Turkish Journal of Pathology - 2022; 38(3)

Towards Development of a Standard Terminology of the World Health Organization Classification of Tumors of the Central Nervous System in the Turkish Language, and a Perspective on the Practical Implications of the WHO Classification for Low and Middle Income Countries

2022-09-01

In our manuscript, we propose a common terminology in the Turkish language for the newly adopted WHO classification of the CNS tumors, also known as the WHO CNS 5th edition. We also comment on the applicability of this new scheme in low and middle income countries, and warn about further deepening disparities between the global north and the global south. This division, augmented by the recent COVID-19 pandemic, threatens our ability to coordinate efforts worldwide and may create significant disparities in the diagnosis and treatment of cancers between the �haves� and the �have nots�.

Invasive Breast Carcinoma of No Special Type with Medullary Pattern: Morphological and Immunohistochemical Features

2022-09-01

Objective: Our study investigated the morphological and immunohistochemical characteristics of invasive breast carcinoma of no special type (IBC-NST) with medullary pattern to explore the inconsistencies between the structural and clinical traits of this category of tumor. Material and Method: The breast carcinoma samples (n = 26) with medullary pattern (defined according to established criteria) were subjected to immunohistochemical assays of the following receptors: ER, PR, HER2/neu, Ki-67, p53, Bcl-2, VEGF, MMP1, E-cadherin, EGFR, Hsp70, Hsp90, CD20, CD3, CD4, CD8, CD68, CD163, CD56, CD138, MPO, S100, IgG, IgM, and PD-L1. Results: IBC-NST with medullary pattern was found to have negative expression of ER, PR, and HER2/neu; strong positive expression of Kі-67, mutant р53, Bcl-2, E-cadherin, EGFR, and PD-L1; moderate positive expression of Hsp70 and Hsp90; and low or negative expression of VEGF and MMP1. Furthermore, there was pronounced variability in the qualitative composition of tumor immune infiltrates with regards to T-lymphocytes, B-lymphocytes, macrophages, plasmocytes, and granulocytes. Conclusion: IBC-NST with medullary pattern has many unfavourable morphological and immunohistochemical prognostic characteristics, which are balanced against the pronounced protective properties of the tumor cells and the qualitative characteristics of the tumor microenvironment. These can lead to a favourable disease course despite the relatively adverse features of the carcinoma cells.

Methylation Profiling of Specific Genes in Ependymomas

Naz KANIT, Pelin YALCIN, Serhat ERBAYRAKTAR, Erdener OZER — 2022-09-01

Objective: Ependymomas are neuroepithelial tumors of the central nervous system with heterogeneous biology and clinical course. The aim of the present study is to investigate the relationship between the methylation status and clinicopathological parameters in ependymomas. Material and Method: DNA methylation status of CDKN2A, RASSF1A, KLF4 and ZIC2 genes were quantitatively analyzed with pyrosequencing in 44 ependymoma tumor tissues. The relationship of methylation profiles with tumor subtype, histological grade and patient age was statistically analyzed. Results: DNA methylation analyses for CDKN2A revealed no difference in methylation levels. Of the 31 included samples for optimal ZIC2 methylation analysis, 10 were hypermethylated (32.3%) and this change was significantly found in the adult spinal ependymomas (p=0.01). KLF4 hypermethylation was observed in 6 of the overall included 35 samples (17.1%); however, there was no statistically significant relation of the methylation status with tumor subtype, histological grade or age group. RASSF1A hypermethylation was observed in overall 40 included samples with varying methylation levels. Higher levels of hypermethylation were significantly related to the grade 3 histology (p=0.01) and spinal ependymomas (p=0.006). The pediatric cases with grade 3 ependymomas and ependymomas of adulthood showed significantly increased RASSF1A hypermethylation levels (p<0.001 and p=0.001, respectively). Conclusion: DNA methylation changes are likely to have biological importance in ependymomas. Both ZIC2 and RASSF1A methylation status may be useful parameters in the subclassification of these tumors.

Analysis of DUX4 Expression in Bone Marrow and Re-Discussion of DUX4 Function in the Health and Disease

2022-09-01

Objective: DUX4 is an embryonic transcription factor (TF) later silenced in somatic tissues, while active in germline testis cells. Re-expression in somatic cells has been revealed to be present in pathologic conditions such as dystrophy, leukemia, and other cancer types. Embryonic cells, cancer cells and testis cells that show DUX4 expression are pluri-multipotent cells. This lead us to question �Could DUX4 be a TF that is active in certain types of potent somatic cells?� As a perfect reflection of the potent cell pool, we aimed to reveal DUX4 expression in the bone marrow. Material and Method: Bone marrow aspiration materials of seven healthy donors aged between 3 and 32 (2 males/5 females) were investigated with qPCR analysis after RNA isolation for the presence of DUX4 full length mRNA expression. Samples have been investigated for protein existence of DUX4 via immunohistochemistry in two donors that had sufficient aspiration material. Results: DUX4 mRNA expression was present in all donors, with higher expression compared to B-actin. DUX4 positive stained cells were also detected by immunohistochemistry. Conclusion: With these results, novel expression for DUX4 in hematopoietic tissue is described. Further studies on the function of DUX4 in hematopoietic cells can shed light on DUX4-related pathways, and contribute to the treatment of DUX4-related diseases such as B-ALL, other cancers, and facioscapulohumeral muscular dystrophy.

Evaluation of Histomorphological Parameters to Predict Occult Nodal Metastasis in Early-Stage Oral Squamous Cell Carcinoma

2022-09-01

Objective: The oral squamous cell carcinoma (OSCC) treatment protocol depends upon lymph node metastasis. Elective neck dissection for early-stage OSCC (pT1/T2) elective neck dissection reduces the morbidity rate. It also reduces the overall survival and thus it becomes important to detect lymph node metastasis in early-stage OSCC. Material and Method: Various histomorphological parameters have been studied to predict nodal metastasis in early-stage OSCC. We aim to evaluate these parameters in the context of nodal metastasis. 78 cases of early-stage OSCC were included in the study with histopathologic parameters like tumor size, grade, tumor depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), worst pattern of invasion (WPOI), and lymph node level. Results: Out of the 78 patients, 32 patients had lymph node metastasis. T stage, DOI, LVI, and WPOI showed statistically significant deviance from the null model (P-values of 0.007, 0.01, 0.04 and 0.02 respectively). The Odds Ratio (OR) of T stage, DOI, LVI and WPOI were 4.45 (95% C.I =1.47-14.1), 4.4 (95% C.I =1.32-15.88), 8.12 (95% C.I =1.002-198.20), and 3.39 (95% C.I =1.24-9.74) respectively. On multivariate analysis (Firth logistic regression) using DOI, LVI, and WPOI as independent variables, only T-stage and WPOI retained statistical significance. Conclusion: The prognostic information supplied by evaluating DOI, LVI, and WPOI warrants the inclusion of these parameters in the standard reporting format for all cases of OSCC.

Clinical Significance of Endometrial Cells in Pap Smear of Women Aged 40 Years and Older

2022-09-01

Objective: To investigate the histopathological follow-up results in women diagnosed with endometrial cells in the Papanicolaou (Pap) test. Material and Method: Between January 2013 to December 2018, women with endometrial cells on the Pap test were searched from the hospital electronic database. The patients with endometrial cells on the Pap test who underwent further histopathological evaluation and who were followed-up for at least 1 year were enrolled in the study, while those who had a Pap test result other than endometrial cells, were lost during follow-up, or had missing data were excluded. Results: Out of 91,142 Pap smears, 121 (0.1%) cytologically had endometrial cells, and of those 65 cases were eligible for final analysis. The mean age of patients with premalignant/malignant lesions (57.7 � 2.9) was higher than those with benign lesions (50.1 � 0.7), with 77% of them in the postmenopausal period. Gynecologic premalignant/malignant lesions were detected in 9 (17.7%) patients including 2 (3.1%) endometrial hyperplasias and 7 (10.8%) endometrial cancers. The menopausal status (p=0.010) and being 50 years and older (p=0.002) were significantly associated with pre-neoplastic or neoplastic changes in patients with endometrial cells. Conclusion: The presence of endometrial cells in Pap tests may be a harbinger of endometrial pathologies, especially at the age of 50 years and over. The menopausal status is another possible determinant in detecting endometrial carcinoma. Further investigation may be suggested in women aged ≥50 years and postmenopausal in the event of endometrial cell detection.

Evidence for Diverse Prognosis in High-Grade Serous Ovarian Carcinoma: Solid, Pseudoendometrioid, and Transitional-Like; So-Called �SET Morphology� and Progesterone Receptor Status

Halit UNER, Metin DEMIR, Dincer GOKSULUK, Ayse KARS, Meral UNER, Alp USUBUTUN — 2022-09-01

Objective: High-grade serous ovarian carcinoma (HGSC) is one of the major tumors of the gynecological system with a poor survival rate and variable microscopic appearance. It was suggested that SET (solid, pseudo-endometrioid and transitional-like) morphology in ovarian HGSC is predictably associated with BRCA deficiencies. In this study, we investigated the microscopic patterns and some immunohistochemical markers predicting the prognosis of serous carcinoma. Material and Method: We re-evaluated 305 HGSC ovarian resections morphologically and calculated the SET morphology percentages for each case. Morphological and immunohistochemical data correlated with the survival and post-treatment disease progression data. Results: The median age at diagnosis was 57 years and the median follow-up period was 3.1 years. The median overall survival (OS) of ovarian carcinoma in SET-predominant tumors (n=60) was 81 months, while for tumors with SET non-dominant morphology (n=63) and non-SET morphology (n=182) it was 59.7 and 44.7 months, respectively. Conclusion: Predominant (more than 50%) SET morphology was significantly associated with increased survival rates of HGSC. Immunohistochemically, p53, ERCC1, ER, and PR antibodies were applied and only PR antibody positivity was found to be associated with borderline statistical significance for increased survival rates. Our results suggest that SET morphology may be a potential predictive and prognostic marker in managing the treatment strategies of HGSC.

Mixed Epithelial and Stromal Tumor Family of Kidney (Adult Cystic Nephroma, Mixed Epithelial and Stromal Tumor): Retrospective Clinicopathological Evaluation

2022-09-01

Objective: Tumors belonging to the mixed epithelial stromal tumor family (MESTF) are rare; thus clinicopathological experience about them are limited. Each epithelial and stromal component shows different patterns in these tumors. Material and Method: Clinicopathological features of 11 MESTF cases that were diagnosed between 2000 and 2021 at a single center were evaluated. Results: Ten of the 11 patients were female (F:M = 10:1). The mean age of the females was 47 (31-63) years; the male patient was 45 years old. The mean tumor diameter was 6.7 (3.5-19) cm. All tumors had varying proportions of cystic and solid components. Eight cases were well circumscribed, and the others had distinct but irregular borders. Two of the tumors with irregular borders were bulging into the renal sinus. The epithelial component was dominant in most cases. In the epithelial component, macrocyst, microcyst, and tubules were the most common patterns and the most common types of lining epithelium were flat, cuboidal and hobnail. The stromal component was variable in most cases and included hypocellular (mostly collagenous) and cellular areas. In most cases, the cellular stroma had an ovarian-like appearance. Among the other features observed, hyalinization and dystrophic calcification were common. The positivity for estrogen and progesterone receptor in the stromal component was observed in almost all female cases. Conclusion: MESTF, which has distinctive features, should be considered in the differential diagnosis of cystic kidney tumors.

Programmed Cell Death Ligand 1 Expression in Cytological and Surgical Non�Small Cell Lung Cancer Specimens in Association with EGFR Mutation and Overall Survival: A Single-Institution Experience

Elif SAYMAN GOKAL, Fugen VARDAR AKER, Zuhal KUS SILAV, Bala Basak OVEN — 2022-09-01

Objective: The aim of this study was to evaluate programmed cell death ligand-1 (PD-L1) expression and the relationship between driver mutations and survival analysis in advanced-stage non-small cell lung carcinoma (NSCLC). Material and Method: A total of 122 advanced-stage NSCLC patients were included in this retrospective study. The patients were diagnosed based on cytological examination and histopathological analysis of biopsy or resection material that had undergone at least 1 molecular analysis. The expression of PD-L1 in tumors and tumor-infiltrating lymphocytes (TIL) was scored and compared with age, sex, organ, biopsy method, tumor subtype, driver mutation status, and overall survival data. Results: There was no statistically significant difference between PD-L1-positivity and age, gender, location, pattern, or pathological diagnosis of the type of sample. When the threshold value for PD-L1 IHC evaluation was accepted as ≥1% and ≥50%, the rate of positivity was 19.7% and 7.4%, respectively. Conclusion: Since there is a wide range of positivity rates reported in the literature, we could not reach a conclusion as to whether the PD-L1-positivity rate we observed was high or low. There is a need for comparative studies where the technique, clones, threshold values, and phases are homogenized. There is an inverse correlation between the EGFR-mutant population and PD-L1 positivity. In terms of overall survival, no relationship was found between PD-L1 positivity, the presence of TIL, and EGFR mutation status.

Analysis of Clinical and Histopathological Findings in Microscopic Colitis

Gozde TOPEL, Ebru CAKIR, Ilgin AYDIN, Fatma Husniye DILEK, Aysegul AKDER SARI — 2022-09-01

Objective: Microscopic colitis is a chronic inflammatory disorder characterized by a triad of chronic diarrhea, endoscopy without significant abnormality, and distinct histopathological features. Histopathologically, microscopic colitis is divided into 3 subtypes; collagenous colitis, lymphocytic colitis, incomplete microscopic colitis. The main purpose of this study was to analyze the detailed clinicopathological parameters of microscopic colitis cases in the Turkish population. Material and Method: The clinicopathological parameters were evaluated in 53 microscopic colitis cases (37 collagenous colitis, 7 lymphocytic colitis, 9 incomplete microscopic colitis) diagnosed between 2010 and 2019. Results: All cases had lymphoplasmacytosis. The presence of ≥20 eosinophils/high power field in the lamina propria was remarkable in 75.7%, 57.1%, and 11.1% of collagenous colitis, lymphocytic colitis, and incomplete microscopic colitis cases, respectively. One of the striking findings was the presence of concomitant Celiac disease in 29% of the lymphocytic colitis cases. In terms of drug use, proton pump inhibitors and nonsteroidal anti-inflammatory drugs were the most commonly used drugs. Conclusion: The mean age in our series is lower than the literature and a distinct male predominance was observed in lymphocytic colitis and incomplete microscopic colitis, contrary to the literature. These suggest that susceptibility to microscopic colitis may differ between ethnic groups. The presence of overt lymphoplasmacytosis, eosinophilic infiltration and epithelial damage are the microscopic features which should alert the pathologist for the diagnosis of complete microscopic colitis. Given that microscopic colitis is a common treatable cause of chronic diarrhea, awareness of the aforementioned histopathological features is of utmost importance for accurate diagnosis and not to miss incomplete cases.

The Site of Lymph Node Metastasis: A Significant Prognostic Factor in Pancreatic Ductal Adenocarcinoma

2022-09-01

Objective: While the presence and number of metastatic lymph nodes (LNs) are important prognostic factors for pancreatic ductal adenocarcinoma (PDAC), there is no recommendation to specify metastatic regional LN localization in the current staging system. The aim of this study was to evaluate the prognostic effect of regional metastatic LN localizations in PDAC. Material and Method: Metastatic sites of 101 consecutive PDAC patients who underwent pancreaticoduodenectomy were classified as peripancreatic, perigastric, hepatica communis, hepatoduodenal, and superior mesenteric artery. The frequency of metastasis in each region and the association between the presence of metastasis in each site and overall and disease-free survival were statistically analyzed. Results: Eighty cases (79.2%) had peripancreatic, 7 (6.9%) had perigastric, 6 (5.9%) had hepatica communis, 7 (6.9%) had hepatoduodenal, and 4 (4%) had superior mesenteric artery LN metastasis. The overall and disease-free survival values were significantly shorter in patients with hepatoduodenal LN metastasis (log rank; p= 0.001, p=0.017, respectively). The presence of metastatic superior mesenteric artery LN was significantly associated with shorter disease-free survival in univariate analysis (p=0.017). Hepatoduodenal LN metastasis was an independent predictor of mortality (p=0.005) in multivariate analysis. Conclusion: The presence of hepatoduodenal LN metastasis is an independent poor prognostic factor for mortality. The presence of metastatic LN in the superior mesenteric artery region was significantly associated with shorter disease-free survival time, although not an independent predictor. We conclude that the metastatic regional LN sites, especially the hepatoduodenal region, have an impact on the prognosis, and should be included in synoptic pathology reports.

Placental Chorangiocarcinoma: Case Report with Literature Review of a Rare Entity

Nishant SAGAR, Parul TANWAR, Nita KHURANA, Poonam KASHYAP — 2022-09-01

Chorangiocarcinoma is an extremely rare tumor seen in the placenta, with only six cases reported in the literature so far. Its morphological characteristics, criteria for diagnosis, and the pathophysiology remain controversial to date. Although it was predominantly considered a benign entity, a solitary case of distant metastasis has been reported in the literature. We present a case of this unusual tumor in the preterm placenta of a 29-year-old female. Grossly seen as a grey white nodule, microscopic examination revealed nests of atypical trophoblastic proliferation surrounded by vascularized stroma. No evidence of basement membrane invasion was noted. On immunohistochemistry, the trophoblastic component expressed pancytokeratin, Beta HCG, and Placental Alkaline Phosphatase with high Ki-67 labelling index. The present case highlights this exceedingly rare entity with emphasis on its morpho-immunohistochemical features along with a review of literature.

Chernobyl Cancer Studies with Overseas Control: High Grade vs. Late Detection

Sergei JARGIN — 2022-09-01