Endometrioid Differentiation Research Articles

A Decade of Therapeutic Challenges in Synchronous Gynecological Cancers from the Bucharest Oncological Institute.

The aim of our study is to present the particularities of a specific subset of gynecological cancer patients in Romania. We present a review of synchronous gynecological neoplasia (SGN) treated in the Bucharest Oncological Institute's surgery departments over a decade. Between 2012 and 2022, 7419 female patients with genital malignancies were treated. We identified 36 patients with invasive synchronous primary gynecological cancers (0.5%) and 12 cases with one primary gynecological and another primary invasive pelvic cancer (rectal/bladder). All recurrent, metastatic, or metachronous tumors detected were excluded. Demographic data, personal history, presenting symptoms, pathologic findings, staging, treatment, and evolution for each case were recorded. Usually, the most common SGN association is between ovarian and endometrial cancer of endometrioid differentiation (low-grade malignancies with very good prognosis). However, we noticed that, given the particularities of the Romanian medical system, the most frequent association is between cervical and endometrial, followed by cervical and ovarian cancers. Moreover, the cancer stage at diagnosis is more advanced. In countries with low HPV vaccination rate and low adherence to screening programs, SGNs can present as extremely advanced cases and require extensive surgery (such as pelvic exenterations) to achieve radicality. This multimodal treatment in advanced cases with high tumor burden determines a reduction in survival, time until progression, and quality of life.

<p>Ultraconservative, Fertility Sparing Treatment of Bilateral Borderline Ovarian Tumors: A Case Report of a 26-Year-Old, 0-Gravida with an Endometrioid Borderline Ovarian Tumor of the Right Ovary and a Sero-Mucinous Borderline Ovarian Tumor of the Left Ovary and a Review of the Literature</p>

Endometrioid borderline ovarian tumors are rare, entailing a lack of data on their natural history as well as the safety of conservative and ultraconservative surgical management, especially in cases with bilateral borderline ovarian tumors including one of endometrioid differentiation. Therefore, we present such a case and provide a review of the literature on endometrioid borderline ovarian tumors. We report the case of a 26-year-old, 0-gravida with an endometrioid borderline ovarian tumor of the right and a sero-mucinous borderline ovarian tumor of the left ovary treated by fertility sparing, ultraconservative surgery with bilateral cystectomy, completed by staging procedures including omentectomy and peritoneal sampling, as well as endometrial sampling by means of curettage. Reviewing the literature and taking into account the course of our case, we propose the feasibility of an ultraconservative management, including endometrial sampling, in young patients with bilateral borderline ovarian tumors including one of endometrioid differentiation who desire to preserve fertility, followed by a closely monitored follow-up.

Endometrioid Adenofibroma: A Case of This Uncommon Benign Tumor of the Ovary Not Associated to Borderline or Endometrioid Carcinoma

Endometrioid adenofibroma is a benign epithelial and stromal tumor with an endometrioid epithelial component. Less than 20% of the surface epithelial tumors of the ovary have endometrioid differentiation. The majority of endometrioid ovarian neoplasms are carcinomas and the benign form is rarely find. Endometrioid adenofibromas are extremely rare, comprise 1% of ovarian epithelial neoplasms. Usually, they are unilateral lesions (83%) and clinical symptoms are non-specific. Ovarian endometriosis (including endometriomas and endometriotic cysts) is by far more common than benign endometrioid neoplasms. Probably it represents endometriomas in which the endometrial stroma is indistinct.

Ovarian seromucinous carcinoma: report of a series of a newly categorized and uncommon neoplasm.

Seromucinous neoplasms are a new category of ovarian epithelial tumor in the revised World Health Organization Classification of Tumours of the Female Reproductive Organs. Borderline variants are well described, but there have been few reports of seromucinous carcinomas. We report the clinicopathologic features in 19 cases of ovarian seromucinous carcinoma in patients aged 16 to 79 years (mean 47). In 16 cases, the neoplasm was unilateral and in 3 cases bilateral. The tumors ranged in size from 1.8 to 18 cm (mean 10.5 cm). The tumors were stage I (n=15), stage II (n=1), and stage III (n=3). The histologic features were highly variable both within and between individual tumors. The majority of neoplasms (12 cases) exhibited a predominant papillary architecture with lesser components of glandular, microglandular, and solid growth. A predominant glandular architecture was present in 6 cases, whereas 1 had a predominantly solid growth. A characteristic feature was an admixture of cell types. Most of the tumors (15 cases) were mainly composed of endocervical-like mucinous cells, whereas in 4 cases there was predominant endometrioid differentiation. Other cell types, present in varying proportions, included hobnail cells, eosinophilic cells, squamous cells, clear cells, and signet-ring cells. An infiltrate of neutrophil polymorphs was a prominent feature in most cases. Most cases also exhibited areas of microglandular architecture with cytoplasmic clearing and intraluminal polymorphs, the features closely resembling cervical microglandular hyperplasia. Areas of stromal hyalinization, adenofibromatous growth, and psammoma bodies were present in a minority of cases. Endometriosis was identified in the same ovary in 10 cases, and in 10 there was a component of seromucinous borderline tumor. Thirteen, 5, and 1 tumor were of grades 1, 2, and 3, respectively (using the FIGO grading system for endometrioid adenocarcinomas of the uterine corpus). A synchronous uterine endometrioid adenocarcinoma was present in 1 case. Immunohistochemically, there was positive staining with CK7 (17/17 cases), estrogen receptor (16/16 cases), progesterone receptor (6/7 cases), CA125 (15/15 cases), PAX8 (8/8 cases), CEA (8/13 cases), CA19.9 (8/9 cases), and WT1 (2/13 cases). CK20 and CDX2 were negative in all cases tested (16 and 14, respectively). p53 showed "wild-type" staining in 4/4 cases, and p16 was focally positive in 5/5 cases. Follow-up information was available in 8 patients. Seven were alive with no evidence of disease (follow-up 3 to 74 mo), whereas 1 patient who initially presented with a stage IIB tumor died of disease at 192 months. Given the characteristic admixture of cell types and the overlapping morphologic features with low-grade serous, mucinous, and endometrioid neoplasms, the most appropriate categorization of seromucinous carcinomas is uncertain, but we believe they are best regarded as a distinct type of ovarian epithelial malignancy and are most similar to endometrioid adenocarcinomas. We recommend grading them in an analogous manner to ovarian endometrioid adenocarcinomas.

Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations

The Cancer Genome Atlas described four major genomic groups of endometrial carcinomas, including a POLE ultramutated subtype comprising ∼10% of endometrioid adenocarcinoma, characterized by POLE exonuclease domain mutations, ultrahigh somatic mutation rates, and favorable outcome. Our aim was to examine the morphological and clinicopathological features of ultramutated endometrial carcinomas harboring somatic POLE exonuclease domain mutations. Hematoxylin and eosin slides and pathology reports for 8/17 POLE-mutated endometrial carcinomas described in the Cancer Genome Atlas study were studied; for the remaining cases, virtual whole slide images publicly available at cBioPortal (www.cbioportal.org) were examined. A second cohort of eight POLE mutated endometrial carcinomas from University of Calgary was also studied. Median age was 55 years (range 33–87 years). Nineteen patients presented as stage I, 1 stage II, and 5 stage III. The majority of cases (24 of the 25) demonstrated defining morphological features of endometrioid differentiation. The studied cases were frequently high grade (60%) and rich in tumor-infiltrating lymphocytes and/or peri-tumoral lymphocytes (84%); many tumors showed morphological heterogeneity (52%) and ambiguity (16%). Foci demonstrating severe nuclear atypia led to concern for serous carcinoma in 28% of cases. At the molecular level, the majority of the Cancer Genome Atlas POLE-mutated tumors were microsatellite stable (65%), and TP53 mutations were present in 35% of cases. They also harbored mutations in PTEN (94%), FBXW7 (82%), ARID1A (76%), and PIK3CA (71%). All patients from both cohorts were alive without disease, and none of the patients developed recurrence at the time of follow-up (median 33 months; range 2–102 months). In conclusion, the recognition of ultramutated endometrial carcinomas with POLE exonuclease domain mutation is important given their favorable outcome. Our histopathological review revealed that these tumors are commonly high grade, have obvious lymphocytic infiltrates, and can show ambiguous morphology. As they frequently harbor TP53 mutations, it is important not to misclassify them as serous carcinoma.

Paratesticular Serous Papillary Borderline Tumor

A 37-year-old male presented with a 2-year history of progressive left scrotal swelling. Ultrasound showed an enlarged left testicle with heterogeneous echogenicity. Serum a-fetoprotein (AFP) and b-human chorionic gonadotropin were negative. There was no evidence of metastatic disease on computerized tomography. Left radical inguinal orchiectomy was performed. Pathological examination of the specimen revealed a 6.0 5.0 5.0 cm multicystic mass surrounded by a dense, pink/white, rubbery capsule involving the epididymis but without invasion of the tunica albuginea. The cystic lining was thick and rubbery, with focal hemorrhage and multiple shaggy papillary excrescences (fig. 1). The cysts were 0.2 to 5.0 cm and filled with thick, brown/ maroon, mucinous fluid and tan/pink, gelatinous material. Histological sections revealed predominantly serous cells with focal endometrioid differentiation (fig. 2). The cells were immunoreactive to estrogen receptor (ER), cytokeratin (CK) 7 and Wilms tumor suppressor gene (WT-1) with negative staining for

Mixed epithelial and stromal tumor of the kidney with endometrioid differentiation associated with pancreatic solid pseudopapillary tumor

Abstract Mixed epithelial and stromal tumor of the kidney (MESTK) is a benign cystic neoplasm. Pancreatic solid-pseudopapillary tumor (SPT) is a typically cystic carcinoma of low malignant potential. We describe a MESTK synchronous with a SPT in a female with an ovarian cystic corpus luteum. Glands showed endometrioid differentiation and the spindle cell stroma created complex leaflet-like structures similar to Mullerian adenofibroma. The SPT consisted of polygonal cells with a pseudopapillary pattern and a cystic area. Expression of estrogen and progesterone receptors in MESTK stromal cells and progesterone receptors in SPT provided a diagnostic clue, confirming the hormonal dependence in pathogenesis. Given that our MESTK is a polypoid tumor with endometrioid differentiation, the differential diagnosis with polypoid endometriosis is considered.

Extra genital heterologous malignant mixed mullerian tumor of primary peritoneal origin

The case of an extragenital heterologous malignant mixed müllerian tumor (MMMT) of primary peritoneal origin occurring in a 76-year-old female is presented. A large tumor was seen between the uterus and rectosigmoid occupying the entire pelvis. The uterus, fallopian tubes and ovaries were uninvolved. The tumor was composed of carcinomatous areas showing endometrioid and serous papillary differentiation and sarcomatous areas showing cartilaginous differentiation. The extragenital primary MMMTs of the female peritoneum are thought to originate from the secondary müllerian system. This case is presented for its rarity. To the best our knowledge, this is the first case of extragenital MMMT of primary peritoneal origin in Indian literature.

No Metastatic Cervical Adenocarcinomas in a Series of p16INK4a-Positive Mucinous or Endometrioid Advanced Ovarian Carcinomas

Epithelial ovarian cancers may represent secondary manifestations of occult extraovarian carcinomas. Such tumors may be misdiagnosed as primary ovarian carcinomas clinically and pathologically. In a recent study, several cases of cervical cancer metastases with primary manifestation as mucinous or endometrioid ovarian carcinomas were described. In all cases, human papillomavirus (HPV) DNA and diffuse p16 immunostaining were detected in the ovarian tumor tissues. To estimate the frequency of occult metastatic endocervical adenocarcinomas in a series of mucinous or endometrioid ovarian carcinomas, 24 ovarian cancers with mucinous and 50 with endometrioid differentiation from the Arbeitsgemeinschaft Gynaekologische Onkologie OVAR-3 database were analyzed for HPV and p16 positivity. The p16 immunostaining was performed using the p16 histology kit (Dako, Glostrup, Denmark), and both nuclear and cytoplasmic staining results were considered positive. Human papillomavirus polymerase chain reaction analysis was performed using 2 consensus primer systems (GP5/GP6 and PGMY09/11) and HPV-16- and HPV-18-specific primers from the L1 and the E6 regions. Six (8%) of 74 tumors were p16-negative, 13 (18%) of 74 showed single positive cells, 28 (38%) of 74 showed focal homogeneous staining, and 27 (36%) of 74 showed complete diffuse staining. In several independent amplifications of different regions of the HPV genome, none of the 73 tumors available for analysis showed the presence of HPV DNA. No ovarian metastases of endocervical adenocarcinomas were found among mucinous and endometrioid adenocarcinomas from a large chemotherapy trial of advanced stage ovarian carcinomas. The p16 staining detected in many primary ovarian adenocarcinomas in the present series seems independent from HPV oncogene activity.

Pathological Characteristics of Cervical Adenocarcinoma in a Multi-center U.S.-based Study

Although human papillomavirus infection plays a role in the development of both cervical adenocarcinoma (AC) and squamous-cell carcinoma (SCC) of the cervix, cytological screening has been less effective in lowering the incidence of AC and its mortality rate in the United States. In contrast to SCC, only the immediate precursor of AC, adenocarcinoma in situ (AIS), has been clearly defined. In addition, the microscopic findings in AC are more diverse, and pathologists have less experience in diagnosing AC and AIS compared with SCC and its preceding lesions. The investigators undertook a detailed pathological review of subtypes of cervical AC. The study population consisted of 154 women ranging in age from 18 to 69 years who, when seen at one of six US medical centers in the years 1992-1996, received a diagnosis of in situ or invasive AC, adenosquamous (AS) tumor, or other rare cervical glandular tumors. Three pathologists jointly carried out a microscopic review of these tumors, and risk factors were identified from questionnaires administered by interviewers. In general, there were no substantial epidemiological differences between women with different histopathological subtypes. Nearly one-fourth of the 154 cervical glandular tumors (23%) were AIS; the remaining 77% were invasive neoplasms. Of the invasive cancers, 45% were AC; 19% were AS; and 20 were unusual types such as adenoid basal, small cell, and undifferentiated carcinomas. A majority of AIS lesions and invasive ACs exhibited endocervical or endometrioid differentiation. Nearly 80% of AS cases were grade 2 or 3, whereas 80% of ACs was grade 1 lesions. Invasive AS tumors were much likelier than ACs to exhibit vascular invasion (42% vs. 10%). AIS was likelier to be present in AC than in AS cases (71% vs. 39%). Approximately two-thirds of carcinomas of any type were stage IB when diagnosed. Both AIS and cribriform patterns were more common in ACs exhibiting cervical intraepithelial neoplasia (CIN). Nonendometrioid ACs were higher-grade tumors than endometrioid lesions. There was no evidence that microglandular hyperplasia was associated with the use of oral contraceptives. These findings show that cervical AS tumors have more aggressive characteristics than do ACs. In addition, AIS may not be a common precursor of AS tumors, making it less likely that screening for AIS or CIN will detect these tumors an early stage.

P16 Expression in Primary Ovarian Mucinous and Endometrioid Tumors and Metastatic Adenocarcinomas in the Ovary

Distinction of primary ovarian epithelial tumors from metastatic adenocarcinomas is challenging for tumors exhibiting mucinous, endometrioid, or mixed endometrioid/mucinous differentiation. Metastatic carcinomas with these types of differentiation can be derived from several sites, including the gastrointestinal tract and the uterus. Most endocervical adenocarcinomas exhibit mucinous and/or endometrioid differentiation; they infrequently metastasize to the ovaries but may simulate primary ovarian tumors [both atypical proliferative (borderline) and carcinoma]. Most are high-risk human papillomavirus (HPV)-related and demonstrate diffuse p16 over-expression due to complex molecular mechanisms by which high-risk HPV transforming proteins interact with cell cycle regulatory proteins. The performance of this expression pattern for identifying metastatic endocervical adenocarcinomas in the ovaries among primary ovarian tumors and other metastatic adenocarcinomas having mucinous and/or endometrioid/endometrioidlike differentiation has not been evaluated. Immunohistochemical expression of p16 was assessed in 195 tumors, including 98 primary ovarian tumors (51 mucinous, 47 endometrioid, and 4 mixed mucinous-endometrioid tumors), 93 metastatic adenocarcinomas of known primary sites (colorectum: 34, endocervix: 19, pancreaticobiliary tract: 17, appendix: 7, stomach: 5), 11 metastatic adenocarcinomas of unknown origin (7 established as noncervical), and 4 adenocarcinomas of uncertain (primary ovarian vs. metastatic) origin. The HPV status of the endocervical adenocarcinomas was determined by in situ hybridization and polymerase chain reaction (when in situ hybridization was negative). Expression was assessed based on the percentage of moderately to strongly positive cells, estimated to the nearest 10%. Mean and median expression values for HPV-positive endocervical adenocarcinomas (99%, 100%; range 90% to 100%) were substantially higher than those for primary ovarian mucinous (5%, 0%; range 0% to 70%) and endometrioid (20%, 10%; range 0% to 100%) tumors, HPV-unrelated endocervical adenocarcinomas (0%, 0%; range 0% to 60%), metastatic adenocarcinomas of unknown origin (11%, 0%; range 0% to 30%), and adenocarcinomas of uncertain (primary ovarian vs. metastatic) origin (40%, 35%; range 0% to 90%); only the 15 HPV-positive endocervical adenocarcinomas and 6 other tumors had values of 80% or greater. Diffuse (>75% positive tumor cells) moderate to strong p16 expression is a sensitive (100%) and specific (97%) marker for identifying HPV-related endocervical adenocarcinomas metastatic to the ovary among the primary ovarian tumors and metastatic adenocarcinomas from other sites that are in the differential diagnosis of ovarian tumors having mucinous and/or endometrioid/endometrioidlike differentiation. p16 is useful as part of a panel of immunohistochemical markers for distinguishing primary ovarian tumors from metastases and, when diffusely positive, can suggest the cervix as a potential primary site for metastatic adenocarcinomas of unknown origin.

Extrauterine Low-Grade Endometrial Stromal Sarcoma

Summary Objective Endometrial stromal sarcoma is a rare cancer that accounts for 0.2% or less of all female genital tract malignancies. We present a case of extrauterine low-grade endometrial stromal sarcoma arising from endometriosis, which was managed by unilateral salpingo-oophorectomy with postoperative high-dose progesterone adjuvant therapy. Case Report A 28-year-old nulligravid woman had suffered from progressive abdominal distension accompanied by a palpable firm mass for about 3 months. An abdominal pelvic mass, measuring 13 × 12 × 8 cm, was seen on pelvic sonography and abdominal computed tomography. The CA125 titer was also elevated. Left salpingo-oophorectomy was performed when frozen section examination of the tumor indicated a benign tumor. However, the pathology of the tumor was extrauterine low-grade endometrial stromal sarcoma with extensive endometrioid glandular differentiation arising from endometriosis. The resection margin was also involved. The patient has been receiving high-dose progesterone therapy for 2 months without any adverse effects, except for an increase in body weight of 2 kg. Conclusions Low-grade endometrial stromal sarcoma typically has an indolent clinical course and favorable prognosis. Surgical resection is the primary therapeutic approach, and adjuvant therapy with radiotherapy, chemotherapy, or progesterone therapy should be considered for the management of residual or recurrent low-grade endometrial stromal sarcomas.

Histologic Type, Organ of Origin, and Wnt Pathway Status: Effect on Gene Expression in Ovarian and Uterine Carcinomas

Ovarian and uterine carcinomas manifest several differentiation patterns resembling those seen in nonneoplastic epithelia of the gynecologic tract. Specific oncogene and tumor suppressor gene defects have been associated with particular differentiation patterns in carcinomas arising in either the uterus or ovary. For instance, ovarian and uterine carcinomas with endometrioid differentiation frequently show beta-catenin mutations. Whereas type of differentiation is considered in the treatment of uterine carcinomas, it does not presently contribute to decisions about treatment of ovarian carcinomas. A widely accepted view is that the accumulation of specific gene defects and gene expression changes underlies phenotypic traits of cancers, including their response to treatment. Using oligonucleotide microarrays to assess gene expression in 103 primary ovarian and uterine carcinomas, we sought to address whether organ of origin or type of differentiation (histotype; endometrioid versus serous) had a more substantial effect on gene expression patterns. We found that effects on gene expression due to organ of origin and histotype are similar in magnitude and are parallel in that organ effects are similar in the two histotypes and histotype effects are similar in the two organs. In addition, ovarian and uterine endometrioid adenocarcinomas with beta-catenin defects show a common gene expression signature largely distinct from that seen in tumors lacking such defects. Our results illustrate how organ of origin, type of differentiation, and specific molecular defects all contribute to gene expression in the most common types of ovarian and uterine cancers. The findings also imply gene expression data will be of value for stratifying ovarian cancer patients for new treatment approaches.

Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.

We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

Microsatellite Instability in Endometrial Cancer: Relation to Histological Subtypes

Fifty-one endometrial cancers were analyzed with regard to whether or how microsatellite instability (MI) was associated with the development of different types of endometrial malignant neoplasms. We investigated 6 loci previously reported as informative for colorectal cancer and a group of 8 loci located on 6q. Replication error (RER+) phenotype was detected in 10 of 51 (19.6%) endometrial cancers (ECs), all but one of which showed endometrioid differentiation. On the contrary, the RER+ phenotype was not detected in serous carcinomas and malignant mixed Müllerian tumors. MI was present in both early and advanced stage ECs. No correlation was found between age, grade, stage, familial pattern, mitotic index, and the RER+ phenotype of ECs. Only 1 of 8 endometrial carcinomas showing MI was associated with mutant p53 expression, while the majority of RER+ tumors were positive for estrogen and progesterone receptors. Our findings suggest that MI plays an early role in endometrial tumorigenesis and is significantly correlated with adenocarcinomas showing endometrioid features (EAs). The frequent involvement of the telomeric region of chromosome 6 in the MI of EA is an indication that this region may be crucial in the process of EA tumorigenesis.

Varieties of Serous Surface Papillary Carcinoma of the Peritoneum in Northern Germany

From a total of 62,858 autopsy files kept over a 30-year period (1961-1990), all cases that met the following criteria were extracted: (a) main tumor masses in the peritoneum with no evidence of origin from any adjacent organ; (b) histologic features suggestive of serous ovarian carcinoma; (c) ovaries definitely recognizable as having either no tumorous involvement or tumor confined to the surface and cortex of the ovaries; and (d) in patients with a history of abdominal operations, availability of slides and reports. From 670 stages III and IV serous carcinomas of the ovary, we retrieved 57 cases (8%) of serous surface papillary carcinoma (SSPC) of the peritoneum. All SSPCs occurred in women with an age range from 47 to 84 years (median 66 years). Eight cases (14%) were grade I, 36 (63%) were grade II, and 13 (23%) were grade III. Histologically, four cases (7%) resembled malignant epithelial mesothelioma in major parts of the tumor, and in one case endometrioid differentiation of the tumor was conspicuous. Additional histochemical and immunohistochemical examinations were performed in 30 cases of SSPC. In 14 cases (47%) neutral mucosubstances were identified by periodic acid-Schiff positivity after diastase predigestion, and in 16 cases (53%) acid mucosubstances were identified by alcian blue staining. In one of these cases the alcian blue-positive substances were abolished under predigestion by testicular hyaluronidase. Tumor cells stained positive for cytokeratin (100% of the cases), B72.3 (90%), Ber-EP4 (83%), CD 15 (57%), placental alkaline phosphatase (53%), CA 125 (43%), vimentin (23%), and carcinoembryonic antigen (10%). The survival rates at 1 year for SSPC (0%) were significantly shorter (p = 0.03) in comparison with stages III and IV ovarian carcinomas (34%). Problems of definition and differential diagnosis of SSPC are discussed.

Uterine Glandular Carcinoma

This study correlated the histologic and immunohistochemical features of cervical and endometrial glandular carcinomas (adenosquamous carcinoma [ADENSQ] and ade nocarcinoma [AC] ) with clinical outcome. A series of 87 uterine glandular carcinomas (53 cervical, 33 endometrial, and 1 arising in both cervix and endometrium) were histologically classified into mullerian subtypes: 28 ADENSQ, 19 serous AC, 19 mu cinous AC, 15 endometrioid AC, and 6 clear cell AC. Utilizing both nuclear and archi tectural features, 66 glandular carcinomas were high histologic grade (3) and 21 were low histologic grade (1 or 2). Immunohistochemical studies performed on 83 of the cases showed: 33 + for monoclonal carcinoembryonic antigen (CEA-M); 38 + for polyclonal CEA (CEA-P); 26 + for placental alkaline phosphatase; 18 + for CA 125; 29 + for CA 19-9; 24 + for vimentin; 60 + for cytokeratin CAM 5.2; and 81 + for cytokeratin AE 1 : 3. The following significant correlations were identified. ADENSQ histology was associated with CEA-M staining (P < .025), and mucinous histology was associated with CA 19-9 staining (P < .025). Cervical primary site was associated with ADENSQ histology (P < .001) and staining with CEA-M (P < .025) and CEA-P (P < .05). Endometrial primary site was associated with endometrioid histology (P < .001). Forty-five patients had recurrent disease, 30 patients were disease-free for more than 1 year, and 12 patients had insufficient follow-up evaluation. Recurrent disease was associated with stage III or IV tumors (P < .001), grade 3 histology (P < .001), serous differentiation (P < .001), invasion to at least the middle third of the myometrium (P < .001) and large size of residual tumor at hysterectomy (mean 3.9 cm versus 1.3 cm, P < .005). Disease-free survival was associated with endometrioid differentiation (P < .05), strong CEA-M staining (P < .001), CEA-P staining (P < .025), and CA 19-9 staining (P < .05). Considering only stage 1 and 2 patients, grade 3 histology ( P < .025), deep myometrial invasion (P < .01), and size (P < .05) were still associated with recurrence and strong CEA-M staining (P < .025) was still associ ated with disease-free survival. However, strong CEA-M staining, deep myometrial invasion, and size of tumor after hysterectomy were all associated with histologic grade. Considering just histologic grade 3 carcinomas in stage 1 and 2 patients, absence of strong CEA-M staining, deep myometrial invasion, and size of tumor was no longer associated with recurrent disease. Histologic grade was the only independent predictor of prognosis in stage I and II patients. Int J Surg Pathol 1 (1): 13-24, 1993

Principles of medical therapy for endometriosis pain

SummaryEndometriosis essentially consists of patches of endometrioid differentiation of the pelvic mesenchyme. Endometriotic tissue is, like the endometrium itself, dependent on ovarian steroid hormones for support. Endometriosis, like endometrium, proliferates under the action of oestradiol, whereas progesterone and the progestagens put an end to epithelial mitosis, and secretory differentiation of the epithelium follows. When oestradiol, and particularly progesterone, are withdrawn, endometriotic tissue, again like endometrium, breaks down and releases locally and to some extent systemically, a range of important prostanoids and peptides that account for the symptoms we attribute to endometriosis, especially pelvic pain in the form of dysmenorrhoea, dyspareunia and tenderness on palpation. This can happen if bleeding and haemosiderin deposition takes place to produce pigmented stigmata or if, in ‘still-to-be’ pigmented endometriosis (Jansen and Russell, 1986), it does not.

Endometrioid differentiation in ovarian sex cord tumor with annular tubules accompanied by gestagenic effect

A case of ovarian sex cord tumor with annular tubules (SCTAT) without Peutz-Jeghers syndrome is presented in which portions of the neoplasm showed endometrioid differentiation. In addition, histologic examination of endometrium obtained from curettings and hysterectomy specimen revealed atrophic glands and a decidual type stroma, indicating a possible gestagenic effect of the ovarian tumor. The latter has so far been only briefly alluded to in the literature, whereas to the best of the authors' knowledge, endometrioid differentiation has not yet been reported to occur in SCTAT.