Background

This is a rare tumor of the uterus characterized by benign appearing glands surrounded by a sarcomatous stroma.

Outline

Epidemiology
Disease Associations
Pathogenesis
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms

EPIDEMIOLOGY

CHARACTERIZATION

Cluster of uterine mullerian adenosarcoma in the Washington, DC metropolitan area with high incidence of sarcomatous overgrowth. Seidman JD, Wasserman CS, Aye LM, MacKoul PJ, O'Leary TJ. Department of Pathology, Washington Hospital Center, DC 20010, USA.

Am J Surg Pathol 1999 Jul;23(7):809-14 Abstract quote Mullerian adenosarcoma is an uncommon variant of uterine sarcoma. Twelve uterine adenosarcomas were diagnosed during a 42-month period at the Washington Hospital Center in Washington, DC. Based on estimated incidence data derived from the US Department of Defense beneficiary population, an estimated relative risk of 15.4 (95% confidence interval, 7.7-31.0) was calculated, indicating a significantly increased incidence of adenosarcoma in the population studied (p<0.0000001). Among 10 patients who underwent hysterectomy, six (60%) of their tumors had sarcomatous overgrowth. In comparison with the previously reported proportion of adenosarcomas with sarcomatous overgrowth, approximately 16%, the proportion with sarcomatous overgrowth was significantly higher than expected (p<0.01). Mullerian adenosarcoma with sarcomatous overgrowth was first described in 1989 and suggests that the cluster of adenosarcomas reported herein may be due in part to the current classification of some uterine tumors as adenosarcoma with sarcomatous overgrowth that previously would have been classified as other types of uterine sarcoma. Nonetheless, even after reviewing and updating the classification of all sarcomas diagnosed at the Washington Hospital Center from 1985 to 1998, the ratio of adenosarcomas to uterine adenocarcinomas during the 1994-1998 period was 4.7 times (p<0.005) that of the 1985-1993 period, suggesting a more modest but real increase in the occurrence of this tumor. Correct classification of mullerian adenosarcomas with sarcomatous overgrowth is important because the limited available data suggest that the prognosis is notably worse than that for adenosarcomas without sarcomatous overgrowth.

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
Mullerian adenosarcoma of the uterine corpus associated with tamoxifen therapy: a report of six cases and a review of tamoxifen-associated endometrial lesions. Clement PB, Oliva E, Young RH. Department of Pathology, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada.	Int J Gynecol Pathol 1996 Jul;15(3):222-9 Abstract quote Six consultation cases of mullerian adenosarcoma of the uterus were encountered in women who were receiving adjuvant tamoxifen therapy for carcinoma of the breast. To our knowledge, only one previous similar case has been reported. The women, who were 48-76 years of age, had received tamoxifen for periods of 6 months to 4 years (mean 2.7 years) in five of the cases; the duration of tamoxifen therapy in the sixth case is unknown. All of the tumors were polypoid endometrial masses that superficially invaded the myometrium in two cases. The microscopic appearance of the tumors was similar to that of previously described uterine mullerian adenosarcomas. These and other recent observations indicate that tamoxifen treatment may be complicated by uterine neoplasms other than endometrial adenocarcinoma. These findings also support previous observations that prolonged exogenous or endogenous hyperestrinism may lead to the development of mesenchymal and mixed epithelial-mesenchymal tumors of the uterus.
Mullerian adenosaracoma of the uterus associated with tamoxifen therapy. Arici DS, Aker H, Yildiz E, Tasyurt A. Department of Pathology, Cumhuriyet Universitesi Tip Fakultesi, Sivas, Turkiye.	Arch Gynecol Obstet 2000 Sep;264(2):105-7 Abstract quote Mullerian adenosarcoma of the uterus is a biphasic tumor exhibiting benign epithelial and malignant stromal component. This tumor may occasionally be associated with tamoxifen therapy which is used as an adjuvant drug for breast carcinoma. Reviewing the literature, we found only 12 adenosarcoma cases associated with tamoxifen therapy Thus, the clinical and pathological findings in a 58 years old postmenopausal woman who developed uterine adenosarcoma, following low dose tamoxifen therapy after 8 years, was discussed in this report.
Adenosarcoma of the uterine corpus associated with ovarian thecoma. Nomura K, Aizawa S, Ushigome S. Department of Pathology, Jikei University School of Medicine, Tokyo, Japan.	Pathol Int 2001 Sep;51(9):735-8 Abstract quote We describe a case of adenosarcoma of the uterine corpus associated with ovarian thecoma in a 67-year-old woman. The patient underwent surgery under a diagnosis of ovarian carcinoma. The 110 x 70 mm-sized ovarian tumor was diagnosed as thecoma. The polypoid tumor of the uterine corpus which measured 30 x 15 mm was diagnosed as adenosarcoma. Cells of both epithelial and stromal elements of the adenosarcoma expressed estrogen receptors (determined by immunohistochemistry). These findings support the view that estrogen stimulation, including that by a pre-existing ovarian thecoma, may play a role in the development of mesenchymal and mixed epithelial / mesenchymal uterine tumors, including adenosarcoma.

 

PATHOGENESIS

CHARACTERIZATION

The expression of epidermal growth factor receptor, HER-2/Neu, p53, and Ki-67 antigen in uterine malignant mixed mesodermal tumors and adenosarcoma. Swisher EM, Gown AM, Skelly M, Ek M, Tamimi HK, Cain JM, Greer BE, Muntz HG, Goff BA. Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle 98195, USA.

Gynecol Oncol 1996 Jan;60(1):81-8 Abstract quote Uterine malignant mixed mesodermal tumors (MMMT) are highly malignant tumors containing both malignant glands and stroma, while adenosarcomas (AS) are less aggressive tumors composed of malignant stroma and benign glands. Immunohistochemistry was used to grade overexpression of p53 protein, HER-2/neu protein, epidermal growth factor receptor (EGFR), and Ki-67 antigen in both the glands and stroma of tissue from 20 women with MMMT and 6 women with AS. EGFR was overexpressed in 2 AS and 9 MMMT, and was more commonly found in the sarcomatous component than the carcinomatous component in MMMT (P = 0.03). p53 was not found in any AS samples and was strongly present in 6 MMMT samples with a random distribution between the malignant components. HER-2/neu protein was not overexpressed in any AS or primary MMMT. Ki-67 antigen, a marker of cell proliferation, was found at higher levels in MMMT than AS samples (P = 0.03) and high Ki-67 antigen expression correlated with a decreased survival in patients with MMMT (P = 0.004). Independent characterization of oncogene proteins in the malignant components of these heterogeneous tumors may provide insight into the histogenesis and behavior of these malignancies.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Mullerian adenosarcoma of the uterus: case report and review of literature. Piura B, Rabinovich A, Meirovitz M, Yanai-Inbar I. Department of Obstetrics and Gynecology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.	Eur J Gynaecol Oncol 2000;21(4):387-90 Abstract quote Mullerian adenosarcoma--a variant of mullerian mixed mesodermal tumor of the uterus--is typically composed of benign but sometimes mildly atypical glandular epithelial elements admixed with malignant sarcomatous stroma. This rare tumor, which accounts for only about 8% of all uterine sarcomas, usually originates in the endometrium and grows as a polypoid mass within the endometrial cavity. The most prevailing presenting symptom is abnormal vaginal bleeding and the most common finding is a polypoid mass protruding through a dilated cervical canal. The case of a woman, who at age 62 presented with symptoms and signs of acute pelvic inflammatory disease and on vaginal examination an infected mullerian adenosarcoma protruding through a dilated cervical canal was discovered, is reported. Treatment consisted of extensive antibiotic treatment and surgery comprised of total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative adjuvant pelvic radiotherapy. One year later, the patient is alive with no evidence of disease.
VARIANTS
Adenosarcoma of the uterine cervix presenting as a cervical polyp. Hino A, Hirose T, Seki K, Uehara H, Sano N. Department of Pathology, University of Tokushima School of Medicine, Japan.	Pathol Int 1998 Aug;48(8):649-52 Abstract quote A case of adenosarcoma arising from the uterine cervix of a 55-year-old female who complained of vaginal discharge is reported. A polyp, 6 x 2 x 1.5 cm in size, identified in the cervical canal was clinically diagnosed as benign cervical polyp and resected. Histologically, the polyp was composed of benign epithelial components and sarcomatous stroma wherein periglandular hypercellularity and some mitoses including atypical ones were noted. Immunohistochemically, stromal cells were positive for muscle-type actins, desmin and estrogen receptor. Adenosarcoma is a rare, biphasic tumor of the uterus and usually presents as a polypoid mass in the endometrial cavity. When they arise from the cervix, adenosarcomas may be confused with benign cervical polyps clinically and pathologically. As the former often recurs, microscopic differentiation is crucial for further treatment.
Vaginal adenosarcoma arising from endometriosis. Judson PL, Temple AM, Fowler WC Jr, Novotny DB, Funkhouser WK Jr. Department of Obstetrics and Gynecology, The University of Minnesota, Minneapolis, Minnesota, 55455, USA.	Gynecol Oncol 2000 Jan;76(1):123-5 Abstract quote OBJECTIVE: Malignant transformation of endometriosis has been well documented. Endometrioid adenocarcinoma is the most common malignancy to occur in this setting, although other carcinomas and rarely stromal tumors can be seen. We present the first case in the literature of adenosarcoma, a rare mixed mullerian or mesodermal tumor, arising in extrauterine vaginal endometriosis. CASE: A 42-year-old woman underwent multiple medical therapies and surgeries for aggressive endometriosis. A pelvic exenteration was abandoned secondary to severe fibrosis, and low-dose radiotherapy was used to control bleeding from vaginal endometriosis. The pathologic diagnosis of recurrent endometriosis was confirmed multiple times over her 4-year course. Excision of a recurrent vaginal mass revealed adenosarcoma with heterologous elements. CONCLUSION: It is important to biopsy or excise recurrent endometriosis, as malignant transformation can occur, giving rise to epithelial, stromal, or mixed epithelial-mesenchymal tumors.
Extrauterine Mullerian adenosarcoma of the peritoneum with an extensive rhabdomyosarcomatous element and a marked myxoid change. Kato N, Zhe J, Endoh Y, Motoyama T. Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.	Pathol Int 2000 Apr;50(4):347-51 Abstract quote A case of extrauterine Mullerian adenosarcoma of the peritoneum in a 20-year-old woman is reported. The tumor was widely based on the abdominopelvic wall and there were no unusual features in the genital organs. The cut surface of the tumor showed a marked gelatinous appearance. The tumor was composed of an admixture of benign Mullerian-type epithelium and sarcomatous stroma. The predominant element of the sarcomatous area was rhabdomyosarcoma, which showed a close resemblance to well-differentiated embryonal rhabdomyosarcoma. In another sarcomatous area, fibroblastic cells without myoblastic properties diffusely proliferated in a marked myxoid background with some collagen bundles. Both the mitotic count and Ki-67 proliferative index of these cells were lower than those of rhabdomyoblastic cells. On follow up, the patient was disease free for 1 year postoperatively, without any subsequent treatment. The present case indicates that extrauterine adenosarcoma can also show histological heterogeneity as do uterine adenosarcomas. The remarkable myxoid change of this tumor seemed to be more largely due to a fibromyxoid element than a rhabdomyosarcomatous element, and the coexistence of the former may be related to the less aggressive behavior of this tumor.
Primary peritoneal mesodermal adenosarcoma: report of a case and review of the literature. Visvalingam S, Jaworski R, Blumenthal N, Chan F. Obstetrics and Gynaecology, Royal North Shore Hospital, Sydney, New South Wales 2117.	Gynecol Oncol 2001 Jun;81(3):500-5 Abstract quote BACKGROUND: Mesodermal (mullerian) adenosarcoma arising from the peritoneum is rare and is thought to arise from pluripotent mesothelial and mesenchymal cells of the pelvic cavity or from endometriotic deposits. CASE: A case of primary peritoneal mesodermal adenosarcoma arising from the omentum is described. A 50-year-old woman presented with sudden abdominal distension. Initial laparotomy revealed a 13-kg mass arising from the omentum, which was determined from frozen and paraffin sections to be serous cystadenofibroma. The tumor recurred within 10 months and weighed 18 kg at a second laparotomy. Histopathology and review of the original tumor established the correct diagnosis of mesodermal adenosarcoma. The patient died from disseminated disease 6 months later. CONCLUSION: Adenosarcomas are difficult to differentiate from adenofibromas or endometriosis histologically because of the presence of large areas of low cellularity and infrequent mitotic figures. In such cases, stromal nuclear atypia and periglandular stromal cuffing are features that are diagnostic of adenosarcoma.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases with a review of the literature. Clement PB, Scully RE. Department of Pathology, Vancouver General Hospital, Canada.	Hum Pathol 1990 Apr;21(4):363-81 Abstract quote One hundred cases of mullerian adenosarcoma of the uterus were encountered in patients 14 to 89 years of age (median, 58 years), who usually had the symptom of abnormal vaginal bleeding. An enlarged uterus and tissue protruding from the external os were the most common findings on pelvic examination. Five patients presented on multiple occasions with "recurrent polyps" that were interpreted retrospectively as adenosarcomas. Primary treatment, known in 97 cases, included some form of hysterectomy in 93 of them, and conservative resection in four cases. Gross examination of the excised uteri disclosed polypoid masses, some of which had spongy cut surfaces, usually filling the endometrial cavity; less commonly, the tumors were confined to the endocervix or the myometrium or involved more than one site. Histologic examination revealed benign or atypical neoplastic glands within a sarcomatous stroma, which typically formed periglandular cuffs of increased cellularity, intraglandular polypoid projections, or both. The sarcomatous stroma was homologous in 78% of the cases and contained heterologous elements in the remainder. The stromal mitotic rate varied from 1 to 40 mitotic figures (MFs) (mean 9) per 10 high-power fields (HPFs). Extensive areas of stromal fibrosis that focally imparted a deceptively benign appearance to the tumor were common. Myometrial invasion was present in 15 cases, but was deep in only four. Recurrent tumor developed in 23 cases at postoperative intervals of 0.5 to 9.5 years (mean 3.4); in one third of such cases, the interval was 5 years or longer. Recurrent tumor was almost always confined to the vagina, pelvis, or abdomen; hematogenous spread occurred in only two cases. The only feature associated with an increased risk for recurrence was the presence of myometrial invasion. Criteria found useful in separating mullerian adenosarcomas from mullerian adenofibromas included, alone or in combination: two or more stromal MFs per 10 HPFs, marked stromal cellularity, and significant stromal cell atypia.
VARIANTS
Mullerian adenosarcoma with ovarian sex cord-like differentiation. A light- and electron-microscopic study. Hirschfield L, Kahn LB, Chen S, Winkler B, Rosenberg S.	Cancer 1986 Mar 15;57(6):1197-200 Abstract quote Mullerian adenosarcoma in which the sarcomatous element showed ovarian sex-cord like differentiation, occurred as a polypoid growth in the uterine cervix of a 53-year-old woman. The tumor was composed of an admixture of benign neoplastic glands and a sarcomatous stroma, the latter containing in addition to endometrial stromal sarcoma, nests of lipid-rich cells resembling ovarian sex-cord elements. This is the first report of such differentiation in Mullerian adenosarcoma. Origin from a focus of cervical endometriosis is postulated.
Adenosarcoma of the uterine cervix: a clinicopathological study of 12 cases. Jones MW, Lefkowitz M. Department of Gynecological and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.	Int J Gynecol Pathol 1995 Jul;14(3):223-9 Abstract quote The clinical and pathologic features of 12 cervical adenosarcomas from the files of the Armed Forces Institute of Pathology are described. The patients ranged in age from 13 to 67 years (mean 37). The majority (58%) presented with abnormal bleeding. All tumors were located in the cervix and consisted of soft, tan, polypoid or papillary masses ranging in size from 1.5 to 4.5 cm. Microscopically, they showed a biphasic pattern with mesenchymal and epithelial components. There was a characteristic stromal condensation below the epithelial surface and around glandular structures. The cytologic atypia of stromal cells was 1+ in three, 2+ in five, and 3+ in four. The mitotic activity ranged from four to 28 (mean 7.0) mitotic figures per 10 high-power fields. One neoplasm contained cartilage and one striated muscle. Myometrial invasion was present in three. Treatment consisted of hysterectomy in nine patients and excisional biopsy in three. Two patients received radiotherapy; one before surgery and the other after hysterectomy. Two were treated with chemotherapy. Follow-up ranged from 9 months to 18.8 years. Nine patients were alive and well with no evidence of recurrent tumor at postoperative intervals of 0.8-18.8 years. One patient died 1 year after diagnosis with intraabdominal metastasis. One developed a recurrent tumor. This study demonstrates a favorable prognosis for patients with cervical adenosarcoma. Similar to patients with uterine adenosarcoma, prognosis is mostly affected by the presence of deep myometrial invasion.

 

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
CD10
Expression of CD10 in Malignant Mullerian Mixed Tumors and Adenosarcomas: An Immunohistochemical Study. Mikami Y, Hata S, Kiyokawa T, Manabe T. Department of Pathology, Kawasaki Medical School Hospital (YM, SH, TM), Kurashiki, Okayama.	Mod Pathol 2002 Sep;15(9):923-30 Abstract quote CD10 has been demonstrated to be positive in endometrial stromal sarcoma (ESS) and thus is useful in establishing the diagnosis, but its expression in malignant mullerian mixed tumor (MMMT) and mullerian adenosarcoma remains to be clarified. In this study, 12 cases of MMMT (9 uterine, 2 tubal, and 1 metastatic), 6 cases of mullerian adenosarcoma (three corporeal, two cervical, and one tubal), and 7 cases of primary uterine sarcomas had their tissues examined immunohistochemically for expression of CD10, desmin, myoglobin, alpha-smooth muscle actin (SMA), and cytokeratin. Of the primary uterine sarcomas, two were primary rhabdomyosarcomas (one cervical and one corporeal), two were ESSs, two were high-grade leiomyosarcomas, and one was a high-grade endometrial sarcoma. Sarcomatous components in all cases of MMMT and mullerian adenosarcoma, as well as all uterine sarcomas, were positive for CD10, showing moderate to marked staining intensity with varying distribution except in one MMMT, which showed weak and very focal staining. In four MMMTs, three adenosarcomas, and one rhabdomyosarcoma, myoglobin- and/or desmin-positive rhabdomyoblastic cells were positive for CD10. The immunoreactivity for CD10 showed the same distribution for alpha-SMA and myoglobin in three and two MMMTs, respectively. In five cases of MMMT, carcinomatous components were focally positive for CD10, and in two cases small populations of round or short spindle cells in sarcomatous components were positive for CD10, alpha-SMA, and cytokeratin (CAM5.2). These results indicate that CD10 expression is not restricted to ESS but can be positive in MMMT and mullerian adenosarcoma as well as in a variety of uterine tumors including high-grade leiomyosarcoma and rhabdomyosarcoma. CD10 expression might be one of the characteristics of mullerian system-derived neoplastic mesenchymal cells.
ELECTRON MICROSCOPY
Mullerian adenosarcoma of the uterus: an ultrastructural study of four cases. Katzenstein AL, Askin FB, Feldman PS	Cancer 1977 Nov;40(5):2233-42 Abstract quote Four cases of uterine mullerian adenosarcoma, a distinctive form of mixed mullerian tumor, were studied by light and electron microscopy. All tumors showed the characteristic histologic pattern of benign neoplastic glands within sarcomatous stroma. Ultrastructurally, both mesenchymal and epithelial cells were seen. The mesenchymal cells showed some features of endometrial stromal cells, including the presence of intracytoplasmic collagen fibers. The epithelial cells formed glands, which resembled benign endometrial glands and were separated from the stroma by a well-defined basal lamina. No transitional cells between the epithelial and mesenchymal cells were seen. The ultrastructural features of these tumors suggest that the sarcomatous portion is of endometrial stromal origin. The glandular portion may arise, along with the stroma, from multipotential stem cells, or the glands may be non-neoplastic entrapped endometrial glands stimulated by the stroma and thus appearing to form an integral part of the tumor.
Adenosarcoma of the uterus with extensive smooth muscle differentiation: ultrastructural study and review of the literature. Fehmian C, Jones J, Kress Y, Abadi M. Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.	Ultrastruct Pathol 1997 Jan-Feb;21(1):73-9 Abstract quote Four cases of Mullerian adenosarcoma were studied by light and electron microscopy and immunohistochemistry. All 4 cases showed the histologic characteristics of adenosarcoma with benign endometrial glands and a malignant stroma. Ultrastructurally, the epithelial component in all cases had the appearance of proliferative endometrial glands, and the malignant mesenchymal cells showed features of endometrial stroma. A distinct basal lamina separating glands from stroma was present. In addition, 2 of the cases showed extensive smooth muscle differentiation which was associated with sarcomatous overgrowth. The smooth muscle features were confirmed by immunohistochemistry. Multiple theories of the histogenesis of this tumor are discussed.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Adenofibroma and adenosarcoma of the uterus: a clinicopathologic study of 35 cases. Zaloudek CJ, Norris HJ.	Cancer 1981 Jul 15;48(2):354-66 Abstract quote The clinical and histopathologic features of ten adenofibromas and 25 adenosarcomas of the uterus were studied. The most useful criterion for distinguishing adenofibroma from adenosarcoma was the frequency of mitotic figures found in the stroma. Adenofibromas had fewer than four mitotic figures per 100 HPF in the most active areas; adenosarcomas had four or more. Myometrial invasion, histologically malignant heterologous mesenchymal elements, and marked atypia of stromal cells were histologic features detected only in adenosarcoma. Of the women with adenosarcoma, ten (40%) had recurrences, with a median interval to recurrence of five years. The only morphologic feature that correlated with aggressive behavior of adenosarcoma was deep myometrial invasion. Adenofibroma and adenosarcoma are in the family of mixed mesodermal tumors, but are distinct clinical and pathologic entities.
The stromal component of large endometrial polyps. Hattab EM, Allam-Nandyala P, Rhatigan RM. Department of Pathology, University of Florida Health Science Center, Jacksonville 32209, USA.	Int J Gynecol Pathol 1999 Oct;18(4):332-7 Abstract quote Benign endometrial polyps belong in the differential diagnosis of adenofibroma and adenosarcoma. There is, however, little information about the range of stromal mitotic activity, stromal cellularity, and stromal atypia in benign endometrial polyps, rendering the differential diagnosis with the aforementioned tumors problematic. In this study, the stroma of 66 polyps 1 cm or more in greatest dimension from 56 patients was analyzed for stromal mitotic activity, cellularity, and atypia. Sixteen (24%) had an almost completely fibrotic stroma that had rare mitoses, little cellularity, and no atypia. However, 50 polyps (76%) had stroma that was predominantly endometrial or was a mixture of endometrial-type stroma and fibrous stroma. In these polyps stromal mitoses were relatively common, averaging 1.2/10 MFs/HPFs (range, 0-5.8 MFs/10 HPFs). Stromal cellularity was frequently equal to or mildly increased over adjacent nonpolypoid endometrial stroma and mild nuclear atypia (enlarged stromal nuclei) was also common. Twelve polyps (24%) from the group of 50 had two or more MFs/10 HPFs, a mitotic rate present in some adenosarcomas. None of these polyps had other features necessary for the diagnosis of adenofibroma or adenosarcoma and follow-up in all patients was uneventful (average follow-up, 96 months). It is concluded that benign polyps that retain areas of endometrial-type stroma often have mitotic activity and that significant stromal mitotic activity (> or = 2 MFs/HPFs) is relatively common. These polyps do not have significant stromal atypia nor do they have a marked increase in stromal cellularity. Thus, in the absence of other supportive features, stromal mitotic activity alone should not be regarded as a worrisome finding.
Uterine adenomyomas excluding atypical polypoid adenomyomas and adenomyomas of endocervical type: a clinicopathologic study of 30 cases of an underemphasized lesion that may cause diagnostic problems with brief consideration of adenomyomas of other female genital tract sites. Gilks CB, Clement PB, Hart WR, Young RH. Department of Pathology, Vancouver Hospital & Health Sciences Centre, BC, Canada.	Int J Gynecol Pathol 2000 Jul;19(3):195-205 Abstract quote We report 30 uterine tumors composed of an admixture of endometrioid glands, endometrioid stroma, and smooth muscle that lacked the characteristic features of atypical polypoid adenomyoma. The patients ranged from 26 to 64 (median 47) years of age. The usual presenting symptom was abnormal vaginal bleeding, which was "massive" in two patients. Six patients were treated by polypectomy only, with hysterectomy performed in the remainder. Twenty-seven adenomyomas were in the corpus (22 submucosal, two mural, and three subserosal) and three in the cervix. The subserosal and submucosal examples were polypoid. The tumors were 0.3 to 17 cm in greatest dimension, and firm with cystic areas often present on sectioning. Focal hemorrhage was described in five cases. On microscopic examination, the tumors were composed of glands and cysts lined by endometrial-type epithelium separated by endometrial stroma and smooth muscle, with smooth muscle predominating. Minor foci of tubal-type epithelium (14 cases), mucinous endocervical-type epithelium (2 cases), and squamous epithelium (1 case) were present. The smooth muscle component was cellular in three cases and contained occasional bizarre nuclei in three cases. The epithelial cells were uniformly bland. No mitotic activity was observed in the epithelial or mesenchymal elements in 20 cases. In the remainder, up to 5 mitotic figures/10 high-power fields were observed in the epithelium (3 cases), the stroma and smooth muscle (3 cases), or both compartments (4 cases). Follow-up in 14 cases revealed no recurrence or extrauterine spread in any case. A diagnosis of adenocarcinoma or adenosarcoma was entertained by the submitting pathologist in five of 14 consultation cases. Adenomyomas are unusual benign uterine tumors that can be misdiagnosed, in part, because the lesion has not often received attention in the literature. The most realistic considerations in the differential diagnosis are atypical polypoid adenomyoma and adenosarcoma. The former, by definition, has epithelial atypia and the latter a malignant (usually low grade) stromal component with typically absent or inconspicuous smooth muscle. Distinction of adenomyoma from adenosarcoma may have significant therapeutic implications, particularly in young women.
Adenosarcoma in a patient with vaginal endometriosis. Anderson J, Behbakht K, De Geest K, Bitterman P. Department of Pathology, Rush Medical College, Chicago, Illinois, USA	Obstet Gynecol 2001 Nov;98(5 Pt 2):964-6 Abstract quote BACKGROUND:Adenosarcoma in a patient with extraovarian endometriosis is a rare event and can be easily overlooked. CASE:A woman with a history of endometriosis underwent multiple resections of a vaginal mass and medical treatment for presumed recurrent endometriosis. Eventually, a vaginal adenosarcoma was diagnosed. CONCLUSION:The possibility of adenosarcoma should be considered if an enlarging mass occurs at the site of extraovarian endometriosis.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience. Verschraegen CF, Vasuratna A, Edwards C, Freedman R, Kudelka AP, Tornos C, Kavanagh JJ. Section of Gynecologic Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.	Oncol Rep 1998 Jul-Aug;5(4):939-44 Abstract quote The records of 41 patients diagnosed with adenosarcoma of the female genital tract between 1982 and 1996 were reviewed. The median age at diagnosis is 51 years (range, 14-84). The most common symptom is vaginal bleeding (71%). Clinical signs at presentation include pelvic mass (37%), uterine polyps (29%), and enlarged uterus (22%). In 71% of patients, the tumor originates from the uterus. Other sites include ovary (15%), pelvis (12%), cervix (2%). A history of thyroid cancer, benign ovarian cyst, and polycystic ovarian disease is found more frequently than expected in this patient population, whereas no relationship to endometriosis is observed. Surgery is the mainstay of treatment, but platin-based chemotherapy given upfront in inoperable patient has definite efficacy. An overall response rate of 92.5% was observed after primary therapy (surgery with or without radiotherapy, and/or chemotherapy), with a median survival of 48 months (range, 1-174). Thirty-eight percent of patients had recurrent disease. The median time to recurrence is 12 months (range, 5-132). Although 60% of patients with recurrence achieved a complete remission after treatment, only 1 (8%) is alive without disease, and 3 (22%), with disease at the time of this analysis. In our series, histologic sarcomatous overgrowth is a predictor of poor prognosis (p<0.03), however myometrial invasion and stage of disease seem to be of less prognostic significance. Adenosarcoma is a tumor with a fair prognosis. Most tumor can be cured with surgery, but recurrence carries a bad prognosis.
Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases. Blom R, Guerrieri C. Department of Gynecological Oncology, University Hospital, Linkoping, Sweden; and Department of Pathology, St. Vincent's Hospital, New York, New York, USA.; Department Pathology, University Hospital, Linkoping, Sweden; and Department of Pathology, St. Vincent's Hospital, New York, New York, USA.	Int J Gynecol Cancer 1999 Jan;9(1):37-43 Abstract quote Eleven patients with uterine adenosarcoma diagnosed between 1970 and 1995 were evaluated according to DNA ploidy, S-phase fraction, p53 and mdm-2 expression, and traditional clinical and pathological prognostic factors, such as tumor stage, grade and mitotic index. DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. The patients ranged in age from 41 to 90 years (median, 76 years). Only one patient was premenopausal at the time of diagnosis and five (45%) were nulliparous. One patient had received previous pelvic irradiation for anal squamous carcinoma. Six of the tumors (55%) were pure adenosarcoma and five (45%) were adenosarcoma with sarcomatous overgrowth. Nine patients had a stage I tumor and two had a stage II tumor. Among the six adenosarcomas we found three DNA diploid tumors, two DNA aneuploid tumors, and one DNA multiploid tumor. All adenosarcomas had an S-phase fraction less than 10%, except one that was not assessable. None was p53 positive and only one overexpressed mdm-2. All five adenosarcomas with sarcomatous overgrowth were DNA aneuploid, three (60%) had an S-phase fraction > 10%, two (40%) were p53 positive, and one (20%) overexpressed mdm-2. Five of the eleven patients suffered recurrences, and three (60%) of these developed lung metastases. During the observation period four (36%) patients (2 adenosarcomas and 2 adenosarcoma with sarcomatous overgrowth) died of disease, three patients died of intercurrent disease without recurrence, and the remaining four are alive with no evidence of disease. The overall five-year survival rate for all stages was 69%; for patients with AS it was 80%, while for those with adenosarcoma with sarcomatous overgrowth it was 50%. There were no variables which correlated with survival. In conclusion, we found hat the typical adenosarcoma had a tendency to be of low stage, have a lower mitotic rate and an S-phase fraction <10%. On the other hand, adenosarcomas with sarcomatous overgrowth were of high grade, had a high mitotic rate, and were DNA aneuploid with an S-phase fraction >10%. None of the variables studied correlated with survival. Tumors that were p53-positive or overexpressed mdm-2 did not behave worse than their negative counterpart. All patients who recurred with distant metastases died of disease.
Adenosarcoma of the uterine body in a 19-year-old woman--three year survival: case report. Fait T, Zivny J, Freitag P, Kuzel D. Department of Gynecology and Obstetrics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.	Eur J Gynaecol Oncol 2001;22(1):61-3 Abstract quote BACKGROUND: Uterine adenosarcoma is a rarely by occurring tumor. It is composed of a benign adenoid structure and a sarcomatous stromal component. The average age of patients with a diagnosis of uterine adenosarcoma is about 70 years. CASE: We present a case of a 19-year-old woman with a rarely occurring uterine adenosarcoma manifesting itself by irregular bleeding and producing fragile polypous matter which was spreading into the vagina. The final diagnosis was made only by repeated biopsies. Abdominal hysterectomy with bilateral salpingo-oophorectomy, appendectomy and revision of iliac lymph nodes were performed. Teleradiotherapy was applied from 4 fields in 25 fractions to a total exposure of 50 Gy. It was followed by six cycles of chemotherapy containing 50 mg/m2 doxorubicin and 5 g/m2 ifosfamid administered in 21-day dose intervals. CONCLUSION: This case should demonstrate the difficulty of making the right diagnosis. Since the end of therapy the patient has been regularly seen in our onco-gynecologic department. Now, 40 months after the end of chemotherapy and 46 months after making the diagnosis, there are no signs of relapse.
Uterine adenosarcoma with sarcomatous overgrowth versus uterine carcinosarcoma: comparison of treatment and survival. Krivak TC, Seidman JD, McBroom JW, MacKoul PJ, Aye LM, Rose GS. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Walter Reed Army Medical Center, Washington, DC 20307, USA.	Gynecol Oncol 2001 Oct;83(1):89-94 Abstract quote OBJECTIVE: Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is a rare variant of uterine sarcoma first described in 1989. This clinicopathologic study was undertaken to compare the treatment and survival of uterine adenosarcoma with sarcomatous overgrowth to that of uterine carcinosarcomas. METHODS: A review of uterine sarcomas diagnosed at Washington Hospital Center from January 1988 to December 1998 was performed. Records were reviewed for demographic data, surgical staging, primary and adjuvant therapy, metastatic site, disease recurrence, and survival. All pathology was reviewed and diagnosis confirmed. Statistical analysis included chi(2) test and Student's t test. Kaplan-Meier survival curves were plotted to estimate the median and 5-year survival times. The log-rank test was used to compare survival times. A P value <0.05 was considered significant. RESULTS: Sixty patients were diagnosed with uterine sarcoma at Washington Hospital Center. Of these, 33 (55%) were uterine carcinosarcomas, 11 (18%) ASSOs, 6 (10%) adenosarcomas, and 10 (17%) leiomyosarcomas. Of the patients diagnosed with uterine ASSO, 3 (27%) were stage I, 3 (27%) stage II, 1 (9%) stage III, and 4 (36%) stage IV. All 11 patients with uterine ASSO underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and tumor debulking. Postoperative adjuvant therapy included chemotherapy (n = 4), radiation (n = 4), combination radiation and chemotherapy (n = 1), and no adjuvant therapy (n = 2). The overall median survival time of patients with uterine ASSO was 13 months. Nine of eleven patients are dead of disease, and two patients (both with stage I) are alive without evidence of disease at 18 and 19 months. Thirty-three patients with carcinosarcoma were identified, with follow-up available on 29 patients. Of these, 10 (34%) were stage I, 6 (22%) stage II, 3 (10%) stage III, and 10 (34%) stage IV. Twenty-seven of the twenty-nine patients diagnosed with carcinosarcoma underwent surgical therapy to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, staging and tumor debulking. Two patients died prior to treatment. Postoperative adjuvant therapy included chemotherapy (n = 9), radiation (n = 13), combination (n = 1), and no further therapy (n = 4). Twenty of the twenty-nine patients are dead of disease; there were nine surviving patients at the time of this report (stage I-5, stage II-3, stage III-1). The median survival of these patients was 31 months, with an overall 5-year survival of 22%. Comparison of the Kaplan-Meier survival curves using the log-rank test suggests a worse prognosis for uterine ASSO. However, this did not reach statistical significance (P = 0.0522). CONCLUSIONS: Patients diagnosed with uterine ASSO have a poor prognosis similar to that of carcinosarcoma. Management should include complete surgical staging. Additional therapy in the form of radiation, chemotherapy, or both has been reported; however, the superiority of one modality could not be determined from our data.
VASCULAR INVASION
Is vascular and lymphatic space invasion a main prognostic factor in uterine neoplasms with a sarcomatous component? A retrospective study of prognostic factors of 60 patients stratified by stages. Rovirosa A, Ascaso C, Ordi J, Abellana R, Arenas M, Lejarcegui JA, Pahisa J, Puig-Tintore LM, Mellado B, Armenteros B, Iglesias X, Biete A. Department of Radiation Oncology, Hospital Clinic i Universitari, Barcelona, Spain.	Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1320-9 Abstract quote BACKGROUND: Sarcomatous neoplasms of the uterine corpus are still a challenge in terms of obtaining prognostic factors and the most optimum complementary treatment to surgery. The most important prognostic factor is stage; relapses usually appear during the first 2 years, and most patients die within the first 3 years. We have performed a multivariate study of prognostic factors, stratifying patients by stage, to determine their impact on overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival. Special emphasis has been given to vascular and lymphatic space invasion (VLSI). METHODS: Sixty patients diagnosed with uterine neoplasms with a main sarcomatous component were treated at Hospital Clinic i Universitari of Barcelona between January 1975 and June 1999. Pathologic type: 32 carcinosarcomas, 14 leiomyosarcomas, 9 adenosarcomas, and 5 endometrial stromal sarcomas. Treatment: 58/60 surgery, 35/60 postoperative radiotherapy, 2/60 exclusive chemotherapy, and 3/60 complementary chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage III, and 2 Stage IV. Variables analyzed: age, stage, vascular and lymphatic space invasion, myometrial invasion, mitotic index, tumor size, unicentricity/multicentricity, necrosis, and radiotherapy. Statistics: the S and Cox proportional risk models. The partial effect of each risk factor was calculated by hazard ratio (HR) with a confidence interval of 95%. RESULTS: Early stages: Multivariate analysis showed that tumor size larger than 8 cm and VLSI had an impact on overall survival (HR = 4.01 and HR = 24.45, respectively). VLSI was present in 23% of the cases. Myometrial invasion greater than 50% had an impact on disease-free survival and local relapse-free survival (HR was 9.75 and 3.20, respectively). VLSI had an impact on distant metastasis-free survival (HR = 2.92). Advanced stages: VLSI was present in 89% of the cases. Only leiomyosarcoma type made the overall survival worse (HR = 10.54). CONCLUSIONS: Vascular and lymphatic space invasion was a relevant prognostic factor in our series, with an impact on overall survival and distant metastasis-free survival in early stages. In advanced stages, VLSI had no impact on survival, but was present in 89% of cases. Myometrial invasion >50% had an impact on local relapse. Advanced stages had a more aggressive behavior, and there was a higher incidence of poor prognostic factors in these stages. Nevertheless, prospective studies are still needed on prognostic factors and on the best treatment option.
TREATMENT
Management of uterine Mullerian adenosarcoma with extrauterine metastatic deposits. Guidozzi F, Smith T, Koller AB, Reinecke L. Department of Obstetrics and Gynaecology, Johannesburg Hospital and University of the Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg, 2193, South Africa.	Gynecol Oncol 2000 Jun;77(3):464-6 Abstract quote OBJECTIVE: The aim of this study was to provide the management and outcome of three patients who presented with uterine Mullerian adenosarcoma associated with extrauterine metastases. METHODS: A retrospective study of three patients who were referred to our hospital was performed. One patient was referred because of vaginal metastatic deposits that were noted during investigations for primary infertility. The other two were referred because of abnormal vaginal bleeding; one of these had a large polyp protruding through her cervix into the vagina. RESULTS: In two patients the preoperative diagnosis and extent of their disease were known while in the third patient the diagnosis was only made postoperatively. All patients had a type II radical abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Two patients were given three cycles of neoadjuvant chemotherapy and pelvic irradiation over 12 weeks. Both of these patients had their diagnosis made preoperatively and the chemotherapy consisted of 240 mg/m(2) carboplatin and 80 mg/m(2) farmorubicin per cycle. The pelvic irradiation consisted of daily fractions of 1.8-Gy irradiation to a total of 45 Gy over the first 6 weeks. The other patient was given the same regime postoperatively. All patients are still alive and free of disease between 34 and 56 months. CONCLUSION: Radical surgery, chemotherapy, and irradiation provide a management option with seemingly favorable outcome for patients with uterine Mullerian adenosarcoma associated with extrauterine metastases.
Ovarian conservation in a woman of reproductive age with mullerian adenosarcoma. Michener CM, Simon NL. Department of Pathology, National Cancer Institute, Bethesda, Maryland, 20892.	Gynecol Oncol 2001 Nov;83(2):424-7 Abstract quote Background Total abdominal hysterectomy with bilateral salpingo-oophorectomy is generally considered optimal therapy for patients with uterine sarcomas. Local resection of the tumor or hysterectomy with ovarian conservation has been used in only a small number of patients. Recurrence risk in women undergoing ovarian-sparing surgery for mullerian adenosarcomas can be difficult to evaluate due to the paucity of literature in this area. We present a reproductive-age woman with a mullerian adenosarcoma and review the literature on conservative surgical management of this class of tumors. Case A 25-year-old nulligravida was diagnosed with a uterine adenosarcoma and the question of conservative surgical therapy arose. Following a literature review, discussion with the patient led to the decision for ovarian preservation at the time of hysterectomy. The pelvis and abdomen were grossly free of metastatic disease at laparotomy and all tumor was confined to the uterus on pathologic examination. She is free of disease 36 months postoperatively and is now considering in vitro fertilization using a surrogate. Conclusion Ovarian conservation can probably be offered safely in carefully selected women of reproductive age with mullerian adenosarcomas.

Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.

Uterus

Last Updated 10/3/2002

Send mail to psdermpath@earthlink.net with questions or comments about this web site.
Copyright © 2002 The Doctor's Doctor