Application of the International System for Reporting Serous Fluid Cytopathology (TIS): A retrospective institutional study.

BACKGROUND: Cytology of serous effusions is an important diagnostic tool for the diagnosis of cancer, staging, and prognosis of the patient. Herein, we retrospectively applied the International System for Reporting Serous Fluid Cytopathology (TIS) and provided the corresponding risks of malignancy (ROMs). METHODS: Pleural, pericardial, and peritoneal effusion samples were retrieved from the archives of our department and reclassified according to the TIS. The ROM for each category was calculated based on available surgical follow-up. RESULTS: A total of 3790 effusions were studied. Pleural samples (1292) were reclassified as follows: 27 (2.1%) as non-diagnostic (ND), 1014 (78.5%) as negative for malignancy (NFM), 86 (6.6%) as atypia of undetermined significance (AUS), 29 (2.3%) as suspicious of malignancy (SFM), and 136 (10.5%) as malignant (M). Pericardial samples (241) were reclassified as follows: 4 (1.6%) as ND, 173 (71.8%) as NFM, 10 (4.1%) as AUS, 7 (3%) as SFM, and 47 (19.5%), as M. Peritoneal cases (2257) were re-categorised as follows: 31 (1.4%) as ND, 1897 (84%) as NFM, 39 (1.7%) as AUS, 53 (2.4%) as SFM, and 237 (10.5%) as M. The respective ROM values for each category were 18.5%, 15%, 45.3%, 93%, and 100% in pleural effusions; 25%, 13.2%, 35%, 100%, and 100% in pericardial effusions; and 19.3%, 10.4%, 43.5%, 100%, and 100% in peritoneal effusions. CONCLUSIONS: Pleural, pericardial, and peritoneal cytology show high specificity and moderate sensitivity in the evaluation of serous effusions. The ROMs reported in our study were mostly concordant with those published according to the TIS.

The value of cytology in distinguishing malignant mesothelioma: An institutional experience of 210 cases reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC).

OBJECTIVE: Malignant mesothelioma (MM) is usually diagnosed by histological examination of tissue samples; however, effusion cytology offers an opportunity to identify a strong possibility for mesothelioma diagnosis at an early stage. We conducted a retrospective analysis of cytological specimens from a large series of histologically proven MM diagnosed over 19 years. The cases were reviewed and reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC). METHODS: A total of 450 cases were identified. Cytological analysis was present in 210 patients (164 pleural and 46 peritoneal effusions). All cases were reviewed and reclassified according to the proposed ISRSFC scheme. A comparison among the cytomorphological features was made throughout the different diagnostic categories. RESULTS: The 210 cases were histologically diagnosed as follows: 192 (91.4%) cases had an epithelioid type and 18 (8.6%) had a sarcomatoid subtype of MM. The cytological cases were reclassified as follows: 2 (0.9%) as non-diagnostic (ND), 81 (38.6%) as negative for malignancy (NFM), 4 (1.9%) as atypia of undetermined significance (AUS), 11 (5.2%) as suspicious for malignancy (SFM), 112 (53.4%) as malignant (MAL). Sarcomatoid cells in the MAL category were characterised cytomorphologically by more pronounced discohesion. In comparison with the epithelioid subtype, the tumour cells appeared solitary with moderate or marked nuclear pleomorphism, and irregular chromatin. CONCLUSIONS: It is important to recognise the cytological characteristics of this aggressive entity to suggest an early and precise possible diagnosis. Morphological features, coupled with clinico-radiological data may help the clinicians in adequately managing the patients.

Diagnostic impact of safety protocols for processing peritoneal washing specimens during the global pandemic of coronavirus disease 2019: A comparative study from 195 cytological samples.

BACKGROUND: The global pandemic of the coronavirus disease 2019 represents a major concern for health services worldwide, and has also induced major changes in cytopathology practice. AIM: We aimed to verify the diagnostic performance of cytological evaluation under a new safety protocol during the pandemic compared to the standard pre-pandemic procedure. We also aimed to assess how cytological diagnoses and sampling were impacted during the pandemic period compared to the pandemic-free period in 2019. MATERIALS AND METHODS: Cytological samples of peritoneal washings taken during the first 10 months of the pandemic emergency in Italy (March 11, 2020 to January 11, 2021) were compared to samples from the preceding 10-month time frame (May 11, 2019 to March 10, 2020). RESULTS: One hundred ninety-five specimens were analysed in the present study. We observed no noticeable differences in cytological diagnoses during the pandemic period compared to the pre-pandemic period. The case numbers by diagnostic category for the pre-pandemic vs pandemic periods, respectively, were as follows: non-diagnostic, 0 vs 0 cases; negative for malignancy, 86 vs 52 cases; atypia of uncertain significance, 7 vs 1 cases; suspicious for malignancy, 0 vs 2 cases; malignant, 42 vs 4 cases. CONCLUSION: While a consistent reduction in the number of cytological examinations has been observed during the COVID-19 period, our institutional safety protocol for processing cytological samples did not affect the diagnostic reliability of peritoneal washing cytology.

Prognostic predictors in recurrent adult granulosa cell tumors of the ovary: a systematic review and meta-analysis.

BACKGROUND: Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT. METHODS: Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value < 0.05 was considered significant. RESULTS: Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively. CONCLUSIONS: In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.

DOG1 as an Immunohistochemical Marker of Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis.

DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43-0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis.

Comparison between cytospin and liquid-based cytology in cerebrospinal fluid diagnosis of neoplastic diseases: A single institution experience.

OBJECTIVE: The current tools available for detecting malignant neoplasms in the cerebrospinal fluid (CSF) are neurological examination, followed by neuroimaging, cytology and molecular techniques. To highlight the role of cytology the diagnosis of metastatic tumours in CSF samples, we present our experience using cytospin and ThinPrep liquid-based cytology. METHODS: A retrospective analysis was conducted using the pathological records of 8181 cytological specimens of CSF, which were diagnosed over a 17-year period. Between 2000 and 2014, a total of 6994 CSF samples were processed using cytospin method and 1187 specimens were examined using ThinPrep method in the period between 2015 and 2017. RESULTS: The most frequent metastatic neoplasm of the first period was non-Hodgkin lymphoma; in the second period the commonest malignancy found was brain tumour (glioblastoma and medulloblastoma). The samples processed by cytospin revealed cytolysis and haemorrhage, while the cases processed by ThinPrep had a clear background. Ten false-positive cases belonging to the suspicious category were processed by cytospin, while there was only one false positive case in the group processed by ThinPrep. The positive predictive value was 95% in cytospin and 100% in Thin Prep with comparable sensitivity, specificity, diagnostic accuracy and negative predictive values. CONCLUSIONS: CSF cytology is a reliable technique for identifying malignancy in CSF. ThinPrep technology can be applied with good results in terms of clear background, cell enrichment, better nuclear details and high cellularity per slide.

The immunocytochemical expression of VE-1 (BRAF V600E-related) antibody identifies the aggressive variants of papillary thyroid carcinoma on liquid-based cytology.

BACKGROUND: The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in cytology and cell block samples is rarely performed, and its diagnostic value in cytology has not been well established. In this study, we sought to determine if VE1 is suitable for fine needle aspiration (FNA) and cell block methods. METHODS: A total of 86 patients who had BRAF V600E mutations were investigated with molecular and immunocytochemical (ICC) analysis in 45 FNA and 41 cell blocks. In total, 83 (96.5%) patients underwent surgical treatment. Assessment of BRAF V600E mutation status was performed in 72 (83.7%) cases. RESULTS: Among the 72 cases analysed, 54 cases agreed (ICC+/BRAF+ or ICC-/BRAF-), seven cases were false positive (ICC+/BRAF-) and 11 cases were false negative (ICC-/BRAF+). False negative cases were not detected in the cell block method. The statistical analysis showed that sensitivity and specificity of ICC for detecting the BRAF V600E mutation were 61% and 77% in FNA samples and 100% and 73% in cell block. CONCLUSION: The use of antibody VE-1 is a reliable method and a negative result of VE1 immunostaining might help to save time and money, restricting the molecular test to antibody-positive cases only. The identification of the aggressive variants of papillary carcinoma might be enabled by the expression of the antibody in neoplastic cells with tall cell features.

The Role of Plasma Cells as a Marker of Chronic Endometritis: A Systematic Review and Meta-Analysis.

Chronic endometritis (CE) is the persistent inflammation of the endometrial lining associated with infertility and various forms of reproductive failures. The diagnosis of CE is based on the histological evidence of stromal plasma cells; however, standardized methods to assess plasma cells are still lacking. In the present paper, we aimed to determine the most appropriate plasma cell threshold to diagnose CE based on pregnancy outcomes. Three electronic databases were searched from their inception to February 2022 for all studies comparing pregnancy outcomes between patients with CE and patients without CE. The relative risk (RR) of pregnancy, miscarriage, and/or live birth rates were calculated and pooled based on the plasma cell threshold adopted. A p-value < 0.05 was considered significant. Nine studies adopting different thresholds (1 to 50 plasma cells/10 HPF) were included. In the meta-analysis, we only found a significant association between miscarriage rate and a plasma cell count ≥ 5/10 HPF (RR = 2.4; p = 0.007). Among studies not suitable for meta-analysis, CE showed an association with worsened pregnancy only when high thresholds (10 and 50/10 HPF) were adopted. In conclusion, our study suggests that the presence of plasma cells at low levels (<5/10 HPF) may not predict worsened pregnancy outcomes. Based on these findings, a threshold of ≥5 plasma cells/10 HPF may be more appropriate to diagnose CE.

Prognostic Value of Chemotherapy Response Score (CRS) Assessed on the Adnexa in Ovarian High-Grade Serous Carcinoma: A Systematic Review and Meta-Analysis.

Background: chemotherapy response score (CRS) is widely used to assess the response of ovarian high-grade serous carcinoma (HGSC) to chemotherapy and is based on pathological examination of omental specimens. We aimed to assess the prognostic value of CRS assessed on the uterine adnexa. Methods: a systematic review and meta-analysis were performed by searching three electronic databases from 2015 inception to September 2021. We included all studies reporting either hazard ratio (HR) with 95% confidence interval (CI) for progression-free survival (PFS) or primary PFS data, for both adnexal and omental CRS in HGSC. HRs with 95% CI were extracted and pooled by using a significant p-value < 0.05. Statistical heterogeneity was assessed by using Higgins' I2. Results: six studies with 691 HGSC patients were included. Adnexal CRS3 vs. CRS1-2 significantly stratified PFS, with a HR of 0.572 (0.447−0.733; p < 0.001). Omental CRS3 vs. CRS1-2 significantly stratified PFS with a similar HR (HR = 0.542; 95% CI 0.444−0.662; p < 0.001). Statistical heterogeneity was 0% in both analyses. Conclusions: adnexal CRS significantly stratifies PFS in HGSC and might be used when omental CRS is not assessable.

Prognostic role of perineural invasion in vulvar squamous cell carcinoma: A systematic review and meta-analysis.

The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently available in the literature. In the present study, we conducted a systematic review and metanalysis of literature data in order to determine if PNI could be an independent prognostic predictor of patient's survival in VSCC. Four electronic databases (PubMed, ISI Web of Science, Scopus and Google Scholar) were searched from their inception to December 2021 for all studies assessing the prognostic value of PNI in VSCC. Multivariate hazard ratios (HRs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were pooled. Six studies with 1048 patients were included. PNI was significantly associated with decreased OS (HR = 2.687; p < 0.001), DSS (HR = 2.375; p = 0.014) and PFS (HR = 1.757; p = 0.001), with no statistical heterogeneity among studies and no significant risk of bias across studies. The present meta-analysis highlights that PNI is independently associated with unfavorable prognosis in patients with VSCC. Therefore, PNI should be included in the pathological report of VSCC and considered in combination with other risk factors as a possible criteria for prognostic assessment adjuvant treatment planning inclusion.

Pericardial metastasis from alveolar rhabdomyosarcoma: A case report.

Alveolar rhabdomyosarcoma (ARMS) commonly occurring in children and adolescents, is a rare and aggressive soft tissue malignancy demonstrating rapid growth and dissemination. Although their histopathologic and immunohistochemical findings are well known, cytomorphological features on serous effusions have not been well documented. A case of metastatic rhabdomyosarcoma diagnosed on cytological examination of the pericardial fluid cytology and discuss the diagnostic difficulties that were encountered in this case has been presented.

An Emerging Anti-p16 Antibody-BC42 Clone as an Alternative to the Current E6H4 for Use in the Female Genital Tract Pathological Diagnosis: Our Experience and a Review on p16ink4a Functional Significance, Role in Daily-Practice Diagnosis, Prognostic Potential, and Technical Pitfalls.

BACKGROUND: To date, useful diagnostic applications of p16 IHC have been documented in gynecological pathology both for HPV-related and non-HPV-related lesions. In the present article, we reported our experience with the novel anti-p16 INK4a antibody (clone BC42), whose expression was tested across all different gynecologic neoplasms; we also compared it to the traditional E6H4 clone. Moreover, we discussed and explored all the diagnostic applications of p16 IHC in gynecologic pathology. METHODS: Consultation cases covering a 5-year period (2016-2020) regarding gynecological neoplastic and non-neoplastic lesions in which immunohistochemistry for p16, clone E6H4 was originally performed, were retrospectively retrieved from the files of our institution. Immunohistochemical staining for p16ink4a (BC42) [Biocare Medical group-Paceco USA; Bioptica Milan] and p16ink4a (E6H4) [Ventana Medical Systems-Arizona USA; Roche] was performed by using the Ventana automated immunostainer (Ventana Medical Systems, Tucson, AZ, USA). The immunostaining pattern was defined as negative, focal/patchy, or diffuse. RESULTS: A total of 196 cases, represented by 36 high-grade SIL/CIN3 of the uterine cervix, 30 cervical adenocarcinomas, 22 cervical squamous cell carcinoma, 70 endometrial carcinomas, 25 high grade serous ovarian carcinomas, 6 uterine adenomatoid tumors, and 10 uterine leiomyosarcomas were included in this study. Results showed concordant staining quality of both clones on all tested neoplastic tissues. CONCLUSIONS: The novel anti-p16 antibody (BC42 clone) appeared as an alternative to the current E6H4 for use in gynecological neoplasms, offering similar levels of positivity and equally reliable staining results.

The combination cytology/epichek test in non muscle invasive bladder carcinoma follow-up: Effective tool or useless expence?

OBJECTIVE: To identify in which cases after cytological diagnosis, the Bladder EpiCheck test could represent an effective tool in non-muscle invasive bladder carcinoma or an useless expence. MATERIALS AND METHODS: 375 patients diagnosed with non-muscle invasive bladder cancer, 269 with high grade urothelial carcinoma and 106 with carcinoma in situ, were treated and followed for 1 year. The treatment was an intravesical instillation of Bacillus Calmette-Guerin in 305 patients and Mitomycin-C in 70 patients. During the follow-up patients were evaluated by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. Bladder EpiCheck test was performed together with cytology in all cases. RESULTS: Analyzing Bladder Epicheck results for each category defined by the Paris System for Reporting Urinary Cytology, we found that the Episcore >60 correlates with histological diagnosis of high grade urothelial carcinoma (HGUC) in atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma (P = 0.0002 Odds Ratio 0.05926 95% Confidence Interval from 0.01127 to 0.3116 and P = 0.0009 Odds Ratio 0.03155 95% Confidence Interval from 0.001683 to 0.5914, Fisher's exact test, respectively), while in Negative for high grade urothelial carcinoma and HGUC patients Episcore is not helpful to identify cases with histological diagnosis of HGUC (P = 0.101 and P = 0.58 Fisher's exact test, respectively). Considering an Episcore ≥ 90 in the HGUC cytological group, this seems not to be correlated with a histological diagnosis of HGUC (P = 0.090 Fisher's exact test). CONCLUSIONS: Cytology and Bladder EpiCheck test in combination may have the potential to reduce cystoscopies in the follow-up of non-muscle invasive bladder cancer only for cytological diagnoses of atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma . Moreover, in patients with a cytological diagnosis of Negative for high grade urothelial carcinoma or HGUC, cytology alone seems to be safe and cost-effective.

Pleural metastasis from auricular melanoma: A brief report.

Primary auricular melanoma is rarely reported. Approximately, it accounts for 1% to 4% of all cutaneous melanoma. Early literature suggested that melanoma of the ear is more aggressive than other melanomas, with a propensity for spreading to both regional lymph nodes and distant sites. Here, we present a case of cytological pleural metastasis from auricular melanoma in a 43-year-old woman. Immunohistochemical staining showed that the tumors cells were positive for S-100 protein and Melan-A. The mutation of the v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E was demonstrated on Sanger sequencing. To our knowledge, this is the first report describing the cytomorphology of metastatic auricular melanoma in pleural effusion.

Cytological features of micropapillary and plasmacytoid variants of urothelial carcinoma.

BACKGROUND: Micropapillary and plasmacytoid variants of urothelial carcinoma (UC) exhibit very aggressive clinical behavior. To date, only a small number of cytology cases have been reported in either of these variants. Herein, we report 15 cases of UC with combined micropapillary and plasmacytoid features based on urine cytology. METHODS: We performed a retrospective analysis of all patients with carcinoma of bladder with predominant plasmacytoid and micropapillary histology who had been seen from 2005 to 2017. A total of 15 cases (six cases of plasmacytoid variant and nine cases of micropapillary variant of bladder cancer) with urine specimen were evaluated. The cytomorphological features were compared between two histological variants. RESULTS: Fifteen urine cytology cases with the diagnosis of high-grade UC were investigated. The ratio man to women was 5:1 with a median age of 79 years (range: 72-90 years). Single-cell pattern, flat sheets, three-dimensional clusters, micropapillae, nuclear grade, cytoplasmic vacuoles, and necrosis, were evaluated in urine samples of micropapillary variant. The cytological features of plasmacytoid are characterized by large, discohesive, isolated tumor cells that have abundant, thick cytoplasm, and eccentrically located, hyperchromatic nuclei with coarse chromatin and inconspicuous nucleoli. CONCLUSION: It is important to recognize the cytological characteristics of these uncommon but aggressive entities to determine a precise diagnosis. Attention to morphological features, together with clinical history and appropriate immunohistochemical studies may be useful to urologist in pre-operative planning and may lead to a more aggressive surgical approach.

Description of a new biosafe procedure for cytological specimens from patients with COVID-19 processed by liquid-based preparations.

BACKGROUND: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents the causative agent of a potentially fatal disease. The spread of the infection and the severe clinical disease have led to the widespread adoption of social distancing measures. Special attention and efforts to protect or reduce transmission have been applied at all social levels, including health care operators. Hence, this reports focuses on the description of a new protocol for the safe management of cytological samples processed by liquid-based cytology (LBC) with an evaluation of the changes in terms of morphology and immunoreactivity. METHODS: From March 11 to April 25, 2020, 414 cytological cases suspicious for SARS-CoV-2 were processed with a new virus-inactivating method suggested by Hologic, Inc, for all LBC specimens. RESULTS: The samples showed an increased amount of fibrin in the background. A slight decrease in cellular size was also observed in comparison with the standard method of preparation. Nonetheless, the nuclear details of the neoplastic cells were well identified, and the immunoreactivity of the majority of those cells was maintained. The cell blocks did not show significant differences in morphology, immunoreactivity, or nucleic acid stability. CONCLUSIONS: Despite some minor changes in the morphology of the cells, the results of this study highlight that the adoption of the new protocol for the biosafety of LBC-processed samples in pathology laboratories is important for minimizing the risk for personnel, trainees, and cytopathologists without impairing the diagnostic efficacy of the technique.

Diagnostic and Prognostic Role of WT1 Immunohistochemical Expression in Uterine Carcinoma: A Systematic Review and Meta-Analysis across All Endometrial Carcinoma Histotypes.

Background: The diagnostic role of Wilms' tumor 1 (WT1) is well known in gynaeco-pathological setting, since it is considered a specific marker of serous histotype and adnexal origin. Moreover, its oncogenic role has been recently highlighted in many cancers and it has also been regarded as a promising target antigen for cancer immunotherapy. However, the relationship between its expression and prognostic role in uterine cancer remains unclear. We analyzed the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma by completing a search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the PICOS (Participants, Intervention, Comparison, Outcomes, Study Design) model through PubMed, Scopus and Web of Science databases to identify studies that fit our search criteria. The objective of the current meta-analysis was to investigate the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma. Materials and Methods: A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to April 2020. Studies were considered eligible if they evaluated the WT1 expression in uterine carcinoma. Results: In total, 35 articles were identified that used uterine carcinoma criteria and provided data for 1616 patients. The overall rate of WT1 expression in uterine carcinoma was 25%. The subgroup analysis of uterine cancer types revealed that WT1 was expressed differently among different histotypes (endometrioid, clear cell, serous carcinoma and carcinosarcoma). Discussion and Conclusions: The WT1 immunohistochemical expression is not limited to serous histotype and/or ovarian origin. In fact, a significant proportion of endometrial adenocarcinomas can also show WT1 immunoreactivity. Moreover, our study suggests that WT1 may be a potential marker to predict the prognosis of patients with uterine cancer, but more studies are needed to confirm its role in clinical practice.

Hormonal Environment and HER2 Status in Extra-Mammary Paget's Disease (eMPD): A Systematic Literature Review and Meta-Analysis with Clinical Considerations.

BACKGROUND: Extra-mammary Paget's disease (EMPD) is a rare neoplasm of epithelial origin, whose precise incidence is not clear. Starting from what is already known, we performed a systematic review and meta-analysis to investigate in male and female patients the immunohistochemical expression of biological markers that could serve as potential prognostic/therapeutic factors, including only human epidermal growth factor receptor 2 (HER2/neu), Estrogen Receptor (ER), Progesterone Receptor (PR), and Androgen Receptor (AR). METHODS: A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to June 2020. RESULTS: A total of 27 studies with 713 patients assessed the role of HER2/neu, AR, ER, and PR expression in male and female with EMPD. The overall rate of HER2/neu expression was 30%, the expression's rate for ER and AR was 13% and 40%, respectively, and the overall rate for PR was 8%. The subgroup analysis revealed that there is a different expression of molecular markers between male and female patients. CONCLUSIONS: This study revealed that AR status and HER2/neu overexpression/amplification have been shown as two fundamental pathogenetic pathways in both female and male patients affected by EMPD.

Performance of a dual-component molecular assay in cytologically indeterminate thyroid nodules.

PURPOSE: Deciding whether patients with a cytologically indeterminate thyroid nodule should be referred for surgery or for active surveillance is an important challenge for clinicians. The aim of this study was to evaluate the performance of a novel dual-component molecular assay as an ancillary molecular method for resolving indeterminate thyroid nodule cytology. METHODS: We selected 156 thyroid nodules from those that had undergone fine-needle aspiration processed by liquid-based cytology and surgical resection between June 2016 and December 2017. The sample set included 63 nodules cytologically classified as indeterminate, and 93 other nodules randomly selected from those with non-diagnostic, benign, suspicious, or malignant cytology. Nucleic acids from each nodule were subjected to next-generation sequencing analysis for mutation detection in 23 genes and to digital polymerase chain reaction (PCR) evaluation for miR-146b-5p expression levels. RESULTS: Used alone, mutation analysis in the indeterminate subset (cancer prevalence: 22.5%) displayed high sensitivity (89%) and NPV (96%). In contrast, the miR-146b-5p assay offered high specificity (93%) and PPV (93%). Combined use of both analyses improved panel performance by eliminating false-negative results. CONCLUSIONS: These preliminary data suggest that a dual-component molecular test can increase the diagnostic accuracy of thyroid cytology alone by reducing the number of nodules that will be classified as indeterminate and increasing those that can be reliably classified as benign. If these findings are confirmed, this test can be considered for use in clinical practice and is expected to reduce diagnostic surgery and health care costs, and to improve patient quality of life.

Cytologic Diagnosis of Oncocytic Neoplasms of the Thyroid Gland: The Importance of the Clinical Scenario.

It is a diagnostic challenge to differentiate benign and malignant thyroid neoplasms made up of Hürthle (or oncocytic) cells on cytologic material. They are large, polygonal cells with marked eosinophilic, granular cytoplasm reflective of overly abundant mitochondria. These cells commonly occur in nodular goiters and dominant adenomatous or hyperplastic nodules though they may also be the predominant component of neoplastic lesions. There are significant controversies concerning the optimal management of patients with oncocytic cell carcinoma. This review provides an overview of the most significant studies addressing the distinction between benign and malignant Hürthle cell lesions on cytology and histology.