Turkish Journal of Pathology最新文献

Objective: Lung cancer, the second most common type of cancer, is the leading cause of cancer-related mortality, with non-small-cell lung carcinoma (NSCLC) being the most prevalent subtype. The presence of EGFR mutations in NSCLC influences tumor behavior and treatment response. The prevalence of EGFR mutation in Iranian patients is limited. This study investigated the frequency of EGFR mutation and its association with PD-L1, ALK, and ROS1 expression in patients with NSCLC from Northwest Iran.

Material and methods: A retrospective analysis was conducted on 647 cases of NSCLC from April 2018 to August 2024 at Imam Reza Hospital in Tabriz, Iran. Histologic diagnoses were confirmed, and patient data were collected. EGFR mutation testing targeted exons 18-21 using Sanger sequencing and Real-Time PCR. ALK and ROS1 rearrangements were assessed using fluorescence in situ hybridization (FISH), while PD-L1 expression was evaluated through immunohistochemistry (IHC). The statistical analysis was performed using SPSS version 27.0.

Results: The cohort comprised 430 males and 217 females, with a median age of 62 years (IQR: 54-70). EGFR mutations were identified in 171 (26.4%) cases, more frequently in females (33.6% vs. 22.8%; p = 0.003). The most common mutation was exon 19 deletion (56.7%), followed by L858R (21.6%). No significant association was found between EGFR mutations and ALK (p = 0.126) or PD-L1 expressions ( p = 0.29). ROS1 mutations were not detected.

Conclusion: This study confirmed the mutual exclusivity of EGFR and ALK mutations and found no significant association with PD-L1. Comprehensive EGFR testing remains crucial to guide targeted therapies. Broader studies are needed to include diverse populations and additional clinical factors to improve personalized treatment.

Objective: We aimed to investigate the association between CMV immunohistochemistry positivity and clinical, endoscopic, histologic, and tissue CMV PCR findings in ileocolonoscopic biopsies of inflammatory bowel disease patients, and to assess the diagnostic value of CMV immunohistochemistry as a reflex test during routine histopathologic evaluation.

Material and methods: We conducted a retrospective analysis of 191 patients (136 ulcerative colitis, 55 Crohn`s disease) between 2018 and 2021. We analyzed clinical data, endoscopic Mayo scores, histologic activity (Simplified Geboes Score), cytopathic changes, CMV immunohistochemistry and tissue CMV PCR results.

Results: CMV immunohistochemistry was positive in 32.4% of cases, significantly associated with ulcerative colitis (p=0.003), symptomatic presentation (p=0.001), extensive colonic involvement (p < 0.001), high histologic activity scores (p < 0.001), and ulceration (p < 0.001). Notably, 74.2% of CMV immunohistochemistry-positive cases had no preliminary clinical suspicion of CMV infection. Viral cytopathic changes were identified in only 30.6% of immunopositive cases on hematoxylin-eosin staining. CMV immunohistochemistry showed a significant correlation with tissue PCR (p < 0.001), although some discordant cases occurred. The PCR-positive group had significantly higher immunopositive cell counts compared to the PCR-negative group (p < 0.001). The number of biopsy fragments did not affect CMV detection by immunohistochemistry.

Conclusion: While evaluating endoscopic biopsies of patients with inflammatory bowel disease, CMV immunohistochemistry assessment as a reflex test may be considered by the pathologist-even in the absence of identifiable viral cytopathic effects with hematoxylin-eosin- particularly when severe histologic inflammation is present. Although the clinical significance of CMV immunohistochemistry could not be fully determined in this study, this approach may increase the likelihood of detecting CMV infection and, in the appropriate clinical context, could contribute to timely diagnosis and management.

Carcinoma cuniculatum (CC) is a rare and distinct clinicopathological variant of well-differentiated squamous cell carcinoma. It is a rare and slow-growing tumor with a peculiar infiltrative growth pattern resembling rabbit burrows (cuniculi). It usually occurs over the plantar aspect of the foot but can also occur at other sites like the oral cavity and genitals. The pathogenesis is unknown, with various hypotheses of trauma as proposed by different authors. It is essential to be aware of this entity as it commonly mimics benign and other low-grade squamous cell carcinoma (SCC). Diagnosis of CC can be challenging and requires repeated histological evaluation and clinical correlation. Herein, we present a case report of CC of the plantar and dorsal aspect of the foot in a 60-year-old male with a history of multiple chronic non-healing ulcers, which was clinically suspected as eumycetoma and remained inconclusive on numerous biopsies.

Objective: Cytological examination of pleural effusion is minimally invasive and low risk but faces challenges due to the lack of architectural features, low cell counts, and overlapping characteristics among reactive mesothelial cells (RMCs), carcinoma cells, and malignant epithelioid mesothelioma (MPM) cells. The aim of this was study to detect the diagnostic accuracy of the expression of HEG1 and Claudin-4 in distinguishing malignant mesothelioma from lung adenocarcinoma in pleural effusion.

Material and methods: The present study was carried out on 84 cases of pleural effusion. Sixty-four representative cell blocks of the studied malignant cases and twenty control cases were stained with HEG1 and Claudin-4 immunostaining, and the results were recorded.

Results: Positive membranous HEG1 immunoexpression was found in 95% of RMCs in benign effusions. Also, positive membranous HEG1 immunoexpression was found in 96% of cases of MPM, and only 2.6% of lung adenocarcinoma cases. There was a statistically significant difference between benign effusion with RMCs and lung adenocarcinoma immunoreactivity. There was a highly statistically significant difference between HEG1 immunoexpression in MPM and lung adenocarcinoma. On the other hand, all cases of benign effusions and all MPM cases had negative Claudin-4 immunoexpression while positive membranous Claudin-4 immunoexpression was found in 94.9% of lung adenocarcinoma cases. There was a statistically significant difference in immunoexpression of Claudin-4 between benign effusion and lung adenocarcinoma. There was a statistically significant difference in the immunoexpression of Claudin-4 between MPM and lung adenocarcinoma.

Conclusion: HEG1 and Claudin-4 IHC staining is extremely valuable in the differential diagnosis between reactive or malignant mesothelial cells and adenocarcinoma in pleural effusion.

Objective: This study aimed to identify the expression profile and prognostic significance of inflammation-associated lncRNAs in chronic viral hepatitis (CVH) and CVH-associated hepatocellular carcinoma (CVH-HCC).

Material and methods: In the first step, lncRNA expression analysis was performed by real-time polymerase chain reaction (RT-PCR) using an array panel of 84 inflammation-associated lncRNAs in 48 formalin-fixed paraffin-embedded (FFPE) tissue samples (12 CVH-HCC, 12 peritumoral cirrhotic parenchyma, 12 nontumoral cirrhotic CVH parenchyma, 12 normal liver samples). In the second step, 7 lncRNAs (DLEU2, HOTAIR, LINC00635, LINC00662, RP11-549J18.1, SNHG16 and XIST) were chosen for RT-PCR assay testing in 72 samples (24 CVH-HCC, 24 peritumoral cirrhotic parenchyma, 24 nontumoral cirrhotic CVH parenchyma samples).

Results: Fifty-six inflammation-associated lncRNAs were significantly up-regulated in the peritumoral cirrhotic parenchyma compared to the normal liver. Expression of 71 lncRNAs was significantly higher in peritumoral cirrhotic parenchyma compared to cirrhotic CVH parenchyma. DLEU2 and SNHG16 were up-regulated both in the tumor and peritumoral cirrhotic parenchyma compared to cirrhotic CVH parenchyma. Expression of LINC00662 was significantly higher in CVH-HCC than in cirrhotic CVH parenchyma. Expression of XIST was also increased in both tumor and peritumoral parenchyma samples, albeit without statistical significance. No significant association was found between lncRNA expressions and survival.

Conclusion: Inflammation-associated lncRNAs DLEU2, SNHG16, LINC00662, and XIST are candidate diagnostic biomarkers in CVH-HCC. More evidence is needed to prove their utility as prognostic markers.

Objective: Fine needle aspiration cytology is the first line of investigation for thyroid lesions. Despite standard reporting formats, the diagnostic accuracy varies across institutions. In this study, we have reviewed our discordant cases on cytology and histopathology and analyzed the diagnostic errors.

Material and methods: The thyroid cases with discrepant cytology and histopathology reports for a period of five years were analyzed for diagnostic errors. The papillary thyroid carcinoma (PTC) cases were studied in detail for all diagnostic parameters. Nuclear scoring was used to improve the detection of PTC.

Results: Of the 166 cases, 18 (10%) had discrepant diagnoses. The sensitivity was 65.62% (CI 46.81-81.43%), specificity 94.78%, positive predictive value 75%, negative predictive value 92.03%, positive likelihood ratio 12.56, negative likelihood ratio 0.36, false positive rate 5.2%, false negative rate 34.3% and accuracy 89.16%. False negative (malignant cases diagnosed as benign) was due to inadequate/wrong site sampling, benign clusters/ cyst macrophages, marginal flares, thin colloid, larger fragments of calcification, and subtle nuclear features. An interesting flower head-like structure was observed in PTC cases. Nuclear scoring on false negative cases improved our diagnostic accuracy. False positivity was due to vigorous aspiration and over-interpretation of nuclear features.

Conclusion: Analysis of our discrepant cases highlighted the importance of multiple passes, sampling all nodules, and ultrasound-guided aspiration to reduce sampling error. Application of nuclear scoring reduced overdiagnosis and missing out on PTC. Tissue fragments and hypercellularity were the major misleading factors in false positive cases.

Aim: To document a case of primary cutaneous Adiaspiromycosis.

Introduction: Adiaspiromycosis is a rare emerging fungal infection caused by Chrysosporium Parvum var Crescens now called as `Emmonsia Crescens` belonging to the genus Emmonsia, order Onygenales, family Ajellomycetes.

Case report: A 38-year-old male presented with an ulcerated nodule over the infra-axillary region with itching for 3 months. The lesion began as small nodule slowly growing to attain the present size. His routine investigations were within normal limits. Serological tests such as HBsAg and HIV were nonreactive. Fine needle aspiration cytology showed `suppurative granulomatous` inflammation. The nodule was excised and sent for histopathological examination. Histopathology showed numerous noncaseating granulomas and suppuration. Amidst suppuration, as well as inside the giant cells and within granulomas, numerous varying sized, thick-walled, round to oval `adiaspores` were seen. There was no evidence of budding or septation or endosporulation. They were PAS and GMS positive. He was treated with topical luliconazole and oral fluconazole. There was no recurrence on follow up of one years.

Conclusion: Adiaspiromycosis is a rare fungal infection and primary cutaneous involvement is a rare distinct entity. Detailed morphological assessment in histopathology is essential for its identification as the organisms are difficult to isolate in fungal culture from human clinical material.

Objective: The tumor microenvironment is a heterogeneous and constantly changing territory that plays an active role in tumor formation and progression. It constantly interacts with tumor cells, plays an active role in tumor development, and even appears as a parameter of prognostic importance, and the importance of the tumor microenvironment in breast cancer has been emphasized by recent studies. In this study, we aimed to retrospectively evaluate the relationship between the tumor microenvironment and prognostic parameters in invasive breast carcinomas of no special type.

Material and methods: A total of 271 cases diagnosed as invasive breast carcinoma of no special type from resection materials in our center between 2007 and 2015 were included in the study. Hematoxylin-eosin stained slides with a thickness of 4-5 micrometers were evaluated in terms of tumor infiltrating lymphocytes, peritumoral and intratumoral desmoplastic reaction, intratumoral and peritumoral tumor budding, stromal features, and tumor growth pattern.

Results: When parameters related to the tumor microenvironment were compared with other prognostic parameters, there was a significant relationship between TILs and tumor grade, size, stage, immunohistochemical subgroup and Ki-67 proliferation index. A significant relationship was detected between intratumoral stromal reaction and tumor grade, size, molecular subgroup and the Ki-67 proliferation index (p < 0.05). When stroma and other prognostic parameters were compared, tumors with desmoplastic stroma had higher grades and higher Ki-67 proliferation indexes, and they were observed more frequently in the triple negative molecular subgroup.

Conclusion: We believe that including parameters related to tumor microenvironment in breast cancer reports, which hold a prognostic and predictive importance, will contribute to patient management. Considering the fact that these can be easily evaluated from routinely used hematoxylin-eosin stained slides, this does not cause additional costs or excessive time loss.

Pheochromocytoma and abdominal paraganglioma (PPGL) are rare catecholamine-producing, keratin-negative, non-epithelial neuroendocrine neoplasms characterized by a unique association with syndromic diseases caused by constitutional mutations in a wide range of susceptibility genes. While PPGLs are recognized for their malignant potential, the risk of metastatic disease varies depending on several clinical, histological, and genetic factors. Accurate diagnosis and prognosis of these tumors require a multidisciplinary approach, integrating insights from various medical specialties. Pathologists play a crucial role in this complex task, as numerous morphological, immunohistochemical, and genetic findings can be linked to worse outcomes. Therefore, it is vital to stay informed about the latest advancements in PPGL pathology. This brief review provides an overview of the challenges associated with PPGLs and highlights the most recent developments in tumor prognostication.