Well-differentiated Endometrioid Adenocarcinoma Research Articles

The Evolving Spectrum of Endometrial Glandular Proliferations With Corded and Hyalinized Features.

We present the clinicopathologic and immunohistochemical features of 14 endometrial glandular proliferations with conspicuous corded and hyalinized (CH) features comprised entirely or predominantly of endometrial hyperplasia. Endometrial glandular lesions ranged in severity from endometrial hyperplasia with and without cytologic atypia (5/14 [36%]) to hyperplasia with architectural complexity bordering on well-differentiated endometrioid adenocarcinoma (3/14 [21%]) to frank corded and hyalinized endometrial carcinoma ("CHEC") (6/14 [43%]). In addition to sex cord-like growth and hyalinized stroma, other common histologic features included prominent spindle cells (11/14 [79%]), keratinizing and/or morular squamous differentiation (10/14 [71%]), and osseous metaplasia (6/14 [43%]). Immunohistochemical characterization revealed aberrant nuclear beta-catenin in all cases (14/14 [100%]); additionally, all cases demonstrated positive estrogen receptors, intact PTEN, PMS2 and MSH6, and wild-type p53 expression. Patients ranged in age from 24 to 58 (mean 38) years. Of 5 patients with hyperplasia with CH features, 2 experienced complete resolution after progestin therapy and none progressed to adenocarcinoma (mean follow-up 15.6mo, range 2 to 64). By contrast, of 2 patients with hyperplasia bordering on CHEC and with available follow-up, both subsequently developed adenocarcinoma, suggesting that even focal increased architectural complexity may predict an elevated risk of malignancy. We conclude that CH morphology is not limited to endometrioid carcinoma and may occur across a spectrum of neoplastic proliferations, including those without sufficient architectural complexity or cytologic atypia to warrant classification as adenocarcinoma. We propose the term "corded and hyalinized endometrial hyperplasia" to describe this precursor lesion and report favorable outcomes with conservative treatment.

A new surgical approach for fertility-sparing management of diffuse endometrial G2 endometrioid adenocarcinoma: a step-by-step technique.

4% of endometrial cancers are diagnosed in young women and 70% are nulliparous. Preserve fertility in these patients is of major interest. It is demonstrated that hysteroscopic resection of focal well-differentiated endometrioid adenocarcinoma, followed by progestins achieve a complete response rate of 95.3%. Recently, fertility-sparing treatment was proposed also in case of moderately differentiated endometrioid tumors, with a relatively high remission rate. To show a new hysteroscopic approach, in case of fertility-sparing treatment of diffuse endometrial G2 endometrioid adenocarcinoma. Stepwise demonstration of the technique with narrated video footage for the fertility-sparing management of diffuse endometrial G2 endometrioid adenocarcinoma, combining the use of a 15 Fr bipolar miniresectoscope and 'three-steps' resection technique (Karl Storz, Tuttlingen, Germany) with a Tissue Removal Device (TRD) (Truclear Elite Mini, Medtronic). negative hysteroscopic assessment and endometrial biopsies at three and six months. Normal endometrial cavity and negative biopsies. Combined hysteroscopic technique, in case of diffuse endometrial G2 endometrioid adenocarcinoma, followed by double progestin therapy (Levonorgestrel releasing Intrauterine Device + Megestrole Acetate 160 mg/daily), may be associated with higher complete response rate; the use of TRD to complete the resection near tubal ostia may reduce risk of post-operative intrauterine adhesions and improve reproductive outcomes. A novel, fertility-sparing surgical approach for diffuse endometrial G2 endometroid adenocarcinoma.

Cancer Arising from Endometriosis

Study Objective Presentation of unique case of postmenopausal patient with previous total hysterectomy, salpingo-oophorectomy and excision of endometriosis who developed cancer originating from endometriosis. Design Case report Setting Endometriosis Referral center Patients or Participants This video presents a 78-year-old G1P1 female with a history of endometriosis who presented with post-coital vaginal bleeding. She had a history of a total abdominal hysterectomy at the age of 46 due to pelvic pain, and later underwent bilateral salpingo-oophorectomy and excision of endometriosis at the age of 56 due to continued pain. She was on hormonal supplementation with transdermal estrogen. Preoperative examination and imaging revealed a 5 cm friable mass at the vaginal cuff and a smaller pelvic mass in the left pelvic sidewall. Interventions The patient underwent multi puncture video laparoscopy. The left pelvic sidewall mass near the left ureter was carefully resected and found to be endometriosis on final pathology. The vaginal cuff mass was also resected. Measurements and Main Results Pathology reported endometriosis juxtaposed with well-differentiated endometrioid adenocarcinoma. Immunohistochemical tumor staining further confirmed gynecological origin. Conclusion The relationship between endometriosis and ovarian cancer has been established, although not fully elucidated. Therefore, among patients with a history of endometriosis, continued regular gynecologic follow up is recommended not only for recurrence but also for possible malignant transformation. Presentation of unique case of postmenopausal patient with previous total hysterectomy, salpingo-oophorectomy and excision of endometriosis who developed cancer originating from endometriosis. Case report Endometriosis Referral center This video presents a 78-year-old G1P1 female with a history of endometriosis who presented with post-coital vaginal bleeding. She had a history of a total abdominal hysterectomy at the age of 46 due to pelvic pain, and later underwent bilateral salpingo-oophorectomy and excision of endometriosis at the age of 56 due to continued pain. She was on hormonal supplementation with transdermal estrogen. Preoperative examination and imaging revealed a 5 cm friable mass at the vaginal cuff and a smaller pelvic mass in the left pelvic sidewall. The patient underwent multi puncture video laparoscopy. The left pelvic sidewall mass near the left ureter was carefully resected and found to be endometriosis on final pathology. The vaginal cuff mass was also resected. Pathology reported endometriosis juxtaposed with well-differentiated endometrioid adenocarcinoma. Immunohistochemical tumor staining further confirmed gynecological origin. The relationship between endometriosis and ovarian cancer has been established, although not fully elucidated. Therefore, among patients with a history of endometriosis, continued regular gynecologic follow up is recommended not only for recurrence but also for possible malignant transformation.

A rare case of grade 1 endometrioid adenocarcinoma of the uterus with omental metastasis with brenner tumor of the ovary in a postmenopausal female

Early-stage endometrial cancer may have microscopic omental metastases which is associated with a poor prognosis. There are no standard guidelines for omentectomy in early-stage endometrial cancer without risk factors. Brenner tumor is a rare ovarian tumor which is usually benign, but rarely, it may be malignant. Some Brenner tumors are endocrinologically active. Various studies have shown an association of Brenner tumor with endometrial hyperplasia, polyp, or early-stage carcinoma, probably due to its estrogen-secreting nature. We report a rare case of well-differentiated endometrioid adenocarcinoma of the uterus with <50% myometrial invasion with omental metastases associated with benign Brenner tumor of the ovary in a postmenopausal female.

Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition

Uterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such as Tp53 and Pten However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressor Fbxw7 in endometrial cancer through defined genetic model systems. Inactivation of Fbxw7 and Pten resulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquired Trp53 mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial-mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.

Vascular Pseudoinvasion: A Case Report and Review of Literature

Abstract In the era of minimally invasive procedures, laparoscopic hysterectomy is preferred over total abdominal hysterectomy as the primary treatment of endometrioid cancer limited to the uterus. Lymphovascular invasion (LVSI) is an important prognostic indicator for this tumor. Studies have observed presence of vascular pseudoinvasion in the surgical specimen excised via laparoscopic hysterectomy. Some studies have reported no increase in LVSI after minimally invasive surgery, implying that there is no vascular pseudoinvasion. Here, we present a 59-year-old female with history of obesity, hypertension, diabetes mellitus, asthma, and biopsy-proven well-differentiated endometrioid adenocarcinoma who underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and sentinel node dissection. An ill-defined friable mass (2.1 cm in maximum dimension) was present in the posterior lower uterine segment and had the morphology of endometrioid adenocarcinoma, grade 1 out of 3, invasive into the outer half of myometrium. There was no true vessel invasion but rather abundant contamination—smearing of tumor into vascular spaces. An immunostain for D2-40 identified no lymphatic invasion. Immunostains for CD31 and CD34 highlighted tumor cells present in vascular spaces consistent with pseudoinvasion. No regional lymph node metastasis was seen. Peritoneal fluid did not show malignant cells. After surgery, the patient received radiotherapy and had no evidence of recurrent disease. It has been proposed that the artifact of vascular invasion as seen in our case could be associated with the technique of laparoscopic hysterectomy. Substantial LVSI, in contrast to focal or no LVSI, has been shown to be the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis, and overall survival. Its presence is a deciding factor for the type of adjuvant therapy. Therefore, it is important to recognize vascular pseudoinvasion to avoid misdiagnosis of LVSI.

Maintenance hormonal therapy after treatment with medroxyprogesterone acetate for patients with atypical polypoid adenomyoma.

As atypical polypoid adenomyoma (APA) has been reported to be a hormone-related tumor, we aimed to analyze the efficacy and safety of maintenance hormonal therapy after fertility-preserving treatment of these patients with medroxyprogesterone acetate (MPA). Data were retrospectively analyzed from patients with APA who were treated with a fertility-preserving regimen including MPA between October 2001 and December 2011. Eighteen patients were treated with MPA and 14 (77.8%) achieved either a complete or a partial response after the planned treatment. Five patients took progestin for maintenance therapy. Eighteen patients were treated for a mean observation period of 96.7 months. While taking the maintenance therapy, no patient had APA relapse. One patient developed well-differentiated endometrioid adenocarcinoma 18 months after she stopped taking maintenance progestin. Eleven patients without maintenance therapy underwent hysterectomy, andnine of them developed well-differentiated endometrial cancer. Through univariate analysis, there was a significant difference in time to hysterectomy between patients with and without maintenance therapy (P = 0.015). Through multivariate analysis, body mass index (BMI), menstrual status before protocol therapy, maintenance treatment, and pregnancy were found to be significantly associated with a lower risk of hysterectomy. No patient had a recurrence of APA after hysterectomy during the observation period (median, 54 months; range, 2-148 months). No patient showed progression while receiving hormonal therapy, including initial protocol therapy. Maintenance hormonal therapy after treatment with MPA was highly effective and safe, particularly in patients with BMI ≧24 kg/m2 and irregular menstruation cycle.

Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women.

The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH). We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is warranted.

Factors affecting pregnancy outcomes in young women treated with fertility-preserving therapy for well-differentiated endometrial cancer or atypical endometrial hyperplasia.

BackgroundPatients hoping to preserve their fertility receive conservative treatment with high-dose medroxyprogesterone acetate (MPA) for well-differentiated endometrioid adenocarcinoma (EC) or atypical endometrial hyperplasia (AEH) . Such treatment generally involves frequent intrauterine operations, including dilation and curettage (D&C) and endometrial biopsy (EMB), which could result in endometritis, endometrial thinning, or intrauterine adhesion. In turn, any of these outcomes could adversely affect implantation and pregnancy development. The current study thus aimed to identify factors that might affect pregnancy following conservative treatment by MPA.MethodsWe compared a pregnancy group (45 patients) with a non-pregnancy group (53 patients) of MPA-treated patients to evaluate the factors affecting clinical pregnancy establishment. We undertook a multivariate logistic regression analysis based on factors shown by univariate analysis to be significantly different between the groups. Univariate analysis identified number of D&C, endometrial thickness, duration of MPA administration, age of pregnancy permission (the age at which a patient was first allowed to attempt pregnancy after disappearance of the lesion), period of disappearance of lesions, and recurrence as independent variables.ResultsThe odds ratios (95 % confidence interval) of multivariate analysis for disease recurrence, endometrial thickness during ovulation, and age of pregnancy permission were 0.283 (0.102–0.785), 1.677 (1.251–2.248), and 0.889 (0.792–0.998), respectively. There was no significant difference in the other independent variables between groups.ConclusionsWe identified three factors considered to affect pregnancy establishment following conservative treatment with MPA: recurrence, endometrial thickness during ovulation, and the age of the pregnancy permission. Introduction of infertility treatment including assisted reproductive technology (ART) soon after achieving tumor disappearance by MPA would therefore be beneficial for patients with disease recurrence, thin endometrium, or a higher age of pregnancy permission.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0136-7) contains supplementary material, which is available to authorized users.

Adult Granulosa Cell Tumor Associated with Endometrial Carcinoma

ABSTRACT Adult granulosa cell tumors account for approximately 1 and 2% of all ovarian tumors and 95% of all granulosa cell tumors. They occur more often in postmenopausal than in premenopausal women, with a peak incidence between 50 and 55 years of age. They are the most common estrogenic ovarian tumors diagnosed clinically. The typical endometrial reaction associated with functional tumors in this category is simple hyperplasia that usually exhibits some degree of precancerous atypicality. The incidence of associated endometrial carcinomas is under 5%, and most of these endometrial cancers are well-differentiated endometrioid adenocarcinomas that carry a good prognosis when detected early. We report the case of a 85-year-old woman with endometrial adenocarcinoma and adult granulose cell tumor of the ovary who presented with postmenopausal bleeding and adnexal mass. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, infracolic omentectomy, and pelvic lymphadenectomy, and the specimen was submitted for histopathological examination. She had a good postoperative recovery and was discharged 5 days after treatment. The association between adult granulosa cell tumors of the ovary and endometrial carcinomas is rare. A high index of suspicion and good imaging and histopathologic analyses are important in making this diagnosis. How to cite this article Baser A, Zaidi AK, Sanghvi N. Adult Granulosa Cell Tumor Associated with Endometrial Carcinoma. J South Asian Feder Obst Gynae 2016;8(3):246-248.

Prognostic factors of regression and relapse of complex atypical hyperplasia and well-differentiated endometrioid carcinoma with conservative treatment

ObjectiveTo evaluate possible prognostic factors regarding regression and relapse of complex atypical hyperplasia (CAH) and well-differentiated endometrioid adenocarcinoma (WDC) treated with conservative treatment. MethodsThe retrospective study reviewed clinicopathologic, treatment, regression and relapse data from patients diagnosed with CAH or WDC who were treated with conservative treatment at 4 institutions. Potential factor evaluation was performed. SPSS 16 was used for statistical analyses. ResultsEighty-eight patients were included (51 had WDC, and 37 had CAH). Regression was evaluated in 88 patients, with a median follow-up of 61 (range 15–95) months. Seventy-seven (87.5%) patients regressed, and 11 (12.5%) had persistent or progressive disease. Univariate and multivariate analyses showed no factors associated with regression. Relapse was evaluated in 71 patients, with median follow-up of 54 (range 8–86) months. Twenty-five/71 (35.2%) patients experienced relapse. On univariate analysis, body mass index (BMI) 30 or higher (p=0.001), WCD at initial biopsy (p=0.017) and positive expression of post-treatment ki67 (p=0.033) were associated to a higher relapse probability. However, only BMI 30 or higher was significant on multivariate analysis (p=0.012). The Kaplan–Meier analysis revealed a higher relapse probability in the patients with BMI 30 or higher (p=0.001). ConclusionObesity seems to be a risk factor for relapse of CAH or WDC with conservative treatment.

Mesonephric Carcinoma of the Ovary: A Report of Two Cases

Mesonephric carcinomas of the female genital tract are rare tumors, mainly occurring in the cervix and exceptionally in the uterine corpus. There seems to be a paradigm that the only mesonephric neoplasms arising from the upper zone of the Wolffian system are FATWOs. Indeed, no cases of mesonephric carcinoma of the ovary have been reported in the recent literature. Herein, we describe two cases of ovarian carcinoma with histologic features consistent with mesonephric adenocarcinoma. In both cases, the initial diagnosis of well-differentiated endometrioid adenocarcinoma was withdrawn because of other coexistent growth patterns, and the presence of admixed mesonephric-type structures. The mesonephric identity of the tumors was supported immunohistochemically, in particular by their uniform negativity for ER and PR, and strong reactivity for CD10.

Lymphovascular Space Invasion in Microcystic Elongated and Fragmented (MELF)-Pattern Well-differentiated Endometrioid Adenocarcinoma is Associated With a Higher Rate of Lymph Node Metastasis

The microcystic elongated and fragmented (MELF) pattern of myoinvasion is a feature of some well-differentiated endometrial endometrioid adenocarcinomas that has been associated with poor prognosis. The myoinvasion in MELF-pattern tumors can be subtle and lead to underestimation of the depth of myometrial invasion resulting in tumor understaging; the presence of lymphvascular space invasion (LVSI) and lymph node metastasis in MELF-pattern tumors can also be subtle and lead to tumor understaging. To investigate the association of MELF-pattern invasion and lymph node metastasis, we reviewed a series of well-differentiated endometrioid adenocarcinomas and correlated the presence of MELF-pattern myoinvasion and LVSI with lymph node metastasis. Cases of T1 stage well-differentiated endometrioid adenocarcinomas with LVSI and a concurrent lymph node dissection were identified from departmental files. Hematoxylin and eosin-stained slides from the hysterectomy specimen and lymph nodes were reviewed for the presence of MELF-pattern myoinvasion, LVSI, and nodal metastasis. MELF-pattern myoinvasion was identified at least focally in 36% of cases. The pattern of LVSI differed between cases with MELF-pattern invasion and conventional-type invasion, as did the pattern of nodal metastasis. A statistically significantly higher rate of lymph node metastasis was present in cases with MELF-pattern invasion than in cases with conventional invasion, and the rate stratified with the proportion of MELF-pattern adenocarcinomas. MELF-pattern cases carry an increased rate of lymph node metastasis even within the subset of endometrioid tumors with LVSI, which has implications in routine clinical practice as it signals the importance of recognizing MELF-pattern myoinvasion.

Relapse as Advanced Carcinosarcoma Following Uterus-Preserving Therapy in a Patient with Early-Staged and Grade 1 Endometrioid Adenocarcinoma: A Case Report and Review of the Literature

Fertility-sparing treatment with high-dose progestin is now used in many young patients with early stage, grade 1 endometrioid adenocarcinoma. The response rate of this therapy is quite good, but the relapse rate is relatively high. If the site of recurrence is limited to the uterus, this may be treated with additional hormone therapy or hysterectomy. We recently experienced a case of a 30-year-old primigravida patient in whom intraperitoneal dissemination of carcinosarcoma occurred during follow-up after apparent complete remission of early-stage grade 1 endometrioid adenocarcinoma. We report the case as an example of a rare high-grade histology tumor that relapsed in an extrauterine site after primary remission had been achieved with high-dose progestin therapy. In a review of the literature through a MEDLINE search, we found 13 articles describing relapse in an extrauterine site, including 6 ovarian metastases, 4 retroperitoneal lymph node metastases, and 3 metastases to organs other than the ovary. Early stage, well-differentiated endometrioid adenocarcinoma of the uterine corpus is generally considered to have a good prognosis, but counseling of patients regarding life decisions is important, with provision of sufficient information on the possibility of extrauterine progression or disseminated recurrence.

Cancerous ‘floater’: a lesson learned about tissue identity testing, endometrial cancer and microsatellite instability

A 46-year-old woman presented with endometrial cells on a pap smear and underwent endometrial curettage. The specimen revealed secretory endometrium and a possible endometrial polyp. In addition, a single 4 mm fragment of well-differentiated adenocarcinoma was found. Tissue identity DNA genotyping was performed and the adenocarcinoma tissue fragment showed a drastically different allelic pattern from that of the background endometrium. To confirm tissue contamination, genotyping of three other tumor specimens—probable sources for a contaminant—was performed but failed to identify a match. Without confirmation of contamination, a second endometrial curettage was obtained from the patient, in which similar adenocarcinoma tissue was once again found. Further workup demonstrated that the patient had a microsatellite unstable (MSI) endometrial adenocarcinoma by immunohistochemistry and molecular testing. The patient subsequently underwent staging surgery, which revealed an early-stage, well-differentiated endometrioid adenocarcinoma. This case study illustrates an uncommon, yet important caveat of tissue identity testing by DNA genotyping, where MSI instability can significantly alter the allelic pattern of DNA polymorphisms in the tumor genome, leading to erroneous conclusion regarding the tissue identity. Awareness of this phenomenon is crucial for a molecular pathologist to avoid interpretation errors of tissue identity testing in a cancer diagnostic workup.

Clinical management of atypical polypoid adenomyoma of the uterus. A clinicopathological review of 29 cases

ObjectiveThe clinical management of atypical polypoid adenomyoma (APAM) of the uterus remains to be established. We collected APAM cases, reviewed the clinicopathological features, and discussed the clinical management. MethodsTwenty-nine patients with APAM were identified by searching the tumor registry of the Japan Clinical Oncology Group (JCOG). Clinical information and histological specimens were obtained from 13 institutional members of the JCOG, and a central pathological review was performed. ResultsThe mean age of the patients was 38years (range, 22–58). Squamous metaplasia was present in 19 cases (65.5%), and well-differentiated endometrioid adenocarcinoma coexisted in 5 cases (17.2%). Primary treatment consisted of dilatation and curettage in 9 patients (31.0%), vaginal resection in 2 patients (6.9%), hysteroscopic transcervical resection (TCR) using hysteroscopy in 10 patients (34.5%), and hysterectomy in 8 patients (27.6%). There were recurrences in 5 (23.8%) of the 21 cases in which fertility was preserved, and the recurrent rate was 10% (1/10) in patients those were treated with TCR and 36.4% (4/11) in those the other treatment options were selected. All patients were alive after primary treatment (a mean follow-up period was 39.6months; range, 1–202). ConclusionThe clinical outcome of APAM is benign. However, differential diagnosis should be performed because of its histological similarity to invasive endometrial carcinoma and the possibility of coexistence with other endometrial neoplasms. TCR is a recommended diagnostic and treatment option for patients who desire to preserve fertility.

Metastasis of endometrial adenocarcinoma in a primary lung adenocarcinoma

Dear Sir, To our knowledge, we report the first case of a metastasis of an endometrial adenocarcinoma in a pulmonary adenocarcinoma. A 72-year-old woman presented to our department with minimal metrorrhagia. The patient was diagnosed 6 years earlier with a mediastinal follicular lymphoma stage 3A according to Ann Arbor classification. Taking into account the characteristics of the lymphoma, therapy abstinence was decided, but the patient was followed up with regular laboratory monitoring l and computed tomography (CT) scans. The mediastinal lymphadenopathy remained stable. A pelvic sonogram made during the gynecology consultation showed a thick endometrium, and biopsies were taken. Histopathological examination of the samples led to a diagnosis of a well-differentiated (grade 1) endometrioid adenocarcinoma. The pelvic MRI showed myometrial infiltration without penetration of the serosa and right external iliac lymph nodes of 2 cm diameter. Chest CT revealed a single welldefined 24-mm mass located in the Fowler segment of the right lung (Fig. 1) which was not seen on previous scans. FDG PET/CT gave rise to a suspicion of a hypermetabolic pulmonary focus. The lesion was not accessible by bronchoscopy, making trans-bronchial biopsy impossible. A diagnostic right lower lobe resection was performed. Macroscopic examination revealed a white-gray solitary nodular mass, measuring 20×20×16 mm in the lung parenchyma. Microscopy revealed the association of two types of malignant tissues. The predominant type presented the typical architectural and cytological pattern of lepidic lung adenocarcinoma. In this area, lining the alveolar lumen, cells were cuboid cylindrical with large irregular nuclei and eosinophilic or clear cytoplasm. Alcian blue staining revealed the presence of extracellular mucins. Within this tumor, a 9-mm nodule of a different malignant tissue was found, characterized by glandular architecture with cavities lined with high cylindrical cells with basophilic, elongated, and nucleolated nuclei (Fig. 2). By immunohistochemistry, the two components were distinct. Tumor cells of the main mass were positive for thyroid transcriptor factor 1 (TTF-1) and cytokeratin 7 (CK7), but negative for estrogen receptor (ER) and progesterone receptor (PR). Inversely, the cells of the minor focus were negative for TTF-1 and CK7 but positive for ER/PR (Fig. 2). A final histological diagnosis was made of metastasis of endometrial adenocarcinoma in a primary lung adenocarcinoma. No metastases were found in other organs. The endometrial cancer was stage IVB according to the FIGO classification, and neoadjuvant chemotherapy based on taxol–carboplatin was initiated. The association in a single tumor mass of a primary cancer containing metastatic tissue is a phenomenon called tumor-to-tumor metastasis. Tumor-to-tumor metastasis and collision tumor have been confounded in some publications, and the incidence of the former cannot be deduced from the number of cases reported [1]. Collision tumor is the term used for the presence of two histologically distinct primary A. Pelissier-Komorek (*) Department of Obstetric Gynecology, University Hospital of Reims, 45 rue Cognacq Jay, 51100 Reims, France e-mail: a.komorek@gmail.com

Adult granulosa cell tumor associated with endometrial carcinoma: a case report

IntroductionIf strict criteria for the diagnosis of carcinoma are used and all patients with granulosa cell tumors are considered, the best estimate of the incidence of associated endometrial carcinomas is under 5%. In patients with granulosa cell tumors, estrogen-dependent endometrial cancers are rarely found, and most of these endometrial cancers are well-differentiated endometrioid adenocarcinomas that carry a good prognosis when detected early.Case presentationWe report the case of a 65-year-old post-menopausal Nigerian woman of the Igbo tribe with an adult granulosa cell tumor that was initially treated as endometrial carcinoma. She underwent a total abdominal hysterectomy and a bilateral salpingo-oophorectomy after histopathologic confirmation of a well-differentiated granulosa cell tumor of the ovary and a nuclear grade 1 adenocarcinoma of the endometrium (International Federation of Obstetricians and Gynecologists stage 1B). She had a good post-operative recovery and was discharged 10 days after treatment.ConclusionThe association between adult granulosa cell tumors of the ovary and endometrial carcinomas is rare. A high index of suspicion as well as good imaging and histopathologic analyses are important in making this diagnosis.

Effectiveness of high-dose progestin and long-term outcomes in young women with early-stage, well-differentiated endometrioid adenocarcinoma of uterine endometrium

We assessed the effectiveness of high-dose progestins as a conservative treatment in young women with endometrial adenocarcinoma. We retrospectively reviewed the hospital data of patients with endometrial cancer that were managed conservatively. Of those women with grade 1 endometrioid endometrial adenocarcinoma, we included those who were younger than 40 years and in whom the disease was clinically confined to the endometrium. A complete response was defined pathologically as the absence of tissue with adenocarcinoma or hyperplasia. Fourteen patients were included. Their mean age was 30.0 ± 4.8 years and the mean follow-up period was 47.3 ± 29.7 months. Twelve patients received 30-500 mg/day medroxyprogesterone acetate and two received 160 or 240 mg/day megestrol acetate. The median duration of treatment was 6 months (range 3-15 months) and 13 (93%) patients showed a complete response. Endometrial pathology reappeared in four patients (4/13, 31%) including two relapses, three of whom developed after the patients gave birth. Six patients used a combined oral contraceptive or a progestin-releasing intrauterine device as a maintenance therapy and experienced no recurrence. Four women (4/7, 57%) conceived successfully seven times with assisted-reproductive technology. No adverse effects of the progestins or tumor-related death were noted. High-dose progestin therapy can be an effective conservative treatment in young patients with well-differentiated early-stage endometrial cancer. If patients wish to preserve their fertility even after they have completed childbearing, maintenance therapy with a cyclic oral contraceptive or a progestin-releasing intrauterine device may be an option to prevent recurrence.

Massive Intra-abdominal Undifferentiated Carcinoma Derived From an Endometrioid Adenocarcinoma in a “Normal-sized” Ovary

We report a case of massive intra-abdominal undifferentiated carcinoma derived from a tiny well-differentiated endometrioid adenocarcinoma of the ovary. The patient, a 56-year-old woman, who presented with a large intra-abdominal mass, underwent cytoreductive surgery with hysterectomy and bilateral salpingo-oophorectomy. Macroscopically, the intra-abdominal mass was composed of fragile and solid tumor components with extensive necro-hemorrhagic areas, mimicking a primary peritoneal tumor. Both ovaries were apparently normal in size, but a cut section of the right ovary revealed a 2-cm solid and cystic tumor showing focal rupture to the peritoneal surface. The intra-abdominal tumor consisted of pleomorphic cells without specific differentiation, showing diffuse sheet-like proliferation. The right ovarian tumor was a histologically well-differentiated endometrioid adenocarcinoma. Both the intra-abdominal undifferentiated tumor and the ovarian adenocarcinoma cells were immunohistochemically positive for keratin AE1/3, Ber-EP4, and CD10. Epithelial membrane antigen was positive only in the ovarian adenocarcinoma component, and vimentin was diffusely positive only in the intra-abdominal undifferentiated tumor component. Calretinin was negative in both tumor components. Allelotype analysis using 24 polymorphic markers located on 12 chromosomal arms showed that the intra-abdominal undifferentiated carcinoma and ovarian adenocarcinoma components had a high concordance rate (88%) of allelic patterns including identical allelic loss patterns at 7 chromosomal loci, suggesting a common genetic lineage. These data suggest that ovarian endometrioid adenocarcinoma, even when small in size, can give rise to a massive undifferentiated carcinoma filling the peritoneal cavity.