Ilias P. Nikas

Expression of EGFR, PD‐L1, and the mismatch repair proteins before and following therapy in malignant serous effusions with metastatic high‐grade serous tubo‐ovarian carcinoma

AbstractAimTo compare the immunochemical expression of EGFR, PD‐L1, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 between matched malignant effusions obtained before and following the administration of chemotherapy in patients with high‐grade serous tubo‐ovarian carcinoma (HGSC).MethodsIn the enrolled HGSCs, matched formalin‐fixed and paraffin‐embedded cell blocks (CBs) from effusions sampled before (treatment‐naïve patients) and during recurrence (following chemotherapy administration), in addition to their matched HGSC tissues obtained from the ovaries at initial diagnosis (treatment‐naïve patients), were subjected to EGFR, PD‐L1, and MMR immunochemical analysis.ResultsEGFR was more often overexpressed in effusions obtained after chemotherapy administration compared to both effusions (100% vs. 57.1%) and their matched tubo‐ovarian tumors (100% vs. 7.1%) from treatment‐naïve patients, respectively. EGFR immunochemistry was concordant in just 9.1% of the effusions sampled during recurrence and their paired ovarian samples before recurrence. Whereas all HGSC treatment‐naïve samples (ovarian lesions and effusions) were PD‐L1 negative, 3/11 (27.3%) malignant effusions obtained during recurrence showed PD‐L1 overexpression. Lastly, none of the tested HGSC samples exhibited MMR deficiency.ConclusionMeasuring biomarkers using CBs from malignant effusions may provide clinicians with significant information related to HGSC prognosis and therapy selection, especially in patients with resistance to chemotherapy.

EUS-FNA Diagnosis of a Metastatic Adult Granulosa Cell Tumor in the Stomach

AbstractGranulosa cell tumors are uncommon ovarian neoplasms, predominantly of the adult type (AGCT). In this report, we present a rare case of a patient with metastatic AGCT to the stomach diagnosed with endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA). A 61-year-old woman without a history of AGCT underwent both a vaginal and an abdominal ultrasound that showed a solid and cystic ovarian mass along with a solid mass in the gastric antral wall. Subsequently, an EUS-FNA was performed to assess the gastric lesion. Cytologic findings showed high cellularity, and the groups of neoplastic cells invaded the muscle layer of the stomach. Notably, these cells formed Call-Exner bodies, whereas some nuclei exhibited nuclear grooves. Immunohistochemistry was performed, revealing positivity for α-inhibin, calretinin, and CD56 in the neoplastic cells, whereas chromogranin, synaptophysin, CD117, and DOG1 were negative. The combination of clinical presentation, radiology, cytomorphology, and immunohistochemistry could facilitate the diagnosis of metastatic AGCT and the management of such patients.

Biomarkers expression among paired serous ovarian cancer primary lesions and their peritoneal cavity metastases in treatment‐naïve patients: A single‐center study

AbstractBackgroundHigh‐grade serous ovarian carcinoma (HGSOC), the most common histologic subtype of ovarian epithelial cancer, is associated with treatment resistance, enhanced recurrence rates, and poor prognosis. HGSOCs often metastasize to the peritoneal cavity, while fluid cytology examination could identify such metastases. This retrospective study aimed to identify potential biomarker discrepancies between paired HGSOC primary tissues and metastatic peritoneal fluid cytology samples, processed as cell blocks (CBs).MethodsTwenty‐four pairs of formalin‐fixed, paraffin‐embedded primary tissues and metastatic CBs from an equal number of treatment‐naïve patients were used, and immunohistochemistry (IHC) for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor, programmed cell death‐1 ligand 1 (PD‐L1), and CD147 was applied.Results13/24 pairs showed discordant EGFR IHC results; in all these 13 patients, EGFR was positive (≥1+ membranous staining intensity found in at least 10% of the cancer cells) in the peritoneal, yet negative in the primary tissue samples. Notably, EGFR IHC was positive in 15/24 of the metastatic, whereas in just 2/24 of the primary HGSOC samples (p < 0.001). Although most PD‐L1 results were concordant, 5/24 and 6/24 pairs exhibited discordant results when stained with the E1L3N and 22C3 clones, respectively. Lastly, CD147 overexpression was found more often in the metastatic rather than the matched primary HGSOCs stained with CD147, though the difference was not significant.ConclusionsCytology from effusions could be considered for biomarker testing when present, even when tissue from the primary cancer is also available and adequately cellular, as it could provide additional information of potential clinical significance.

Diagnostic Performance of the Newly Developed WellPrep® Liquid-Based Cytology System and Its Comparison with SurePathTM in Cervical Squamous Lesions

Introduction: WellPrep® (WP), a fully automated, one-step liquid-based cytology (LBC) platform using an all-in-one closed chamber, has recently been developed as a next-generation LBC technology. This study aimed to evaluate the diagnostic performance and cytomorphologic features of WP regarding cervical cytology and also to compare WP with the SurePathTM (SP), one of the most widely used LBC systems used worldwide. Methods: Cervicovaginal samples were taken from 212 females who enrolled in the study, and each sample was split and subsequently used for WP and SP LBC. Following the exclusion of seven cases with insufficient quality, a total of 205 cases were used for subsequent analysis. Among them, 75 (36.6%) received histologic follow-up. All cases were interpreted according to the Bethesda System, while three experienced pathologists evaluated their cytomorphologic features. Results: The diagnostic concordance rate between the two LBC technologies was 84.4% (kappa = 0.776). Furthermore, the diagnostic concordance rates between SP and histology and between WP and histology were 73.3% (kappa = 0.516) and 70.7% (kappa = 0.497), respectively. The two LBC methods showed comparable sensitivity, specificity, and area under the curve (AUC) for histologic HSIL+ (SP: sensitivity 82.8%, specificity 84.8%, and AUC 0.838; WP: sensitivity 79.3%, specificity 87.0%, and AUC 0.831). No significant difference was found regarding the sensitivity, specificity, and AUC between SP and WP (p = 0.586, p = 0.670, and p = 0.924, respectively). In terms of cytomorphologic features, WP revealed more often than SP the presence of coarse chromatin (p = 0.031) and mitoses (p = 0.008) but less commonly perinuclear clearing (p = 0.001). Conclusion: This is the first study demonstrating that WP has a comparable performance to SP. In conclusion, WP may be an alternative LBC technology for cervical cancer screening.

Challenging the concept of “risk of malignancy” in cytology

AbstractSeveral standardized systems for nongynecological cytopathology have been published following the successful implementation of The Bethesda System for Reporting Cervical Cytology. Each of these systems comprises a set of reporting categories accompanied by a risk of malignancy. However, in most cases, these risk of malignancy estimates have not been based on high‐quality evidence and often may not be consider proper “risks” (because they have been estimated based on cross‐sectional studies). This commentary discusses the problems related to the data used to generate these risks. To make nongynecological cytopathology reporting more evidence‐based, large‐scale prospective cohort studies and randomized trials, in addition to high‐quality systematic reviews and meta‐analyses, should be performed.