- Email: [email protected]
Hysteroscopic treatment of atypical polypoid adenomyoma diagnosed incidentally in a young infertile woman
CASE REPORT Hysteroscopic treatment of atypical polypoid adenomyoma diagnosed incidentally in a young infertile woman Attilio Di Spiezio Sardo, M.D.,a Ivan Mazzon, M.D.,b Virginia Gargano, M.D.,a Costantino Di Carlo, M.D.,a Maurizio Guida, M.D.,a Chiara Mignogna, M.D.,c Giuseppe Bifulco, M.D.,a and Carmine Nappi, M.D.a a
Department of Gynaecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Naples; b Endoscopic Gynecologic Unit, Nuova Villa Claudia, Rome; and c Department of Biomorphologic and Functional Sciences, Anatomic Pathology Section, University of Naples ‘‘Federico II,’’ Naples, Italy
Objective: To describe the conservative treatment of an atypical polypoid adenomyoma (APA) in a young infertile patient using a modification of the technique previously reported for the conservative treatment of stage IA endometrial cancer. Design: Case report. Setting: Department of Gynaecology and Obstetrics and Pathophysiology of Human Reproduction of the University of Naples ‘‘Federico II.’’ Patient(s): A 35-year-old woman diagnosed incidentally with an APA during routine investigation for primary infertility. Intervention(s): Conservative resectoscopic treatment using a four-step technique in which each step is characterized by a pathological analysis: the removal of the APA (step 1), the removal of endometrium adjacent to the APA (step 2), the removal of the myometrium underlying the APA (step 3), and multiple random endometrial biopsies (step 4). Main Outcome Measure(s): Complete resection of the APA and ruling out of any malignancy. Result(s): The conservative surgery was effective as histological examination of all specimens confirmed an APA confined to the endometrium without any other premalignant or malignant lesion. Transvaginal ultrasound and office hysteroscopy with target biopsies at 1 and 6 months after surgery were negative for atypia and malignancy. Conclusion(s): Our technique under a close, intermittent postoperative surveillance might represent a good therapeutic option for those women with APA who wish to preserve their fertility as well as for those at high medical risk for hysterectomy. (Fertil Steril 2008;89:456.e9–12. 2008 by American Society for Reproductive Medicine.) Key Words: Atypical polypoid adenomyoma, conservative treatment, hysteroscopy, infertility, resectoscope
Atypical polypoid adenomyomas (APAs) are uncommon tumors of the uterus (<150 cases reported), usually occurring in premenopausal women and typically presenting with abnormal uterine bleeding (1). Less frequently, patients with APA suffer from vaginal discharge, pelvic pain, or postcoital spotting (2). An associated clinical history of infertility is not uncommon (2–4). Histologically, APA is characterized by an intimate admixture of benign endometrial glands with structural atypia and a stroma consisting predominantly of benign appearing smooth muscle. Squamous metaplasia is found in more than 90% of the cases, and therefore it can be a useful marker Received January 4, 2007; revised and accepted February 27, 2007. Reprint requests: Attilio Di Spiezio Sardo, Department of Gynecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Via Pansini 5, Naples, Italy (FAX: 390817462905; E-mail: [email protected]).
456.e9
for this lesion (2). However, cytologic atypia of the squamous epithelium is unusual (2). Although most cases are benign (3, 5), APA has been occasionally found to coexist with or to precede the development of an endometrioid adenocarcinoma of the endometrium (EEC), which may be either within the APA or elsewhere in the uterus (6–9). According to the data collected in a recent review of international literature, the average risk of EEC in women with APA is about 8.8%, which is considerably higher than the overall risk of 0.8% reported in women with endometrial polyps (10). The definite diagnosis of APA can be established only by histological findings. Most lesions are usually detected on endometrial biopsy or dilation and curettage specimens obtained from patients with abnormal bleeding. On the other hand, some APAs have been incidentally discovered in uteri removed for other pathologies (i.e., leiomyomata) or during
Fertility and Sterility Vol. 89, No. 2, February 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/08/$34.00 doi:10.1016/j.fertnstert.2007.02.061
routine hysteroscopy performed for infertility or suspected intrauterine growth. These lesions are typically located in the isthmus or in the lower part of the endometrial cavity (11). Hysteroscopy may also have an important role in the treatment of APAs. Indeed, while in postmenopausal women simple hysterectomy is the treatment of choice (6, 7), in young women who wish to preserve their fertility, local resection and a careful postoperative follow-up might represent an appropriate treatment. We report the successful hysteroscopic resection of APA in a young infertile patient using a new technique, similar to that already described for the conservative treatment of EEC (12). CASE REPORT A 35-year-old woman was referred to the Department of Obstetrics and Gynaecology of University Hospital ‘‘Federico II’’ in Naples, Italy, for primary infertility. The patient provided an informed consent to perform the study. The study was eventually approved by our Institutional Review Board. Her menarche occurred at the age of 12, and menstrual periods were regular, presenting approximately every 28 days with 4–5 days of flow. Her family and personal history were negative for genital neoplasia. Basic hormonal dosage in the initial follicular phase, progestin dosage in the luteal phase, and analysis of partner’s semen were within the normal range. Physical and bimanual pelvic examinations were normal. Transvaginal ultrasound showed a polypoid mass in the uterine cavity with smooth surface and homogeneous isoechogenicity relative to the myometrium (Fig. 1A). A vaginoscopic hysteroscopy was performed by one of the authors (A.D.S.S.) with a 5-mm continuous-flow operative office hysteroscope with a 2.9-mm rod lens (Bettocchi office hysteroscope; Karl Storz, Tuttlingen, Germany). Neither analgesia nor local anaesthetics were administered to the pa-
tient. Distension of the uterine cavity was obtained using normal saline solution, and the intrauterine pressure was automatically controlled by an electronic irrigation and suction device (Endomat, Karl Storz). The intrauterine pressure was set at 45 mmHg, which is the balance of irrigation flow around 200 mL/minute and a vacuum of 0.2 bar. Endoscopic vaginal and cervical explorations were normal. An irregular exophytic lesion of 1.5–2 cm in diameter growing up from the right uterine wall was detected (Fig. 1B). Both the morphology and color were suggestive of a polyp, while its consistency and vascularization were indicative of a myomatosus lesion. Because of the hard consistency of such a lesion, a 5-Fr twizzle electrode was used to perform a wide-target biopsy. The biopsy was interpreted by the pathologist as APA. After accurate counseling and taking into account her desire to preserve fertility, the patient was targeted for a conservative approach. An operative hysteroscopy was performed by one of the authors (A.D.S.S.) under general anaesthesia; the cervix was dilated to 10 mm with Hegar’s dilators, and a 9-mm resectoscope (Karl Storz) with a 0 lens was introduced. Distension of the uterine cavity was obtained using 1.5% glycine solution, and the intrauterine pressure was automatically controlled by an electronic irrigation and suction device (Endomat, Karl Storz). A 5-mm cutting loop electrode and 100 W of pure cutting output power were used to resect the exophytic lesion (step 1). The procedure (steps 2 and 3) continued according to the technique described by Mazzon et al. (12) for conservative treatment of stage IA endometrial cancer (Fig. 2). Furthermore, multiple random endometrial biopsies were performed (step 4). For each step, a pathologic analysis was performed (Fig. 2). Histological examination of specimen A confirmed an APA, while the other specimens (B, C, D) were negative for APA or other premalignant or malignant lesions.
FIGURE 1 Ultrasonographic (A) and hysteroscopic (B) appearance of APA.
Di Spiezio Sardo. Hysteroscopy and atypical polypoid adenomyoma. Fertil Steril 2008.
Fertility and Sterility
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FIGURE 2 Technique for conservative hysteroscopic treatment of APA. Step 1: resection of APA; step 2: removal of endometrium near the lesion; step 3: removal of myometrium under lesion; step 4: multiple random endometrial biopsies. For each step a pathologic analysis is done.
Di Spiezio Sardo. Hysteroscopy and atypical polypoid adenomyoma. Fertil Steril 2008.
The patient underwent a transvaginal and office hysteroscopy with target biopsies 1 and 6 months after surgery, which were negative for atypia and malignancy. At this time, the patient is trying to achieve a spontaneous pregnancy. DISCUSSION According to World Health Organization 2002 classification ‘‘Tumour of the breast and female genital organs,’’ APAs are defined as mixed epithelial and mesenchymal tumors of the uterine corpus (13). Their hystogenesis remains uncertain, even if some investigators (14, 15) suggest that an important role in their development might be exerted by hyperestrogenism, mainly in those cases accompanied by endometrial hyperplasia or endometrioid type adenocarcinoma. Additionally, uterine APAs have been described in patients with Turner’s syndrome who received hormone replacement therapy for several years (3, 16).
A recent review of 136 cases has estimated that the average risk of coexistence with EEC is about 8.8% (10). Among the 12 cases with endometrial adenocarcinoma, the carcinoma was located within the APA or in association with its base in nine cases, while in the remaining three cases it was identified in the adjacent endometrium (10). Moreover, the presence of recurrent or residual APA after local excision was reported in 30.1% of the cases, thus indicating a continued risk for the development of malignant disease in patients in whom a complete excision of APA cannot be guaranteed (10). Taking into account the severe degree of glandular atypia in some cases of APA, the frequent association with endometrial adenocarcinoma and the potential for recurrence after local excision, simple hysterectomy should be preferred in perimenopausal or postmenopausal women to obtain a complete removal of the lesion.
Although most cases are benign, APA cannot be classified as a totally benign endometrial lesion, and thus it should be carefully evaluated. Indeed it has been observed that varying degrees of glandular atypia may occur in APA, including endometrial hyperplasia and even carcinoma in situ (1, 3).
A conservative treatment has been proposed (2, 6, 14) in women who wish to retain their uterus or in those at high medical risk for hysterectomy. Indeed APAs are often detected in young nulliparous women, sometimes during a workup for infertility.
Longacre et al. observed that APAs exhibiting severe architectural complexity are more likely to be associated with EEC and suggested the term APA of low malignant potential (APA-LMP) for this morphological variant to emphasize the potential risk for myometrial invasion (2).
Blunt curettage represents the conventional conservative approach, but it has three main limitations: [1] it does not offer the possibility of visualizing the entire uterine cavity; [2] it might miss small focal lesions or make the entire lesion unavailable for histological examination, and [3] the differential
456.e11
Di Spiezio Sardo et al.
Hysteroscopy and atypical polypoid adenomyoma
Vol. 89, No. 2, February 2008
diagnosis between APA and endometrial carcinoma with myometrial invasion could be difficult in a curettage specimen (3). On the other hand, operative hysteroscopy allows a panoramic visualization of the uterine cavity, thus making possible the sampling of multiple and well-localized specimens. Vilos et al. describes the only reported case of APA treated by operative hysteroscopy, in which the resection of the lesion was followed by an endometrial ablation (17). We propose a different hysteroscopic technique for the treatment of APA, which could be useful for women who wish to preserve their fertility. Such treatment consists of four steps, each of those characterized by a pathological analysis: the removal of the APA (step 1), the removal of the endometrium adjacent to the APA (step 2), the removal of the myometrium underlying the APA (step 3), and multiple random endometrial biopsies (step 4). If any of the specimens obtained from steps 2 to 4 is positive for neoplastic lesion, the conservative treatment should be converted into a radical one (hysterectomy). Our technique offers four main advantages in comparison with blunt curettage and Vilos’s technique: [1] preservation of fertility (the endometrium is not completely resected); [2] complete removal of the lesion (step 1) thus rendering the whole lesion available for histological examination; [3] the pathological analysis of specimen A, B, and Ds, which allows the detection of those EECs located within the APA or in association with its base as well as those developing in the adjacent endometrium; [4] the pathological analysis of specimen C, which allows the distinction between APA and EEC with myometrial invasion; indeed APAs are usually well demarcated from the underlying myometrium (3) and neither desmoplasia nor inflammatory features (typically associated with the myometrial invasion of EEC) are detected. Our technique represents a slight modification on the technique previously described for the conservative treatment of EEC (12). The main difference lies in the introduction of a further step (multiple endometrial biopsies), which allows the assessment of the endometrium distant from the APA, and in fact such surgery does not require a following hormone therapy regimen of megestrol acetate. In conclusion, we believe that our technique under a close, intermittent postoperative surveillance might represent a good therapeutic option in those women who wish to preserve their fertility as well as in those at high medical risk for hysterectomy. A close cooperation between the patholo-
Fertility and Sterility
gist and the hysteroscopist needs to be emphasized; indeed, a complete understanding of the histological profile of APA together with an accurate examination of all the specimens obtained is crucial to the surgeon in choosing the best treatment and modulating its radicality.
REFERENCES 1. Mazur MT. Atypical polypoid adenomyomas of the endometrium. Am J Surg Pathol 1981;5:473–82. 2. Longacre TA, Chung MH, Rouse RV, Hendrickson MR. Atypical polypoid adenomyofibromas (atypical polypoid adenomyomas) of the uterus: a clinicopathologic study of 55 cases. Am J Surg Pathol 1996;201:1–20. 3. Young RH, Treger T, Scully RE. Atypical polypoid adenomyoma of the uterus: a report of 27 cases. Am J Clin Pathol 1986;86:139–45. 4. Fukunaga M, Endo Y, Ushigome S, Ishikawa E. Atypical polypoid adenomyomas of the uterus. Histopathology 1995;27:35–42. 5. Delprada WJ, Stevens SM, Baird PJ. Atypical polypoid adenomyoma: a case report with ultrastructural examination. Pathology 1985;17:522–5. 6. Sugiyama T, Shunichiro O, Nishida T, Okura N, Tanabe K, Yakushiji M. Two cases of endometrial adenocarcinoma arising from atypical adenomyoma. Gynecol Oncol 1998;71:141–4. 7. Mittal KR, Peng XC, Wallach RC, Desmopoulos RI. Coexistent atypical polypoid adenomyoma and endometrial adenocarcinoma. Hum Pathol 1995;26:574–6. 8. Buenerd A, Dargent D, Scoazec JY, Berger G. Carcinomatous transformation of an atypical polypoid adenomyofibroma of the uterus. Ann Pathol 2003;23:63–6. 9. Staros EB, Shilkitus WF. Atypical polypoid adenomyoma with carcinomatous transformation: a case report. Surg Pathol 1991;4:157–66. 10. Heatley MK. Atypical polypoid adenomyoma: a systematic review of the English literature. Histopathology 2006;48:609–10. 11. Ota S, Catasus L, Matias-Guiu X, Bussaglia E, Lagarda H, Pons C, et al. Molecular pathology of atypical polypoid adenomyoma of the uterus. Hum Pathol 2003;34:784–8. 12. Mazzon I, Corrado G, Morricone D, Scambia G. Reproductive preservation for treatment of stage IA endometrial cancer in a young woman: hysterocopic resection. Int J Gynecol Cancer 2005;15:974–8. 13. Bo¨cker W. WHO classification of breast tumors and tumors of the female genital organs: pathology and genetics [in German]. Verh Dtsch Ges Pathol 2002;86:116–9. 14. Athas JM, Bluemke DA, Isacson C, Sheth S. Large cervical adenomyoma occurring in a first-trimester gravid uterus: radiologic-pathology correlation. Am J Roentgenol 1996;167:514–5. 15. Gilks CB, Young RH, Clement PB, Hart WR, Scully RE. Adenomyomas of the uterine cervix of of endocervical type: a report of ten cases of a benign cervical tumor that may be confused with adenoma malignum. Mod Pathol 1996;9:220–4. 16. Press MF, Scully RE. Endometrial ‘‘sarcomas’’ complicating ovarian thecoma, polycystic ovarian disease and estrogen therapy. Gynecol Oncol 1985;21:135–54. 17. Vilos GA, Ettler HC. Atypical polypoid adenomyoma and hysteroscopic endometrial ablation. J Obstet Gynaecol Can 2003;25:760–2.
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Department of Gynaecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Naples; b Endoscopic Gynecologic Unit, Nuova Villa Claudia, Rome; and c Department of Biomorphologic and Functional Sciences, Anatomic Pathology Section, University of Naples ‘‘Federico II,’’ Naples, Italy
Objective: To describe the conservative treatment of an atypical polypoid adenomyoma (APA) in a young infertile patient using a modification of the technique previously reported for the conservative treatment of stage IA endometrial cancer. Design: Case report. Setting: Department of Gynaecology and Obstetrics and Pathophysiology of Human Reproduction of the University of Naples ‘‘Federico II.’’ Patient(s): A 35-year-old woman diagnosed incidentally with an APA during routine investigation for primary infertility. Intervention(s): Conservative resectoscopic treatment using a four-step technique in which each step is characterized by a pathological analysis: the removal of the APA (step 1), the removal of endometrium adjacent to the APA (step 2), the removal of the myometrium underlying the APA (step 3), and multiple random endometrial biopsies (step 4). Main Outcome Measure(s): Complete resection of the APA and ruling out of any malignancy. Result(s): The conservative surgery was effective as histological examination of all specimens confirmed an APA confined to the endometrium without any other premalignant or malignant lesion. Transvaginal ultrasound and office hysteroscopy with target biopsies at 1 and 6 months after surgery were negative for atypia and malignancy. Conclusion(s): Our technique under a close, intermittent postoperative surveillance might represent a good therapeutic option for those women with APA who wish to preserve their fertility as well as for those at high medical risk for hysterectomy. (Fertil Steril 2008;89:456.e9–12. 2008 by American Society for Reproductive Medicine.) Key Words: Atypical polypoid adenomyoma, conservative treatment, hysteroscopy, infertility, resectoscope
Atypical polypoid adenomyomas (APAs) are uncommon tumors of the uterus (<150 cases reported), usually occurring in premenopausal women and typically presenting with abnormal uterine bleeding (1). Less frequently, patients with APA suffer from vaginal discharge, pelvic pain, or postcoital spotting (2). An associated clinical history of infertility is not uncommon (2–4). Histologically, APA is characterized by an intimate admixture of benign endometrial glands with structural atypia and a stroma consisting predominantly of benign appearing smooth muscle. Squamous metaplasia is found in more than 90% of the cases, and therefore it can be a useful marker Received January 4, 2007; revised and accepted February 27, 2007. Reprint requests: Attilio Di Spiezio Sardo, Department of Gynecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Via Pansini 5, Naples, Italy (FAX: 390817462905; E-mail: [email protected]).
456.e9
for this lesion (2). However, cytologic atypia of the squamous epithelium is unusual (2). Although most cases are benign (3, 5), APA has been occasionally found to coexist with or to precede the development of an endometrioid adenocarcinoma of the endometrium (EEC), which may be either within the APA or elsewhere in the uterus (6–9). According to the data collected in a recent review of international literature, the average risk of EEC in women with APA is about 8.8%, which is considerably higher than the overall risk of 0.8% reported in women with endometrial polyps (10). The definite diagnosis of APA can be established only by histological findings. Most lesions are usually detected on endometrial biopsy or dilation and curettage specimens obtained from patients with abnormal bleeding. On the other hand, some APAs have been incidentally discovered in uteri removed for other pathologies (i.e., leiomyomata) or during
Fertility and Sterility Vol. 89, No. 2, February 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/08/$34.00 doi:10.1016/j.fertnstert.2007.02.061
routine hysteroscopy performed for infertility or suspected intrauterine growth. These lesions are typically located in the isthmus or in the lower part of the endometrial cavity (11). Hysteroscopy may also have an important role in the treatment of APAs. Indeed, while in postmenopausal women simple hysterectomy is the treatment of choice (6, 7), in young women who wish to preserve their fertility, local resection and a careful postoperative follow-up might represent an appropriate treatment. We report the successful hysteroscopic resection of APA in a young infertile patient using a new technique, similar to that already described for the conservative treatment of EEC (12). CASE REPORT A 35-year-old woman was referred to the Department of Obstetrics and Gynaecology of University Hospital ‘‘Federico II’’ in Naples, Italy, for primary infertility. The patient provided an informed consent to perform the study. The study was eventually approved by our Institutional Review Board. Her menarche occurred at the age of 12, and menstrual periods were regular, presenting approximately every 28 days with 4–5 days of flow. Her family and personal history were negative for genital neoplasia. Basic hormonal dosage in the initial follicular phase, progestin dosage in the luteal phase, and analysis of partner’s semen were within the normal range. Physical and bimanual pelvic examinations were normal. Transvaginal ultrasound showed a polypoid mass in the uterine cavity with smooth surface and homogeneous isoechogenicity relative to the myometrium (Fig. 1A). A vaginoscopic hysteroscopy was performed by one of the authors (A.D.S.S.) with a 5-mm continuous-flow operative office hysteroscope with a 2.9-mm rod lens (Bettocchi office hysteroscope; Karl Storz, Tuttlingen, Germany). Neither analgesia nor local anaesthetics were administered to the pa-
tient. Distension of the uterine cavity was obtained using normal saline solution, and the intrauterine pressure was automatically controlled by an electronic irrigation and suction device (Endomat, Karl Storz). The intrauterine pressure was set at 45 mmHg, which is the balance of irrigation flow around 200 mL/minute and a vacuum of 0.2 bar. Endoscopic vaginal and cervical explorations were normal. An irregular exophytic lesion of 1.5–2 cm in diameter growing up from the right uterine wall was detected (Fig. 1B). Both the morphology and color were suggestive of a polyp, while its consistency and vascularization were indicative of a myomatosus lesion. Because of the hard consistency of such a lesion, a 5-Fr twizzle electrode was used to perform a wide-target biopsy. The biopsy was interpreted by the pathologist as APA. After accurate counseling and taking into account her desire to preserve fertility, the patient was targeted for a conservative approach. An operative hysteroscopy was performed by one of the authors (A.D.S.S.) under general anaesthesia; the cervix was dilated to 10 mm with Hegar’s dilators, and a 9-mm resectoscope (Karl Storz) with a 0 lens was introduced. Distension of the uterine cavity was obtained using 1.5% glycine solution, and the intrauterine pressure was automatically controlled by an electronic irrigation and suction device (Endomat, Karl Storz). A 5-mm cutting loop electrode and 100 W of pure cutting output power were used to resect the exophytic lesion (step 1). The procedure (steps 2 and 3) continued according to the technique described by Mazzon et al. (12) for conservative treatment of stage IA endometrial cancer (Fig. 2). Furthermore, multiple random endometrial biopsies were performed (step 4). For each step, a pathologic analysis was performed (Fig. 2). Histological examination of specimen A confirmed an APA, while the other specimens (B, C, D) were negative for APA or other premalignant or malignant lesions.
FIGURE 1 Ultrasonographic (A) and hysteroscopic (B) appearance of APA.
Di Spiezio Sardo. Hysteroscopy and atypical polypoid adenomyoma. Fertil Steril 2008.
Fertility and Sterility
456.e10
FIGURE 2 Technique for conservative hysteroscopic treatment of APA. Step 1: resection of APA; step 2: removal of endometrium near the lesion; step 3: removal of myometrium under lesion; step 4: multiple random endometrial biopsies. For each step a pathologic analysis is done.
Di Spiezio Sardo. Hysteroscopy and atypical polypoid adenomyoma. Fertil Steril 2008.
The patient underwent a transvaginal and office hysteroscopy with target biopsies 1 and 6 months after surgery, which were negative for atypia and malignancy. At this time, the patient is trying to achieve a spontaneous pregnancy. DISCUSSION According to World Health Organization 2002 classification ‘‘Tumour of the breast and female genital organs,’’ APAs are defined as mixed epithelial and mesenchymal tumors of the uterine corpus (13). Their hystogenesis remains uncertain, even if some investigators (14, 15) suggest that an important role in their development might be exerted by hyperestrogenism, mainly in those cases accompanied by endometrial hyperplasia or endometrioid type adenocarcinoma. Additionally, uterine APAs have been described in patients with Turner’s syndrome who received hormone replacement therapy for several years (3, 16).
A recent review of 136 cases has estimated that the average risk of coexistence with EEC is about 8.8% (10). Among the 12 cases with endometrial adenocarcinoma, the carcinoma was located within the APA or in association with its base in nine cases, while in the remaining three cases it was identified in the adjacent endometrium (10). Moreover, the presence of recurrent or residual APA after local excision was reported in 30.1% of the cases, thus indicating a continued risk for the development of malignant disease in patients in whom a complete excision of APA cannot be guaranteed (10). Taking into account the severe degree of glandular atypia in some cases of APA, the frequent association with endometrial adenocarcinoma and the potential for recurrence after local excision, simple hysterectomy should be preferred in perimenopausal or postmenopausal women to obtain a complete removal of the lesion.
Although most cases are benign, APA cannot be classified as a totally benign endometrial lesion, and thus it should be carefully evaluated. Indeed it has been observed that varying degrees of glandular atypia may occur in APA, including endometrial hyperplasia and even carcinoma in situ (1, 3).
A conservative treatment has been proposed (2, 6, 14) in women who wish to retain their uterus or in those at high medical risk for hysterectomy. Indeed APAs are often detected in young nulliparous women, sometimes during a workup for infertility.
Longacre et al. observed that APAs exhibiting severe architectural complexity are more likely to be associated with EEC and suggested the term APA of low malignant potential (APA-LMP) for this morphological variant to emphasize the potential risk for myometrial invasion (2).
Blunt curettage represents the conventional conservative approach, but it has three main limitations: [1] it does not offer the possibility of visualizing the entire uterine cavity; [2] it might miss small focal lesions or make the entire lesion unavailable for histological examination, and [3] the differential
456.e11
Di Spiezio Sardo et al.
Hysteroscopy and atypical polypoid adenomyoma
Vol. 89, No. 2, February 2008
diagnosis between APA and endometrial carcinoma with myometrial invasion could be difficult in a curettage specimen (3). On the other hand, operative hysteroscopy allows a panoramic visualization of the uterine cavity, thus making possible the sampling of multiple and well-localized specimens. Vilos et al. describes the only reported case of APA treated by operative hysteroscopy, in which the resection of the lesion was followed by an endometrial ablation (17). We propose a different hysteroscopic technique for the treatment of APA, which could be useful for women who wish to preserve their fertility. Such treatment consists of four steps, each of those characterized by a pathological analysis: the removal of the APA (step 1), the removal of the endometrium adjacent to the APA (step 2), the removal of the myometrium underlying the APA (step 3), and multiple random endometrial biopsies (step 4). If any of the specimens obtained from steps 2 to 4 is positive for neoplastic lesion, the conservative treatment should be converted into a radical one (hysterectomy). Our technique offers four main advantages in comparison with blunt curettage and Vilos’s technique: [1] preservation of fertility (the endometrium is not completely resected); [2] complete removal of the lesion (step 1) thus rendering the whole lesion available for histological examination; [3] the pathological analysis of specimen A, B, and Ds, which allows the detection of those EECs located within the APA or in association with its base as well as those developing in the adjacent endometrium; [4] the pathological analysis of specimen C, which allows the distinction between APA and EEC with myometrial invasion; indeed APAs are usually well demarcated from the underlying myometrium (3) and neither desmoplasia nor inflammatory features (typically associated with the myometrial invasion of EEC) are detected. Our technique represents a slight modification on the technique previously described for the conservative treatment of EEC (12). The main difference lies in the introduction of a further step (multiple endometrial biopsies), which allows the assessment of the endometrium distant from the APA, and in fact such surgery does not require a following hormone therapy regimen of megestrol acetate. In conclusion, we believe that our technique under a close, intermittent postoperative surveillance might represent a good therapeutic option in those women who wish to preserve their fertility as well as in those at high medical risk for hysterectomy. A close cooperation between the patholo-
Fertility and Sterility
gist and the hysteroscopist needs to be emphasized; indeed, a complete understanding of the histological profile of APA together with an accurate examination of all the specimens obtained is crucial to the surgeon in choosing the best treatment and modulating its radicality.
REFERENCES 1. Mazur MT. Atypical polypoid adenomyomas of the endometrium. Am J Surg Pathol 1981;5:473–82. 2. Longacre TA, Chung MH, Rouse RV, Hendrickson MR. Atypical polypoid adenomyofibromas (atypical polypoid adenomyomas) of the uterus: a clinicopathologic study of 55 cases. Am J Surg Pathol 1996;201:1–20. 3. Young RH, Treger T, Scully RE. Atypical polypoid adenomyoma of the uterus: a report of 27 cases. Am J Clin Pathol 1986;86:139–45. 4. Fukunaga M, Endo Y, Ushigome S, Ishikawa E. Atypical polypoid adenomyomas of the uterus. Histopathology 1995;27:35–42. 5. Delprada WJ, Stevens SM, Baird PJ. Atypical polypoid adenomyoma: a case report with ultrastructural examination. Pathology 1985;17:522–5. 6. Sugiyama T, Shunichiro O, Nishida T, Okura N, Tanabe K, Yakushiji M. Two cases of endometrial adenocarcinoma arising from atypical adenomyoma. Gynecol Oncol 1998;71:141–4. 7. Mittal KR, Peng XC, Wallach RC, Desmopoulos RI. Coexistent atypical polypoid adenomyoma and endometrial adenocarcinoma. Hum Pathol 1995;26:574–6. 8. Buenerd A, Dargent D, Scoazec JY, Berger G. Carcinomatous transformation of an atypical polypoid adenomyofibroma of the uterus. Ann Pathol 2003;23:63–6. 9. Staros EB, Shilkitus WF. Atypical polypoid adenomyoma with carcinomatous transformation: a case report. Surg Pathol 1991;4:157–66. 10. Heatley MK. Atypical polypoid adenomyoma: a systematic review of the English literature. Histopathology 2006;48:609–10. 11. Ota S, Catasus L, Matias-Guiu X, Bussaglia E, Lagarda H, Pons C, et al. Molecular pathology of atypical polypoid adenomyoma of the uterus. Hum Pathol 2003;34:784–8. 12. Mazzon I, Corrado G, Morricone D, Scambia G. Reproductive preservation for treatment of stage IA endometrial cancer in a young woman: hysterocopic resection. Int J Gynecol Cancer 2005;15:974–8. 13. Bo¨cker W. WHO classification of breast tumors and tumors of the female genital organs: pathology and genetics [in German]. Verh Dtsch Ges Pathol 2002;86:116–9. 14. Athas JM, Bluemke DA, Isacson C, Sheth S. Large cervical adenomyoma occurring in a first-trimester gravid uterus: radiologic-pathology correlation. Am J Roentgenol 1996;167:514–5. 15. Gilks CB, Young RH, Clement PB, Hart WR, Scully RE. Adenomyomas of the uterine cervix of of endocervical type: a report of ten cases of a benign cervical tumor that may be confused with adenoma malignum. Mod Pathol 1996;9:220–4. 16. Press MF, Scully RE. Endometrial ‘‘sarcomas’’ complicating ovarian thecoma, polycystic ovarian disease and estrogen therapy. Gynecol Oncol 1985;21:135–54. 17. Vilos GA, Ettler HC. Atypical polypoid adenomyoma and hysteroscopic endometrial ablation. J Obstet Gynaecol Can 2003;25:760–2.
456.e12