High Incidence of Appendiceal Neoplasms in the Elderly: A Critical Concern for Non-Surgical Treatment.

OBJECTIVE: Appendiceal neoplasms (ANs) are rare tumors that are often discovered incidentally during histopathological examinations. The increasing incidence of ANs is a critical issue in the non-operative management of acute appendicitis. This study aimed to document the temporal trends over a 12-year period by analyzing the clinical presentation, imaging findings, and histopathological features of ANs. SUBJECTS AND METHODS: Health records of patients who underwent appendectomy from 2011 to 2022 were examined. Demographic and clinical data, laboratory results, imaging findings, and histopathological features were documented. The characteristics of both ANs and non-neoplastic cases were evaluated. RESULTS: A total of 22,304 cases were identified, of which 330 (1.5%) were diagnosed with ANs. The odds ratio for ANs increased with age, with the highest odds ratio observed in patients aged 70 or older. Receiver Operating Characteristic analysis showed that age and appendiceal diameter were significant predictors of ANs. An optimal age cut-off point of 28.5 years was determined, yielding a sensitivity of 72% and a specificity of 64%. For appendiceal diameter, the optimal cut-off was found to be 9.5 mm, exhibiting a sensitivity of 77% and a specificity of 56%. CONCLUSION: Although the incidence of ANs remains relatively low, a steady increase has been observed over the past decade. The increasing rate of ANs raises concerns regarding non-surgical management options. The results of this study highlight the importance of considering ANs as a potential diagnosis in older patients and in patients with an appendix diameter greater than 9.5 mm. These findings may have implications for treatment and management.

The association of miR-204 and mir-483 5p expression with clinicopathological features of Wilms tumor: Could this provide foresight?

BACKGROUND: Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement of up-to-date treatment protocols, the survival rates of Wilms tumor have increased. However, metastases or local relapses are still observed in 15% of patients. The search for reliable biomarkers to identify at-risk patients is ongoing to predict the variability in treatment success. Currently, the evaluation of clinical, histopathological and genetic features are common diagnostic methods; however, epigenetic features can be examined with microRNA expression analyses and might allow us to comment on the behavior of the tumor and treatment response. METHODS: In this study, we aimed to evaluate the relationship between microRNA-204 and microRNA-483-5p expression with clinicopathological data and the effect on Wilms tumor survival. For this purpose, the expression levels of RNU6B, microRNA-204 and microRNA-483-5p were evaluated in tumor and normal tissue by qreal time-polymerase chain reaction. We also investigated the relationship between microRNA expression levels with the clinicopathological and histological features of Wilms tumor. RESULTS AND CONCLUSION: The results of our study indicate that the relative expression levels of microRNA-204 in Wilms tumor tissues were significantly lower than that in adjacent normal tissues. By contrast, tumor tissue had a higher microRNA-483-5p expression than the corresponding normal tissues. A statistically significant difference between microRNA-204 expression level with age and the presence of anaplasia was observed. The upregulation of microRNA-483-5p was found to have a significant correlation with patients after preoperative chemotherapy and complete tumor necrosis. Taken together, our data suggest that microRNA-204 could play a critical role as a tumor suppressor, whereas microRNA-483-5p acts as an oncogene in Wilms tumor progression. More importantly, microRNA-204 might be a novel predictive biomarker for anaplastic histology and could be useful for developing therapeutic interventions targeting this marker.

Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma.

BACKGROUND/AIM: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. MATERIALS AND METHODS: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. RESULTS: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. CONCLUSION: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.

Comparison of surgical techniques used for prevention of neuroma in order to make more clear the role of the epineurium. An experimental study.

AIM: Several studies have been conducted for the prevention of neuroma and recently published experimental studies include interventions on epineurium. The techniques which include interventions on epinerium were compared to reveal the role of epinurium in neuroma prevention. MATERIAL E METHODS: 55 Sprague-Dawley rats were divided into five groups. Two of the groups were negative and positive controls. The proximal nerve stump was left "free" in the negative control group, while the stump was implanted in a muscle pocket in the positive control group following sciatic nerve transection. Experimental groups include epineural ligation, epineural stripping and epineural capping procedures. Follow-up period was six months. After sacrification of the rats, histopathologic and immunohistochemical examinations were conducted as well as real-time PCR studies for the assessment. Statistical analysis was performed. RESULTS: The most prominent neuroma formation was detected in the epineural capping group, while the least neuroma was observed in the epineural ligation group. DISCUSSION: Statistically significant differences were obtained when the three experimental groups were compared with both control groups. Interestingly there was no significant difference in-between the control groups in terms of preventing neuroma formation. CONCLUSION: epineural ligation group were found to be superior to both control groups as well as experimental groups. Use of epineural capping was concluded to increase the formation of neuroma rather than preventing. Intramuscular implantation of nerve stump had no preventive effect on neuroma formation. KEY WORDS: Capping, Epineurium, Ligation, Neuroma, Stripping.

Retrospective analysis of the appendiceal neoplasms: sampling technique may influence neoplasm detection.

BACKGROUND AND AIMS: Appendiceal neoplasms are uncommon entities that are usually determined incidentally during the histopathological examination. Different techniques used for the macroscopic sampling of appendectomy material may affect the determinating neoplasms. MATERIALS AND METHODS: H&E-stained slides of 1280 cases who underwent appendectomy between 2013 and 2018 were reviewed retrospectively for histopathological features. RESULTS: Neoplasms were determined in 28 cases (3.09%); 1 lesion was observed in the proximal part of the appendix, 1 covering the entire length from proximal to distal and 26 in the distal part. In the 26 cases that observed in the distal part, the lesion was seen on both sides of the longitudinal section of the distal appendix in 20 cases, while it was seen on only one distal longitudinal section in the remaining 6 cases. CONCLUSION: The vast majority of appendiceal neoplasms are seen in the distal part of the appendix, and, in some cases, neoplasms might be seen on only one side of the distal section. Sampling only one-half of the distal part of the appendix, where tumours are most often observed, could result in some neoplasms being missed. Therefore, sampling the whole distal part would be more beneficial to determine small diameter tumours that do not create macroscopic findings.

Novel marker to predict rupture risk in tubal ectopic pregnancies: the systemic immune-inflammation index.

OBJECTIVES: Ectopic pregnancy is a life-threatening condition; delaying treatment can result in mortality or serious complications. Identification of a biomarker that can predict tubal rupture may be helpful for guiding treatment. In this study, we evaluated the association between serum ß-hCG, biochemical markers, Systemic Immunity-inflammation Index (SII) score, and the trophoblastic invasion stage. MATERIAL AND METHODS: Tubal pregnancy was classified into three groups based on the depth of trophoblastic infiltration: stage I - limited to the mucosa; stage II - invaded the muscular layer, and stage III - invaded the serosa/subserosa of the tuba uterine. The association between groups, serum ß-hCG, biochemical markers, and the SII score were assessed. RESULTS: There was no significant difference between the groups, hemoglobin, platelet count, MPV, RDW, NLR or PLR values (p > 0.05). A ROC analysis was performed to evaluate the accuracy of serum ß-hCG predictions for infiltration level. At a 95% confidence interval upper limit, cut-off value of the serum ß-hCG that best predicted stage III trophoblastic infiltration, was 2799 mIU/mL, with 78.9% sensitivity, 53.8% specificity (positive predictive value was 71.4%, and a negative predictive value was 63.6%). Moreover, ROC curve analysis showed that The SII value of 792 was the best predictor of trophoblastic infiltration at stage III, with a sensitivity of 92.3% and a specificity of 63.1%. CONCLUSIONS: A linear relationship exists between depth of trophoblastic infiltration and serum ß-hCG and the SII were observed. These findings suggested that the SII score can be used for predicting tubal ectopic pregnancy rupture.

Comparison of surgical techniques used for prevention of neuroma in order to make more clear of the role of the epineurium: an experimental study.

AIM: Several studies have been conducted for the prevention of neuroma and recently published experimental studies include interventions on epineurium. The techniques which include interventions on epinerium were compared to reveal the role of epinurium in neuroma prevention. MATERIAL E METHODS: 55 Sprague-Dawley rats were divided into five groups. Two of the groups were negative and positive controls. The proximal nerve stump was left "free" in the negative control group, while the stump was implanted in a muscle pocket in the positive control group following sciatic nerve transection. Experimental groups include epineural ligation, epineural stripping and epineural capping procedures. Follow-up period was six months. After sacrification of the rats, histopathologic and immunohistochemical examinations were conducted as well as real-time PCR studies for the assessment. Statistical analysis was performed. RESULTS: The most prominent neuroma formation was detected in the epineural capping group, while the least neuroma was observed in the epineural ligation group. DISCUSSION: Statistically significant differences were obtained when the three experimental groups were compared with both control groups. Interestingly there was no significant difference in-between the control groups in terms of preventing neuroma formation. CONCLUSION: epineural ligation group were found to be superior to both control groups as well as experimental groups. Use of epineural capping was concluded to increase the formation of neuroma rather than preventing. Intramuscular implantation of nerve stump had no preventive effect on neuroma formation. KEY WORDS: Capping, Epineurium, Ligation, Neuroma, Stripping.

Seeds or Parasites? Clinical and Histopathological Features of Seeds and Parasites in the Appendix.

OBJECTIVE: Parasites and plant seeds may both be found in appendectomy specimens. Each plant seed has a different appearance and can thus exhibit wide variations under the microscope. Fragmented seeds may histologically mimic parasites. The differential diagnosis between seeds and parasites can be challenging in such cases. This study aimed to determine the incidence of parasites, seeds, and foreign bodies in appendectomy materials and highlight the most characteristic histopathological features associated with these structures. MATERIAL AND METHOD: In this study, pathology slides of 9,480 patients, who underwent appendectomy between 2010 and 2021, were reviewed, and cases that contained parasites, seeds, or foreign bodies were identified. We reviewed the literature on seeds and parasites in appendectomy specimens. RESULTS: Parasites were observed in 56 (0.6%) cases. Of these cases, 45 had Enterobius vermicularis (80%), and 11 had Taenia subspecies (20%). Plant seeds were observed in 47 cases (0.5%), and were macroscopically recognizable in 5 of them as olive, lemon, and cherry seeds. Parasites and seeds were usually observed in the lumen of appendix vermiformis, filled with abundant fecal materials. CONCLUSION: Seeds are seen in approximately 0.5% of the appendectomy specimens. Though rarely seen, the fragmented seed appearance may cause diagnostic difficulties. In this context, the key morphological features of parasites and plant seeds outlined in this study may be helpful in their differential diagnosis.

DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection.

Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases of PPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p < 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent of DICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1-related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs.

Evaluation of the mir-126, mir-182, and mir-486-5p Expression Signature of Head and Neck Squamous Cell Carcinomas and Lung Squamous Cell Carcinomas.

OBJECTIVE: Although squamous cell carcinomas (SCCs) originating from different anatomic localizations display a similar histological appearance under light microscopy, they may differ in terms of epigenetic and genetic features. The aim of this study was to analyze mir-126, mir-182, and mir-486-5p expression levels in head and neck SCCs and lung SCCs, and to identify localization-specific miRNA expression profiles. MATERIAL AND METHOD: The expression levels of mir-126, mir-182, and mir-486-5p were analyzed in lung, oral cavity, laryngeal, and hypopharyngeal SCCs in 40 patients, using quantitative real-time polymerase chain reaction. RESULTS: The findings showed that lung, oral cavity, laryngeal, and hypopharyngeal SCCs have distinct mir-126 and mir-486-5p expression profiles. It was also observed that mir-126 and mir-486-5p expression levels were highly specific to the tumor localization. CONCLUSION: These findings highlighted that SCCs originating from different anatomic localizations have different miRNA expression profiles. miRNA expression analysis can be used to predict the primary localizations of those SCCs.

Retrospective analysis of the appendiceal neoplasms: sampling technique may influence neoplasm detection.

BACKGROUND AND AIMS: Appendiceal neoplasms are uncommon entities that are usually determined incidentally during the histopathological examination. Different techniques used for the macroscopic sampling of appendectomy material may affect the determinating neoplasms. MATERIALS AND METHODS: H&E-stained slides of 1280 cases who underwent appendectomy between 2013 and 2018 were reviewed retrospectively for histopathological features. RESULTS: Neoplasms were determined in 28 cases (3.09%); 1 lesion was observed in the proximal part of the appendix, 1 covering the entire length from proximal to distal and 26 in the distal part. In the 26 cases that observed in the distal part, the lesion was seen on both sides of the longitudinal section of the distal appendix in 20 cases, while it was seen on only one distal longitudinal section in the remaining 6 cases. CONCLUSION: The vast majority of appendiceal neoplasms are seen in the distal part of the appendix, and, in some cases, neoplasms might be seen on only one side of the distal section. Sampling only one-half of the distal part of the appendix, where tumours are most often observed, could result in some neoplasms being missed. Therefore, sampling the whole distal part would be more beneficial to determine small diameter tumours that do not create macroscopic findings.

Promoter region mutations of the telomerase reverse transcriptase (TERT) gene in head and neck squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to assess the prevalence of TERT promoter region mutations in tumor samples of patients with squamous cell carcinoma at different sites of the head and neck region and correlate it with patients' clinicopathologic data. STUDY DESIGN: Mutations in promoter region of the TERT gene were analyzed with polymerase chain reaction-based direct sequencing method using formalin-fixed, paraffin-embedded tumor samples of 189 HNSCCs. TERT promoter region mutations were assessed in terms of age, gender, location, smoking, alcohol consumption, and overall survival. RESULTS: TERT promoter region mutations were detected in the oral cavity (75%); larynx (8.4%), hypopharynx (16.6%), and oropharynx (0%). TERT promoter region mutations are associated with younger age and female gender and have a reverse relationship with smoking and alcohol consumption. CONCLUSIONS: We found statistically significant higher rates of TERT promoter region mutations in tumor samples of patients with squamous cell carcinoma in the oral cavity compared with other locations in the head and neck region.

Primary Synovial Sarcoma of the Thyroid: Challenges in Cytologic Diagnosis and Review of the Literature.

BACKGROUND: Primary synovial sarcoma (SS) of the thyroid (PSST) is extremely rare. Its differential diagnosis from other neoplasms is essential since it has different management protocols and prognosis. CASE: A 26-year-old man with a 4.5-cm solid lobulated mass was seen at an outside hospital. Fine needle aspiration (FNA) was interpreted as a papillary carcinoma, and a total thyroidectomy was performed. The final histologic diagnosis was spindle epithelial tumor with thymus-like differentiation (SETTLE). No metastases were detected at that time, and the patient received radioactive iodine treatment. Two years post-surgery, he was seen at our hospital with a local recurrence, and FNA was considered as consistent with SETTLE. The mass was resected, and a left modified radical neck dissection was performed. The tumor revealed necrosis and a high mitotic index. Following histologic, immunohistochemical, and molecular studies, the tumor was classified as a PSST. The patient received chemotherapy and targeted immunotherapy, but he died 41 months after the initial presentation. CONCLUSION: The main diagnostic pitfall of PSST is SETTLE. The presence of mitotic figures and basal lamina material, negative staining for smooth muscle actin, and positive staining for transducer-like enhancer of split 1 antibody favor SS over SETTLE. SYT gene rearrangement is essential to establish the definitive diagnosis of PSST.