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Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer

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Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer Journal of Cancer Therapy, 2011, 2, 458-462 doi:10.4236/jct.2011.24061 Published Online October 2011 (http://www.SciRP.org/journal/jct) Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer Iori Kisu, Kouji Banno*, Megumi Yanokura, Yusuke Kobayashi, Arisa Ueki, Asuka Ono, Kenta Masuda, Wataru Yamagami, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan. Email: *[email protected] Received June 8th, 2011; revised June 30th, 2011; accepted August 8th, 2011. ABSTRACT Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pathologi- cally, APAM consist of irregularly proliferated endometrial gland cells and interlacing bundles of smooth muscle cells within the stroma, and have a similar form to adenocarcinoma, adenofibroma, adenosarcoma, and carcinosarcoma. Therefore, differential diagnosis is required in many cases. APAM is pathologically classified as a benign lesion and clinically has a comparatively favorable outcome. However, treatment and follow-up observation should be performed carefully because recurrence and residual lesions occur in many patients after conservative treatment. Concomitant development of endometrial adenocarcinoma also occurs in many cases and it is difficult to differentiate this disease from APAM. Thus, diagnosis of APAM should be made carefully, particularly since the number of cases of endometrial adenocarcinoma has increased in recent years. Furthermore, APAM tends to develop during a woman’s reproductive years, and fertility sparing treatment should be considered. Here, we review the clinicopathological characteristics of APAM, including the difficulty of diagnosis as a benign or malignant uterine tumor, and we examine the relationship between APAM and endometrial cancer. Keywords: Atypical Polypoid Adenomyoma, Endometrial Adenocarcinoma, Atypical Endometrial Hyperplasia, Transcervical Resectoscope, Fertility Sparing 1. Introduction ferentiated endometrioid adenocarcinoma based on the samples by dilatation and curettage is difficult, and a Atypical polypoid adenomyoma (APAM) was first re- method to avoid erroneous diagnosis is urgently re- ported by Mazur in 1981 as a tumor that mainly con- quired. sisted of proliferated endometrial glands and smooth muscle cells [1]. Clinically, APAM is a rare sessile poly- It is unclear whether APAM is a precancerous lesion poid tumor that occurs in the uterus of premenopausal of endometrioid adenocarcinoma. Appropriate treatment women manifests with abnormal genital bleeding, men- and follow-up of APAM patients are required for this struation disorder, and hypermenorrhea. reason and because residual lesions and recurrence can APAM have an epithelial component consisting of occur after conservative treatment. APAM also tends to endometrial glands with complex branches of cellular develop during a woman’s reproductive years, and con- and structural atypia. In some cases, it is difficult to dif- sideration of fertility sparing treatment is important. The ferentiate APAM from atypical endometrial hyperplasia significant increase in endometrial cancer in recent years (AEH). The stroma mainly consists of smooth muscle suggests the need for increased awareness of APAM tissues, including various ratios of fibroblasts. Tumors among gynecologic oncologists. requiring pathological differential diagnosis from APAM 2. Definition and Clinical Presentation of include adenocarcinoma, adenofibroma, adenosarcoma, APAM and carcinosarcoma. Since the stroma in APAM consists of smooth muscle, differential diagnosis from well-dif- APAM develops in the fundus, lower part, and cervix of Copyright © 2011 SciRes. JCT Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer 459 the uterus as a polypoid tumor that shows extroversive 45% of APAM cases, which were referred to as “APAMs development on transvaginal ultrasonography, MRI, CT, with low malignant potential.” Complications of well- PET-CT, and hysteroscopy. Differential diagnosis of differentiated endometrioid adenocarcinoma and inva- APAM is required from endometrial polyp, submucosal sion in the muscle layer are also observed in some cases myoma, and uterine body cancer. Diagnosis of APAM is [8]. straightforward when observed as a polypoid lesion from The stroma consists of smooth muscle cells that show the external cervical os. In T2-weighted MRI, both high bundle proliferation with less atypia, and myofibroblasts and low intensity areas are observed. In PET, accumula- (intermediates between smooth muscle cells and fibro- tion of 18F-FDP is generally viewed as a marker of a ma- blasts) [4,7]. Although atypia of these stromal cells is lignant tumor, but moderate accumulation may also oc- seen in some APAM cases, the level of atypia is not high. cur in benign diseases such as leiomyoma. Such accu- Mitosis is also observed, but 2 or more mitoses in 10 mulation in benign diseases is related to the active pro- fields of a high-power microscope have not been found liferation potential of the tumor cells, and thus APAM [4]. The smooth muscle component of the stroma may should be suspected in a case with a polypoid lesion in also be incorrectly identified as muscle invasion of en- the uterus for which accumulation differs from that in dometrioid adenocarcinoma, and care is required in in- normal uterine myoma [2]. Visually, APAM appears as terpreting the results. The cytoplasm is smaller than that single or multiple polypoid nodular lesions with smooth of smooth muscle cells in the normal muscle layer, and yellow to ash gray surfaces. The size varies from ≤1 cm polarity is lost in many cases. The endometrium of the to several centimeters, with lesions of ≤2 cm being most non-tumor area shows high estrogen activity [9]. common. Cytological finding shows hyperplasia of the endo- At present, APAM is histopathologically classified as metrium and a cluster of smooth muscle cells with less a benign lesion of mixed epithelial and mesenchymal atypia. The latter finding is important for diagnosis, but a tumors (Table 1) [3] with a clear border with normal comprehensive perspective is required based on clinical tissues and no invasive proliferation. APAM consist of presentation and images. Since concomitant development irregularly proliferated endometrial glands and interlac- of endometrial adenocarcinoma can occur in many cases, ing bundles of smooth muscle cells. The endometrial a diagnosis based only on cytological finding should be gland shows various levels of structural and cellular a- made carefully [10]. A DNA ploidy test shows that all typia, with a multilayered glandular epithelium, cribri- cases are DNA diploid and that the S-phase fraction is form pattern, solid lesion, irregular branching, and papil- low [11]. lary arrangements. Squamous metaplasia and squamous APAM tends to develop in comparatively young pre- morule are found in about 90% of APAM cases, accom- menopausal women, and especially in nulligravid women, panied by elimination of the gland structure or necrosis with many cases having infertility. The average age at in some cases [4-6]. Advanced cellular atypia such as which APAM is diagnosed is about 40 years old [4], but the lesion may develop in postmenopausal women in rare polygonal cells, a large nucleus, and a large nucleolus are cases. Abnormal genital bleeding is the chief complaint also observed in some cases. Longacre et al. [7] de- in most cases, and menstruation disorder and hyper- scribed images with partly similar characteristics to those menorrhea may also occur. Diagnosis should include of the structure of well-differentiated glandular cancer in data for menstrual history, pregnancy history, delivery history, history of hormone therapy, obesity, hyperten- Table 1. Classification of mixed epithelial and mesenchymal sion, diabetes, ovulation disorder, and infertility [7,12, tumors. 13]. Benign mixed epithelial and mesenchymal tumors Concomitant development of APAM has been re- Adenofibroma ported in a patient with Turner’s syndrome who was re- Adenomyoma ceiving long-term administration of an estrogenic drug atypical polypoid adenomyoma [14]. This suggests a relationship between long-term Malignant mixed epithelial and mesenchymal tumors stimulation by estrogen and a neoplasm in the uterine epithelium or stroma. Hyperprolactinemia may also cause Adenosarcoma homologous amenorrhea, anovulation and infertility, and development heterologous of APAM has been reported after long-term continuous Carcinofibroma estrogen stimulation of precursor cells of the endometrial Carcinosarcoma stroma in a woman with ovulation disorder [15]. Devel- homologous opment of APAM may be affected by estrogen because heterologous the disease often develops in premenopausal and nul- Copyright © 2011 SciRes. JCT 460 Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer ligravid women, and the endometrium shows endo- in patients who receive conservative treatment, because metrial hyperplasia or proliferation. it is very difficult to differentiate these cases from pa- 3. Developmental Mechanism of APAM tients who develop APAM and carcinoma concomitantly. The rate of transition to carcinoma in patients with com- Many aspects of the histogenesis of APAM are unclear. plex AEH
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