Primary Ovarian Mucinous Tumors Research Articles

Immunohistochemical Expression of SATB2 and PAX8 in Differentiating Primary from Metastatic Ovarian Mucinous Neoplasms

Abstract Background Accurate stratification of an ovarian mucinous neoplasm as primary or secondary is always challenging. The ovary is a frequent metastatic site for primary gastrointestinal malignancies that shows overlapping histomorphological and immunohistochemical features with primary ovarian mucinous carcinomas. This study assessed the value of immunohistochemical expression of SATB2 and PAX8 in this diagnostic dilemma as single and combined panels. Methods Immunohistochemical staining for SATB2 and PAX8 was performed on 80 cases of mucinous ovarian neoplasms subdivided into 53 primary ovarian mucinous neoplasms (POMNs) and 27 secondary ovarian mucinous tumors of gastrointestinal (GI) origin (12 metastatic adenocarcinomas of colonic origin, 7 metastatic adenocarcinomas of appendiceal origin and 8 metastatic adenocarcinomas of gastric origin). Expression was correlated with different clinicopathologic parameters. Results PAX8 positive immunostaining was detected in 38/53 cases (71.69%) of POMNs with null positivity in the sub-group of secondary ovarian mucinous tumors of GI origin (0/27). On the other hand, SATB2 positive immunohistochemical staining was detected in 16/27 cases (59.26%) of the secondary ovarian mucinous tumors of GI origin. None of the studied POMNs showed any positive immunostaining for SATB2 (0/53). Conclusion A Profile of SATB2- /PAX8+ and SATB2+ / PAX8- can be used to differentiate POMCs from secondary ovarian mucinous tumors of GI origin, respectively, with a 100% specificity. This warrants the use of SATB2 and PAX8 in clinical practice for helping in the dilemma of diagnosing an ovarian mucinous neoplasm with higher precision. Moreover, PAX8 expression is associated with some clinico-pathologic parameters providing the basis for further studies for the possible usage of PAX8 as prognostic marker.

Immunohistochemical expression of SATB2 and PAX8 in differentiating primary from metastatic ovarian mucinous neoplasms.

Accurate stratification of an ovarian mucinous neoplasm as primary or secondary is always challenging as they show overlapping histomorphological and immunohistochemical features. Immunohistochemical staining for SATB2 and PAX8 was performed on 80 cases of mucinous ovarian neoplasms subdivided into 53 primary [25 primary ovarian mucinous carcinomas (POMCs) and 28 mucinous borderline tumors (MBTs)] and 27 secondary (12 of colonic origin, 7 of appendiceal origin, and 8 of gastric origin). Expression was correlated with different clinicopathologic parameters. PAX8-positive immunostaining was detected in 38 out of 53 cases (71.69%) of primary ovarian mucinous neoplasms (POMNs) with null positivity in the secondary ovarian mucinous tumors (0/27). SATB2-positive expression was detected in 16 out of 27 cases (59.26%) of the secondary ovarian mucinous tumors. None of the studied POMNs showed any positive immunostaining for SATB2 (0/53). A profile of SATB2-/PAX8+ and SATB2+/PAX8- can be used to differentiate POMNCs from secondary ovarian mucinous tumors of GI origin, respectively, with 100% specificity. PAX8 expression is associated with some clinicopathologic parameters providing the basis for the possible usage of PAX8 as prognostic marker.

The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors

BackgroundPrimary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. MethodsSeventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. ResultsMutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). Conclusionp53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

Mucin-producing tumors of the ovary——preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors

ObjectiveTo investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs).MethodsThis retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance.Results35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%.ConclusionsPatients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor.

Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA. Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed. Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up. Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.

Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance

In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53 mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC. We assessed p53 expression for the three recognised patterns of aberrant staining in ovarian carcinoma [overexpression ('all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tumours (strong nuclear p53 staining in ≥12 consecutive tumour cells) and correlated the results with next generation sequencing (NGS) in all qualitatively sufficient cases (92/123). Aberrant p53 expression was present in 25/75 (33.3%) MBT, 23/33 (69.7%) MC (75% of MC with expansile invasion and 61.5% with infiltrative invasion), and 10/15 (66.7%) tumours equivocal between MBT and MC. Regarding the 92 tumours with paired IHC and mutation results, 86 showed concordant results and six cases were discordant. Three discordant MBT cases showed aberrant expression but were TP53 wild-type on sequencing. Three cases had normal p53 expression but contained a TP53 mutation. Overall, IHC predicted the TP53 mutation status with high sensitivity (94.1%) and specificity (92.7%). The accuracy of IHC was 93.5% with a positive predictive value of 94.1% and a negative predictive value of 92.7%. When comparing MC cases with wild-type TP53 versus those with TP53 mutation, there were no significant differences concerning disease-free survival, local recurrence-free survival, or metastases-free survival (p>0.05). In the MBT subgroup, there were no events for survival analyses. In conclusion, using an independent large sample set of ovarian mucinous tumours, the results of our study confirm that the suggested refined cut-off of strong nuclear p53 staining in ≥12 consecutive tumour cells reflect high accuracy, sensitivity and specificity for an underlying TP53 mutation but the TP53 mutation status has no prognostic significance in either MC or MBT.

Distinguishing primary mucinous ovarian tumors from metastases of non-gynecologic mucinous cancers: Can we leverage next-generation sequencing?

5582 Background: Primary mucinous ovarian cancers (MOC) are histopathologically challenging to differentiate from ovarian metastases of non-gynecologic origin, with this distinction being critical for appropriate management and prognosis. We compared the somatic gene variant landscape of MOC to that of non-gynecologic mucinous tumors. Methods: Data were extracted from the American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 13.0 via cBioPortal. This publicly available, multi-institutional database provides next generation sequencing (NGS) genomic profiles of tumors. We queried this database for samples of MOC, mucinous colorectal cancer (MCRC), mucinous appendiceal cancer (MAC), mucinous breast cancer (MBC) and gastric type mucinous cancer (GMC). Frequencies of somatic gene variants including mutations, copy number alterations and structural variants were compared using Chi-squared or Fischer’s exact tests, using the Benjamini-Hochberg method to control for multiple hypothesis testing with q-values reported. Results: A total of 883 tumors were included for analysis: 358 MCRC, 268 MAC, 157 MOC, 59 MBC and 41 GMC samples. Compared to MAC, MOC samples had higher variant frequencies of CDKN2A (33.3% vs 0.4%, q<0.001), CDKN2B (24.0% vs 0.0%, q<0.001), TP53 (64.3% vs 23.5%, q<0.001), ERBB2 (14.3% vs 1.1%, q<0.001) and CDK12 (13.2% vs 0.0%, q<0.001), whereas GNAS variants were more common in MAC (45.5% vs 5.7%, q<0.001). Compared to MCRC, MOC samples had higher variant frequencies of CDKN2A (33.3% vs 2.3%, q<0.001), CDKN2B (24.0% vs 3.7%, q<0.001), TP53 (64.3% vs 42.9%, q<0.001), KRAS (69.4% vs 51.1%, q<0.001) and ERBB2 (14.3% vs 5.3%, q<0.001), whereas MCRC had higher variant frequencies of 57 genes, with the largest differentials among APC (48.8% vs 2.6%, q<0.001), SMAD4 (25.2% vs 5.8%, q<0.001) and TCF7L2 (19.0% vs 0.0%, q<0.001). Samples of MOC had significantly higher rates of KRAS variants compared to GMC (69.4% vs 31.7%, q<0.001) and lower rates of STK11 variants (1.9% vs 22.0%, q<0.001). Compared to MBC, MOC samples had higher variant rates of CDKN2A (33.3% vs 3.4%, q<0.001), TP53 (64.3% vs 10.2%, q<0.001) and KRAS (69.4% vs 0.0%, q<0.001), whereas MBC samples had higher variant frequencies of 11 genes, with the largest differentials among GATA3 (32.1% vs 0.8%, q<0.001), FGF3 (30.4% vs 2.4%, q<0.05) and CCND1 (28.1% vs 1.6%, q<0.001). Conclusions: NGS demonstrates that MOCs carry a distinct genetic signature compared to mucinous tumors of non-gynecologic origin, most commonly with significantly higher variant frequencies of CDKN2A, CDKN2B and lower variant frequencies of GNAS, APC, STK11 and GATA3. This provides rationale for prospective studies evaluating genetic signatures as an adjunct to histopathology in the diagnosis of primary MOC.

Claudin18.2 as a potential therapeutic target for primary ovarian mucinous carcinomas and metastatic ovarian mucinous carcinomas from upper gastrointestinal primary tumours

BackgroundThe vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC).MethodsImmunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases.ResultsAmong 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively.ConclusionClaudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories

Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (κ = 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.

Misdiagnosed appendiceal mucinous neoplasms and primary ovarian mucinous tumors present with different pre- and intraoperative characteristics.

ObjectiveTo identify the differences between the pre- and intraoperative characteristics in misdiagnosed appendiceal mucinous neoplasms (AMNs) and those in primary ovarian mucinous tumors (POMTs) and to establish an effective model for differentiating AMNs from pelvic mucinous tumors.MethodsThis study enrolled 70 AMN patients who were misdiagnosed with ovarian tumors and 140 POMT patients who were treated from November 1998 to April 2021 at Peking Union Medical College Hospital. The clinical features and operative findings of the two groups of patients were collected and compared.ResultsThere were significant differences in age and menopausal status, but no difference in the patients’ clinical manifestations between the two groups. The preoperative serum CA125 and CA199 levels were not different between the two groups. The CEA level (31.04 ± 42.7 vs. 7.11 ± 24.2 ng/ml) was higher in the misdiagnosed AMN group (P < 0.001). The AMNs were smaller than the POMTs that were measured preoperatively by ultrasonography (US) (P<0.05) and measured at surgery (P<0.05). Furthermore, the patients with AMNs more commonly had multinodularity and ascites noted on the preoperative US (P<0.001), on CT (P<0.001), and at surgery (P< 0.001). The two groups also differed in the presence of bilateral disease, in the appendiceal appearance and peritoneal dissemination. Subsequently, a prediction model was developed using multivariable logistic regression, which was evaluated through internal validation.ConclusionsThe suspicion of a nongenital organs originated tumor especially origing from appendiceal should be considered in a patient who is older, tumor size less than 12cm, multinodular, presence of mucinous ascites, and elevated serum CEA levels. Bilateral ovarian involvement, peritoneal dissemination, and an abnormal appendiceal appearance found during surgery were the typical features associated with AMNs.

Mucinous ovarian cancer: A rare entity with variable clinical presentation and management (148)

Mucinous ovarian cancer: A rare entity with variable clinical presentation and management (148)

The cytokeratin 17 expression in primary ovarian tumors has diagnostic but not prognostic significance.

We assessed the value of cytokeratin 17 (CK17) expression for the differential diagnosis between primary ovarian mucinous tumors and metastases from the gastrointestinal tract (GIT) and the significance of CK17 expression in a broad spectrum of primary ovarian tumors with respect to their prognosis. The sample set consisted of 554 primary ovarian tumors and 255 GIT tumors. In the primary ovarian tumors, a higher CK17 expression (in > 10% of tumors cells) was present only in 0-11.4% of all tumors (including mucinous tumors, micropapillary serous borderline tumors, clear cell, endometrioid, and high-grade serous carcinomas). The only exception was low-grade serous carcinoma, where higher CK17 expression was present in 24% of cases. Concerning GIT tumors, the higher levels of CK 17 expression (in > 10% of tumor cells) were observed in the upper GIT tumors (68.5% of pancreatic ductal adenocarcinoma, 61.6% of gallbladder adenocarcinoma, and 46% of gastric adenocarcinoma), which differs substantially not only from most of the primary ovarian tumors, but also from colorectal carcinoma (3.7%; p < 0.001). The results of our study suggest that expression of CK17 can potentially be used as an adjunct marker in differential diagnosis between primary ovarian mucinous tumors and metastases from the upper GIT, but not from colorectal carcinoma. However, in GIT tumors, CK17 can be used in the differential diagnosis between adenocarcinomas of the upper and lower GIT. Statistical analysis did not reveal strong association of CK17 expression with clinicopathological variables or patient outcomes in any primary ovarian tumors.

Synchronous Mucinous Carcinomas of Ovary and Appendix: A Case Report With Diagnostic Pitfalls and Review of Corresponding Literature

Background Diagnosis of the primary ovarian mucinous neoplasms occasionally poses a challenge because historically most tumors diagnosed as primary ovarian were documented as metastases from gastrointestinal and pancreatobiliary tracts. This challenge is attributed to the overlapping histologic features, the gray zone, between primary and metastatic mucinous neoplasms in the ovary. While presentation of both primary and metastatic mucinous tumors manifests by the presence of an ovarian mass, determination of the site of origin is clinically significant, because most treatment guidelines are based on the tissue of origin. Case Presentation We present an unusual case of mucinous adenocarcinoma of the ovary and the appendix with diagnostic pitfalls and challenges of immunohistochemical profile. Conclusion Utilization of molecular analysis in challenging cases of ovarian neoplasms helps to narrow down the gray zone and lessens the misdiagnosis of primary ovarian mucinous tumors.

Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach.

The morphological spectrum of primary ovarian mucinous and seromucinous tumours is broad, and presents an array of diagnostic challenges, many unique to these tumour types. This reflects the heterogeneous nature of these lesions, their varied histogenesis and evolving classification systems over recent decades, with further modification to the seromucinous category incorporated in the recently published 5th edition of the World Health Organisation (WHO) Classification of female genital tumours. In this review we provide an update on the classification of these neoplasms and discuss their histogenesis and diverse morphology, focusing on areas which are diagnostically problematic. We also cover tumour grading, differential diagnosis, immunohistochemistry, the recent elucidation of the molecular underpinnings of ovarian mucinous neoplasia and discuss the gross and intra-operative handling of these tumours. A number of diagnostic issues remain unresolved, highlighting the importance of further research on this front, as well as a multidisciplinary approach in the care of patients with ovarian mucinous and seromucinous neoplasia.

Immunohistochemical Loss of DPC4 in Tumors With Mucinous Differentiation Arising in or Involving the Gynecologic Tract.

DPC4 immunohistochemistry (IHC) is usually part of the work-up of mucinous neoplasms in the ovary where the distinction between an ovarian primary and metastatic pancreaticobiliary adenocarcinoma (PanACa) must be made. Although DPC4 IHC is lost in about 55% (46%-61%) of PanACas and typically retained in most primary ovarian mucinous neoplasms, no study has evaluated the expression of this marker in a large cohort of neoplasms arising in or involving gynecologic (GYN) organs. In this study, we retrospectively analyzed the expression of DPC4 IHC in a total of 251 tumors and lesions related to the GYN tract in which DPC4 IHC stain was performed during the initial pathology evaluation. Of these, 138 were primary GYN tumors and lesions, 31 were metastatic GYN tumors involving non-GYN sites, and 83 were metastatic non-GYN tumors involving the GYN tract. We identified 27 cases with loss of DPC4 IHC expression of which 20 cases met the inclusion criteria (i.e. clinical information was available to determine the site of tumor origin). We observed that loss of DPC4 nuclear expression was most commonly seen in tumors of endocervical origin (n=7), of which 5 were gastric-type cervical adenocarcinomas (GCxACa) and 2 were usual-type cervical adenocarcinomas, either primary or metastatic. This was followed by tumors of the pancreaticobiliary tract (n=5), ovary (n=2), and appendix (n=1). In addition, 1 gastric-type vaginal adenocarcinoma (GVaACa) also showed loss of DPC4. Our findings indicate that in female patients with mucinous neoplasms involving the ovary or other sites, with loss of DPC4 by IHC, and negative pancreaticobiliary imaging, the possibility of an occult GCx/GVaACa, and rarely an ovarian primary must be considered.

Clinicopathological Characteristics of Gastric-type Endocervical Adenocarcinoma Misdiagnosed as an Endometrial, Ovarian or Extragenital Malignancy, or Mistyped as Usual-type Endocervical Adenocarcinoma.

The diagnosis of gastric-type endocervical adenocarcinoma (GEA) is challenging because its differential diagnosis includes not only gynecological tumors, but also extragenital tumors. We reviewed the electronic medical records and all available slides to investigate the clinicopathological characteristics of eight misdiagnosed GEA cases. Three tumors were initially misdiagnosed as endometrial carcinoma. They displayed extensive endomyometrial involvement and complex glandular architecture, but no severe nuclear pleomorphism. Another three tumors were misclassified as usual-type endocervical adenocarcinoma because of mucin-poor, pseudoendometrioid glands, apical mitotic figures, and karyorrhectic debris. The two remaining tumors presenting as adnexal masses mimicked primary ovarian mucinous tumor and metastatic cholangiocarcinoma. The varying pathological characteristics of GEA reflect the variability in clinical manifestations and its diagnostic difficulties. It is challenging to make an accurate diagnosis based solely on histological features. When suspecting GEA, clinicians should consider more comprehensively the clinicopathological context, along with immunostaining results.

Gross mucinous multinodular appearance aids in the identification of ovarian metastases in low-grade appendiceal mucinous neoplasms during intraoperative consultation

Ovarian metastases of low-grade appendiceal mucinous neoplasms (LAMNs) show grossly abundant nodular mucous cells, with a gross mucinous multinodular appearance and a histological resemblance to primary ovarian mucinous tumors (POMTs). This study aimed to elucidate the utility of gross features including the gross mucinous multinodular appearance and available clinical information at the time of intraoperative consultation, in distinguishing the ovarian metastases of LAMNs from POMTs or the ovarian metastases of colorectal cancer (CRC). In total, 776 patients with primary ovarian tumor and 68 patients with ovarian metastases underwent intraoperative consultation during 1998–2018. Of the total cases, 4 ovarian metastases of LAMNs, 19 ovarian metastases of CRC, and 50 POMTs (36 borderline tumors and 14 carcinomas) were identified. The gross features including the gross mucinous multinodular appearance were analyzed based on the gross photographs obtained before formalin fixation and the available clinical information collected during intraoperative consultation. The analysis indicated that the ovarian metastases of LAMNs significantly presented with gross mucinous multinodular appearance (4/4 vs. 0/50, P < 0.0001), extraovarian disease (4/4 vs. 2/50, P < 0.0001), ovarian surface involvement (3/4 vs. 2/50, P = 0.0016), and abnormal appendix (4/4 vs. 0/50, P < 0.0001) as compared to POMT. Moreover, the gross mucinous multinodular appearance was a distinguishable feature between the ovarian metastases of LAMNs and ovarian metastases of CRC (4/4 vs. 0/19, P = 0.0001). Based on these results, we proposed an algorithm to diagnose ovarian tumors using the gross mucinous multinodular appearance. Thus, recognizing unique gross features including the gross mucinous multinodular appearance would be useful for both pathologists and surgeons to accurately diagnose ovarian metastases of LAMNs during intraoperative consultation.

Diagnostic Discordance in Intraoperative Frozen Section Diagnosis of Ovarian Tumors: A Literature Review and Analysis of 871 Cases Treated at a Japanese Cancer Center

This study examined the accuracy and pitfalls associated with frozen section diagnosis of primary ovarian tumors and ovarian metastases based on the 2014 World Health Organization classification (WHO) criteria and proposed improvements from a pathologist's perspective. We microscopically reviewed 871 cases of primary ovarian tumor (N = 802) and ovarian metastasis (N = 69) and compared the results of frozen sections with the final diagnosis. Malignant potential concordance (benign, borderline, or malignant) and specific discordant diagnosis rates were analyzed. Finally, we conducted a unique literature review of specific diagnostic errors in the frozen section diagnosis of primary ovarian tumors. Of 802 primary ovarian tumors, 50 (6.2%) cases showed discordant diagnoses in which mucinous carcinoma (40.5%), low-grade serous carcinoma (LGSC; 31.3%), and mucinous borderline tumor (18.4%) were frequently misinterpreted. Of 69 ovarian metastases, all 4 cases of low-grade appendiceal mucinous neoplasm (LAMN) were misdiagnosed as primary ovarian mucinous tumor. A literature review revealed that mucinous/serous borderline tumor or carcinoma accounted for approximately 70% of 217 reported discordant diagnoses. In the present study, the concordance rate of malignant potential of the tumor was comparable to that previously reported. Even in the 2014 WHO classification, primary ovarian mucinous borderline tumor/carcinoma and LGSC still comprised the majority of discordant cases. Grossing methods that reduce sampling error are required. LAMN was frequently misinterpreted as a benign or borderline ovarian mucinous tumor. To prevent this error, a differential algorithm integrating clinical information and gross findings should be developed.

Clinicopathological Characteristics of Pseudomyxoma Peritonei Originated from Ovaries.

ObjectiveThis study aims to demonstrate clinicopathological characteristics and immunohistopathological phenotypes of pseudomyxoma peritonei (PMP) originated from ovaries.MethodsThe primary origin of PMP was explored by reviewing H&E sections retrospectively and performing a series of immunohistochemical staining on CK7, CK20, CDX2, CEA, Villin, SATB2, CA125, ER, PR, and MUC.ResultsAmong 310 PMP patients, a few originated from extra-appendix, whereas eight cases were of ovarian origin (2.6%), including three teratoma-associated ovarian mucinous tumors and five primary ovarian mucinous tumors with spontaneous or iatrogenic rupture, respectively. Most peritoneal metastases were acellular mucin or low-grade mucinous carcinoma peritonei (6/8, 75%), while the rest were high-grade mucinous carcinoma peritonei (2/8, 25%). Tumors were positive for CK20, CDX2, CEA, and Villin. SATB2 was specifically diffuse positive in teratoma-associated ovarian mucinous tumors, and negative in primary ovarian mucinous tumors. Differential expression of MUC was observed in these tumors.ConclusionPMP of ovarian origin is extremely rare. The precise diagnosis requires serial sections of the appendix or suspicious tissue to exclude appendiceal mucinous neoplasms, as well as comprehensive analysis of clinical features, surgical findings, histopathological characteristics, and immunohistochemistry on specific biomarkers.

A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7−/CK20+/CDX2+/PAX8−. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1–50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.