The Evolution of Ovarian Carcinoma Subclassification

The phenotypically informed histotype classification remains the mainstay of ovarian carcinoma subclassification. Histotypes of ovarian epithelial neoplasms have evolved with each edition of the WHO Classification of Female Genital Tumours. The current fifth edition (2020) lists five principal histotypes: high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), mucinous carcinoma (MC), endometrioid carcinoma (EC) and clear cell carcinoma (CCC). Since histotypes arise from different cells of origin, cell lineage-specific diagnostic immunohistochemical markers and histotype-specific oncogenic alterations can confirm the morphological diagnosis. A four-marker immunohistochemical panel (WT1/p53/napsin A/PR) can distinguish the five principal histotypes with high accuracy, and additional immunohistochemical markers can be used depending on the diagnostic considerations. Histotypes are further stratified into molecular subtypes and assessed with predictive biomarker tests. HGSCs have recently been subclassified based on mechanisms of chromosomal instability, mRNA expression profiles or individual candidate biomarkers. ECs are composed of the same molecular subtypes (POLE-mutated/mismatch repair-deficient/no specific molecular profile/p53-abnormal) with the same prognostic stratification as their endometrial counterparts. Although methylation analyses and gene expression and sequencing showed at least two clusters, the molecular subtypes of CCCs remain largely elusive to date. Mutational and immunohistochemical data on LGSC have suggested five molecular subtypes with prognostic differences. While our understanding of the molecular composition of ovarian carcinomas has significantly advanced and continues to evolve, the need for treatment options suitable for these alterations is becoming more obvious. Further preclinical studies using histotype-defined and molecular subtype-characterized model systems are needed to expand the therapeutic spectrum for women diagnosed with ovarian carcinomas.

Evaluation of P40 and Napsin A in the Differential Diagnosis of Non Small Cell Bronchogenic Carcinoma on Small Lung Biopsies

BACKGROUND :- Lung cancer is the leading cause of cancer-related mortality over word wide, Although the pathological diagnosis of lung carcinoma is limited as only small specimen available for diagnosis.the availability of targeted therapies has created a need for precise subtyping of non-small cell lung carcinoma . Several recent studies have demonstrated that the use of Immunohistochemical markers can be helpful in differentiating lung squamous cell carcinoma (LSCC) from lung adenocarcinoma (LAC) not on surgically resected material but also on small biopsy samples and cytology. AIM (1) To classify the non small cell lung carcinoma into major categories like squamous cell carcinoma (LSCC) and adenocarcinoma (LAC) and other categories by applying immunohistochemicalmarker like p40 (truncated p63) and Napsin A (2) To analyse the sensitivity and specificity of p40 and Napsin A in light of histomorphology and/or other relevant immunohistochemical markers available, using appropriate statistical tests. Material and methods:- This study was a one and half year (18 months) prospective study from Jan 2017 to June 2018, conducted in department of pathology on patients attending the outpatient and inpatient department of TB and respiratory disease, a total of 210 bronchoscopic guided biopsies / transthoracic (CT/MRI /guided) small tissue biopsies from the patients suspected of lung malignancy were incorporated in the study. 20 corresponding resection specimens (wedge resection and lobectomy) were also included in the study for correlation of morphology and immunohistochemical findings on small biopsies. RESULTS:-In our study IHC for both p40 and napsin –A aided in subtyping of 71.9% cases of non small cell lung carcinoma and this diagnostic accuracy was found to be statistically significant with p-value < 0.05.,on statistical analysis we found that napsin-A had a sensitivity of 90% and specificity of 80%. Also, positive predictive value and negative predictive value were seen to be 88.0% and 81.8% respectively.

Desmoplastic fibroblastoma (collagenous fibroma) on the mandibular ridge: case report and review of immunohistochemical markers

The desmoplastic fibroblastoma (DF) is a rare benign soft-tissue tumor of fibroblastic and myofibroblastic origin, and its occurrence in the oral cavity is rare. This study details a new case of an elevated lesion in the alveolar ridge of a 59-year-old woman, painful during mastication. The histopathological exam showed non-encapsulated stellate-to-spindle cells proliferation in a hypocellular collagen-rich stroma. Tumor cells were strongly and diffusely positive for vimentin, and some cells were focally positive for α-smooth muscle actin, CD99, and β-catenin. The exams were conclusive for DF diagnosis. The patient is in the follow-up period, and no recurrent lesions were detected within one year. Despite having similar clinical, pathological, and immunohistochemical features to the cases previously described, the DF in this report is at an unusual oral site and associated with painful symptomatology. Immunohistochemistry is an important tool in DF cases where the histopathological examination is not conclusive.

Neuroendocrine Neoplasms of Breast:A Rare Breast Tumor Worthy of Attention

Background: Neuroendocrine neoplasms of breast(NENB) is a rare and underrecognized subtype of breast neoplasms.The clinical significance, prognostic risk factors and optimal treatment modalities are limited. This study was focused on clinical and pathological features of 27 NENB cases to improve the understanding of these diseases and to further investigate the behavior of these neoplasms and to provide more factual evidence.Methods: We retrospectively analyzed the clinicopathological features and follow-up data of 27 patients diagnosed with NENB at the First Affiliated Hospital of Bengbu Medical College between February 2003 and February 2015.Results: The proportion of NENB from all invasive breast carcinomas(BC) in our hospital was 0.24% (27/11352). The expression of specific immunohistochemical markers was different: 48.1% cases showed the expression of chromogranin A (CgA)(13/27), CD56 was positive in 77.8%cases (21/27), the positive rate of INSM1 and synaptophysin (Syn) were 85.2%（23/27）and 100.0% (27/27). NENB occurred in older patients (median age,64 ).11cases (40.7%) were well-differentiated NETs and 16 cases (59.3%) were poorly differentiated NEC. In NETs, The positive rate of ER was 10/11 (90.9%) , while in NECs, The positive rate of ER was 9/16(56.3%) , On the basis of immunophenotypes, most of NENBs were of the luminal molecular subtype ,6 cases were luminal A and 15cases were luminal B ,6 cases were triple negative breast cancer(TNBC) and had no HER-2 overexpression subtypes. Conclusions: NENB more likely occures in elderly patients.Well-differentiated NETs are more often positive for hormone receptors than poorly differentiated NEC. NENBs are almost negative for HER-2. The combination of INSM1 is an effective supplement and improvement for traditional neuroendocrine markers.

Emerging Biomarkers in Thyroid Practice and Research

Thyroid cancer is the most common endocrine malignancy. Recent developments in molecular biological techniques have led to a better understanding of the pathogenesis and clinical behavior of thyroid neoplasms. This has culminated in the updating of thyroid tumor classification, including the re-categorization of existing and introduction of new entities. In this review, we discuss various molecular biomarkers possessing diagnostic, prognostic, predictive and therapeutic roles in thyroid cancer. A comprehensive account of epigenetic dysregulation, including DNA methylation, the function of various microRNAs and long non-coding RNAs, germline mutations determining familial occurrence of medullary and non-medullary thyroid carcinoma, and single nucleotide polymorphisms predisposed to thyroid tumorigenesis has been provided. In addition to novel immunohistochemical markers, including those for neuroendocrine differentiation, and next-generation immunohistochemistry (BRAF V600E, RAS, TRK, and ALK), the relevance of well-established markers, such as Ki-67, in current clinical practice has also been discussed. A tumor microenvironment (PD-L1, CD markers) and its influence in predicting responses to immunotherapy in thyroid cancer and the expanding arena of techniques, including liquid biopsy based on circulating nucleic acids and plasma-derived exosomes as a non-invasive technique for patient management, are also summarized.

The morphology of the elements of the myocardial contractile apparatus question and research prospects

Background. Over the past 50 years, specific methods for studying the ultrastructure of the heart have been rapidly developed. The complex interaction of various research methods makes it possible to more accurately form a representation of the spatial structure of the components of the myocardial contractile apparatus. Objective. To conduct a content analysis of the results of the study of the composition of the myocardial contractile apparatus. Conduct a broad analysis of literary references and form an understanding of the spatial structure of the components of the myocardial contractile apparatus in the prospect of research at different levels of cell organization. Methods. Processing of information sources was carried out by the method of complex meta-analysis of data analysis. Results. The morphological characteristics of the myocardial contractile apparatus include a number of broad profile elements. The system of composite elements of the contractile apparatus of cardiomyocytes is the most formed and developed in the structure of the cytoplasmic complex of organelles in the group of contractile cardiomyocytes. The complex of the contractile apparatus is represented by myofibrils, each of which consists of thousands of sarcomeres telophragm connected in series, containing actin (thin) and myosin (thick) myofilaments. The main methods for studying the contractile apparatus of the myocardium include how immunohistochemistry and transmission electron microscopy provide an understanding of the structure of components at various levels of organization of histoarchitectonics and ultrastructure of organelles.. The contractile apparatus of the myocardium includes species-specific organelles, which basically belong to a number of basic hardware systems of cardiomyocytes. Conclusion. Immunohistochemical methods should clearly show the localization of individual tipes of elements in the protein structure of the contractile apparatus of the myocardium, and therefore should include in the study methods the use of the following immunohistochemical markers that can show the configuration of thin and thick myofilaments. The results of analytical review and analysis of information sources on the characteristics of the components of the myofibrillar complex gives a choice of specific research methods and forms a more detailed understanding of the spatial organization of the morphology of the myocardial contractile apparatus.

State-of-Art in the Age Determination of Venous Thromboembolism: A Systematic Review

Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), requires a forensic age determination to ascertain their causal relationship with recent events, such as trauma or medical treatment. The main objective of this systematic review is to identify the current state-of-the-art immunohistochemical methods for age determination of fatal VTE. A literature search was performed through different databases, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Within the study, we have selected only cases represented by deceased patients for DVT and/or PTE in which thromboembolic material was collected during an autoptic examination and then subjected to a histological and an immunohistochemical investigation. Studies based on animal models were not included. We assessed bias risk. A database-based search produced a total of 19 articles. After excluding duplicate items from the selection, 14 articles were reviewed. Ten articles were excluded because they did not meet the inclusion criteria. The results have pointed out 4 studies that were included in the present analysis for a total of 157 samples of DVT and 171 PTE samples. These were analyzed using traditional histological and immunohistochemical techniques. The results must be interpreted with a critical eye because of their heterogeneity in terms of time, geography, and study design. The present review highlights the importance of associating specific immunohistochemical markers with a histological analysis for the timing of DVT/PTE fatal events. Further future experiences will hopefully endorse actual knowledge on the subject to increase the accuracy in the assessment of thrombus-embolus age.

U lympho tế bào T dạng viêm mỡ dưới da ở trẻ em

TÓM TẮT U lympho tế bào T dạng viêm mỡ dưới da (Subcutaneous panniculitis - like T - cell lymphoma - SPTCL) là một u lympho hiếm gặp với tổn thương chủ yếu ở bề mặt da và tổ chức mỡ dưới da. SPTCL có thể xảy ra ở cả người lớn và trẻ nhỏ, độ tuổi trung bình được chẩn đoán là 30 tuổi, nữ nhiều hơn nam. Trong SPTCL, bệnh nhân có nhiều nốt tổn thương ở mô mỡ dưới da và có thể gây loét bề mặt da. Tổn thương này được biết đến như viêm mỡ dưới da. Cơ chế bệnh sinh chưa rõ ràng nhưng có sự tham gia của yếu tố di truyền. Chẩn đoán SPTCL vẫn còn là thách thức, chủ yếu dựa vào sinh thiết da với sự bộc lộ của các dấu ấn hóa mô miễn dịch (HMMD). Điều trị SPTCL chưa thống nhất, phụ thuộc vào triệu chứng nhưng thường sử dụng steroid hoặc các thuốc ức chế miễn dịch (ƯCMD). Một số bệnh nhân với SPTCL tiến triển cần điều trị hóa chất. Về tiên lượng, SPTCL thường tiến triển chậm, tuy nhiên khoảng 20% bệnh nhân có hội chứng thực bào máu (Hemophagocytic lymphohistiocytosis - HLH), những bệnh nhân này kém đáp ứng với điều trị và có tiên lượng xấu hơn. Chúng tôi báo cáo một bé trai 13 tháng tuổi vào viện vì sốt và nhiều khối tổn thương dưới da. Bệnh nhân được chẩn đoán viêm mô tế bào và điều trị kháng sinh 2 tuần nhưng bệnh không thuyên giảm. Sau đó, bệnh nhân được sinh thiết tổn thương dưới da, dựa trên kết quả nhuộm HMMD, chúng tôi kết luận phù hợp với SPTCL. ABSTRACT SUBCUTANEOUS PANNICULITIS - LIKE T - CELL LYMPHOMA IN A CHILD Subcutaneous panniculitis - like T - cell lymphoma (SPTCL) is a rare type of lymphoma that mainly affects the skin and subcutaneous fat tissue. SPTCL can occur in both adults and children. The average age at diagnosis is 30 years old, with more women than men. In SPTCL, the patient has multiple nodules in the fat layer under the skin, and these can cause swelling. This is known as panniculitis. The pathogenesis is unknown, but genetic factors may be involved. Diagnosis of SPTCL is challenging, mainly based on skin biopsies with staining of immunohistochemical markers. Treatment of SPTCL is inconsistent, depending on symptoms but usually using steroids or immunosuppressive drugs (ACEIs). Some patients with advanced SPTCL require chemotherapy. In terms of patients who have hemophagocytic lymphohistiocytosis (HLH), which is less responsive to treatment and has a worse prognosis. We report a 13 - month - old boy admitted to the hospital with fever and multiple subcutaneous lesions. The patient was diagnosed with cellulitis and treated with antibiotics for 2 weeks, but the disease did not improve. Then, the patient had a skin lesion biopsy. Based on the results of immunohistochemical staining, we concluded that it was suitable for SPTCL. Keywords: Subcutaneous panniculitis - like T - cell lymphoma, Immunohistochemical, Hemophagocytic lymphohistiocytosis.

Attenuating Effect of Vitamin E against Silver Nano Particles Toxicity in Submandibular Salivary Glands

Silver nanoparticles (AgNPs) are extensively used in many industries due to their superior antimicrobial properties. However, it is evident from many studies that AgNPs has cytotoxic potential through its effect on excessive formation of reactive oxygen species (ROS). The aim of this study was to examine the toxic effect of AgNPs on the submandibular salivary glands and the attenuating effect of vitamin E, as a natural antioxidant, against this toxicity. Thirty Albino rats were divided into 3 groups (n = 10): control group, AgNPs group receiving 2 mg/kg daily for 28 days, and AgNPs and vitamin E group receiving AgNPs the same as the previous group in addition to vitamin E at a dose of 100 mg/kg. Microscopic, ultrastructural, and cytokeratin immune-reactivity examination of the glands were performed. The AgNPs group showed noticeable degeneration in all structures of the gland as evident in the histological and ultrastructural examination. The AgNPs and vitamin E group revealed an improvement of the glandular elements. A significant increase in cytokeratin immune expression was found after comparison of both groups (p = 0.01). This current study shows that vitamin E has powerful antioxidant properties, which can combat the cytotoxic effect caused by AgNPs. Further studies are deemed necessary to confirm this finding using other immunohistochemical markers, such as myosin and E-cadherin.