caution and combined with gross and light microscopic features.

Uterus-like mass of the small bowel mesentery.

A case of a uterus-like mass arising from the mesentery is reported. A mass measuring 14x11 cm was noted in the small bowel mesentery of a 59-year-old woman. Histologically, the lesion consisted of endometrial-type and fallopian tube-type mucosa surrounded by thick bundles of smooth muscle cells. Since the first report by Cozzutto in 1981, 10 cases of uterus-like mass, that included seven ovarian and three extraovarian cases, have been reported. To our knowledge, the present lesion was the first case originating from the mesenteric region. Three hypotheses of this rare lesion: (i) congenital anomaly; (ii) metaplasia; and (iii) heterotopia theories are reviewed.

Uterine adenomyoma of endocervical type.

A uterine adenomyoma of endocervical type was presented histopathologically in a 44-year-old woman. She had a mural tumor of the uterine endocervix, which showed a well-circumscribed margin and multiple cysts filled with mucin. Histologically, the tumor was composed of a proliferation of endocervical glands and smooth muscle. The glandular epithelial components were cystic and occasionally papillary, but neither component showed cytological atypia. A differential diagnosis of the uterine endocervical tumor should include adenomyoma of endocervical type.

Adenomyoepithelioma of the skin: a case report with immunohistochemical and ultrastructural observations.

AIMS: The histological, immunohistochemical and electron microscopic features of a primary adenomyoepithelioma of skin, a rare sweat gland tumour, are reported. METHODS AND RESULTS: The tumour occurred on the back of a 92-year-old woman. It was composed of well-formed tubules lined by epithelial cells surrounded by clear or spindled myoepithelial cells. Immunohistochemically, the epithelial cells exhibited strong cytokeratin (CAM5.2) and weak carcinoembryonic antigen positivity. The myoepithelial cells showed diffuse positivity for smooth muscle actin and focal positivity for S100 protein. Ultrastructurally, the myoepithelial cells contained myofilaments with focal densities and hemidesmosomes. They were limited by well-formed basal lamina. The tumour was associated with a small eccrine spiradenoma. CONCLUSION: We predict that the tumour will behave in a benign fashion. There is no evidence of recurrence or metastasis 28 months later.

Peritoneal endometriosis and "endometriotic" nodules of the rectovaginal septum are two different entities.

OBJECTIVE: To compare histologically and stereologically the endometriotic nodule of the rectovaginal septum to peritoneal endometriosis. DESIGN: Morphometric investigation, cytokeratin and vimentin content, and steroid receptor evaluation were performed on endometriotic tissue from the peritoneum (n = 52) and rectovaginal nodules (n = 68). SETTING: An academic teaching hospital. PATIENTS: Biopsies were taken from 120 patients undergoing a laparoscopy for infertility and/ or pelvic pain (52 from typical black peritoneal endometriotic implants and 68 from endometriotic nodule of the rectovaginal septum). None of the patients were treated. RESULTS: Mitotic activity was found to be significantly different in peritoneal and rectovaginal endometriosis. The evaluation suggested that the stroma is not mandatory for the invasion of glandular epithelium in the rectovaginal nodule, which is, like a adenomyoma, a circumscribed nodular aggregate of smooth muscle and glandular elements. Cytokeratin and vimentin content as well as the estrogen receptor (ER) and P receptor (PR) content were significantly lower in both types of lesion when compared with eutopic endometrium. But vimentin immunoreactivity in epithelium, as well as the ER and PR content, were significantly lower in nodules when compared with black peritoneal lesions. CONCLUSION: It is suggested that the rectovaginal endometriotic nodule is a different disease from peritoneal endometriosis and must be called rectovaginal adenomyosis or rectovaginal adenomyoma. Its histopathogenesis probably is not related to the implantation of regurgitated endometrial cells but to the metaplasia of Müllerian rests.

Atypical polypoid adenomyomas of the uterus.

We performed a clinicopathological immunohistochemical, ultrastructural, and flow cytometric study on six cases of atypical polypoid adenomyoma of the uterus including one with an adenocarcinoma within it. The tumours occurred in nulliparous women aged 22-48 years (average, 33.0 years); three arose in the uterine corpus, and three in the endocervix. Histologically, they were composed of endometrial glands admixed with a stromal component of interlacing bundles of smooth muscle cells. The glands exhibited varying degrees of architectural and cytological atypia. Most of the stromal cells showed strong staining for HHF35, alpha-smooth muscle actin, and vimentin, and some cells contained desmin. Electronmicroscopy, in one case, confirmed the presence of a well-differentiated smooth muscle component. The stromal component may arise as a result of extensive metaplasia of endometrial stromal cells. Uninvolved endometrium showed ciliated cell metaplasia in three patients, and atypical complex hyperplasia in two. One patient had a well-differentiated adenocarcinoma of endometrioid type arising in an endocervical atypical polypoid adenomyoma. All tumours had a diploid DNA content and relatively small S phase fraction (average, 6.23%). The follow-up periods ranged from 4 to 42 months (average, 13.5 months), and all patients were alive and well. Although the histogenesis of atypical polypoid adenomyoma of the uterus remains uncertain, it is suggested that it may arise because of oestrogen-related factors.