Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study.

Background: The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms. Methods: This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test. Results: Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = -0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001). Conclusions: The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.

Correlation between interleukin-6 expression in post-mortem core liver biopsy and degree of liver injury in patients with fatal COVID-19.

Excessive release of interleukin-6 (IL-6) during the progression of coronavirus disease 2019 (COVID-19) induces cytokine storms, resulting in multi-organ damages including liver injury, similar in nature with mechanism of viral hepatitis. Systemic IL-6 has been associated with the incidence of liver injury among COVID-19 patients; however, studies on IL-6 expression in the liver tissue are completely lacking. The aim of this study was to measure the IL-6 expression in the liver tissues and to determine its correlation with the degree of liver injury in fatal COVID-19 patients. Through this first cross-sectional study, IL-6 expression was measured through immunohistochemical staining and the degree of liver injury was identified based on level of serum alanine aminotransferase (ALT). The Spearman correlation test was used to identify the correlation between IL-6 expression and the degree of liver injury. A total of 47 deceased COVID-19 patients were included and IL-6 expression was observed in all post-mortem liver specimens, ranging from mild to strong expression. Liver injury at various degrees (mild to severe) was found in more than half (59.5%) of the cases. The Spearman correlation analysis suggested a statistically insignificant correlation between liver IL-6 expression and the degree of liver injury (r=0.152; p=0.309). In conclusion, even IL-6 expression was observed in all post-mortem liver specimens, there was an insignificant correlation between IL-6 expression in the liver tissue with the degree of liver injury among fatal COVID-19 patients, suggesting that IL-6 was not the only main factor contributing to liver damage in COVID-19 patients.

Giant Fibroepithelial Polyps of the Vulva in a Woman with Uterine Myoma and Primary Infertility: A Case Report and Literature Review.

BACKGROUND Reproductive health is closely related to long-term quality of life and maternal well-being in obstetrics. The overall incidence of fibro-epithelial polyps in the general population is about 46%, but a location on the vulva is quite rare, and is very rare when the size is more than 5 cm. CASE REPORT A 23-year-old woman reported irregular bleeding and a mass on the vulva. After anamnesis, physical examination, biopsy, and radiology imaging, the patient was diagnosed with uterine myoma, primary infertility, and a large solid and benign mass on the vulva. The mass found on the vulva was apparently unrelated to intra-abdominal organs and urogynecology. After performing an excision accompanied by a laparoscopic myomectomy, the histopathological results showed that the mass on the vulva was a 16×11×6 cm fibroepithelial polyp weighing 700 g. After 7 months of therapy, the submucosal uterine myoma recurred. Submucosal uterine myomas were found rooted into the vaginal canal, so the surgeon performed an extirpation operation. Eight months later, the patient succeeded in having a pregnancy that ended in delivery by cesarean section. CONCLUSIONS Giant fibroepithelial polyps are very rare. Management is by excision accompanied by a laparoscopic myomectomy. They affect reproductive health and require appropriate management and diagnosis.

p16INK4A Expression in Condyloma Acuminata Lesions Associated with High-Risk Human Papillomavirus Infection.

OBJECTIVE: The objective of this study was to discover the possible correlation between p16INK4A expression and the LR/HR-HPV infection in condyloma acuminate (CA) lesions. MATERIALS AND METHOD: This cross-sectional study was conducted during January-December 2017 on 33 CA patients. The expression of p16INK4A was detected by immunohistochemistry (IHC) staining. The positive interpretation was carried out by scoring which score 0 was negative, score 1 was sporadic, score 2 was focal, and score 3 was diffuses. The HPV genotypes were identified by reverse line blot, and 40 genotypes of HPV detected, including HR-HPV (HPVs 16, 18, 26, 31, 33,35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68a, 68b, 69, 73, and 82) and LR-HPV (HPVs 6, 11, 40, 42, 43, 44, 54, 55, 61, 62, 64, 70, 71, 72, 81, 83, 84, 87, 89, and 90). RESULTS: The expression of p16INK4A was significantly correlated with HR-HPV infection. Patients infected with HR-HPV had 0.644 times higher possibility to express p16INK4A gene compared to those infected with LR-HPV. LR-HPV genotypes detected in CA patients were HPVs 6, 11, 42, 61, 54, 81, 87, 89, and 90 and HR-HPV genotypes were HPVs 18, 26, 45, 51, 52, 67, 68B, 69, and 82. LR-HPV was found in 19/33 of patients and HR-HPV was in 14/33 of patients. The expression of p16INK4A in CA lesions was diffuse in15.2% of patients, was focal in 24.2% of patients , was sporadic in 39.4% of patients were, and was negative in 21.2% of patients . In LR-HPV group, there was no diffuse expression, focal expression was observed in 15.8%, sporadic in 47.4%, and negative in 36.8%, while in HR-HPV group, p16INK4A expression was detected in all lesions , in a way that its expression was diffuse in 35.7%, focal in 35.7%, and sporadic in 28.6%. CONCLUSION: IHC is a routine method in histopathological diagnosis, therefore the detection of p16INK4A expression by IHC can be used as a biomarker for HR-HPV infection diagnosis.

GENOTYPING OF HUMAN PAPPILOMAVIRUS IN CERVICAL PRECANCEROUS LESION AND SQUAMOUS CELL CARCINOMA AT DR. SOETOMO HOSPITAL, SURABAYA, INDONESIA.

BACKGROUND: Cervical cancer caused by human papilloma virus (HPV), is the second most common cancer for women. This cancer is distributed worldwide, with ~80% of cases are found in the developing countries. In Indonesia, data of HPV genotypes are still limited and do not represent all regions of the country. Thus, here we report genotyping of HPV samples collected from the Dr. Soetomo Hospital Surabaya Indonesia patients, in 2013. MATERIALS AND METHOD: A cross sectional study was performed using 68 paraffin blocks of low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) cervix. RESULT: This study showed that HPV genotypes found in LSIL samples are HPV 16, 18, 6/33 or 68/72. Furthermore, those in HSIL are HPV 16, 18, 52, 59, 67, 6/18, 6/45, 16/67, 26/61, or 52/67, while in SCC are HPV 16, 18, 45, 52, 56, 16/18 or 16/45. Single-genotype infection, i.e. by HPV 16, 18, 45, 52, 56, 59, or 67, was observed in 86.77% (59/68) of samples, whereas multiple-genotype infections, i.e. by HPV 6/18, 6/33, 6/45, 16/18, 16/45, 16/67, 26/61, 52/67, or 68/72, was found in 13.23% (9/68) of the samples. CONCLUTIONS: The mostly HPV genotype identified in this study is HPV 16 (62.68%), then followed by HPV 18 (20.9%), HPV 45 (5.97%), 52 (5.97%), and 67 (4.48%). HPV 16 and 18 have used as vaccine, and HPV 45 has cross reaction with HPV 18, then HPV 52 and 67 should be considered as the second-generation HPV vaccines.