CASE PRESENTATION SUPERVISION: DR MOHAMMADIZADE PRESENTATION: DR HEYDARI

 REFRENCES:  - ROSAI AND ACKERMAN'S SURGICAL PATHOLOGY-VOL 2  BLAUSTAIN,S PATHOLOGY OF THE FEMALE GENITAL TRACT  - PATHOLOGY OF THE FEMALE REPRODUCTIVE TRACT, THIRD EDDITION,GEORGE L. MUTTER,JAIME PRAT  - DIAGNOSIS OF ENDOMETRIAL BIOPSIES AND CURETTINGS, MAZUR & KURMAN

A Virgin 19 years old girl CC : AUB, Vaginal mass lesion PH/E: A vaginal mass that connect to cervix with a thin pedicle

MACROSCOPIC Two pieces with grayish color and rather firm consistency, total size 5/5*5*2/5

GROSS

MICROSCOPIC In the background of a myomatous and fibromyomatous stroma, endometrioid type glands are seen. there is significant glandular crowding with focal back-to-back architecture and sheet pattern. Glands have a psoudostratified epithelium with larg and hyperchromic nuclei,ploumorphism and high N/C ratio and lost nuclear polarity. the disordered arrangement of atypical glands among a dense extensive morular squamous metaplasia.

H&E Low power field

H&E HIGH POWER FIELD

H&E High power field

 DDX:  - Endometrial polyp - Adenomyomatous polyp( polypoid adenomyoma)  - Atypical polypoid adenomyoma  - Endometrial adenocarcinoma with myometrial invasion  - Endometrial hyperplasia

 Endometrial polyps having smooth muscle fibers (NOT CONNECTED WITH BLOOD VESSEL WALLS) in addition to the customary gland & stroma & designated as ADENOMYOMATOUS POLYPS or POLYPOID ADENOMYOMAS. They have a characteristic firm consistency & a graish color.  An important variation on the them is the ATYPICAL POLYPOID ADENOMYOMA OR ADENOMYOFIBROMA

 These tend to occure in premenopausal women (average age 40 years) & present with AUB usually in the form of menorrhagia. In some cases, the diagnosis is made during investigations for infertility. Occasional cases occur in postmenopausal women, and rare examples have been described in patients with Turner’s syndrome who have been prescribed unopposed estrogens. A single study has investigated molecular events in atypical polypoid adenomyoma and found MLH-1 promotor hypermethylation in some cases, a molecular alteration characteristic of some atypical hyperplasias and endometrioid adenocarcinomas

 Atypical polypoid adenomyoma is most commonly located in the lower uterine segment, although some cases involve the fundus, uterine body, or endocervix. In most cases, the lesion has an obvious polypoid gross appearance, in the form of either a sessile or broad-based polyp, but sometimes the polypoid nature is not grossly obvious, especially in smaller lesions

GROSS APPEARANCE OF AN ATYPICAL POLYPOID ADENOMYOMA.THE TUMOR PRESENTS AS A BROAD- BASED POLYPOID MASS IN THE LOWER UTERINE SEGMENT

 Histology shows architecturally irregular endometrioid type glands that may be widely separated and haphazardly arranged or somewhat crowded and arranged in groups, sometimes with a vaguely lobular pattern. The endometrioid epithelium varies in appearance from cuboidal to low columnar to pseudostratified. The nuclei are usually round, sometimes with prominent nucleoli, and exhibit mild or, at the most, moderate cytological atypia.  Occasional foci of ciliated or mucinous epithelium may be present.A characteristic histological feature that is present in most, but not all, cases is abundant squamous morule formation sometimes, the morules exhibit central necrosis.  The glands are set in an abundant stroma, which varies from obviously smooth muscle in nature to fibromyomatous. Endometrial stroma is not present. The stromal cells are often arranged in short interlacing fascicles. Occasional mitotic figures may be identified within the stroma.

ATYPICAL POLYPOID ADENOMYOMA: MUSCLE WITH ADMIXED GLANDS HAVING SQUAMOUS MORULES

ATYPICAL POLYPOID ADENOMYOMA: GLANDS HAVING SQUAMOUS MORULES

 Microscopically they are identified by the fact that the glands accurring between the endometrial stroma & atypia some times approaching the appearance of the carcinoma in situe.(of low malignant potential) the danger is to misdiagnose them as adenocarcinomas with myometrial invasion.

 underlying myometrium is usually rounded and well delineated but occasionally there is merging with underlying adenomyosis. In some cases, there is significant glandular crowding with a back-to-back architecture and stromal exclusion, such that there are foci, which are virtually indistinguishable from, and which are best regarded as, grade I endometrioid adenocarcinoma. The term atypical polypoid adenomyoma of low malignant potential has been used for lesions with marked architectural complexity, but this term is not recommended

 The behavior is generally benign but cases have been seen with local recurrences, carcinomatous transformation & coexistence endometrial or ovarian endometrial carcinoma.

 Very rarely, there is underlying myometrial invasion, and/or an endometrioid adenocarcinoma is present in the surrounding endometrium. Atypical polypoid adenomyoma is generally a benign lesion, but there is a risk of recurrence if curettage or polypectomy is undertaken. In one series, 45% of cases treated by curettage or polypectomy recurred. Given this risk of recurrence and the small, but definite, risk of transition to endometrioid adenocarcinoma, which was estimated at 8.8% in one meta-analysis, hysterectomy is the treatment of choice if the diagnosis is made on biopsy or polypectomy.

 Within a fragmented endometrial sample the disordered arrangement of atypical glands among a dense muscular stroma can easily by confused as myoinvasive adenocarcinoma. The presence of characteristic & extensive morular squamous metaplasia.(present in >90% of examples)  Lack of cribriform or solid architecture & absence of stromal desmoplasia are helpful in excluding adenocarcinoma.

 The most important differential diagnosis is an endometrioid adenocarcinoma exhibiting myometrial invasion or with a prominent desmoplastic stroma, an obviously important distinction since most atypical  polypoid adenomyomas exhibit a benign behavior with a potential for conservative management. Recognition of the polypoid nature of the lesion assists in establishing the diagnosis. Marked cytological atypia favors a myoinvasive adenocarcinoma since in atypical polypoid adenomyoma, there is usually no more than mild to moderate cytological atypia.

 The differential diagnosis can also include a benign endometrial polyp in which there may be a minor component of smooth muscle within the stroma. So called typical adenomyomatous polyps or adenomyomas also occur and are composed of benign endometrioid type glands in a myomatous stroma. Often, endometrioid stroma surrounds the glands and this in turn is surrounded by smooth muscle. Rarely a carcinosarcoma enters into the differential diagnosis because of the admix ture of epithelial and stromal elements. However, both the epithelial and mesenchymal components of a carcinosarcoma are obviously malignant and typically high grade.

 Approximately half persist or recur locally after conservative treatment by curettage. Atypical polypoid adenomyomas have been associated with endometrial adenocarcinoma & its precursore lesions(EIN or atypicall endometrial hyperplasia)either of wich may be present within the main polypoid mass or elsewhere in the endometrium. It is the fore important to look carefully for coexisting carcinoma & examine the naitive endometrium for EIN, if either are present they should be separately diagnosed.

 hysterectomy is the treatment of choice if the diagnosis is made on biopsy or polypectomy. In a woman who wishes to retain her uterus and in whom a confident diagnosis of atypical polypoid adenomyoma has been made on biopsy or polypectomy, complete removal by curettage or polypectomy may be undertaken with close follow- up and imaging. Successful pregnancies have ensued in patients managed in this way.

 Immunohistochemistry is of little value in distinguishing between atypical polypoid adenomyoma and a myoinvasive endometrioid adenocarcinoma since the stromal component of atypical polypoid adenomyoma and myometrium infiltrated by carcinoma are both desmin and smooth muscle actin positive. It has been suggested that CD10 may be of value since this is negative in the stromal component of atypical polypoid adenomyoma while the myoinvasive glands of endometrioid adenocarcinoma are typically surrounded by CD10 positive stromal cells.

PR (POSITIVE)

ER(POSITIVE)

VIMENTIN(POSITIVE)

CD10(FOCALLY POSITIVE)

CK7(FOCALLY POSITIVE)

KI 67

CK20(NEGATIVE)

CEA(NEGATIVE)

 CASE FALLOW UP:  - Hysteroscopy : multiple uterin polyps (sessile & broad- based polyp)  - Curettage : Adenomyomatous polyp & proliferative surrounding stroma  - MRI : fore evaluation of myometraial invasion in base of polypectomy, Closed fallow up with imaging