A detailed morphological and immunohistochemical comparison of primary endometrial and tubo-ovarian high-grade serous carcinomas and their corresponding omental metastases.

Increasingly, high-grade serous carcinomas (HGSCs) of fallopian tube/ovarian origin are managed initially with neoadjuvant chemotherapy (NACT) and pre-treatment diagnosis is often based upon relatively limited core biopsy and/or cytology specimens. Endometrial HGSC can also present with adnexal and peritoneal metastasis, thus mimicking a primary tubo-ovarian neoplasm, but the role of NACT in these cases is less established. Immunohistochemistry has been considered useful in this distinction but with a wide range of reported findings in the literature. In this study we have examined tumour growth patterns and the expression p16, Ki-67, WT1, PAX2, HER2, ER-α, ER-ß, PR, and BAF250a in 18 tubo-ovarian and 14 endometrial HGSCs, comparing the findings in primary and omental sites. Metastatic tubo-ovarian carcinomas demonstrated significantly more varied architectural patterns than metastatic endometrial HGSCs (median 2.5 versus 1). None of the immunohistochemical markers proved completely reliable but only endometrial HGSC were WT1 negative (7/14 metastatic tumours) or demonstrated over-expression of HER2 (2/14 cases). Micropapillary tumour elements more often showed retained PAX2 and WT1 expression, low Ki-67 labelling, and (in endometrial tumours) PR staining. Diverse architectural patterns suggest tubo-ovarian origin in a metastatic HGSC. Immunohistochemical results should be cautiously interpreted, particularly in small specimens.

Evaluation of pathology review at gynaecological oncology multidisciplinary team meetings: a 5-year prospective analysis of cases with major diagnostic discordance.

Multidisciplinary team meetings (MDTs) play an essential role in the management of patients with newly diagnosed and recurrent cancers, and often include review of pathology specimens that were initially assessed in external departments. Many studies have demonstrated a low but significant rate of diagnostic disagreement following such review but the pathological findings have seldom been detailed. We present a prospective 5-year study of all external cases reviewed at the Western Australian Gynaecological Oncology MDT focusing upon those cases with major diagnostic discordance likely to impact patient management. In total, 1275 cases were reviewed of which 132 (10.4%) were considered discordant including 48 (3.8%) with major discordance. Different interpretation of the presence and/or extent of tumour invasion accounted for a significant proportion of cases and in particular some adenocarcinoma and squamous carcinoma variants were initially reported to show only in situ or minimally invasive disease. Endometrial high-grade serous carcinoma was under-recognised and on occasion reassignment of tumour origin including metastasis to the gynaecological tract was facilitated by additional clinical information and supported by appropriate immunohistochemistry. This study supports the role of pathology review at MDTs and highlights problematic lesions that may merit a low threshold for additional opinion and ancillary studies.

Histological comparison of partial hydatidiform mole and trisomy gestation specimens.

The distinction between partial hydatidiform mole (PHM) and trisomy gestation is not always straightforward histologically and it is unclear which morphological features, alone or in combination, provide the greatest diagnostic accuracy. We performed a comparative review of 89 products of conception (POC) specimens including 54 PHMs and 35 trisomy gestations, assessing the following in each case: trophoblastic atypia, cistern formation, multifocal trophoblast proliferation, lace-like trophoblast, villous enlargement, large trophoblast inclusions, scalloped villous shape, stromal apoptosis, small round villous inclusions, and fibrillary stromal collagen. There was a significant difference in the presence of trophoblast atypia, cistern formation, multifocal trophoblast proliferation, lace-like trophoblast, large trophoblastic inclusions, small round villous inclusions, fibrillary collagen (all p<0.01), and apoptosis (p=0.028), between PHM and trisomy cases. Fibrillary collagen was more common in trisomy specimens whereas the other features were more common in PHMs. There was no significant difference in villous enlargement or scalloped villous shape between the two groups. The combination of cistern formation, multifocal trophoblast proliferation and large trophoblast inclusions correctly classified 83 (93.3%) of cases where the presence of at least two features was considered diagnostic of PHM. While cytogenetic analysis is arguably the gold standard for diagnosis, this study demonstrates that histological assessment permits accurate distinction of PHM and trisomic gestations in the great majority of cases.

Cytologic findings in stratified mucin-producing intraepithelial lesion of the cervix: A report of 34 cases.

BACKGROUND: Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon variant of in situ carcinoma of the cervix. This study aimed to identify the cytologic features of SMILE since these have not been well documented previously. METHODS: The study group comprised 34 consecutive cases of SMILE encountered at a single institution in which a corresponding Papanicolaou smear, taken up to 12 months before histologic diagnosis, was available for review. The presence of associated cervical neoplastic lesions including cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), and invasive carcinoma was recorded. The linear extent and distribution of the SMILEs was also noted. RESULTS: Most Pap smears had been reported to show possible or definite high-grade CIN although 3 cases reported the presence of a high-grade glandular abnormality. No case had a prospective cytologic diagnosis of SMILE. Histology revealed concurrent CIN and/or AIS in all cases, and 1 specimen (3%) showed invasive adenocarcinoma. Following smear review, 23 of the 31 cases that included endocervical material showed recurrent cytologic features that appeared consistent with SMILE. These included three dimensional cell clusters with nuclear stratification and crowding, mild nuclear atypia, cytoplasmic vacuoles, mitotic figures, and apoptosis. CONCLUSION: SMILE is almost always associated with additional HPV-related neoplastic lesions although only one patient (3%) had invasive carcinoma, a lower rate than recorded in other studies. Consistent cytologic features associated with SMILE were identified but these were relatively subtle. However, increased awareness of these features may permit prospective diagnosis and this could influence patient management.

Value of cytology in the intraoperative assessment of ovarian tumors: a review of 402 cases and comparison with frozen section diagnosis.

BACKGROUND: Intraoperative pathological assessment is frequently requested in patients with suspected ovarian neoplasia so that optimal surgical management can be performed. In this study the accuracy of intraoperative cytology has been assessed and the results compared with frozen section diagnosis. METHODS: The study comprised 402 ovarian tumors that were submitted for intraoperative assessment in which both cytology preparations, usually scrape smears, and conventional frozen sections were examined. Each technique was evaluated independently, although the diagnosis transmitted to the surgeon was based upon the combination of the clinical, macroscopic, histological, and cytological information. The results were compared with the final pathological diagnosis in each case and cases with discordant diagnoses were reviewed. RESULTS: There were 226 benign lesions, 35 borderline epithelial neoplasms, and 141 malignant tumors according to the final pathological diagnosis. All benign lesions were accurately categorized using both frozen section and cytology. Thirty (86%) of the borderline tumors and 137 (97%) of the malignant tumors were accurately identified on frozen section, whereas the corresponding results for cytology were 23 (66%) and 131 (93%), respectively. There were no false-positive diagnoses with either technique and the overall accuracy was 97.8%. Cytological evaluation provided better morphologic detail, permitted wider tumor sampling, and directed appropriate ancillary investigations in some cases. CONCLUSIONS: Overall, frozen section was more accurate than smear preparations in this series. However, cytology has a complementary role in the intraoperative assessment of ovarian neoplasia and provides a more specific diagnosis in some cases.

Comparison of proliferation indices in primary adult-type granulosa cell tumors of the ovary and their corresponding metastases: an analysis of 14 cases.

Adult-type granulosa cell tumors (GCTs) of the ovary are generally low-grade malignancies, but late metastases are relatively common. Limited data suggest that recurrent GCTs may exhibit altered morphology and/or biologic behavior, but few studies have directly compared primary and recurrent tumors in individual patients. Fourteen GCTs in which histologic material was available from both the primary tumor and one or more metastases were reviewed, and the mitotic index (MI) and Ki-67 labelling index (KI) were evaluated using carefully specified methodology. The findings were also correlated with the time interval to tumor recurrence. The median interval to first recurrence was 6.6 years (range: 2.2 to 12.2 yr). There were only minor differences in tumor morphology between the primary and metastatic GCTs. None of the cases exhibited high-grade (sarcomatoid) transformation. There was a wide range in MI and KI in the GCTs and no consistent correlation was seen between these indices in the paired primary and recurrent neoplasms. There was also no association between the MI and the KI and the time interval to metastasis. In conclusion, metastatic GCTs generally maintain their morphologic features even after multiple recurrences over many years. Cellular proliferation in GCT is variable, and there is no uniform alteration in proliferation indices between paired primary and metastatic lesions. Therefore, data derived from the analysis of primary GCT may not always be applicable to recurrent tumors. These findings may have implications for management including the potential response of GCT to adjuvant therapies.

Intraoperative assessment of clear cell carcinoma of the ovary.

Frozen section is a reliable technique in gynecologic pathology and is widely used to guide intraoperative management in patients presenting with ovarian masses. However, there are limited data regarding the diagnostic accuracy of frozen section in specific subtypes of ovarian neoplasia. Our impression that primary clear cell carcinoma (CCC) causes disproportionate diagnostic difficulty led us to review the intraoperative and final histopathologic reports from a consecutive series of 44 CCC that were subject to frozen-section assessment and to compare the results with a similar number of primary serous and endometrioid carcinomas. The original intraoperative slides from those CCC with discordant diagnoses were also reviewed. Review of the diagnostic reports showed that CCC was less frequently specifically identified than serous or endometrioid carcinomas on frozen section (44% cases compared with 55% and 65%, respectively), although the differences were not statistically significant. Difficulties in distinguishing primary ovarian carcinoma from tumors metastatic to the ovary occurred in a minority of cases of all histologic subtypes, but was slightly more frequent in CCC. Two CCC were misdiagnosed as borderline epithelial tumors and 1 case as a dysgerminoma. Review of the frozen-section slides from the CCC with discrepant intraoperative diagnoses showed features suggestive or indicative of the correct diagnosis in 7 (39%) of 18 cases.

Adenocarcinoma in situ of the uterine cervix: screening and diagnostic errors in Papanicolaou smears.

BACKGROUND: Little attention has been given to the reasons for failure to detect adenocarcinoma in situ (AIS) of the uterine cervix in Papanicolaou (Pap) smears. In the current study, the authors examined a series of screening or diagnostic errors in cases in which the final histologic diagnosis was either AIS or AIS combined with a high-grade squamous intraepithelial lesion (AIS + HSIL). METHODS: Smears obtained in the 3 years before histologically proven AIS or AIS + HSIL was diagnosed and within a specified 6-year period (1993-1998) were reviewed and reclassified. All were conventional Pap smears. The smears studied were those with a review diagnosis of possible or definite high-grade epithelial abnormality that initially were reported by a cytotechnologist to be negative (screening error) or that were reported by a pathologist to be negative, unsatisfactory, or indicative of a low-grade epithelial abnormality (diagnostic error). A semiquantitative, blinded assessment of the frequency of cytologic criteria for the diagnosis of AIS was made for smears with erroneous diagnoses compared with a series of smears that yielded true-positive findings. RESULTS: Sampling errors, which were defined as cases in which smears did not have sufficient evidence for a diagnosis of possible or definite AIS or HSIL on review, accounted for 35.1% and 36% of all smears from patients with a biopsy diagnosis of AIS and patients with a biopsy diagnosis of AIS + HSIL, respectively. With regard to AIS, there were 3 screening errors and 5 diagnostic errors, accounting for 10.4% of 77 smears. Minimal, poorly preserved material was evident in four smears, including three smears with only one sheet of abnormal glandular cells. In four other smears, there was a moderate amount of adequately preserved glandular material, mainly in large sheets, with varying degrees of crowding and hyperchromasia. With regard to AIS + HSIL, there were 6 screening errors and 6 diagnostic errors, accounting for 13.5% of 89 smears. In those smears, there generally was a moderate amount of abnormal material in the form of crowded groups of suboptimally preserved, hyperchromatic squamous cells. Only two of those smears yielded findings of possible abnormal glandular cells. Only 3 of 20 errors occurred in smears that were examined during the last 3 years of the study. In the semiquantitative assessment, smears with erroneous findings were shown to contain far less abnormal material than true-positive smears and to exhibit a corresponding paucity of diagnostic criteria. CONCLUSIONS: Sampling errors were the main cause of false-negative reports in cases of AIS and AIS + HSIL. The primary factors that contributed to screening or diagnostic errors in AIS were minimal, poorly preserved abnormal material and an overly conservative approach to the assessment of unusual large sheets or aggregates of glandular cells. With regard to AIS + HSIL, most laboratory errors were related to the presence of crowded groups of squamous epithelial cells. There were fewer errors in the last 3 years of the study, raising the possibility of improvement over time.