Turkish Journal of Pathology - 2023; 39(1)

Proportionality of Clinical Outcome and Placental Changes to the Increasing Severity of Maternal Hypertension- An Observational Study

Priyadharshini BARGUNAM, Parvathi JIGALUR, Purushotham REDDY — 2023-01-01

Objective: Preeclampsia and eclampsia remain the major causes of maternal and perinatal mortality and morbidity worldwide, causing 12�15% of direct maternal deaths. Although preeclampsia and related hypertensive disorders of pregnancy continue to affect 8% of all pregnancies, the incidence of preeclampsia has increased 40% in recent years. This study was carried out to analyse the different placental lesions and fetal outcome in different grades of maternal hypertension and to see if there is a linear relationship of the same. Material and Method: A total of 539 placenta specimens received at the department of Pathology from October 2017 to March 2019 were collected after obtaining informed consent. Of the 539 placentas, 87 hypertensive cases were graded and grouped according to the severity as gestational hypertension, mild preeclampsia, severe preeclampsia, eclampsia, and chronic hypertension and compared with 88 normotensive cases. The gross and microscopic findings were tabulated and analysed using the Statistical Package for the Social Sciences (SPSS) software. Results: Incidence of fetal death and growth restriction increased with increasing grade of maternal hypertension (p= 0.001). Abnormal shape of placenta (p= 0.034) and abnormal umbilical cord insertion (p= 0.028) were seen significantly more in the hypertensive group than in the normotensive group. Infarct and abnormal vasculo-syncytial membrane (p< 0.05) and abnormal villous maturation (p= 0. 039) were significantly increased in the hypertensive group than the normotensive group. Conclusion: The incidence of adverse fetal outcome and placental changes suggestive of feto-maternal malperfusions shows a proportional trend with the increasing grade of maternal hypertension.

Problems in Postmortem Pathology Training

Ali R�za T�MER, Emirhan ESK�C�O�LU, Cenk S�KMENS�ER, Tu��e FINDIKO�LU — 2023-01-01

Objective: In Turkey, autopsy performers, namely forensic medicine practitioners, are neither pathologists nor have properly received pathology training during residency in contrast to the Anglo-Saxon model of forensic medicine practices, since the current curriculum of forensic medicine residency lacks adequate training in post-mortem histopathology. Likewise, pathologists lack a specific post-mortem pathology clerkship. In this study, we intended to determine whether forensic physicians in Turkey find themselves competent in post-mortem histopathology or were adequately trained during their residencies. Material and Method: Turkish forensic medicine practitioners were administered an online questionnaire whereby self-evaluations of their histopathology knowledge and their views on histopathology training during forensic medicine residency were assessed. The 151 physicians who completed the questionnaire made up the study group. Results: It was found out that the majority of Turkish forensic medicine practitioners (85.4%) did not find the histopathology training during their residency adequate. Similarly, 85.4% of the participants indicated their incompetence in histopathological examination of post-mortem tissue of any kind, and showed their willingness for further training in pathology. 66.9% strongly agreed that post-mortem histopathology requires training that is distinct from surgical pathology. In case of providing post-mortem histopathology training within the scope of forensic medicine residency, topics such as microscopic morphology of post-mortem changes, histological changes related to injuries, and estimation of wound age are expected to be beneficial to 88.7% 83.4%, and 83.4% of the participants respectively. Conclusion: The current curriculum should be revised in a way that the surgical pathology clerkship meets forensic physicians� needs, so that they can then refer more difficult, non-routine histopathological consultations to pathologists who are also well-trained in postmortem histopathology. Consideration should also be given to establishing a subspecialty training - a master�s or doctoral degree programs in forensic pathology.

TOX Outperforms FOXP3, CD4 and GATA3 in Histopathological Diagnosis of Early Mycosis Fungoides

2023-01-01

Objective: Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The early stage of MF is a difficult diagnostic case, as it is often confused with many benign inflammatory dermatoses (BID). The study aimed to evaluate the diagnostic utility of TOX, FOXP3, CDD4 and GATA3 in differentiating early stages of MF from histologically overlapping BID lesions. Material and Method: A retrospective cross-sectional study was performed, in which immunohistochemistry (IHC) was used to evaluate the expression of TOX, FOXP3, CD4 and GATA3 in formalin-fixed paraffin-embedded (FFPE) sections of skin lesions from 30 cases with BID and 30 patients with early-stage MF. Results: The association between TOX expression and early-stage MF was statistically significant (P <0.001). TOX had the highest sensitivity of 96.77% and accuracy of 85.71% in diagnosis of MF; followed by CD4 with sensitivity of 85.71% and accuracy of 78.95%; and then, GATA3 with sensitivity of 76.7% and finally FOXP3 with sensitivity of 70.0%. Conclusion: TOX is suggested to be of higher diagnostic value in the early stages of MF than the conventionally used CD4 and other markers examined.

BRAF, NRAS, KIT, TERT, GNAQ/GNA11 Mutation Profile and Histomorphological Analysis of Anorectal Melanomas: A Clinicopathologic Study

2023-01-01

Objective: Primary anorectal melanomas (AMs) are uncommon neoplasms with aggressive behavior. Molecular profile and clinicopathologic features of AMs are still not well established. In this study, we aimed to investigate BRAF, NRAS, KIT, TERT, and GNAQ/GNA11 mutation status and clinicopathologic features of AMs. Material and Method: All diagnostic slides of 15 AMs were reviewed. Histopathological and follow-up information were documented. Mutations in exon 15 of the BRAF gene; exons 2 and 3 of the NRAS gene; exons 9, 11, 13, 17, and 18 of the KIT gene; and exons 4 and 5 of the GNAQ/GNA11 genes and mutations in the promoter region of the TERT gene (chr.5, 1,295,228C>T and 1,295,250C>T) were analyzed. Results: BRAF(V600E) and KIT(V555I and K642E) mutations were observed in one (7%) and two cases (14%), respectively. NRAS, TERT and GNAQ/GNA11 mutations were not detected. The mean age was 65. Patients presented with rectal mass, rectal bleeding, pain, and weight loss. 73% of the lesions were macroscopically polypoid. The most common tumor cell type was epithelioid. Mean tumor thickness was 10.4 mm. One third of the cases lacked pigmentation. In situ melanoma was present in one third of the cases. Among 14 patients with follow-up data, 12 succumbed to disease. The mean overall survival was 36 months. Conclusion: AMs are uncommon tumors with dismal survival, usually occurring in the elderly in various gross and microscopic appearances. In terms of molecular profile, BRAF and KIT mutations are rarely detected. Profiling of larger cohorts is required to elucidate the pathogenesis and to identify potential molecular indicators that may contribute to the development of individualized targeted therapies.

Microsatellite Instability Status and the Expression of p16 and Cyclin D1 Proteins in Uterine Adenosarcoma and Their Clinicopathological Significance

2023-01-01

Objective: Uterine adenosarcoma has low malignant potential, except in cases with sarcomatous overgrowth (SOG) and a high-grade morphology. We here point out the prognostic clinicopathological and immunohistochemical features as well as the microsatellite instability (MSI) status of high- and low-grade adenosarcomas. Material and Method: In this study, DNA mismatch repair proteins, p16, cyclin D1, ER, PR, and CD10 were examined in uterine adenosarcoma cases using immunohistochemistry. The association between these proteins and clinicopathological parameters was also evaluated. Results: ER, PR and CD10 expressions were lower and weaker in high-grade adenosarcomas with SOG compared to low-grade adenosarcomas without SOG (p < 0.05). p16 positivity was more frequent in high-grade adenosarcomas than low-grade adenosarcomas (p < 0.05). There was no statistically significant difference between cyclin D1 positivity, MSI, and other clinicopathological parameters (p ≥ 0.05). Cyclin D1 positivity and loss of CD10 expression were associated with shorter disease-free survival (DFS). Loss of ER and CD10 expression was associated with shorter overall survival (OS) (p < 0.05). MSI was not associated with DFS or OS (p ≥ 0.05). Conclusion: These results suggested that p16 positivity, and loss of ER, PR, and CD10 expression were predictors of high-grade morphology. Additionally, the current study showed that cyclin D1-positive tumors had high recurrence rates; however, no significant relationships were found between MSI and DFS or OS in patients with uterine adenosarcoma. Further investigations are required to determine the importance of p16, cyclin D1, and MSI in uterine adenosarcomas.

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

2023-01-01

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.

cERBB-2/Her-2 Neu Overexpression and Prognostic Significance in Uterine Carcinosarcoma

2023-01-01

Objective: There is not enough data in the literature regarding Her-2 overexpression in uterine carcinosarcomas or its association with the prognosis. The aim of this study was to determine the Her-2 overexpression rate in uterine carcinosarcoma and to evaluate its relationship with the prognosis. Material and Method: Her-2 protein and gene status were evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively, in hysterectomy specimens from 51 patients with uterine carcinosarcoma. Results: Her-2 protein expression in the epithelial component was negative in 42 patients (score 0 in 33 cases, score (+1) in 9 cases), score (+2) in 7 patients and score (+3) in 2 patients. None of the patients had Her-2 protein expression within the sarcomatous component of the tumors. Her-2 gene was not amplified in epithelial or mesenchymal tumor areas according to the FISH method. There was no difference between the Her-2 overexpression negative and positive groups in terms of disease-free survival (DFS) and overall survival (OS). Her-2 overexpression was significantly higher in tumors of patients diagnosed at 65 years or older (p=0.046). Conclusion: In our study, no relationship could be shown between Her-2 overexpression and prognosis in uterine carcinosarcoma. More comprehensive studies are needed to illustrate the relationship between Her-2 overexpression and carcinosarcoma prognosis.

Evaluation of MUC1, MUC2, MUC5AC, and MUC6 Expression Differences in Lung Adenocarcinoma Subtypes by Using a Final Immunoreactivity Score (FIRS)

2023-01-01

Objective: Lung adenocarcinomas are divided into acinar, lepidic, papillary, micropapillary, and solid predominant subtypes according to the current World Health Organization (WHO) classification. We designed this retrospective study to demonstrate profiles of MUC expression (MUC1, MUC2, MUC5AC, and MUC6) of different histologic patterns within the same tumor among pulmonary adenocarcinomas and investigate correlations of MUC expression with clinicopathologic features. Material and Method: We analyzed the expression of mucins (MUC1, MUC2, MUC5AC, and MUC6) in a series of 99 resected lung adenocarcinomas, which included a total of 193 patterns (71 acinar, 30 lepidic, 25 papillary, 20 micropapillary, 34 solid and 13 mucinous) and calculated a final immune reactivity score (FIRS) per tumor. Results: MUC1 IRS scores were significantly higher in lepidic and solid patterns compared with mucinous patterns (p=0.013). MUC2 expression was seen only in three cases (1 acinar, 2 mucinous). MUC5AC and MUC2 expression was more common in mucinous patterns (p<0.001 and p=0.028, respectively). MUC6 expression was only detected in seven patterns and the expression was weak. No significant difference was seen among histologic patterns for the staining scores of MUC6. Mucinous adenocarcinoma differed from other histologic subtypes regarding MUC1 and MUC5AC expression. Mucinous adenocarcinoma showed less MUC1 expression with lower IRS scores and higher MUC5AC expression. Tumor size (p=0.006), lymphatic invasion (p=0.018), vascular invasion (p=0.025), perineural invasion (p=0.019), MUC1 IRS scores (p=0.018), and MUC1 IRS scores >8.5 (p=0.018) were significant predictors for lymph node metastasis. Conclusion: An alternative scoring for MUC1 can be used as a predictor for lymph node metastasis regardless of the histologic subtype.

High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients

2023-01-01

Objective: The mortality incidence of endometrial carcinomas (ECs) has increased in recent years. Therefore, recent studies have focused on the cellular and microenvironmental properties of ECs. Tumor-infiltrating lymphocytes (TILs), a component of the microenvironment, have been found to be associated with the prognosis in many tumors. Although TILs were mostly evaluated by immunohistochemical studies in ECs, in our study, the evaluation was done with a light microscope as a practical approach, and we aimed to determine the prognostic importance of TILs in endometrioid ECs. Material and Method: 104 patients were included in the study. TILs in the stromal area (sTILs) were evaluated on hematoxylin and eosin (HE) stained-sections at X200 objective. The presence of TILs was evaluated as follows; 0-10% as low, 20-40% as moderate, and 50-90% as intense. Then TILs were grouped as low and high. Results: Tumors with high TILs were more prone to have FIGO (International Federation of Gynecology and Obstetrics) grade 1 tumors, low nuclear grade, early pathological stage, smaller size, no lymphovascular invasion, myometrial invasion below 50%, and no cervical involvement. In the presence of high TILs, the overall survival showed significant increase but no significant correlation was found with disease-free survival. Conclusion: Interest in the molecular properties of ECs has increased in recent years. TIL, which can be easily evaluated in HE sections, is an important parameter in patient selection for molecular tests and determining the prognosis of patients.

The Prognostic Impact of Tumor Border Configuration, Tumor Budding and Tumor Stroma Ratio in Colorectal Carcinoma

2023-01-01

Objective: Tumor border configuration, tumor budding and tumor stroma ratio are reliable histopathological parameters that play a central role in the invasion-metastasis cascade. This study aimed to investigate the prognostic impact of these parameters and a new combined score in colorectal cancer. Material and Method: A cohort of 103 colorectal cancer surgical specimens was retrospectively evaluated for tumor border configuration, tumor budding and tumor stroma ratio using H&E sections. A combined risk score was then constructed to divide cases into low risk-tumors and high risk-tumors. Results: Infiltrating tumor border, high tumor budding, low tumor stroma ratio and high combined risk score were associated with positive lymph node involvement, presence of metastasis, high tumor grade, lymphovascular invasion, poor overall survival and short recurrence-free survival. Infiltrating tumor border, high tumor budding and high combined risk score were associated with advanced T stage. High tumor budding, and low tumor stroma ratio were associated with perineural invasion. Infiltrating tumor border was associated with increased tumor size and conventional adenocarcinoma, high tumor budding and low tumor stroma ratio. Low tumor stroma ratio was associated with high tumor budding. On multivariate survival analysis, tumor stroma ratio was found to be an independent predictor for overall survival and recurrence-free survival. Conclusion: Tumor border configuration, tumor budding, tumor stroma ratio and the newly constructed combined risk score are potential predictors of outcome in colorectal cancer patients, suggesting that their incorporation in the routine histopathological evaluation could be useful in determining the prognosis of colorectal cancer cases.

Epithelioid Hemangioendothelioma in the Tongue: A Rare Case Report

Deniz SURMELI CIRKIN, Ilke Evrim SECINTI, Esin DOGAN, Gul SOYLU OZLER — 2023-01-01

Epithelioid hemangioendothelioma is a rare malignant vascular neoplasm caused by the proliferation of neoplastic endothelial cells. Epithelioid hemangioendothelioma may develop in any organ, but it is commonly observed in the extremities. The tongue is a very unusual location for epithelioid hemangioendothelioma. A 55-year-old male patient presented to the outpatient head and neck clinic with lumps in the tongue, pain, and limitation of motion. The polypoid mass detected in the anterior midline of the tongue was excised. Microscopically, the tumor cells included slightly pleomorphic oval or round vesicular nuclei with an eosinophilic cytoplasm that variably contained vacuoles. There were 4 mitoses per 10 high power fields and there was no necrosis. In immunohistochemical study, the tumor cells were positively stained with CD31 and CD34 whereas they were negatively stained with TFE3, SMA, S-100, HHV-8 and EMA. The patient was diagnosed with �epitheloid hemangioendothelioma�. Only ten cases have been reported in the tongue in the literature. Our case was the eleventh case, and we aimed to report this case as a rare entity with an unusual location.

A Rare Entity: Primary Pulmonary Meningioma

2023-01-01