Morphologic features of prostate cancer-encased native vessels: An image analysis study.

BACKGROUND: Vasculature plays a crucial role in the progression of prostate cancer (PC). Changes to the prostatic native vessels have not been studied since 2000 when Garcia et al. demonstrated marked media hypercellularity and increased artery thickness in prostatic native arteries within PC. We aim to further evaluate and characterize prostatic native vessels with a more accurate method with the use of virtual slides and digital analysis. DESIGN: Pathologist-annotated whole-mount digital slides from 96 entirely submitted prostatectomies were annotated for PC (color-coded by Gleason) using Omero platform. A subset of 44 cases met criteria for further analysis of media thickness, cellularity, and wall thickness to lumen ratio. Cases were included based on containing ≥5 native arteries (≥100 µm diameter) encased on at least 3 sides by PC, with vessels (≥100 µm diameter) designated as controls if they were ≥ 1000 µm away from PC. Annotated vessels were segmented and processed using Matlab 2023b. Mean media thickness (corrected for oblique sections), media: lumen ratio (based on numbers of pixels), and media cellularity (nuclei count) were studied by analysis with SPSS by linear mixed model with nested random effects for subject and slide to account for repeated measures. RESULTS: Vessels encased by PC showed greater media thickness (p=0.02), cellularity (p=0.02) and wall thickness/lumen ratio (p= <0.001) compared to vessels away from PC. These values showed an increasing trend according to stage in cellularity (p=0.14), media thickness (p=0.12) and wall thickness/ lumen ratio (p= 0.33) with higher stage (pT3). A Gleason group comparison showed a borderline-significant gradewise trend when analyzing wall thickness/lumen ratio (p=0.06). Grade 5 emerged as significantly different (p=0.02) from grades 3 or 4 non-cribriform. CONCLUSIONS: Similar to the 2000 study, increased media thickness and hypercellularity of vessels encased by PC were evident compared to controls. Borderline grade-dependent increased vessel cellularity changes were seen, suggesting a possible role in PC progression; the predictive value of these changes for outcome is uncertain. Whether the etiology of changes reflects locally increased intravascular pressure of vessels within tumor should be investigated.

Recurrence of gigantic overhanging bleb post excision: a case report.

Purpose: To report the case of an extremely large overhanging bleb, extending from superior fornix to limbus, in a 57-year-old poorly controlled diabetic, six years after trabeculectomy for an uncontrolled primary open angle glaucoma (POAG) with recurrence, months after complete excision. Methods: An overhanging bleb is defined as a filtering cicatrix which has been massaged downward over the cornea by eyelid action. It has been linked to anti-metabolite use during glaucoma filtering surgery. Despite being functional, these blebs result in patient discomfort ranging from foreign body sensation and lacrimation to dysphotopsia. A 57-year-old male presented with complaints of reduced vision, foreign body sensation, watering, and difficulty in eye closure in the left eye (OS) for past 6 months. He had undergone trabeculectomy with mitomycin C 6 years ago for advanced primary open-angle glaucoma with no follow-up beyond the initial one 4 weeks post-surgery. Results: At presentation, he had a giant multi-loculated, cystic filtering bleb (15 mm x 8 mm x 4-5 mm), which was carefully excised. Amniotic membrane was used as an anti-fibrotic as well to cover the defect. Seven months after surgery, there was recurrence of this overhanging cystic bleb when it was again excised with debulking of the conjunctiva done and cryotherapy applied to its margins. Conclusion: Although multiloculated cystic overhanging blebs have been documented before, such a large (posterior extent till fornix), thick-walled multiloculated bleb with histopathological evidence of chronic inflammatory process has not been reported prior.

Ultrafiltration in Heart Failure: A Review.

Ultrafiltration is an effective method to get rid of fluid retention and congestion in patients with acute decompensated heart failure (HF) without affecting the circulating volume. Although its efficacy in comparison to diuretics is debatable, the evaluation of our analysis is based on various studies that comprise published clinical trials on ultrafiltration and studies comparing the efficacy of diuretics and ultrafiltration. Apart from this, we also look at literature that provides shortcomings of the said procedure and its scope for future advancements. Heart failure ultimately leads to volume overload, which is a highly concerning complication. Diuretics have been used as a first-line treatment for fluid overload but are becoming inefficacious due to the development of resistance and renal dysfunction. Ultrafiltration, on the other hand, is an attractive alternative to counter volume overload and congestion, which are unresponsive to medical therapy. There is also evidence that it significantly decreases the probability of future episodes of decompensation. There are, however, disagreements about whether ultrafiltration is an effective method to improve mortality in these patients. There is a lack of conclusive studies demonstrating the superiority of one fluid removal method over another. Hence, it is imperative to continue searching for the most effective method to treat congestion. Priority should be given to more mechanistic studies regarding ultrafiltration.

Ventricular Septal Rupture Management in Patients With Acute Myocardial Infarction: A Review.

Untreated myocardial infarction (MI) can potentially lead to many fatal complications which require immediate management. One of them is ventricular septal rupture (VSR) which necessitates the hemodynamic stabilization and closure of the septal rupture. Conventional treatment strategy involves surgical repair; however, percutaneous transcatheter repair using an occluder device is a promising upcoming approach. We conducted a detailed review of various published articles and examined the trends in incidence, risk factors, and pathophysiology of MI leading to VSR followed by an in-depth analysis of the various management strategies for the same. In the current clinical scenario, thrombolysis is an imperative management strategy that has been shown to decrease the occurrence of VSR by manifolds, more specifically in patients having ST-elevated MI. Delayed surgical closure remains the main treatment for post-infarction VSR. Other newer modalities, such as percutaneous closure devices and mechanical circulatory supports, are attractive alternative or complementary strategies to treat such patients, both postoperatively and perioperatively. However, earlier surgical repair in VSR increases the risk of mortality, and the optimal timing for VSR closure remains controversial. Despite surgical closure of VSR being the traditional treatment, it presents a considerably high operative risk. Although newer interventions such as percutaneous closure devices and mechanical circulatory supports provide impressive outcomes, their efficacy in high-risk patients remains inconclusive.

Introducing a novel histopathological scoring system to assess disease activity and chronicity in cutaneous lichen planus: A proposal.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory disorder caused by an autoimmune attack by cytotoxic T-cells. The clinical course is variable, with episodes of remission and exacerbation. A clinicopathological scoring system for cutaneous LP is not available for effectively assessing disease severity and monitoring treatment response. This study was designed with the aim of proposing an objective and reproducible scoring system, comprising histopathological features of active and chronic disease, and to correlate these scores with clinical morphology groups. METHODOLOGY: This is a retrospective study of 200 cases of cutaneous LP, which were categorized into five clinical groups (I-V) at the time of biopsy. The corresponding histopathological feature was assigned a score based on feature of active and chronic disease. Individual scores were summated to calculate a histopathological index (index [AI] and chronicity index [CI]). The comparison of indices between various clinical groups was performed by Mann-Whitney U test. RESULTS: The median AI was lowest (1) for post-inflammatory hyperpigmentation (clinical group I) and highest (7) for the bullous group (clinical group IV). The median CI (7) was highest for the scarring group (clinical group V). The difference between median AI of clinical group I (post-inflammatory hyperpigmentation) and rest of the groups (clinical groups II, III, IV, and V) was statistically significant (p value <0.05). CONCLUSION: We present this clinico-histopathological scoring system as a reliable and facile method of assessing the activity and severity of LP.

Putting It All Together: Postmortem Diagnosis of a Rare Ichthyosis Syndrome.

Neu-Laxova syndrome (NLS) is a rare lethal disorder with autosomal recessive inheritance and is characterized by multiple congenital anomalies. Our case of NLS presented with severe intrauterine growth restriction (IUGR), abnormal facial features, severe central nervous system malformations, skeletal muscle contractures, and the hallmark signs of NLS: ichthyotic skin and excessive subcutaneous tissue with edema. Additionally, testing amniotic fluid from a prior pregnancy with a fetus showing similar abnormalities revealed several regions of homozygosity; one of these regions involved chromosome 1p13.2-p11.2, where the PHGDH gene is located. Based on the pattern of findings on serial fetal ultrasounds, postmortem neonatal exams, gross and microscopic exams, radiographs, and genetic analysis in conjunction with the clinical history and the prior pregnancy with the above-described molecular alteration, a final diagnosis of NLS was made. This rare developmental disorder is characterized by heterogenous neuroectodermal defects. Fetal ultrasound in the second trimester can help diagnose it. It is postulated to be caused by loss-of-function mutations in the PHGDH (phosphoglycerate dehydrogenase), PSAT1 (phosphoserine aminotransferase 1), and PSPH (phosphoserine phosphatase) genes, which are responsible for de novo L-serine synthesis.

Alteration in key oncoprotein expression in gastric adenocarcinoma - An immunohistochemical study.

Objective: This study was conducted to evaluate the frequency and clinicopathologic correlates of human epidermal growth factor receptor 2 (HER-2)/neu and betacatenin (BC) oncoproteins in gastric adenocarcinoma and to seek correlation if any between their expression status. Materials and Methods: This cross-sectional analytical immunohistochemistry (IHC) study was performed on 50 cases of gastric adenocarcinoma. HER-2/neu immunoexpression was scored as per criteria by Ruschoff et al. as positive (3+), equivocal (2+), and negative (1+, 0). Aberrant BC expression was categorized as nuclear, cytoplasmic, and reduced membranous immunoexpression. Protein expression results of both oncoproteins were correlated with conventional clinicopathological parameters. Correlation between immunoexpression profiles of both proteins was also analyzed. P <0.05 was considered statistically significant. Results: HER-2/neu positivity (2 + and 3+) was seen in 94% of the cases; almost 60% had strong (3+) expression. All cases showed aberrant BC immunoexpression (any pattern) except 2 cases that revealed negative expression (a form of aberrant immunoexpression) and were removed from analysis due to a very small number. The pattern of BC expression was as follows: nuclear expression (38%), cytoplasmic expression (82%), reduced membranous expression (96%), no staining (4%) cases. HER-2/neu expression correlated with age. No significant correlation was found between any of the 2 oncoprotein immunoexpression and other clinicopathological parameters (P > 0.05). Concordance between protein expression of HER-2/neu and BC was seen in >93% cases, however, the correlation was not significant. Conclusion: HER-2/neu and BC oncoprotein expression are frequently dysregulated in gastric adenocarcinomas. The significance of pathways involving HER-2/neu and BC in gastric carcinogenesis should be explored.

Resected cytokeratin-negative small cell lung carcinoma.

Small cell lung carcinoma (SCLC), a malignancy of neuroendocrine origin, can show varied morphologies and patterns but is typically positive for at least one neuroendocrine marker and almost always for cytokeratins. It is essential to distinguish this tumour due to its characteristic genetic features, aggressive behaviour, propensity for metastasis and responsiveness to chemotherapy. We hereby present a rare case of a pulmonary mass that showed morphological features of an SCLC but lacked cytokeratin expression on biopsy as well as resection specimens. Various cytokeratins were tested on multiple blocks and at different laboratories. A broad differential diagnosis was considered and ruled out including small round blue cell tumours, non-SCLC and metastasis. After performing an extensive work-up to identify the origin of this tumour, it was finally diagnosed as SCLC with expression of neuroendocrine markers synaptophysin and CD56, and intracytoplasmic electron dense neurosecretory granules (250-350 nm) however lacked cytokeratin expression.

A Review of Morphologic Findings in Peripheral Blood Smears of COVID-19 Patients.

INTRODUCTION: Peripheral smear examination is a simple and cost-effective test that is routinely performed while monitoring patients diagnosed with COVID-19. We sought to summarize the peripheral blood morphologic findings in patients with COVID-19 infection. METHODS: A systematic review was conducted using a standardized keyword search on Medline database (PubMed), med RXIV, Google Scholar, EMBASE, and SCOPUS for studies discussing peripheral blood smear or morphologic blood findings in patients diagnosed with COVID-19. RESULTS: A total of 28 studies were included in the review. Normocytic normochromic anemia was the most frequently encountered red blood cell finding. Neutrophilia was seen in most of the studies. A variety of morphological changes were observed in neutrophils, including pyknotic nuclei, variable shapes, toxic granules, and cytoplasmic vacuolization. Hyposegmented neutrophils, pseudo-Pegler Huet forms, and hypogranular forms were common findings reported by many studies. Lymphopenia was reported by most studies. Lymphocytes showed numerous morphological changes, including reactive forms, Downey forms, increased large granular lymphocytes, and plasmacytoid cells. The presence of giant platelets was seen frequently. CONCLUSIONS: The peripheral blood in COVID-19 shows a spectrum of findings, mostly reactive changes in neutrophils, monocytes, lymphocytes, and platelets. Increased neutrophil/lymphocyte ratio and higher neutrophil counts have been associated with poor prognosis, which potentially could help triage patients, but this needs to be confirmed in larger studies.

A Case of Drug-Induced Stevens-Johnson Syndrome.

INTRODUCTION: Stevens-Johnson syndrome is a rare but consequential and often life-threatening disorder that is most often drug-induced. CASE PRESENTATION: An 81-year-old Black man presented with 5 days of dysphagia, odynophagia, and rash. He said he had begun a course of trimethoprim-sulfamethoxazole 6 days prior for a presumed urinary tract infection. Owing to the cutaneous lesions and punch biopsy findings, he was diagnosed with drug-induced Stevens-Johnson syndrome. DISCUSSION: Stevens-Johnson syndrome is associated with a relatively high mortality rate. It is most commonly drug-induced and presents with extensive erythema, erosions, and blisters throughout the body. CONCLUSIONS: Stevens-Johnson syndrome is a rare and often life-threatening disease. Early diagnosis and management is important for delivering high-quality patient care.

Unmasking Hypoxia in Cirrhosis Patients: Six-Minute Walk Test as a Screening Tool for Hepatopulmonary Syndrome.

Background: Hepatopulmonary syndrome (HPS) is one of the complications of advanced cirrhosis which has a serious impact on prognosis of patient. Finding arterial deoxygenation early and initiating higher-level treatment is one of the most critical strategies in the therapy of HPS. In this study, we aimed to assess the utility of six-minute walk test (6MWT) in the diagnosis of HPS. Materials and Methods: We have enrolled 100 consecutive cirrhosis patients referred to the Liver Clinic of a tertiary care centre of India for >1 year. The Child-Pugh score and the MELD score were used to determine the severity of cirrhosis. All the patients underwent transthoracic contrast echocardiography, arterial blood gas measurements on room air, 6MWT, and chest imaging. Results: A total of 100 patients were included in the study after fulfilling the inclusion criteria. HPS was present in 21 out of 100 patients (21%). Median (twenty fifth to seventy fifth percentile) MELD score in patients with HPS was 29 (26-33), which was significantly higher as compared to patients without HPS 22 (14.5-26); P <.0001. The 6MWT was positive in 20 (95.23%) HPS patients, while only 1 patient (4.77%) of HPS had negative 6MWT. If 6MWT is positive, then there was 76.92% probability of HPS and if 6MWT is negative, then 98.65% chances of no HPS. Conclusion: The 6MWT is a simple and effective screening test for HPS, it helps in identifying the patients early who have a potential to deteriorate. This simple intervention would help in prioritizing patients for liver transplantation as liver transplant is the only effective treatment for HPS.

Mucormycosis following COVID-19 infection-An epidemic developing in a pandemic, a case series from a tertiary care hospital of India.

When the world is still struggling to fight the Coronavirus disease-19 pandemic, an epidemic of mucormycosis following the COVID-19 infection is increasing in India. Mucormycosis is a rare life-threatening fungal infection with a high mortality rate. Is this increase due to the rampant usage of corticosteroids, some immune dysfunction in COVID-19, uncontrolled blood sugar, increased ferritin, use of industrial oxygen, use of unsterile mask, or use of unsterile water as a humidifier in oxygen delivery systems? This remains a question. In this case series, we present five cases of rhino-orbito-cerebral mucormycosis which followed after the COVID-19 infection in these patients. We have included patients' clinical, laboratory, and radiological data in this case series and reviewed the literature.

Static smartphone images supplemented by videoconferencing for breast telepathology.

BACKGROUND: Both static images and videoconferencing by smartphone have been tried for telepathology. Combining the two approaches for telepathology might offset some of the limitations of both techniques. METHODS: A total of 150 cases of breast pathology were retrieved and were photographed by a trained junior pathologist using a smartphone camera and binocular microscope and the images were sent as Google photos attachments with email to three pathologists. The pathologists opened the emailed attachments during separate prescheduled google meet videoconferencing sessions and rendered the diagnosis verbally to the junior pathologist. The pathologists were given the option of asking for live dynamic images of the cases during the meet which were transmitted using the rear camera of the smartphone with the video option of google meet. RESULTS: The overall concordance rates for the three pathologists were 96.6%, 99.3% and 98.0% (Mean 98.0%). The reporting pathologists asked for dynamic live images in 23, 20 and 18 cases respectively. Out of these 61 cases, a discrepant diagnosis was made in 7 cases (11.4%). The reporting pathologist was satisfied with the quality of static images (Mean Likert score 4.2/5). However, concerns were raised on the consistency of video quality (Mean Likert score 2.5/5). The screen share option of Google meet was found useful to discuss specific features of the case. (Mean Likert Score 4.6/5) CONCLUSION: The combined approach to telepathology has shown some promise and it is hoped that with adequate training the discordance can be reduced.

Undifferentiated carcinoma with osteoclast-like giant cells: A pathologic-radiologic correlation of a rare histologic subtype of pancreatic ductal adenocarcinoma.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an exceedingly rare subtype of pancreatic ductal adenocarcinoma. Histologically, UC-OGC is characterized by three cell types namely, a neoplastic mononuclear cell component, non-neoplastic osteoclast-like giant cells, and a non-neoplastic mononuclear histiocytic component. The behavior of this tumor is unpredictable; but many patients survive many years after diagnosis. UC-OGC may have a better prognosis compared to conventional pancreatic adenocarcinoma due to its slower local spread, less aggressive nature, better response to surgical resection and/or chemotherapy, and fewer metastases. Due to likely differences in prognosis and significant impact on patient management, it is important to distinguish this subtype from other types of pancreatic adenocarcinoma. We report a case of a small (<1 cm) undifferentiated carcinoma with osteoclast-like giant cells of the posterior pancreatic body discovered incidentally on magnetic resonance image (MRI) scan of a middle-aged man. The radiologic and pathologic findings are presented along with a discussion of the differential diagnosis of this exceedingly rare entity.

CC-LA: determining optimal switching angles in a cascaded H-bridge multilevel inverter with the aid of binary cat cubpool-based lion algorithm.

A multilevel inverter (MLI) is a power electronic device that includes the capability to offer the preferred voltage level (alternating) in the output. Accordingly, selective harmonic elimination (SHE) or pulse width modulation (PWM) methodologies were deployed widely. However, these techniques are not appropriate in a certain situation which involves a huge number of switching angles if an excellent primary guess is not obtainable. Hence, this paper intends to determine the optimum switching angles of a cascaded H-bridge multilevel inverter (CH-MLI) using a hybrid lion optimization algorithm (LOA) and binary cat swarm algorithm (BCSO). The objective of optimizing the switching angle is to generate the needed fundamental voltage and minimize the harmonic content. This is done by resolving the transcendental equations characterizing the harmonic content. The switching angles, i.e., α1, α2.... αm, should be tuned in such a way that it satisfies the condition [Formula: see text]. Here, the optimal tuning of switching angles is done by the proposed binary cat cubpool-based lion algorithm (BCC-LA). In addition, the analysis is done for the proposed method over the state-of-the-art models in terms of total harmonic distortion (THD), and the impact of varying loads is also examined for the proposed and traditional models, and thus, the superior performance of the proposed model is validated.

Anastomosing Hemangioma of Ovary with Stromal Luteinization Masquerading as Sex Cord-Stromal Tumor on Intraoperative Consultation.

Anastomosing hemangiomas (AHs) are benign vascular tumor with rare occurrence in the ovary and the majority being asymptomatic. We report one such case of AH with stromal luteinization. A 35-year-old female had complaints of abdominal pain and heavy menstrual bleeding for 2 years. Her lactate dehydrogenase was markedly raised. Following the clinical suspicion of germ cell tumor, exploratory laparotomy and right salpingo-oophorectomy were done. On frozen section due to extensive stromal luteinization, diagnosis of sex cord-stromal tumor was suggested. However, the case was finally diagnosed with AH with extensive stromal luteinization. This case highlighted the potential mimics of AH due to coexistent raised biomarkers and secondary changes, thereby posing a diagnostic dilemma on intraoperative consultation.

Tanycytic ependymoma: highlighting challenges in radio-pathological diagnosis.

BACKGROUND: Tanycytic ependymoma (TE) (WHO grade II) is a rare and morphologically distinct variant of ependymoma with only 77 cases reported worldwide so far. Variable clinical and radio-pathological features lead to misdiagnosis as WHO grade 1 tumors. On imaging, differentials of either schwannoma, meningioma, low-grade glial (like angiocentric glioma), or myxopapillary ependymoma are considered. In this study, we aim to discuss clinical, radiological, and pathological features of TE from our archives. METHOD: We report clinicopathological aspects of six cases of TE from archives of tertiary care center between 2016 and 2018. Detailed histological assessment in terms of adequate tissue sampling and immunohistochemistry was done for each case. RESULT: The patient's age ranged between 10 and 53 years with a slight male predilection. Intraspinal location was seen in two cases (intramedullary and extramedullary), three cases were cervicomedullary (intramedullary), and one was intracranial. One case was associated with neurofibromatosis type 2. Four cases mimicked as either schwannoma or low-grade glial tumor on squash smears. On imaging, ependymoma as differential was kept in only two cases and misclassified remaining either as low-grade glial or schwannoma. DISCUSSION: In initial published reports, the spine is the most common site (50.4%) followed by intracranial (36.4%) and cervicomedullary (3.9%). They have also highlighted the challenges in diagnosing them intraoperatively and radiologically. Treatment is similar to conventional ependymoma if diagnosed accurately. A multidisciplinary approach with the integration of neurosurgeon, neuroradiologist, and neuropathologist is required for accurate diagnosis and better treatment of patients.

HER-2/neu over expression in gall bladder adenocarcinoma: A quest for potential therapeutic target.

BACKGROUND: Gall bladder carcinoma (GBC) is an aggressive malignancy with high mortality and aggressive course, with palliation as the only available option. OBJECTIVES: To evaluate frequency of HER-2/neu overexpression in GBC and to seek its correlation, if any with conventional clinicopathological parameters and survival. METHODS: Immunohistochemistry (IHC) was performed on 200 cases of GBC, 32 cases of dysplasia, and 100 cases of chronic cholecystitis. Fluorescent in situ hybridization (FISH) was performed on 30 randomly selected cases of GBC to validate IHC. HER-2/neu overexpression (IHC 3+/FISH amplification ≥2.2) was correlated with clinicopathological parameters by Chi-square test.P < 0.05 was considered significant. Survival analysis was done by log-rank test and Kaplan-Meier analysis. RESULTS: HER-2/neu overexpression was seen in 14% (28/200) GBC cases but was not found in dysplasia and chronic cholecystitis. Majority of these cases were ≤grade 2 and in advanced stage, however this was not statistically significant. A lower mean survival in HER-2/neu positive group as compared to HER-2/neu negative group (17.1 ± 2.3 month versus 67.6 ± 8.5 month, respectively) was observed. Concordance between IHC and FISH was seen in 18/19 cases. CONCLUSION: This study delineates a subset of GBC patients with HER-2/neu overexpression, in whom targeted therapy can offer a survival benefit.

Cellular mesenchymal epithelial transition (C-MET) gene copy number variation in gastric adenocarcinoma: A pilot search for new marker for targeted therapy in HER-2/neu resistance.

Increasing HER-2/neu resistance in gastric carcinoma has encouraged search for new biomarkers for targeted therapy. Cellular mesenchymal epithelial transition (C-MET) is one such tyrosine kinase inhibitor proposed for personalized salvage treatment. We determined frequency of C-MET gene copy number variation (CNV) by Fluorescent in-situ hybridization (FISH) in gastric adenocarcinoma (GAC) and sought its correlation with conventional clinicopathologic parameters. Dual-coloured FISH was done on 32 GAC cases. C-MET gene and centromere 7 signals were counted under fluorescent microscope and ratio was calculated for each case. Correlation between C-MET CNV and conventional clinic-pathologic parameters was done by Fischer exact test. CNV was identified in the form of amplification and polysomy (3.1% each) and associated with poorer prognostic parameters. Our pilot study highlights limited subset of patients that may benefit from anti-C-MET-targeted therapy and thus could be a novel biomarker for targeted intervention in GAC.