A Correlation of Tumour Budding and Tumour-Stroma Ratio with Clinicopathological Factors in Oral Squamous Cell Carcinoma.

Objectives: This study aimed to analyse the association of tumour budding (TB) and tumour-stroma ratio (TSR) with clinicopathological parameters that can be easily viewed on routine haematoxylin and eosin (H&E)-stained slides to provide an easy and cost-effective method for prognosticating oral squamous cell carcinoma (OSCC). Methods: This study was conducted at the ESIC Medical College and Hospital in Faridabad, India, from July 2022 to October 2022. In patients with histologically diagnosed OSCC, TB and TSR were evaluated via routine H&E-stained sections and correlated with clinicopathological parameters. Statistical analysis was performed using Chi-squared test. Results: A total of 50 patients were included. The mean age of participants was 61 ± 12.72, and the male-to-female ratio was 7.1:1. Most of the tumours were located on the tongue (46%), followed by the buccal mucosa (26%), gingivobuccal sulcus (12%) and retromolar trigone (8%). The palate and alveolus were the other sites involved, constituting 4% each. TB and TSR were both found to be significantly associated with the tumour grade, lymph node metastasis and tumour size. A highly significant correlation was also found between TB and TSR (P = 0.001). Conclusions: Both TB and TSR can be easily evaluated on routine H&E sections; they are highly reproducible and were found to be reliable independent prognostic markers in OSCC. Therefore, this simple and cost-effective method of prognostication, which is currently lacking in clinical practice, will help clinicians to identify patients with poor prognosis and thus individualise their treatment plan.

Liesegang Rings in a Patient With Pulmonary Tuberculosis: The First Report.

Liesegang rings are eosinophilic, concentric, lamellated structures that can assume a variety of shapes and sizes ranging from a few microns to hundreds of microns. To date, Liesegang rings have been reported in around 30 examples in the English literature, in the kidney, breast, female genital tract, and skin, and only a single report in the lung associated with allergic bronchopulmonary aspergillosis. Liesegang rings are usually incidental discoveries and have been associated with benign cystic lesions, inflammatory diseases, fibrosis, and tissue necrosis. Their typical appearance helps differentiate them from their mimics including parasites, foreign materials, corpora amylacae, and psammoma bodies. We report Liesegang rings in a 62-year-old male patient with pulmonary tuberculosis to create awareness about this rare entity among pathologists to avoid its misdiagnosis as a parasitic infection.

Adhatoda vasica and Tinospora cordifolia extracts ameliorate clinical and molecular markers in mild COVID-19 patients: a randomized open-label three-armed study.

BACKGROUND: SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. METHODS: A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19-65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. RESULTS: We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85-14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14-14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62-13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. CONCLUSIONS: All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27.

Congenital Unilateral Hypoplasia of Kidney with Mesonephric Remnants in the Ureter: A Case Report.

Mesonephric remnants persist as an appendix of epididymis and paradidymis in efferent ductules in males and skene's glands and Gartner's ducts in females. The mesonephric remnant in the renal parenchyma is extremely rare and only a few cases have been reported in the literature. We present a case with a non-functioning atrophic left kidney. Histopathology showed variable-sized ducts filled with colloid-like material surrounded by collagenized stroma. The ureter showed hypertrophied muscle and a few ducts lined by flattened and a few by columnar epithelium resembling epididymis suggestive of mesonephric remnants. IHC for CD10, PAX 8, and GATA3 was positive. A diagnosis of congenital unilateral hypoplasia of kidneys and ureter with mesonephric remnants was given.

A critical appraisal of mucormycosis in COVID- 19 patients in a tertiary care centre in India.

Background and Purpose: Morbidity and mortality of opportunistic fungal infections in COVID-19 patients are less studied and defined. The patients receiving immunosuppressive therapy, broad-spectrum antibiotics, corticosteroids, and invasive and non-invasive ventilation are the high-risk groups. Materials and Methods: The demographic profile as well as clinical and radiological findings of all the patients with COVID-19 suspected of Mucormycosis (MM) were recorded. The tissue samples from all the patients were sent for microbiological (KOH mount and culture) and histopathological analysis for confirmation of MM. Results: In total, 45 COVID-19 patients suspected of MM were included in the study and MM was confirmed in 42 patients. The mean age of the patients was 50.30±14.17 years with a female: male ratio of 1.1:1. The most common symptom was headache (52.38%) followed by purulent nasal discharge (38.09%) and facial pain in 33.33% of the cases. The ocular symptoms included a diminution of vision (33.33%) and redness of the eye (2.38%). The most common site of involvement was rhino-orbital (42.85%) followed by sinonasal (23.80%) and rhino cerebral (19.04%). Majority (38.09%) of the patients were diagnosed with stage II of Rhino-orbital-cerebral Mucormycosis (ROCM) based on radiology. A history of diabetes mellitus and steroids was present in 97.61% and 85.71% of the cases, respectively. Moreover, KOH was positive for MM in 97.61% of the cases while the culture was positive in only 35.71% of the cases. In addition, on histopathology, MM was confirmed in 64.28 % of the cases. Mixed growth with Aspergillus species and Rhizopus species was observed in 14.28% of the cases in culture and 11.90% of the cases in histopathology test. Furthermore, angioinvasion was found in 23.80% of the cases according to the histopathology test. Conclusion: Based on the results, the most common conditions associated with MM in COVID-19 patients were diabetes mellitus and steroid therapy. A high level of clinical suspicion aided with diagnostic tests, including KOH mount, culture, histopathology, and radiology which helped the early detection of opportunistic fungal infection in COVID-19 patients to ensure timely treatment.

Synchronous Occurrence of Adult Granulosa Cell Tumor with Fibroma in One Ovary and Brenner Tumor in Other Ovary: An Extremely Unusual Case.

Ovarian tumors are a common form of neoplasia in women and it accounts for about 30% of female genital cancers. A coexistence of ovarian tumors with the same histogenetic origin such as germ cell or epithelial or sex cord stromal, but different histologic subtype is relatively common, whereas a synchronous occurrence of tumors with different histogenetic origin is rare. We report a case of 58-year-old woman with the synchronous presentation of adult granulosa cell tumor with fibroma (ovarian tumors with the same origin (sex cord stromal) but different histologic type) in one ovary and Brenner tumor (epithelial origin) in other ovary. Our patient presented with postmenopausal bleeding and was diagnosed with this rare combination of ovarian tumors on histopathology supplemented with immunohistochemistry. On extensive literary search, there is only a single report of mixed ovarian tumor composed of Brenner tumor and adult-type granulosa cell tumor. Our case is different from the above-mentioned report as although, in our patient both tumors coexisted, but in contralateral ovaries.

Xanthogranulomatous Change in a Leiomyoma: First Report of an Extremely Rare Variant/Degenerative Change.

Xanthogranulomatous inflammation, a specific form of chronic inflammation, is marked by parenchymal destruction, proliferative fibrosis, and infiltration of typical foamy histiocytes admixed with hemosiderin-laden macrophages and foreign-body giant cells. Myometrial xanthomatosis, a term designated for nodular or diffuse histiocytic hyperplasia of the myometrium, has been reported in association with pregnancy-related procedures. Moreover, a 2-3-fold increase in histiocytic counts has been observed in leiomyomatous areas than in adjacent normal myometrium. The first evidence of collections of lipid-laden macrophages was documented in the form of yellowish degeneration of uterine leiomyomas. We report a case of xanthogranulomatous change in a leiomyoma in a 47-year-old female who presented with abnormal uterine bleeding. To the best of our knowledge, this is the first report of xanthogranulomatous variant/degenerative change in a leiomyoma. This case highlights a new variant of leiomyoma which both gynecologists and pathologists should be aware of as it may pose a diagnostic challenge both clinically as well as pathologically.

The aqueous root extract of Withania somnifera ameliorates LPS-induced inflammatory changes in the in vitro cell-based and mice models of inflammation.

Introduction: Most critically ill COVID-19 patients have bronchitis, pneumonia, and acute respiratory distress syndrome (ARDS) due to excessive inflammatory conditions. Corticosteroids have largely been prescribed for the management of inflammation in these patients. However, long-term use of corticosteroids in patients with comorbidities such as metabolic, cardiovascular, and other inflammatory disorders is ideally not recommended due to safety issues. A potential and safer anti-inflammatory therapy is therefore the need of the hour. Withania somnifera (WS), a well-known herbal medicine used during the pandemic in India to prevent SARS-CoV2 infection, also possesses anti-inflammatory properties. Methods: In the present study, we, therefore, evaluated the effect of the aqueous extract of the roots of W. somnifera in the cell-based assays and in the experimental animal models of LPS-induced inflammation. Results: In the NCI-H460, A549 cells and human peripheral blood mononuclear cells (PBMCs) pre-treatment with W. somnifera reduced the LPS-induced expression of the pro-inflammatory cytokines. In addition, W. somnifera extract also showed potent anti-inflammatory activity in the lung tissues of BALB/c mice challenged intranasally with LPS. We observed a marked reduction in the neutrophil counts in the broncho-alveolar lavage (BAL) fluid, inflammatory cytokines, and fibrosis in the mice lungs pre-treated with W. somnifera. Results obtained thus suggest the potential utility of W. somnifera extract in reducing airway inflammation and recommend the clinical evaluation of W. somnifera extract in COVID-19 patients with a high propensity for lung inflammation.

Expression of Epidermal Growth Factor Receptor (EGFR) and ß-catenin in Colorectal Carcinoma and its Correlation with Tumor Grade and Stage.

Colorectal cancer (CRC) is considered the result of the cumulative effect of multiple mutations within the cell that allow it to escape growth control and regulatory mechanisms. EGFR overexpression has been suggested as a factor of poor prognosis in various cancers. ß-catenin plays a role in the Wnt signaling pathway of colorectal cancers. An analytical cross-sectional study was conducted over a period of two years comprising 20 colectomy specimens. Clinicopathological details were documented, and immunohistochemistry (IHC) for EGFR and ß-catenin was performed. EGFR-Brown membranous staining was observed; ß-catenin-Brown membranous or nuclear staining was observed. IHC scoring was done, taking into account the intensity of staining and the percentage of positive tumor cells. The mean age of patients with colorectal carcinoma was 47.45 ± 14.8 (mean + SD) years. No statistically significant difference was noted in the EGFR immunoexpression and tumor grade (p value = 0.361) as well as the TNM stage (p value = 0.699). There was no statistically significant difference between ß-catenin immunoexpression and tumor grade (p value = 0.444) and TNM stage (p value = 0.911). A statistically significant difference was noted in the EGFR and ß-catenin immunoexpression (p = 0.0001). EGFR and ß-catenin expression was observed in 50% and 65% of cases, respectively. EGFR and ß-catenin expression was not associated with histological tumor grade and TNM stage of the tumor. In the present study, EGFR expression was significantly associated with ß-catenin immunoexpression.

Primary leiomyosarcoma of ovary: A rare malignancy as an incidental finding.

Primary leiomyosarcoma (PLMS) of the ovary is extremely rare tumors comprising 1% of ovarian tumors. About 3% of all ovarian malignancies are primary ovarian sarcomas. Only 72 cases have been reported till date. A 57-year-old postmenopausal female presented with abdominal pain for the last 6 months. Ultrasonography and MRI revealed a heterogeneously enhancing solid lobulated mass in the left adnexa abutting the fundus of the uterus and bowel loops. The endometrial cavity was normal. Ovarian markers CA 125, CEA, CA 19.9, and all hematological parameters were within normal limits. LDH was near normal (284 IU/ml). The specimen was sent for frozen section and a diagnosis of malignant spindle cell lesion of ovary was rendered. Histopathology of the ovarian mass revealed intersecting fascicles of tumor cells consisting of ovoid to spindle-shaped cells having a moderate amount of cytoplasm. Bizarre and atypical cells were seen singly dispersed and in small aggregates along with the brisk mitotic activity. Focal areas of necrosis and hemorrhage were also noted. Immunohistochemistry showed strong positivity for smooth muscle actin and Caldesmon while focal positivity for Desmin and Epithelial Membrane Antigen (EMA) was noted. The lesion was negative for Inhibin, Calretinin, and CD 117 and S100. The final diagnosis of primary ovarian Leiomyosarcoma was given based on histopathology and Immunohistochemistry. PLMS of the ovary are rare incidental findings in postmenopausal women. These are highly malignant tumors and carry a poor prognosis. Hence, early diagnosis and surgical treatment with cytoreduction improve patient survival.

Cellular Leiomyoma versus Endometrial Stromal Sarcoma: A Report of a Rare Case Presenting a Diagnostic Challenge on Intraoperative Frozen Section.

Endometrial stromal sarcomas (ESSs) account for approximately 0.2% of all uterine malignancies. Cellular leiomyoma (CL) often simulates low-grade ESS due to similar cytology. We report the case of a 34-year-old female with a mass per abdomen. Frozen sections showed a tumor with many thin- and thick-walled vessels along with hyaline material. A differential diagnosis of CL and endometrial stromal tumor was suggested. The index case was diagnostically challenging to pathologists. Paraffin sections supplemented by immunohistochemistry (smooth muscle actin, CD10, and beta-catenin) favored CL. Frozen section sometimes leads to over/underestimation of tumor in view of small sampling area of tumor.

Pure Cutaneous Rosai Dorfman Disease: An Uncommon Location for a Rare Histiocytic Proliferative Disorder.

RosaiDorfman disease (RDD) is a rare, self-limiting disease of uncertain etiology involving lymph nodes as well as extranodal sites. Isolated or pure cutaneous RDD (PCRDD) without lymph node involvement is very unusual accounting for only 3% of all described cases of RDD. The clinical features of PCRDD are quite different from RDD according to the literature on extranodal RDD, thereby emphasizing that PCRDD is a distinct clinical entity. Histopathology remains the gold standard for the diagnosis of both systemic and PCRDD with the presence of characteristic emperipolesis observed in histiocytes while immunohistochemistry (IHC) (S100, CD 68 positive, and CD 1a-negative) serves as a useful adjunct. We hereby report a case of a 36-year-old female who presented with a tender, indurated plaque on the left forearm with a clinical differential diagnosis of borderline tuberculoid leprosy/sarcoidosis and lupus vulgaris. However, on histopathology, a diagnosis of RDD was performed and confirmed on IHC. This case highlights the need to create awareness among young pathologists and clinicians about PCRDD to prevent overzealous treatment.

COVID-19 Associated Coagulopathy in an Indian Scenario: A Correlation with Disease Severity and Survival Status.

Covid-19 pandemic reveals that the virus causes Covid-19 associated coagulopathy and it is well known that thrombotic risk is associated with ethnicity. To describe the Covid-19 associated coagulopathy in Indian population and to correlate it with the disease severity and survivor status. A cross sectional descriptive study of 391 confirmed Covid-19 cases was carried out over a period of 1.5 months. Patients were categorised as mild to moderate, severe and very severe and also labelled as survivors and non survivors. Prothrombin time (PT), International normalised ratio (INR), activated partial thromboplastin time, D dimer, Fibrin degradation products (FDP), fibrinogen and thrombin time and platelet counts were investigated among the subgroups. Mean age was higher in patients with severe disease (57.62 ± 13.08) and among the non survivors (56.54 ± 12.78). Statistically significant differences in D dimer, FDP, PT, INR and age were seen among the 3 subgroups and survivors. Strong significant positive correlation was noted between D dimer and FDP (r = 0.838, p < .001), PT and INR (r = 0.986, p < 0.001). D dimer was the best single coagulation parameter as per the area under curve (AUC: 0.762, p < 0.001) and D dimer + FDP was the best combination parameter (AUC: 0.764, p = 0) to differentiate mild moderate from severe disease. Raised levels of D dimer, FDP, PT, PT INR and higher age correlated positively with disease severity and mortality in Indian Population.

The effect and correlation of smoking with platelet indices, neutrophil lymphocyte ratio and platelet lymphocyte ratio

ABSTRACT Introduction: Smoking is associated with the occurrence and progression of cardiovascular diseases, inflammatory disorders and malignancies. Objective: To study the platelet indices, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in smokers and their correlation with smoking pack-years. Method: A total of 110 smokers and 110 non-smokers were included. The smokers were grouped into three groups: mild (<5 pack-years), moderate (5-10 pack-years) and heavy (>10 pack-years). The platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) were noted. The NLR and PLR were calculated and the statistical analysis was made using the Student's T-test, Analysis of Variance (ANOVA) and Spearman's correlation coefficient. Results: The platelet count, PCT and PDW were significantly higher with mean values: 218.56 ± 121.31 vs 203.23 ± 80.35 (p-value = 0.038), 0.27 ± 0.10 vs 0.26 ± 0.10 (p-value = 0.041) and 12.54 ± 1.45 vs 11.99 ± 1.70 (p-value = 0.001) in smokers and non-smokers, respectively. The PLR differed significantly with mean values: 119.40 ± 84.81 in smokers and 181.99 ± 313.09 in non-smokers, with a p-value of 0.045. A significant positive correlation was found between pack-years of smoking and platelet count and PLR with the Pearson correlation coefficient of 0.250 and 0.198 and p-values, 0.008 and 0.037, respectively. The Platelet Count, PCT, MPV and PDW varied significantly between mild, moderate and heavy smoker groups, with p-values of 0.045, 0.010, 0.015 and 0.017, respectively. Conclusion: The platelet indices and inflammatory markers NLR and PLR are derived from routine blood investigations, which are easily available and inexpensive. The monitoring of platelet indices, along with the PLR, can be used as early predictors of morbidity in smokers.

Association of Hematologic biomarkers and their combinations with disease severity and mortality in COVID-19- an Indian perspective.

BACKGROUND: COVID-19 is a systemic viral infection with a significant impact on the hematopoietic system, hemostasis as well as immune system. It would be of utmost importance to explore if the most routinely used tests could serve as an aid in determining patient's clinical status or predicting severity of the disease. METHODS: A prospective cross-sectional study was conducted on 506 Covid-19 positive patients and 200 controls over a period of two months (June and July 2020). The cases were sub-classified based on disease severity into mild to moderate (n=337), severe (n=118) and very severe (n=51) and based on survivor status into survivors (n=473) and non-survivors (n=33). RESULTS: There were statistically significant differences in WBC count, Absolute neutrophil count (ANC), Absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) Red blood cell distribution width (RDW-SD) and RDW CV between covid cases vs controls; among the clinical subgroups and among the survivors and non-survivors. There was a significant strong positive correlation between various parameters, that is, NLR and MLR (r: 0.852, P=0), MPV and PDW (r: 0.912, P=0), MPV and PLCR (r: 0.956, P=0), PDW and PLCR (r: 0.893, P=0). NLR (AUC: 0.676, P=0) was the best single parameter and NLR+RDW-CV was best combination parameter as per area under curve (0.871) of ROC to distinguish severe from mild to moderate disease. CONCLUSIONS: Leucocytosis, neutrophilia, lymphopenia and monocytosis were characteristic findings in covid cases while NLR and NLR+RDW-CV emerged as the most effective single and combination CBC parameters in distinguishing mild to moderate and severe cases respectively.

Xanthogranulomatous change in a pleomorphic adenoma: An extremely rare variant/degenerative change. Is it fine needle aspiration induced?

Pleomorphic adenoma (PA) is the most common benign salivary gland tumor characterized by morphological diversity, metaplastic changes, degeneration, cystic change, altered differentiation, and rarely malignant transformation, thereby may create a diagnostic dilemma on cytology. Xanthogranulomatous (XG) inflammation within a PA could be due to XG sialadenitis coexistent with PA or preoperative fine-needle aspiration cytology (FNAC) induced histologic alteration. The argument in favor of this hypothesis is that the changes seen in the histopathology would not be present in the cytology, implying that the alterations were most likely due to the traumatic injury of needling rather than spontaneous change of the lesions themselves. These FNAC induced changes are focal in most of the cases, so the underlying lesion is readily identifiable, but on rare occasions they are so extensive that it can masquerade as a malignancy. We report a case of XG change in a PA in a 39-year-old male of 8 years standing. Through this case we wish to emphasize that knowledge of a previous FNAC and its potential effects on histology of the subsequent surgical specimen is necessary to avoid potential misdiagnosis.

An analysis of hematological, coagulation and biochemical markers in COVID-19 disease and their association with clinical severity and mortality: an Indian outlook.

BACKGROUND: The "cytokine storm" (CS) in COVID-19 leads to the worst stage of illness which can be controlled only with timely intervention. There is an urgent need to identify laboratory markers of disease progression for optimum allocation of resources in developing countries like India. METHODS: A cross-sectional study was conducted on 100 COVID-19 positive patients over two months. The cases were sub-classified based on disease severity into mild to moderate (n=61), severe (n=26) and very severe (n=13) and into survivors (n=85) and non-survivors (n=15) based on survivor status. These patients were tested for hematological parameters (total blood lymphocyte counts, NLR, PLR, platelet indices etc.), coagulation markers (D-dimer, fibrin degradation products (FDP), fibrinogen etc.) and biochemical markers (LDH, ferritin, IL-6, procalcitonin, hs-CRP). RESULTS: Statistically significant differences were observed in hematological variables (ANC, NLR and ESR), coagulation parameters (D-dimer, FDP, fibrinogen and thrombin time) and biochemical markers (LDH, ferritin, IL-6, procalcitonin and hs-CRP) with regard to subcategories based of disease severity as well as survivor status. There was strong correlation between NLR, D-dimer, IL-6, procalcitonin and ferritin. IL-6 emerged as the single best marker of disease severity (AUC: 0.997, P=0.00), however procalcitonin, LDH, D-dimer, FDP and NLR could also predict severe disease with a good sensitivity and specificity. CONCLUSION: To conclude, study demonstrates a plethora of biomarkers which could be utilized to accurately identify the hyperinflammation and tissue damage reminiscent of cytokine storm in COVID-19 patients so that timely, safe, and effective therapies can be administered to prevent progression and potentially reduce mortality.