Assessment of clinical and histopathological characteristics in COVID-19-associated mucormycosis (CAM) patients correlating with outcome: A hospital-based cross-sectional study.

Background: The second wave of the COVID-19 pandemic led to a very dreaded complication of mucormycosis. Immunosuppressive action of the COVID-19 virus, co-morbidities, for example, diabetes mellitus (DM), hypertension, use of steroids, and humidified oxygen, are among the important factors that make the patients susceptible to developing mucormycosis. Objective: The present study was conducted to identify and understand all the significant histological changes including the type and extent of tissue involvement, the pattern of inflammation, the volume of fungal hyphae, hemorrhage, etc., in patients with COVID-19 associated mucormycosis (CAM) and correlate with clinical outcome. Method: It was a retrospective cross-sectional observational study involving all the patients of CAM, who underwent debridement or biopsy over a period of 5 months, from April 01, 2021, to August 31, 2021. CAM was classified based on the radiological evaluation, clinical features, and organs involved. Different demographic, clinical, laboratory, and histologic parameters were recorded. The variables were assessed for their association with poor clinical outcomes using multiple logistic regression. P < 0.05 was considered statistically significant. Results: A total of 146 patients were included in the study with a mean age of 49.4 years and 71.2% were male. Sino-naso-palatal was the most common type of CAM (32.9%), while sino-naso-cerebral was the least common (14.3%). DM was present in 54.1% of patients, out of which 26.6% were recently diagnosed. The death occurred in 21.9% of patients. Maximum mortality was observed in CAM of sino-naso-cerebral involvement (42.9%). Total leucocyte count (TLC) [OR = 0.87; 95%CI: 0.76-0.97; P = 0.02] and C-reactive protein (CRP) [OR = 0.97; 95%CI: 0.96-0.99; P = 0.008] were significantly associated with poor outcomes. Other factors, that is, high prothrombin time, DM, ferritin, and the involvement of muscle, skin, and cartilage, were also associated with poor clinical outcomes but were not statistically significant. Similarly, high fungal volume and the presence of thrombosis were also associated with poor outcomes but were not statistically significant. Conclusion: CAM more commonly affects males with co-morbidities. TLC and CRP were significantly associated with poor outcomes. Histologically, the involvement of skin, muscle, and cartilage and the presence of excessive fungal hyphae and thrombosis were also associated with poor outcomes.

Effectiveness of sentinel lymph node biopsy and bilateral pelvic nodal dissection using methylene blue dye in early-stage operable cervical cancer-A prospective study.

OBJECTIVE: To evaluate the effectiveness of methylene blue dye in detecting sentinel lymph nodes (SLNs) in women with early-stage operable (defined as FIGO I-IIA) cervical cancer. It also aims to evaluate procedural challenges and accuracy. METHOD: This prospective study, which focused on 20 women with early-stage cervical cancer, was carried out between June 2016 and December 2017. These patients had SLN mapping with methylene blue dye injections and thorough examinations, including imaging. All patients underwent radical hysterectomy and complete bilateral pelvic lymphadenectomy. No additional investigation was done on the lymph node in cases where a metastasis was found in the first H&E-stained segment of the sentinel node. RESULT: 20 patients were included in the analysis. The median age of the subjects was 53, and 95 % of them had squamous cell carcinoma. 90 % of the time, the identification of SLNs was effective, and 55 SLNs were found, of which 52.7 % were on the right side of the pelvis and 47.3 % on the left. The obturator group had the most nodes, followed by the external and internal iliac groups in descending order of occurrence. Metastasis was detected in 3 patients, resulting in a sensitivity of 100 % and a specificity of 93.75 % for SLN biopsy. Notably, no false-negative SLNs were found. Complications related to methylene blue usage included urine discoloration in 30 % of patients. CONCLUSION: This trial highlights the promising efficacy and safety of methylene blue dye alone for SLN identification in early-stage operable cervical cancer, with a notably higher success rate. Despite limitations like a small sample size, healthcare professionals and researchers can build upon the insights from this study to enhance cervical cancer management.

Epithelial-Myoepithelial Carcinoma of Nasal Cavity at an Unusual Age: A Case Report and Review of Literature.

Introduction: Epithelial-myoepithelial carcinoma (EMC) was recognised as a distinct pathologic entity in World Health Organisation classification. It is an extremely rare low grade carcinoma of salivary gland, with characteristic biphasic tubular structures. It predominantly occurs in Parotid gland but can also be seen in nasopharynx, lacrimal gland, paranasal sinuses, larynx, lung. Nasal EMC (excluding the paranasal sinuses as primary tumour site) are very rare with only 13 cases reported till date. In this case report, we described a case of nasal EMC extending into nasopharynx, its clinical features and management. We have also done a literature review of all the relevant cases of nasal EMC. Material and Methods: We searched the PubMed database for articles between January 1950 and December 2022 for nasal EMC for this review. Results: We found 13 relevant case reports of nasal EMC and median age was 58 years with female preponderance. We found that our patient was the youngest to be reported till date. Two cases, including the current study, showed epicentre of the tumour in posterior nasal cavity, extending to choana and nasopharynx. Most common presentation was epistaxis, followed by nasal obstruction. Only 4 out of 14 cases had information on surgical margin status, out of which only one has positive surgical margin. Five patients (including the patient in the current study) received adjuvant radiotherapy; however 6 patients (42.8%) did not receive any adjuvant radiotherapy.

Differential expression of CK7, CK20, CDX2 in intestinal and pancreatobiliary types of preriampullary carcinoma.

CONTEXT: Incidence of periampullary carcinoma is low, approximately 0.5-2% of all gastrointestinal malignancies. Histologic subtyping has a prognostic bearing. The purpose of this study is to differentiate periampullary carcinomas based on immunohistochemistry (IHC) by using cytokeratin 7 (CK7), cytokeratin 20 (CK20), caudal type homeobox 2 (CDX2). AIMS: To analyze the usefulness of IHC as single/panel of markers that included CK7, CK20, and CDX2. SETTINGS AND DESIGN: This was a prospective study done from January 2017 to September 2018. SUBJECTS AND METHODS: A total 50 pancreaticoduodenectomy specimens were evaluated and classified as intestinal (INT) and pancreaticobiliary (PB) types based on their morphological and immunohistochemical features, respectively. The morphologic subtypes, expression of IHC markers were correlated with different histologic parameters. STATISTICAL ANALYSIS: Chi-square test was used to study the association between different IHC markers with histologic parameters. Probability (P) values <0.05 were regarded as statistically significant. RESULTS: The expression of CK7, CK20, CDX2 were studied in 50 cases to classify them as INT and pancreatobiliary subtypes. CK7 has high sensitivity (88.2%), CDX2 has high specificity (96.4%), CK20+/CDX2+ has both high sensitivity (94.2 percent) and specificity (89.2 percent) in differentiating INT from pancreatobiliary subtypes. The morphologic subtypes showed correlation with two variables (tumor grade, pathologic T stage). CK20 and CK20/CDX2 expression showed a positive correlation with tumor grade, pathologic T staging, and lymphovascular invasion. CONCLUSIONS: In conclusion, morphological classification can significantly discriminate histologic types, IHC plays a moderate role. However, the combined expression of CK20 and CDX2 is helpful in subtyping.

Effect of Correction of Hyperthyroidism with Anti-thyroid Drugs on the Glycated Hemoglobin in Non-diabetic Patients with Primary Hyperthyroidism.

BACKGROUND: Glycated hemoglobin (HbA1c) levels are dependent not only on the average blood glucose levels over the preceding 2 - 3 months but also on the turnover of erythrocytes. Hyperthyroidism is known to be associated with an increase in erythrocyte turnover that may falsely lower the HbA1c in relation to the level of glycemia. OBJECTIVES: To assess the impact of medical correction of hyperthyroidism on HbA1c, independent of changes in the fasting plasma glucose and 2-hour post-oral glucose tolerance test plasma glucose. METHODS: Adult patients with overt hyperthyroidism (n = 36) were tested for their hemoglobin, reticulocyte percentage, HbA1c and fasting and post-oral glucose tolerance test (OGTT) 2-hour plasma glucose, both at baseline and following at least three months of near normalization of serum thyroxin on Carbimazole treatment. RESULTS: Correction of hyperthyroidism in 36 patients was associated with an increase in the hemoglobin (P = 0.004) and a rise in HbA1c (P = 0.025), even though no significant change was observed in both the fasting (P = 0.28) and post OGTT two-hour plasma glucose (P = 0.54). Also, the proportion of patients with HbA1c ≥ 5.7% rose from 3/36 to 10/36; P = 0.016, while the proportion of patients with either abnormal fasting or abnormal post OGTT 2-hour plasma glucose or both did not show any significant change (P = 0.5). The sensitivity of HbA1c to diagnose prediabetes increased from 20% to 50% post- treatment. CONCLUSIONS: Glycated hemoglobin is falsely low in relation to glycemia in patients with untreated hyperthyroidism.

Estrogen and progesterone receptor in meningiomas: An immunohistochemical analysis.

BACKGROUND: Meningiomas are common slow-growing primary intracranial neoplasms attached to the dura mater and are composed of neoplastic meningothelial cells. Increased incidence of meningiomas in women with an increased tumor growth during pregnancy and a possible association with breast cancer suggested that female sex hormones have been involved in the growth of meningiomas. Antihormonal-targeted therapy would be beneficial in such patients. AIM: The aim of this study is to correlate the expression of estrogen receptor (ER) and progesterone receptor (PR) in meningiomas with gender, location, histological subtypes, and grade. MATERIALS AND METHODS: This is a 3½-year prospective and retrospective study of intracranial and intraspinal meningiomas. Clinical details of all the patients were noted from the computerized hospital information system. Immunohistochemistry for ER and PR was performed. Statistical analysis was performed using Chi-square test. RESULTS: During the study period, there were 80 Grade I, 18 Grade II, and 2 Grade III meningiomas categorized as per the World Health Organization 2007 classification. The female-to-male ratio was 1.9:1 and the mean age was 47.8 years. ER was expressed in 2% of meningiomas. PR was expressed in 67.5% of Grade I and 66.6% of Grade II and none of Grade III meningiomas. Brain-invasive meningiomas showed 54.5% PR immunopositivity and negative for ER. CONCLUSION: ER and PR were expressed in 2% and 66% of meningiomas, respectively. Statistically significant relationship was not found between the positivity of PR in females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas.

Value of cytokeratin-19, Hector Battifora mesothelial-1 and galectin-3 immunostaining in the diagnosis of thyroid neoplasms.

BACKGROUND: Diagnosis of types and aggressiveness of thyroid cancers is difficult. The "gold standard" in diagnosis is using routine hematoxylin and eosin staining. Several markers have been investigated for differentiating them among which cytokeratin-19 (CK-19), Hector Battifora mesothelial cell (HBME-1), and galectin-3 are found to be most commonly used. Most studies have evaluated the single expression of markers in various thyroid lesions. AIMS AND OBJECTIVES: To know the value of immunohistochemical expression of CK-19, HBME-1, and galectin-3 in diagnosing thyroid neoplasms. To study the expression and compare the results of HBME-1, CK-19, and galectin-3 immunohistochemical markers in histopathologically diagnosed malignant lesions and nonmalignant lesions and demonstrate their usefulness in differentiating them. MATERIALS AND METHODS: A prospective study was carried out on thyroidectomy specimens sent in 10% buffered formalin to Department of Pathology, SVIMS, Tirupati, from May 2013 to August 2014. Sensitivity and specificity for each marker and their combination in diagnosis were calculated. RESULTS: Among 120 cases, nonmalignant lesions were 70 (58.33%) and malignant lesions 50 (41.67%). Among nonmalignant lesions, 65 (93%) were adenomatous goiter and 5 (7%) were follicular adenomas. In malignant lesions, 48 (96%) were papillary carcinoma and 1 (2%) each of follicular carcinoma and anaplastic carcinoma. Among papillary carcinomas, classical were 26 (54.16%) followed by 17 follicular variant (35.41%). Galectin-3 had highest sensitivity of 90% and HBME-1 had highest specificity of 97.14%. CONCLUSIONS: Panel of HBME-1+ galectin-3 or CK-19, HBME-1, and galectin-3 increase the accuracy of diagnosis in histopathologically difficult cases.

Familial Swyer syndrome: a rare genetic entity.

Swyer syndrome is a pure gonadal dysgenesis associated with a 46 XY karyotype and primary amenorrhea in a phenotypic female. Individuals in this syndrome are at an increased risk for development of gonadal malignancies. Swyer syndrome (gonadal dysgenesis) running in families is rare event and few such scenarios were reported in the literature. Here we are presenting this rare entity involving three affected siblings born to a non-consanguineous couple. Index case - A 23-year-old female with primary amenorrhea is presented with a mass per abdomen. The clinical findings and laboratory investigations revealed hypergonadotropic hypogonadism picture and, imaging revealed a left ovarian tumor. Primary surgical debulking of ovarian cancer was done, histopathology of which revealed a dysgerminoma FIGO stage IIIC. The family history of the patient revealed a similar pattern as the elder sister had primary amenorrhea and had succumbed to ovarian cancer and the younger sister also has primary amenorrhea. Karyotype of all the three patients revealed a male genotype with a female phenotype. The early diagnosis of the patients with Swyer syndrome is very important because of the increased risk for the development of malignancy. This is a rare event to have two sisters with ovarian cancers in three siblings affected with familial gonadal dysgenesis syndrome each of them having a different genotype and first of its kind to ever be reported in literature.

Atypical Parathyroid Adenoma with Multiple Brown Tumors as Initial Presentation: A Rare Entity.

Brown tumors seen in hyperparathyroidism are rare, non-neoplastic lesions because of abnormal bone metabolism, and they can mimic benign bone tumors or malignancy. Although biopsy is considered as the gold standard for diagnosis, it can be inconclusive. As the diagnosis of brown tumors is often challenging, a high index of suspicion is essential for diagnosis. We present a case of 21-year-old woman who presented with multiple painful bony lesions, which were initially misdiagnosed as fibrous dysplasia. Due to persistent bone pain and deterioration in her physical mobility, she was referred to tertiary care centre. After thorough clinical workup, she underwent Tc-99m methylene diphosphonate bone scintigraphy that raised strong clinical suspicion of hyperparathyroidism and brown tumors. Subsequently, Tc-99m-methoxy isobutyl isonitrile (MIBI) parathyroid scintigraphy revealed a solitary MIBI avid focal lesion, suggestive of left inferior parathyroid adenoma. Later parathyroidectomy was performed and histopathological examination confirmed it as atypical parathyroid adenoma.

Expression of p53 & epidermal growth factor receptor in glioblastoma.

BACKGROUND & OBJECTIVES: Glioblastoma (GB) is the most frequent brain tumour, manifesting at any age, with a peak incidence between 45 and 75 years. Primary and secondary GBs constitute relatively distinct disease entities in evolution, in expression profiles and in therapeutic response. Histopathologically, primary and secondary GBs are indistinguishable. The aim of this investigation was to study the immunohistochemical (IHC) expression of p53 and epidermal growth factor receptor (EGFR) in GB with the objective of categorizing the morphological variants of GB into primary and secondary based on the presence of low-grade areas and knowing the variable expression of p53 and EGFR in primary and secondary GB. METHODS: A total of 28 patients with GB were studied and categorized into primary and secondary based on the presence of low-grade areas, i.e. discernible astrocytic morphology, gemistocyte and oligodendroglia. Tumours with the presence of combination of the above features or any one of the above features were taken as secondary GB, whereas tumours with highly pleomorphic areas were considered as primary GB. IHC was done on the representative tissue blocks for p53 and EGFR. RESULTS: Majority of the patients were in the fifth and sixth decades of life with a mean age of 46.96±13 yr with male preponderance (male:female 2.5:1). Mean age of presentation was 48.93±12 yr in primary and 44.69±15 yr in secondary GB. All cases of GB were classified into primary (53.57%) and secondary (46.43%) based on morphology. EGFR was more frequently expressed than p53. Based on IHC, 50 per cent of cases were classified into primary, three per cent into secondary and 47 per cent as unclassified. INTERPRETATION & CONCLUSIONS: Histopathological features, i.e. presence of low-grade areas, may play a role in classifying GB into primary and secondary. EGFR has a pivotal role in gliomagenesis. Combination of p53 and EGFR alone may not be sufficient to clarify GB into primary and secondary.

Human epidermal growth factor receptor 2/neu protein expression in meningiomas: An immunohistochemical study.

BACKGROUND: Meningiomas are common slow-growing primary central nervous system tumors that arise from the meningothelial cells of the arachnoid and spinal cord. Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c-erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity expressed in meningiomas and various other tumors. It can be used in targeted therapy for HER2/neu positive meningiomas. AIM: To correlate the expression of HER2/neu protein in meningiomas with gender, location, histological subtypes, and grade. MATERIALS AND METHODS: It was 3½ years prospective (March 2010-October 2011) and retrospective (May 2008-February 2010) study of histopathologically diagnosed intracranial and intraspinal meningiomas. Clinical details of all the cases were noted from the computerized hospital information system. Immunohistochemistry for HER2/neu protein was performed along with scoring. Statistical analysis was done using Chi-square test to look for any association of HER2/neu with gender, location, grade, and various histological subtypes of meningiomas at 5% level of significance. RESULTS: A total of 100 cases of meningiomas were found during the study period. Of which, 80 were Grade I, 18 were Grade II, and 2 were Grade III meningiomas as per the World Health Organization 2007 criteria. The female-male ratio was 1.9:1 and the mean age was 47.8 years. HER2/neu protein was expressed in 75% of Grade I and 72.2% of Grade II and none of Grade III meningiomas. About 72.7% brain invasive meningiomas showed HER2/neu immunopositivity. CONCLUSION: HER2/neu protein was expressed in 73% of meningiomas. Statistically significant difference of HER2/neu expression was not seen between females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas.

Helicobacter pylori in Cholecystectomy Specimens-Morphological and Immunohistochemical Assessment.

INTRODUCTION: Helicobacter pylori (H.pylori) is associated with gastritis, peptic ulcer, gastric carcinoma and gastric lymphoma. Current literature describes presence of H.pylori in various extra-gastric locations and its association with many diseases. Apart from the conventional location of gastric and duodenal mucosa, H.pylori have been isolated and cultured from gallbladder. AIM: Analysis of cholecystectomy specimens to detect H.pylori by means of immunohistochemical staining. MATERIALS AND METHODS: There were a total of 118 cholecystectomy specimens received in the Department of Pathology in three months duration. We have performed immunostaining for H.pylori in 45 consecutive cases of cholecystectomy specimen. Clinical and other investigational information were retrieved from the medical records department. For each case, routine Haematoxylin and Eosin stain was studied. Immunohistochemistry (IHC) was done using purified polyclonal Helicobacter pylori antiserum. RESULTS: Majority of the patients had undergone laparoscopic cholecystectomy for the presenting complaint of right hypochondrial pain. Multiple pigmented stones were present in majority (27/45) of them. Immunostain for H.pylori was positive in ten cases. Six of these cases had pigmented gall stones, two had stones not specified and in two of the cases there were no stones. CONCLUSION: Helicobacter pylori is present in gall bladder and is commonly seen in association with stones. A more detailed study of cholecystectomy cases (both neoplastic and non-neoplastic) with serological, culture and molecular data of H.pylori is desirable to study the pathogenesis of cholecystitis, its association with gall stones and other gall bladder disorders.

Histopathological and Immunohistochemical Evaluation of Meningiomas with Reference to Proliferative Markers p53 and Ki-67.

INTRODUCTION: Meningiomas are slow growing primary central nervous system (CNS) tumours attached to the duramater, which arise from the meningothelial cells of the arachnoid. Grading of meningioma based on histological findings assisted with supplementary immunohistochemical studies, predicts the prognosis of meningioma with good precision. AIM: To evaluate proliferative markers and correlate with various histological subtypes and grade. MATERIALS AND METHODS: A total of 224 meningiomas, diagnosed between January1995 and October 2011were graded according to WHO 2007 criteria. Immunostaining for p53 and Ki-67 markers were performed on 100 cases. RESULTS: There was female predominance. There were 194 Grade I, 24 Grade II and 6 Grade III meningiomas. Brain invasion noted in 18(8%) meningiomas predominantly in grade III followed by grade II. Recurrence was seen in 7 (3.1%) cases, most common in psammomatous followed by angiomatous meningioma. Immunostaining showed p53 positivity in 72.5% of grade I, 83.3% of grade II and all the cases of grade III tumours. Ki-67 Labelling Index (LI) consistently increased from grade I to grade III tumours. CONCLUSION: p53 and Ki-67 LI correlated well with increasing histological grade and biological behaviour of meningioma.

A study of primary glomerular diseases in adults; clinical, histopathological and immunofluorescence correlations.

Introduction: The frequency of primary glomerular diseases is variable from one part of the world to the other. Data published from India has shown wide range of variation in the different regions of the country. Objectives: This study reports the frequency of primary glomerulonephritis (GN) in adults in the Rayalaseema region of south India. Materials and Methods: The study is based on prospective evaluation of renal biopsies done during 2 years 4 months period (May 2010-August 2012). A total of 137 cases of primary GN were studied by light microscopy and immunofluorescence (IF). The patients age range between 15-74 years. Results: Most frequent primary GN was membranous nephropathy (MN) constituting 35.8%, followed by minimal change disease (MCD) at 16.7%. Conclusion: This study demonstrates that MN is the most common primary GN encountered in the adults, the second more frequent is MCD. This result is in contrast to previous reports from India where IgA nephropathy (IgAN) and MCD were reported as the most common primary GN in whole population.

Hormone receptor status (estrogen receptor, progesterone receptor), human epidermal growth factor-2 and p53 in South Indian breast cancer patients: A tertiary care center experience.

UNLABELLED: Breast cancer, in India, is the second commonest cancer in females. Receptor status with ER/PR/Her 2 is now routinely done in patients with invasive carcinoma. The tumour suppressor gene, p53, is also present in most breast cancers. Proteins produced by a mutated p53 gene, accumulate in the nucleus of tumour cells and are detected by immunohistochemistry (IHC). We have undertaken this study with the aim to evaluate the ER, PR, HER-2 and p53 expressions in invasive breast carcinomas by IHC and to compare the HER-2 expression with various clinicopathological parameters. MATERIALS AND METHODS: In this retrospective single institutional study from January 2001 to December 2010, 389 cases of histopathologically diagnosed infiltrating carcinoma of breast were evaluated taking into account various parameters like age, tumour size, grade, lymph node involvement, ER and PR. HER-2 and p53 was done in 352 cases. RESULTS: The age range was 23-90 years with a mean of 50.7 years. Majority of tumours were T2 (79.6%) and Grade II (60.9%). Our data showed overall 47.6% ER, 48.8% PR, 29.6% HER-2 and 69.2% p53 positivity. There was no significant correlation between HER-2 and age, tumour size, lymph node status, ER, and PR. There was significant correlation between HER-2 and tumour grade (P = 0.031), p53 (P < 0.001). There was no inverse correlation between HER-2 and combined ER, PR status. Triple-negative breast cancers which constituted 22.7% of our cases did not reveal any correlation with various parameters. CONCLUSION: In our study, ER status was low, and incidence of p53 was high. These findings suggest that many of the tumours in Indian females may be of an aggressive type, and novel treatment approaches may be tried. We conclude that the assessment of all four markers is desirable.

Thyrolipomatosis: an inquisitive rare entity.

It is rare to find diffuse presence of mature adipose tissue inside thyroid gland which defines thyrolipomatosis. We report a case of a 32-year-old hyperthyroid female on suppression therapy since the past 2 years presenting with diffuse thyroid swelling. She underwent total thyroidectomy and the histopathology revealed features of thyrolipomatosis. As fat containing lesions of thyroid include not only non-neoplastic lesions but neoplasms also, including an occasional malignant one, rendering a correct diagnosis is essential.