Tumor Educated Platelets as a Biomarker for Diagnosis of Lung cancer: A Systematic Review.

INTRODUCTION: Lung cancer is one of the commonest cause of cancer associated mortality worldwide. Platelets have emerged as key players in cancer development and progression by supporting tumor growth, and dissemination. In the present systematic review, we analyzed RNA transfer between cancer cells and platelets and explored potential role of different platelet RNA profiles as onco-signature in diagnosis, subtyping, disease progression and treatment monitoring in carcinoma lung carcinoma. MATERIALS AND METHODS: The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Manual of Systematic Reviews and Meta-analysis that included seven studies on patients with lung cancer, with data on tumor-educated platelets, and control group. The outcome measured was based on sensitivity, specificity, and ROC. PUBMED, SCOPUS, Central Cochrane Registry of Controlled Trials and Science Direct databases were searched using specific search terms until October 2023. QUADAS - 2 tool was used to assess quality, risk of bias and applicability concerns. RESULTS: The analysis revealed AUC > 70% for different platelet mRNAs, with sensitivity and specificity of more than 60 %. AUC and sensitivity were highest for ITGA2B (AUC 0.922; sensitivity 92.8%). lncRNA GTF2H2-1 was the most specific platelet RNA. On QUADAS-2 tool, 3/7 articles were unclear in reference standards, patient flow timing, and 1/7 had high bias in both aspects. For applicability, 1/7 studies were unclear in reference standards, and 2/7 in index tests. CONCLUSION: TEP RNA can aid in early diagnosis of lung cancer and of proven utility in its early-stage detection. TEP RNA can also monitor disease progression and treatment response.

The spectrum of microvascular patterns in adult diffuse glioma and their correlation with tumor grade.

BACKGROUND: Primary brain tumors constitute the leading cause of cancer-related mortality. Among them, adult diffuse gliomas are the most common type, affecting the cerebral hemispheres and displaying a diffuse infiltrative pattern of growth in the surrounding neuropil that accounts for about 80% of all primary intracranial tumors. The hallmark feature of gliomas is blood vessel proliferation, which plays an important role in tumor growth, tumor biological behavior, and disease outcome. High-grade gliomas exhibit increased vascularity, the worst prognosis, and lower survival rates. Several angiogenic receptors and factors are upregulated in glioblastomas and stimulate angiogenesis signaling pathways by means of activating oncogenes and/or down-regulating tumor-suppressor genes. Existing literature has emphasized that different microvascular patterns (MVPs) are displayed in different subtypes of adult diffuse gliomas. METHODS: We examined the distribution and biological characteristics of different MVPs in 50 patients with adult diffuse gliomas. Haematoxylin and eosin staining results, along with periodic acid-Schiff and CD34 dual-stained sections, were examined to assess the vascular patterns and correlate with different grades of diffuse glioma. RESULTS: The present observational study on adult diffuse glioma evaluated tumor grade and MVPs. Microvascular sprouting was the most common pattern, while a bizarre pattern (type 2) was associated with the presence of a high-grade glioma. Vascular mimicry was observed in 6% of cases, all of which were grade 4 gliomas. CONCLUSIONS: This study supplements the role of neo-angiogenesis and aberrant vasculature patterns in the grading and progression of adult diffuse gliomas, which can be future targets for planning treatment strategies.

The Role of Cytomorphometric Image Analysis in the Diagnosis of Thyroid Nodules.

Introduction Fine needle aspiration cytology (FNAC) plays a vital role in the diagnosis of thyroid nodules. However, it is challenging due to the heterogeneity of thyroid nodules, overlapping cytomorphological features, and interobserver variability. Cytomorphometric analysis turns subjective observations into quantitative values. In this study, we performed cytomorphometric image analysis on cytological smears of thyroid nodules, classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Materials and methods A retrospective analysis of Papanicolaou (PAP) and Hematoxylin & Eosin (H&E) stained fine needle aspirate smears from 50 patients with thyroid nodules with available follow-up histopathology was performed for a period of two years (March 2021 - March 2023), after obtaining approval from the institutional human ethical committee (IHEC-LOP/2020/IM0355). The nodules were categorized according to TBSRTC and were then subjected to cytomorphometric image analysis. Each nucleus was analyzed for 14 parameters, including aspect ratio, intensity, diameter, perimeter, roundness, area, fractal dimension, feret diameter, circularity, radii, fournier description, and chromatin texture parameters such as heterogeneity and clumpiness. The data obtained was analyzed through relevant statistical methods using SPSS version 23 (IBM Inc., Armonk, New York) and was compared by using the analysis of variance (ANOVA) test and post hoc test. Results Our results revealed that cytomorphometric image analysis not only distinguishes benign and malignant thyroid nodules but also can aid in categorizing thyroid nodules with predominant follicular patterns, such as follicular variant of papillary carcinoma, follicular adenoma and follicular carcinoma (p<0.001). Conclusions Morphometric analysis of cytological smears combined with cytomorphology has the potential to be an important tool in the diagnosis of thyroid nodules. It can improve diagnostic accuracy for better treatment and improved prognosis.

Preliminary Experience in Post-COVID-19 Mycoses: A Pathologist's Perspective.

Background Coronavirus disease is caused by the severe acute respiratory syndrome coronavirus-19. Because of co-morbidities and indiscriminate use of steroids and antibiotics, the incidence of opportunistic fungal infections has increased in COVID-affected individuals. Aims and objectives The aim of the study is to analyze the various tissue reaction patterns of COVID-19-associated mucormycosis in the surgical debridement specimens using routine hematoxylin and eosin (H&E) stain and special stains like periodic acid-Schiff (PAS), Grocott-Gomori's methenamine silver (GMS), Masson trichrome (MT) and Prussian blue (PB), and to understand the pathogenesis of COVID-19 sequelae. Materials and methods This retrospective observational study was conducted after the approval from the Institute Human Ethical Committee (IHEC) on 45 tissue samples of COVID-associated mucormycosis using routine H&E and histochemical stains such as PAS, GMS, MT, and PB. Detailed demographic profiles, clinical information, radiological findings, and relevant microbiological data in available cases, like reports on potassium hydroxide (KOH) mount preparation, and fungal culture reports on Saboraud's Dextrose Agar (SDA) medium were collected. The different histomorphological tissue reaction patterns were observed and analyzed. Results All the surgical debridement specimens from post-COVID cases had histomorphology of mucormycosis displaying broad, aseptate, ribbon-like fungal hyphae with right-angle branching (45/45). Six of the 45 cases also reveal thin, narrow septate, acute angle branching hyphae, indicating co-existing Aspergillosis (6/45). The histological tissue reaction patterns observed were categorized as extensive tissue necrosis (100%), vascular proliferation (82%), angioinvasion (58%), giant cell reaction (53%), fibrin thrombi (47%), septic thrombi and angiodestruction (40%), fungal osteomyelitis (33%), necrotizing granulomas (31%). Conclusion This study infers that post-COVID-19 associated mucormycosis, alterations in the local tissue microenvironment are found to have a favorable effect on colonizing fungi and result in destructive tissue reactions such as angioinvasion, angiodestruction, necrosis, necrotizing granulomas, suppurative inflammation, and iron pigment deposition. The spectrum of morphological changes reflects the host's immune status.

Unusual coexistence of Stewart-Treves syndrome and sickle cell anaemia: a case of dual pathology.

Chronic lymphoedema can rarely be complicated by an angiosarcoma. This combination called Stewart-Treves syndrome usually observed in upper limb in patients of post-mastectomy with axillary lymph node resection. Here, we report a male patient who had a 10-year history of right leg elephantiasis. Later on, he developed two large ulceronodular masses in the same leg with few satellite nodules in the surrounding skin. With the clinical suspicion of malignancy, a wedge biopsy was performed which revealed histological features of angiosarcoma with sickled red cells. The above knee amputation specimen received further confirmed the histological diagnosis. The investigation for haemoglobinopathy also suggested the presence of sickle cell trait. This report describes a multifocal tumour as a rare manifestation of Stewart-Treves syndrome in a post-filariasis case with sickle cell trait, which is an extremely uncommon combination.

Lymphocytic Hypophysitis: An Underrated Disease.

Lymphocytic hypophysitis (LYH) is a rare inflammatory disease in which lymphoplasmacytic infiltration of the pituitary gland can potentially lead to panhypopituitarism. This entity was first recognized in 1962 by Goudie and Pinkerton. We report the case of a 36-year-old nonpregnant female operated for a presumed nonsecreting pituitary adenoma. On intraoperative squash cytology and histology of excision biopsy confirmed the diagnosis of LYH. Review of the literature shows that most reported cases have occurred in women during pregnancy or during postpartum period. Many were accurately diagnosed only after biopsy or at necropsy. It is suspected to be an autoimmune endocrinopathy as concomitant lymphocytic infiltration of the thyroid and pituitary glands has been noted and antipituitary antibodies have been found in some instances. Clinically and radiologically, LYH may mimic a nonsecretory pituitary adenoma. Intraoperative diagnosis may prevent unnecessary excision of potentially functioning pituitary.

Primary Vaginal Amelanotic Melanoma: A Diagnostic Conundrum.

Primary vaginal amelanotic melanoma (PVAM) is an exceptionally rare aggressive malignancy having a poor prognosis. PVAM shows a high incidence of recurrence, regional spread, and early metastasis that contribute to a high mortality rate. The majority of primary vaginal malignant melanomas are pigmented, and <10% are amelanotic. Because of the absence of melanin pigment in tumor cells, PVAM may mimic other common vaginal malignancies having a more favorable prognosis and may lead to diagnostic conundrum. Knowledge regarding varied histological features and immunohistochemistry can help in establishing the correct diagnosis. Magnetic resonance imaging (MRI) provides valuable information related to the extent of vaginal malignancy and the involvement of regional lymph nodes. Conservative surgery is used for early-stage disease, whereas advanced stages are treated with radical surgery, chemotherapy, radiotherapy, immunotherapy, and targeted therapy.

Clear-cell meningioma: Intraoperative diagnosis by squash cytology: Case report and review of the literature.

Clear-cell meningioma (CCM), an unusual subset of meningioma has prominent, clear-cell morphology. It is a wolf in sheep's clothing characterized by benign histologic attributes, but tendency for recurrence (61%) and metastasis. Therefore, WHO has classified it as grade II meningioma. Fine-needle aspiration cytology diagnosis is simple, rapid, cost-effective and reliable procedure primarily aimed at preoperative diagnosis of advanced and metastatic extracranial tumor. Preoperative and/or intraoperative cytodiagnosis of CCM demand expertise in the evaluation of cytology smears. However in case of intra operative evaluation of squash smears there is a time constraint and a very small tissue material obtained by stereotactic biopsy are available for interpretation. Knowledge of clinical features including age, anatomical locations, neuroimaging findings and cytomorphologic features, are prerequisites for arriving at definitive cytodiagnosis. We describe intra operative squash cytology of CCM in a 16-year-old female, located in cerebello-pontine angle. The diagnosis of CCM offered on squash cytology was subsequently confirmed on histopathology and immunohistochemistry. It typically showed pattern less sheets and groups of polyhedral, clear cells with monomorphic, round nuclei having a bland chromatin and inconspicuous nucleoli. Separation of CCM from other tumors having clear -cell morphology and variants of meningioma is important because of its high recurrence rate and mortality.

Renal Clear Cell Sarcoma - Anaplastic Variant: A Rare Entity.

Clear Cell Sarcoma of Kidney (CCSK) is known for its morphologic diversity, aggressive behaviour, tendency to recur and metastasis to bone. Amongst the various morphologic subtypes, anaplastic CCSK is associated with worse prognosis. Here, we report a case of this rare variant of CCSK. A five-year-old boy presented with history of lump and pain in abdomen since one week. The Computed Tomography (CT) scan revealed a large mass occupying the middle and inferior pole of right kidney. The clinical impression was Wilms tumour. Nephrectomy specimen was received and the diagnosis of CCSK anaplastic variant was offered only after excluding the differentials and after performing ancillary tests such as Immunohistochemistry (IHC). Thus, this case emphasizes the diagnostic challenges on morphology and the essential role of IHC in arriving at a definitive diagnosis, because failure to do so may deprive the child from optimal treatment.

Comparative evaluation of six parametric Robinson and three parametric Howell's modification of Scarf-BloomRichardson grading method on breast aspirates with histopathology: A prospective study.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a quick method to assess the tumor grade before its removal which will help clinicians to decide on the appropriate neo adjuvant therapy. This is essentially true in developing countries where core needle biopsy still is not used as a standard practice to sample breast carcinoma. Assessment of biological aggressiveness by cytological grading (CG) without removing the would be of immense value. The National Cancer Institute, Bethesda, sponsored conference had recommended that tumor grading on FNA material should be incorporated in cytology reports for prognostication. AIM: The present study was carried out to evaluate which among the two, five parametric Robinson or three parametric Scarf-BloomRichardson (SBR) cytology grading method corresponds better with the histological grading (HG) in breast carcinoma. MATERIALS AND METHODS: FNAC of 150 cases of ductal carcinoma breast with subsequent histological confirmation was studied to assess the tumor grade on cytology by two distinct methods Robinson and Howell's modification of SBRmethod and then correlated with histologic grade. RESULTS: Comparative analysis revealed concordance of 76% by Robinson and 68% by SBR with Kappa value of 0.6683 and 0.4505 and diagnostic accuracy of 86.7% and 78.7%, respectively. CONCLUSIONS: We conclude that Robinson method showed a better correlation and higher kappa value of agreement in comparison with SBR method. Robinson method of CG is simpler, objective, and easily reproducible for grading breast carcinomas.

Cytodiagnosis of chondromyxoid fibroma.

Chondromyxoid fibroma (CMF) is an unusual tumor that predominantly affects long bones of young adults. We present two cases of CMF that were diagnosed on cytology. The specific cytological features included varying combinations of chondroid, myxoid and fibroid elements. These features when correlated with clinico-radiological findings helped to arrive at a correct diagnosis. Thus a definitive diagnosis of CMF can be made on cytology based on which further line of treatment can be planned.

Adenoid cystic carcinoma of the external auditory canal: report of two cases.

Adenoid cystic carcinoma occurring in the external auditory canal is very rare. Two cases are being reported. One was diagnosed on cytology based on which surgery was planned. In the second case, fine needle aspiration procedure had to be abandoned due to severe pain and a biopsy was required for its diagnosis. Morphologically, it resembles its more common salivary gland counterpart. Though severe pain during needling may be a limiting factor, adenoid cystic carcinoma of external auditory canal can be confidently diagnosed on cytology based on which surgical management can be planned.

Haematological study in sickle cell homozygous and heterozygous children in the age group 0-6 years.

Sickle cell anaemia is a common and widespread haemoglobinopathy with large clinical heterogeneity. The present study, was undertaken to determine seven different haematological parameters (Haemoglobin percent, RBC count, PCV, MCV MCH, MCHC, Reticulocyte count) on total 102 heterozygous (SA) and homozygous (SS) sickle cell children under six years of age. In addition, fetal haemoglobin (HbF) level was estimated in SS children and correlated with clinical status, gender and ethnic background. Mean HbF was 16.79%. Higher HbF level was associated with less severe clinical feature. HbF was not influenced by gender and ethnic background. In homozygous children mean values of MCV, MCH, MCHC were decreased while reticulocyte count was increased as compared to control (AA) children and (SA) children (P < 0.05) We conclude that, in sickle cell disease, HbF was a good prognostic indicator. Higher HbF level along with microcytic hyopochromic indices and lower MCHC was found to be a feature of the study population.