Are We Where We Want to Be in Undergraduate Pathology Education?

OBJECTIVE: This review which aims to examine the recent and current status of pathology education in medical schools, and covers the publications related to undergraduate pathology education published between 2010 January and June 2023. MATERIAL AND METHOD: A search was performed through PubMed, Google Scholar, Semantic Scholar, and Ulakbim search engines for the Science Citation Index, Science Citation Index Expanded, Emerging Sources Citation Index, Directory of Open Access Journals, Scopus, PubMed as well as TR Dizin indexed articles. The findings are categorized into two periods as 2010 January - 2020 April (pre-COVID-19 pandemic) and May 2020 - 2023 June. A total of 24 reviews/editorials/letters to the editor and 63 research articles in the pre-pandemic period and 11 reviews/ editorials/ letters to the editor and 35 research articles between 2020 May and 2023 June are included in the analysis. RESULTS: Currently, medical education generally depends on core education programs with defined learning objectives and outcomes. Moreover, problem-based, case-based, and team-based interactive learning are being used along with traditional didactic courses. Additionally, digital/ web-based/remote education methods have gained prominence after the COVID-19 pandemic. The virtual or augmented reality and 3D drawing applications are offered as a solution for the autopsy and macroscopy courses. A scarce number of publications are found on measuring and evaluating the effectiveness of learning. CONCLUSION: Artificial intelligence in pathology education is a topic that looks likely to become important in the near future. National and international comprehensive standardization is a necessity. A joint effort and collective intelligence are needed to achieve the desired goals in undergraduate pathology education.

Is it possible that we can increase the lymph node number in cases with rectum tumor receiving neoadjuvant therapy?

Background: Though the recommended sampled lymph node number in colorectal carcinomas is at least 12, due to shrinkage after preoperative neoadjuvant chemoradiotherapy (NCRT), it can be difficult to attain that number. Aim: Our aim is to increase the lymph node number by applying alcohol fixation on the formalin-fixed resection materials of the patients that received or not received neoadjuvant therapy and to evaluate the changes in staging due to obtained lymph nodes. Settings and Design: Non-randomized controlled trial. Materials and Methods: Lymph node dissection was performed in the resection materials with rectum tumor which were formalin- and afterwards, alcohol-fixed. The number of lymph nodes obtained by both of the methods and status of metastasis were evaluated statistically. Results: Of the total 76 rectal tumors, 57 had and 19 had not received NCRT. The number of lymph node was adequate in 89.5% cases with no NCRT and in 63.2% cases with NCRT. While no change was observed after the alcohol fixation in the cases fulfilling adequacy criterion among those with no NCRT (p = 1.000), the adequacy rate increased from 63.2% to 87.7% in those with NCRT (p < 0.001). Although statistically insignificant, there was a change in pN stage in eight cases. In three of them, the stage varied from pN0 to pN1c, and in five cases, from pN1a to pN1b. Conclusion: Using solutions as alcohol during fixation might facilitate the identification of metastatic lymph nodes, might change the stage of the disease and therefore, might affect the patient-based therapy.

Mitotic Activity in Gastrointestinal Stromal Tumors: Can we use Phosphohistone H3 Immunohistochemistry Instead of Hematoxylin and Eosin for Mitotic Count?

Objectives: In gastrointestinal stromal tumors (GIST), malignancy potential is determined by the prognostic disease risk stratification based on mitosis, tumor size, and location. Phosphohistone H3 (PHH3) is an immunohistochemical marker showing mitotic activity in cells. In this study, we aimed to evaluate mitosis in GIST with PHH3, compare the results with hematoxylin and eosin (HE) stained slides, and examine its relationship with other prognostic data. Methods: Clinicopathological findings and survival were determined in GIST cases diagnosed between 2006 and 2017. The prognostic risk score was calculated according HE- and PHH3-based mitosis. The cases were classified as Group I: HE + and PHH3 + and Group II: HE + and PHH3-. They were also grouped as those diagnosed before and after 2012 and the staining results of HE and PHH3 were re-analyzed. Results: Ninety-eight cases were included in the study. Mitosis was detected with both HE and PHH3 in 63.3% of the cases (62/98 cases) (Group I) while in 36.7% of cases, it was detected with HE but not with PHH3 (Group II). In only two cases, the risk score changed with PHH3 (very low → intermedier grade). The ratio of HE + and PHH3 + cases in 2012 and after was significantly higher than HE + and PHH3 - cases. A statistically significant relation was found between HE- and PHH3-based risk scores (p<0.05). There was a significant difference between HE-based risk score groups in terms of survival (p<0.05), while no difference was observed between the PHH3-based risk score groups (p>0.05). Conclusion: In GIST cases, PHH3 can be used to determine mitosis in more recent blocks, taking into account the technical conditions of the laboratory, but it does not seem to be superior to mitosis detected by HE. Research should continue on new survival determinants for GIST.

Correlation of REG1A, Claudin 7 and Ki67 expressions with tumor recurrence and prognostic factors in superficial urothelial urinary bladder carcinomas.

Aim: Superficial urothelial urinary bladder tumors are neoplasms that frequently recur and have a potential for invasion and metastasis. REG gene family is composed of various acute phase reactants, lectins, antiapoptotic factors, and growth factors that are effective on pancreatic island cells, neural cells, and epithelial cells. REG1A and REG1B are two forms of the human REG1 gene. It is reported that they are expressed in several cancers and are correlated with the prognosis of the patient. Claudins are integral transmembrane proteins that interconnect cells. However, their role in human tumorigenesis is extremely controversial. The aim of this study is to evaluate the relationship of REG1A, claudin 7 protein expressions, and Ki67 proliferation index in superficial urothelial urinary bladder tumors with well-known parameters of prognosis and tumor recurrence, and also to clarify whether these parameters are independent prognostic factors or not. Materials and Methods: A hundred and eleven patients diagnosed with superficial urothelial carcinoma between 2011 and 2016 years in our hospital and followed up in our urology clinic were included in this study. The slides prepared from paraffin blocks were immunohistochemically stained with REG1A, claudin 7, and Ki67 antibodies. Results: REG1A showed positive staining in 37 (33%) and negative staining in 74 (67%) of urothelial tumors. Claudin 7 was positive in 24 (22%) and negative in 87 (78%) cases. REG1A expression showed a positive correlation with tumor stage and tumor recurrence; a high Ki67 proliferation index was positively correlated with tumor stage and grade. The loss of claudin 7 expression was related to tumor recurrence. Besides, tumors with REG1A expression and claudin 7 loss had a shorter survival independent of recurrence. Conclusion: In urothelial tumors, REG1A expression and loss of claudin 7 might be significant markers of prognosis that predict tumor recurrence.

Clinicopathological Evaluation of 15 Ectopic Adrenal Tissues.

BACKGROUND: Ectopic adrenal tissue is a rare condition associated with embryological development defects seen in many different areas in the abdomen and pelvis. Here, we aimed to discuss the clinicopathological features of ectopic adrenal tissues diagnosed in our clinic, in light of the literature. METHODS: We included cases of ectopic adrenal tissues incidentally detected in the specimens from patients undergoing operation for various diagnoses during 2012- March 2020. The cases were examined according to gender, age, location and accompanying pathological diagnoses. During this period, 15 cases of ectopic adrenal tissues (6 paratubal, 3 paraovarian, 2 paratesticular, 1 spermatic cord, 1 paraaortic, 1 liver capsule, 1 omentum) were detected accompanied by two endometrial carcinomas, two serous cystadenomas, one seminoma, one mixed germ cell tumor, one bilateral ovarian serous carcinoma and hepatic high-grade colon adenocarcinoma metastasis. RESULTS: In this report, the fifth ectopic adrenal tissue accompanying a malignant testicular tumor, the fifth and sixth ectopic adrenal tissues occurring with ovarian serous cystadenoma, the first case observed with serous cystadenocarcinoma and the first case detected with hepatic adenocarcinoma metastasis are presented. Our cases are mostly women and adult men. CONCLUSION: Ectopic adrenal tissues can lead to hormonal problems and also to adrenal cortex and medulla neoplasms. Microscopically, they may be confused with clear cell gynecological and germ cell tumors. If the ectopic focus is misdiagnosed as an implant, a benign entity may be incorrectly reported as malignant. Also, it is important to prevent mis-staging in malignancies. For precise diagnosis, an immunopanel such as inhibin, melan A, and calretinin can be performed.

Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) Immunohistochemistry in Pheochromocytoma, Head and Neck Paraganglioma, Thoraco-Abdomino-Pelvic Paragangliomas: Is It a Good Idea to Use in Routine Work?

BACKGROUND: In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with immunohistochemistry; compare with Pheochromacytoma of the Adrenal Gland Scaled Score (PASS) classification and analyse the differences between pheochromocytoma (Pheo), head-neck paragangliomas (HNPGL) and thoraco-abdominal-pelvic paraganglioma (TAPPGL) sub-groups. METHODS: A total 114 PPGL cases (73 HNPGL, 15 TAPPGL and 27 Pheo belonging to 112 cases) are included. Immunohistochemically, SDHB and Ki-67 are investigated and malignancy risks are determined by PASS classification. Results are assessed statistically with chi-square test and p <0,01 is considered significant. RESULTS: SDHB mutations are observed in 20 of 114 (17.54 %) PPGL cases, 3 (11,12%) of which is Pheo, 12 (16,44) is HNPGL, and 5 (35,71%) is TAPPGL (P <0,02). While 15/82 (18,29%) cases with SDHB mutations do not have a malignancy potential according to PASS classification, 5/32 (15,63%) cases has (p=0,73). TAPPGL, HNPGL and Pheo sub-groups have a significant difference between SDHB expression (p <0,02), malignancy potential according to PASS classification (p <0,0001) and Ki-67 proliferation index (p <0,0001). CONCLUSION: To identify patients for molecular pathological examination, routine application of SDHB immunohistochemistry to PPGL tumors are suggested especially in HNPGLs.

Endobronchial ultrasound-guided transbronchial fine needle aspiration: Determinants of adequacy.

BACKGROUND: This study aims to evaluate the factors influencing the adequacy of endobronchial ultrasound-guided transbronchial fine needle aspiration specimens. METHODS: A retrospective analysis of 1,700 endobronchial ultrasound-guided transbronchial fine needle aspiration samples obtained from 822 patients (500 males, 322 females; mean age 56±13 years; range 16 to 83 years) was performed between March 2011 and March 2014 at our center. Variables potentially associated with sampling adequacy, such as all cytological materials and procedure notes (lymph node and/or lesion size, localization, needle pass number, and slide number) were examined. RESULTS: The overall specimen adequacy was 79.8%. The specimen adequacy was associated with needle pass number (p≤0.001). Adequacy rate was 66.9% for one needle pass and 85.8% for three needle passes. According to the sampling regions, adequacy rates showed a difference [69.2%-85.8%; (p≤0.005)]. In the multivariate logistic regression analysis of subcarinal (7) lymph node station, patient age (odds ratio, 0.983; 95% confidence interval, 0.966-1.000; p=0.049) and number of slides (odds ratio, 1.240; 95% confidence interval, 1.062-1.448; p=0.006) were independent determining factors of specimen adequacy. While independent determinants of specimen adequacy for the right paratracheal (4R) region were lymph node size (odds ratio, 1.486; 95% confidence interval, 0.973-2.268; p=0.067) and number of slides (odds ratio, 1.418; 95% confidence interval, 1.146-1.756; p=0.001), they were lymph node size (odds ratio, 1.594; 95% confidence interval, 0.960-2.645; p=0.071) and number of needle passes (odds ratio, 2.277; 95% confidence interval, 1.360-3.811; p=0.002) for the right interlobar (11R) region. Independent determinant of specimen adequacy for the left paratracheal (4L) lymph node station was the number of needle passes (odds ratio, 1.656; 95% confidence interval, 0.955-2.869; p=0.072). CONCLUSION: During endobronchial ultrasound-guided transbronchial fine needle aspirations, particularly when rapid on site evaluation cannot be applied, consideration of factors affecting adequacy according to lymph node localizations may increase the chance for obtaining materials with suitable quality for cytologic evaluation.

Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma.

In many cancers, mast cell density (MCD) in the tumor microenvironment is associated with tumor progression and, to a greater extent, angiogenesis. Our study was designed to investigate the correlation between MCD, tumor lymphangiogenesis, and several well-established prognostic parameters in breast cancer. One hundred and four cases of invasive breast carcinoma diagnosed in our clinic between 2007 and 2011 were included. Mast cells and lymphatic vessels were stained with toluidine blue and D2-40, respectively, and their densities were calculated in various areas of tumors and lymph nodes. The variables of MCD and lymphatic vessel density (LVD) were compared using prognostic parameters as well as with each other. As tumor size and volume increased, MCD increased comparably in metastatic lymph nodes; intratumoral and peritumoral LVD also increased. Lymphovascular invasion, lymphatic invasion, perineural invasion, and estrogen receptor positivity were positively related to intratumoral MCD. The relationship between peritumoral MCD and nontumoral breast tissue MCD was statistically significant. Stage was correlated with MCD in metastatic lymph nodes. Metastatic lymph node MCD and intratumoral MCD were also significantly related. Stage, lymphatic invasion, perineural invasion, lymphovascular invasion, and metastatic lymph node MCD were all correlated with intratumoral and/or peritumoral LVD. As nuclear grade increased, intratumoral LVD became higher. In breast carcinoma, MCD, depending on its location, was related to several prognostic parameters. Notably, mast cells may have at least some effect on lymphangiogenesis, which appears to be a predictor of tumor progression.

Review of Hydatid Cyst with Focus on Cases with Unusual Locations.

OBJECTIVE: This study has been conducted so as to contribute to health statistics of hydatid cyst by the data obtained from our clinic, and to discuss hydatid cysts in unusual locations. MATERIAL AND METHOD: Cases diagnosed as hydatid cyst at Dr. Lutfi Kirdar Kartal Research and Education Hospital Pathology Clinic between 2007 and 2015 have been evaluated based on criteria such as age, sex and location. RESULTS: A total of 364 cases, 209 females and 155 males, have been included in the study. The subjects in the cases are aged between 4 and 81 (mean: 38.84). Regarding the sites, 254 (69.8℅) of the cases are located in liver, and 53 (14.6℅) in the lung. Fifty-seven cases (15.6℅) have been detected in unusual sites other than the lung or liver. The rate of isolated organ involvement, other than the lung and liver, has been found to be 10.3℅. CONCLUSION: Since hydatid cyst can be found in all the body sites, it should be taken into account in the differential diagnosis of all cystic lesions.

Epithelioid trophoblastic tumor.

OBJECTIVE: To describe a case of epithelioid trophoblastic tumor (ETT) in a postmenopausal woman, which had several peculiar features that differentiate it from previously reported ETTs. CASE REPORT: ETT of the uterus is a rare form of trophoblastic tumor with only 100 cases distinguished until now. Our case differs from the previously reported ones due to its several exceptional features. Our patient had no history of trophoblastic or gynecological disease; is postmenopausal; had endocervical extension from the beginning; recurrences and metastasis at follow up; and had a high Ki-67 index and a normal beta-human chorionic gonadotropin value. CONCLUSION: Because precise differential diagnosis will alter the therapeutic approach and prognosis, it is necessary for treating physicians to be aware of these unusual presentations.

The value of COX-2 expression in the prognostic parameters of invasive ductal carcinoma of the breast.

Cyclooxygenase is an enzyme that changes the immune response to malign cells and catalyzes prostaglandins that may have an impact on cell proliferation. The purpose of this study was to examine the relation between established clinicopathological parameters in breast carcinomas and COX-2 protein expression. COX-2, estrogen receptor (ER), progesterone receptor (PR) and c-erB-2 primary antibodies were assessed in the slides prepared from the paraffin blocks of 62 invasive ductal carcinoma cases. The relation between ER, PR, and c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age were evaluated. The results were analyzed statistically. Cytoplasmic COX-2 expression was seen in 75.8% of all breast carcinomas. In both univariate and multivariate logistic regression analysis, there was a positive correlation between COX-2 expression and negative ER status, respectively (P=0.0173) (P=0.016). There was any statistically significant relation between PR positivity, c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age (P≥0.05). Given that there was found a statistically significant relation between COX-2 expression and negative ER status, which is considered a poor prognostic parameter, suggests that COX-2 expression can have a place among the other prognostic parameters of breast carcinoma.

The relationship of COX-2 expression with estrogen receptor, progesterone receptor and prognostic parameters in endometrial carcinomas.

AIM: Endometrial cancer (EC), which is the most common gynecologic cancer, develops as a result of disruption of the delicate balance between cell proliferation and cell loss, or apoptosis through activation of oncogenesis, or loss of tumor suppressor genes. Among the biochemical factors proposed to give a more detailed characterization of EC biology, estrogen receptors (ER) and progesterone receptors (PR) play a major role. Most of the studies in the literature have shown increased expression of cyclooxygenase-2 (COX-2) in EC. Recent experiments suggest that COX-2 antagonizes cell apoptosis, increases the invasiveness of malignant cells and promotes angiogenesis. The aim of this study was to investigate the expression of COX-2 in EC, to study its correlation to established menstrual status, grade, myometrial invasion, lymph node status, stage and ER and PR status. MATERIAL & METHODS: The study was performed on 72 ECs. Immunohistochemically was analyzed for ER, PR, and COX-2. RESULTS: COX-2 positivity was found in 91.7% of the cases. In 61 cases (84.7%) there was ER positive staining, and in 59 cases (81.9%) PR positive staining was observed. We have not found a statistically significant relation between COX-2 and prognostic factors, ER and PR. CONCLUSIONS: A high expression rate still suggests a probable relation with endometrial carcinogenesis. If such a relation exists, new therapeutic options might be available in the future.

The relationship of cerb B 2 expression with estrogen receptor and progesterone receptor and prognostic parameters in endometrial carcinomas.

BACKGROUND: Endometrial carcinoma (EC) is the most common malignancy of the female genital tract. Gene alterations and overexpression of various oncogenes are important in tumor development. The human HER 2 neu (c-erbB-2) gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network. The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer, to study its correlation to established prognostic parameters and estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: Immunohistochemical (IHC) analyses of ER, PR and c-erbB-2 were performed in 72 EC cases. RESULTS: We detected a positive staining with c erbB 2 in 18.1% of the cases and determined a statistically significant relation between c-erbB-2 and PR. We could not find a statistically significant relation between c-erbB-2 staining and ER. There was not a statistically significant difference between c-erbB-2 and histological grade. The highest level of c-erbB-2 was found in grade 2 cases. There was not any statistically significant relation between c-erbB-2 and menstrual status, myometrial invasion, lymph node status, stage and survival. CONCLUSIONS: Although our study provides additional evidence of the potential prognostic role of c-erbB-2, further prospective and controlled studies are required to validate their clinical usefulness.