HER-2 overexpression in female genital tract clear cell carcinomas: Evaluation of different scoring guidelines, clinicopathological features and prognostic impact.

BACKGROUND: Clear cell carcinoma (CCC) is a rare high-grade adenocarcinoma associated with poor response to platinum-based chemotherapy agents in the female genital tract. Human epidermal growth factor receptor 2 (HER2) overexpression is routinely used as a biomarker for targeted therapy in breast and gastric carcinomas, but its role in CCC remains unclear. METHODS: In this study, HER2 overexpression was evaluated by immunohistochemistry (IHC) using College of American Pathologists (CAP) HER2 scoring guidelines for breast and endometrial serous carcinoma (ESC) on tissue microarray blocks. In equivocal and positive cases, fluorescence in situ hybridization (FISH) was performed. IHC score 3, and all amplified cases on FISH test were considered positive. RESULTS: Thirty-six cases of ovarian (OCCC), 36 endometrial (ECCC), and 2 cervical CCC were included. According to ESC and breast scoring guidelines, 20 % and 15.1 % of ECCC and 14.7 % and 6 % of OCCC were HER2 positive, respectively. Both cases of cervical CCC were negative. Scoring based on breast carcinoma guideline showed higher concordance (100 %) with gene amplification results, in comparison with ESC guideline (82.7 %). On multivariate survival analysis, HER2 positive ECCC and OCCC (based on ESC scoring methods) had significantly lower overall and disease-free survivals (OS, DFS) (P < 0.05). CONCLUSION: HER2 immunoscoring based on ESC guideline can yield a higher sensitivity with relevant clinical and prognostic features in OCCC and ECCC. HER2 can be considered a potential biomarker for targeted therapy and future clinical trials.

Pathogenic role of Twist-1 protein in hydatidiform molar pregnancies and investigation of its potential diagnostic utility in complete moles.

BACKGROUND: Complete and partial moles (PM) are the most common gestational trophoblastic diseases. Due to some overlapping morphological findings, ancillary studies may be necessary. METHODS: In this cross-sectional study, 47 cases of complete mole (CM) and 40 cases of PM were randomly selected based on histopathological criteria. Only those cases that were agreed upon by two expert gynecological pathologists and confirmed by the P57 IHC study were included. The expression level of the Twist-1 marker in villi stromal cells, as well as syncytiotrophoblasts, was evaluated quantitatively (percentage of positive cells), qualitatively (staining intensity) and as a total comprehensive score. RESULTS: Expression of Twist-1 is higher and more intense in villous stromal cells of CMs (p < 0.001). Moderate to strong staining intensity in more than 50% of villous stromal cells, can differentiate CM and PM with 89.5% sensitivity and 75% specificity. In syncytiotrophoblasts of CM, Twist-1 expression was significantly lower than PM (p < 0.001). Negative or weak staining intensity in less than 10% of syncytiotrophoblasts, can distinguish CM and PM with 82.9% sensitivity and 60% specificity. CONCLUSION: A higher expression of Twist-1 in villous stromal cells of hydatidiform moles is a sensitive and specific marker for the diagnosis of CMs. An elevated expression of this marker in villous stromal cells suggests another pathogenic mechanism for more aggressiveness of CMs in addition to the characteristics of trophoblast cells. The opposite result was obtained in the expression of Twist-1 in the syncytiotrophoblasts, compatible with defects in the process of formation of these supportive cells in CMs.

Immunohistochemical expression of PD-L1 and its correlation with microsatellite status in endometrial and ovarian clear cell carcinomas: a cross-sectional study.

BACKGROUND: Clear cell carcinoma is an uncommon histologic subtype of ovarian and endometrial carcinoma with poor response to Platinium-based chemotherapy agents at high stages. Blockage of Programmed cell Death Ligand-1 (PD-L1), can be used in targeted immunotherapy. This study investigated Mismatch Repair Deficiency (MMR-D) status, PD-L1 expression, and the correlation between PD-L1 expression and microsatellite instability (MSI) status in ovarian and endometrial clear cell carcinomas. METHODS: Ovarian clear cell carcinoma (OCCC) (n = 28) and endometrial clear cell carcinoma (ECCC) (n = 28) samples were evaluated for PD-L1 (in tumoral and peri-tumoral inflammatory cells), MSH6 and PMS2 expression by immunohistochemistry (IHC) study. PD-L1 expression > 1% in tumor cells and > 5% in peritumoral inflammatory cells were considered positive. RESULTS: The prevalence of PD-L1 expression was higher in ECCC (20/28, 71.43%) compared to OCCC tumor cells (16/28, 57.15%) (p > 0.05), while expression in peritumoral inflammatory cells was significantly higher in ECCC (25/28, 89.29%) compared to OCCC (11/28, 39.28%) (p < 0.05). MMR-D was observed in 5 cases, four OCCCs and one ECCC, among which, four (80%) showed PD-L1 expression in peritumoral inflammatory and tumor cells. The only OCCC case with extensive PD-L1 expression in tumor cells (> 50%) exhibited MSH6/MSH2 loss. No significant correlation was noted between PD-L1 expression and the pathologic stage or survival. CONCLUSION: PD-L1 expression was significantly associated with clear cell morphology, especially in the endometrium, independent of MMR protein status.

Post-pubertal ovarian yolk sac tumor with unusual follicular growth pattern, simulating struma ovarii.

Yolk sac tumors (YST), formerly known as endodermal sinus tumors, are uncommon ovarian neoplasms. They are most common in the second and third decades of life and are rare in women older than 39 years of age. YST exhibit various histologic patterns. Microfollicular pattern resembling thyroid tissue has not been reported. We introduce here a case of yolk sac tumor in a 39 y/o female, presented with pelvic masses and high level of serum Alpha-fetoprotein (Alpha Fetoprotein) (> 1000 IU/ml). The patient underwent left salpingo-oophorectomy. On microscopic study, morphologic findings demonstrated a neoplasm composed of follicular structures with eosinophilic intraluminal content, resembling struma ovarii on low-power field. On Immunohistochemistry study, the tumor cells were positive for Alpha-fetoprotein and Glypican-3. Epithelial Membrane Antigen (EMA), Thyroglobin (TG), Thyroid transcription Factor-1 (TTF1) and sex-cord stromal markers were negative. This case introduces a new histomorphologic pattern of yolk sac tumor in a middle-aged woman. It is important to know that yolk sac tumor can exhibit various histological appearances. Regarding patient's clinical and laboratory findings, this differential diagnosis should be kept in mind for proper diagnosis of similar cases.

Solitary metastases of lower extremity myxoid liposarcoma to breast: A case report and review of literature.

Solitary breast metastases from myxoid liposarcoma are extremely rare. Resection with negative margins seems as an effective treatment leading to improved survival.

Comparison of Patient-collected and Lab Technician-collected Nasopharyngeal and Oropharyngeal Swabs for Detection of COVID-19 by RT-PCR.

BACKGROUND & OBJECTIVE: A simple approach to prevent close contact in healthcare settings during the COVID-19 outbreak is to train patients to collect their own nasopharyngeal and oropharyngeal swabs and deliver them to medical laboratories to have them processed. The aim of our study was to compare lab technician- with patient- collected oropharyngeal and nasopharyngeal samples for detection of the coronavirus disease 2019 (COVID 19) using rapid real-time polymerase chain reaction (rRT-PCR). METHODS: Fifty adult patients with flu-like symptoms and radiologic findings compatible with atypical pneumonia who were admitted to the infectious diseases ward of Imam Khomeini Hospital Complex, Tehran, Iran, with a clinical diagnosis of COVID-19 from February 28 to April 27 of 2020 were randomly selected and entered in our study. Two sets of naso- and oropharyngeal swabs were collected, one set by a lab technician and the other by the patients, and the COVID-19 rRT-PCR test was performed. RESULTS: Of 50 selected cases, in seven patients all collected naso- and oropharyngeal swabs tested positive, and in 22 patients all samples tested negative for COVID-19 in rRT-PCR. Discrepancies between rRT-PCR results of lab technician- and patient-collected swabs were observed in 12 nasopharyngeal and 13 oropharyngeal specimens. Positive lab technician-collected and negative patient-collected samples were observed in 10 and 5 nasopharyngeal and oropharyngeal specimens, respectively. Negative lab technician-collected and positive patient-collected samples were observed in two and seven nasopharyngeal and oropharyngeal specimens, respectively. The overall percentage of agreement among both nasopharyngeal and oropharyngeal swabs taken by a lab technician and patients was 76% with a kappa value of 0.49 (P=0.001). CONCLUSION: Based on our findings, lab technician-collected naso- and oropharyngeal swabs cannot be replaced by patient-collected ones with regard to COVID-19 rRT-PCR.

Potential Role of Exogenous Melatonin Supplement in Delirium Prevention in Critically Ill Patients: A Double-Blind Randomized Pilot Study.

Critically ill patients often suffer from disturbance of sleep-wake cycle and consequently delirium development, in intensive care units (ICU). In this study, we aimed to evaluate the effect of exogenous melatonin on delirium development and its related adverse sequelae in the subgroup of medical and surgical ICU patients. We performed a double-blind placebo-controlled randomized pilot study in adult patients admitted to the ICU. Recruited patients according to the considered inclusion criteria were randomized into treatment or placebo groups. Melatonin or placebo was administered in the first 24 h after admission, for 5 consecutive days. Incidence of delirium within 8 days of admission was reported as primary outcome in the different subgroups, and other pertinent clinical characteristics were evaluated as secondary outcomes. Out of the total of 172 patients assigned for the 2 study groups, 70 patients in placebo group and also 67 in melatonin group completed the study. We observed no therapeutic effect of melatonin on delirium prevention in ICU patients (percent of delirium in melatonin versus placebo group were 4.5% and 1.4% respectively). However, our findings indicated that melatonin might be more useful in preventing delirium development in medical ICU patients as compared to the surgical ICU patients. There were no intergroup differences in secondary outcomes with the follow-up ending on May 2016. Our findings suggested melatonin might be a potential option for prevention of delirium in medical ICU patients.