Meningioma Prognostic Tool Based on Correlation of Histopathological Grading and Immunohistochemistry.

Objectives: Meningiomas are slow-growing brain neoplasms classified into three grades based on morphological criteria. While these grades are simple, they do not always correlate with patient outcomes. This study aimed to evaluate the status of estrogen receptor (ER), progesterone receptor (PR), and proliferation marker Ki-67/molecular immunology borstel-1 (MIB-1) in the three grades of meningioma. Methods: We evaluated the data of meningioma patients who were seen in our tertiary center over 10 years-8.5 years retrospectively and 1.5 years prospectively. Their archival hematoxylin and eosin stained slides were reviewed and re-graded according to the World Health Organization 2021 criteria. Immunohistochemical analysis for ER, PR, and Ki-67 was performed on all grade 2 and grade 3 meningiomas and 30 cases of grade 1 formalin-fixed, paraffin-embedded samples. Results: Of the 276 cases included in the study, there were 231 (83.7%) cases of grade 1 meningioma, 34 (12.3%) cases of grade 2, and 11 (4.0%) cases of grade 3. ER was positive in 26.0% of grade 1 tumors, 5.8% of grade 2, and 0.0% of grade 3. PR was positive in 70.0% of grade 1 tumors, 20.0% of grade 2, and 18.0% of grade 3. The Ki-67/MIB-1 labeling index (LI) was 2.1 in grade 1, 6.3 in grade 2, and 13.4 in grade 3 tumors. For both PR and Ki-67, the differences between grades 1, 2, and 3 tumors were significant (p < 0.001). There was a significant inverse relationship between mean Ki-67 LI and PR status, with increasing grade of tumor. Conclusions: Ki-67/MIB-1 LI has significant positive correlations with meningioma grade and its recurrence, which makes it a useful auxiliary method for the routine assessment of meningiomas, especially in patients with borderline atypia. The expression of PR, on the other hand, is a positive prognostic indicator and has a substantial correlation with histological grade. In cases of subtotal resection, high proliferative/recurrence rates, and borderline histopathology, the PR status in combination with the MIB-1 LI can offer insights into the behavior and the recurrence probability of a meningioma.

Investigating dysregulation of TGF-ß1/SMAD3 signaling in Atopic Dermatitis: A Molecular and Immunohistochemical Analysis".

Atopic Dermatitis (AD) is a persistent and recurring inflammatory condition affecting the skin. An expanding corpus of evidence indicates the potential participation of TGF-ß1 in the modulation of inflammation and tissue remodeling in AD. The primary objective of this study was to examine the aberrant modulation of TGF-ß1/SMAD3 signaling through a comprehensive analysis of their molecular and protein expression profiles. The study encompassed an aggregate of 37 participants, which included 25 AD patients and 12 controls. The assessment of mRNA and protein levels of TGF-ß1 and SMAD3 was conducted utilizing quantitative real-time PCR and immunohistochemistry, whereas serum IgE and vitamin D levels were estimated by ELISA and chemiluminescence, respectively. Quantitative analysis demonstrated a 2.5-fold upregulation of TGF-ß1 mRNA expression in the lesional AD skin (p<0.0001). Immunohistochemistry also exhibited a comparable augmented pattern, characterized by moderate to strong staining intensities. In addition, TGF-ß1 mRNA showed an association with vitamin D deficiency in serum (p<0.02), and its protein expression was linked with the disease severity (p<0.01) Furthermore, a significant decrease in the expression of the SMAD3 gene was observed in the affected skin (p = 0.0004). This finding was further confirmed by evaluating the protein expression and phosphorylation of SMAD3, both of which exhibited a decrease. These findings suggest that there is a dysregulation in the TGF-ß1/SMAD3 signaling pathway in AD. Furthermore, the observed augmentation in mRNA and protein expression of TGF-ß1, along with its correlation with the disease severity, holds considerable clinical significance and emphasizes its potential role in AD pathogenesis.

A complete spectrum of congenital cystic adenomatoid malformation of the lung deceptive clinical presentations and histological surprises; a single institutional study from a tertiary care hospital in North India.

Background: Congenital Cystic Adenomatoid Malformations (CCAM) are rare congenital anomalies of the lungs characterised by bronchopulmonary foregut malformations due to a sudden arrest in the development of the bronchial tree in the first trimester of the gestational period. Aim: : The present study was aimed to describe the clinical and histopathological profiles of the patients and study patient outcomes after 1 year of surgical resection. Methods: All patients diagnosed with CCAM by histological examination of tissue obtained on surgical resection during the study period were included in the study. Data, such as patient demographics and clinical, radiological and histopathological findings, were recorded, and follow-up information was taken on OPD follow-up till 1 year after surgery regarding respiratory infections, haemoptysis or mortality. Results: : Out of 21 patients, 11 were female and included in the study between the ages of 1 month and 32 years, with >50% younger than 2 years. Most patients in the study had recurrent pneumonia, with difficulty in breathing being the second most common presenting complaint. All patients had undergone computed tomography (CT) of the lungs, which was able to diagnose cystic lesions accurately in >80% of cases. Histologically, all cases were classified based on recent Strocker's classification, and Type 1 was the most commonly observed with 13 cases, followed by Type 2 in five and Type 3 in three patients. There was no evidence of malignant transformation in any of the cases. There was 100% survival at the end of 1 year, with six patients having respiratory infections and none of the patients getting hospitalised over 1 year after surgery. Conclusion: CCAM is a rare congenital anomaly associated with significant morbidity and may present at any age. It can be histologically classified into three subtypes, with Type 1 being the most common. Early surgical management is mandatory to prevent complications such as recurrent infections, respiratory distress, pneumothorax, lung abscess and malignant transformation. All patients included in the study had undergone surgical resection, and there was 100% survival at 1-year follow-up.

Differential expression of SLITRK6 gene as a potential therapeutic target for urothelial carcinoma in particular upper tract cancer.

BACKGROUND: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC. METHOD: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot. RESULTS: Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (∼75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively. CONCLUSION: To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.

Primary pulmonary adenoid cystic carcinoma- clinicopathological features and predictors of poor outcome.

Introduction: Primary pulmonary adenoid cystic carcinoma is a rare disease. Its clinico-pathological features, course of disease, therapeutic strategy, and survival data have not been fully elucidated. We aimed to study the clinicopathological characteristics of primary pulmonary adenoid cystic carcinomas in north India. Methods: This study was a retrospective, single-centre, cohort study. The database of the hospital was searched for a period of seven years to identify all patients with primary pulmonary adenoid cystic carcinoma. Results: Out of 6050 lung tumors, 10 were primary adenoid cystic carcinomas. The mean age of diagnosis was 42 (±12) years. Six patients had the lesion in the trachea, main bronchus or truncus intermedius and four had parenchymal lesions. Seven patients had resectable tumours. Three patients achieved an R0 resection, two achieved R1 resection and two had R2 resection. On histopathological examination, almost all of the patients had cribriform pattern. Only four patients (57.1%) showed positivity for TTF-1 staining. The five-year survival of patients with resectable tumour and un-resectable tumour was 85.7% and 33.3%, respectively (P = 0.01). The predictors of poor outcome included non-operability of the tumour, presence of metastasis at the time of diagnosis, and macroscopically positive tumour margin during surgery. Conclusion: Primary pulmonary adenoid cystic carcinoma is a unique and rare tumour that affects relatively younger individuals, males and females, as well as smokers and non-smokers equally. The features of bronchial obstruction are the most common. Surgery is the primary modality of treatment and completely resectable lesions have the best prognosis.

Unveiling the TGF- ß1 paradox: Significant implication of TGF- ß1 promoter variants and its mRNA and protein expression in atopic dermatitis.

BACKGROUND: Atopic Dermatitis (AD) is a chronic inflammatory skin disorder with evidence of lichenification in later stages. There is mounting evidence supporting the role of TGF- ß1 in mediating inflammation as well as subsequent tissue remodeling, often resulting in fibrosis. Given the role of genetic variants in the differential expression of TGF-ß1 in various diseases, this study seeks to ascertain the role of TGF-ß1 promoter variants (rs1800469 and rs1800468) in AD susceptibility, as well as their association with TGF- ß1 mRNA expression, TGF- ß1 serum levels and skin prick test positivity in Atopic Dermatitis patients. METHODS: An aggregate of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for TGF-ß1 promoter polymorphisms by PCR-RFLP. TGF- ß1 mRNA was quantified by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and serum TGF- ß1, and total IgE levels were determined by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites and food allergens. RESULTS: A higher frequency of TT genotypes of rs1800469 (OR = 7.7, p = 0.0001) and GA+AA genotypes of rs1800468 (OR-4.4, p < 0.0001) were observed in AD cases than those in controls. Haplotype analysis demonstrated that TG haplotype carriers had an increased risk of AD (p = 0.013). Quantitative analysis revealed a significant upregulation of both mRNA (p = 0.0002) and serum levels (p < 0.0001) of TGF- ß1 with a substantial positive correlation between them (Correlation coefficient=0.504; p = 0.01). Moreover, serum TGF-ß1 levels were associated with quality of life (p = 0.03), the severity of the disease (p = 0.03), and House dust mite allergy (p = 0.01) whereas TGF-ß1 mRNA levels positively correlated with disease severity(p = 0.02). Stratification analysis revealed that the TT genotype of rs1800469 was associated with higher IgE levels (p = 0.01) and eosinophil percentage(p = 0.007) whereas the AA genotype of rs1800468 correlated with elevated serum IgE levels (p = 0.01). Besides, no significant association of genotypes with mRNA and serum expression of TGF-ß1 was observed. CONCLUSION: Our study indicates that TGF-ß1 promoter SNPs bear a significant risk of AD development. Moreover, upregulation of TGF-ß1 mRNA and serum levels and their association with disease severity, quality of life, and HDM allergy suggests its role as a diagnostic/prognostic biomarker that could help in the development of new therapeutic and prevention strategies.

Lung schwannomas, an unusual entity: A series of five cases.

Schwannomas are benign slow-growing tumours arising from the Schwann cells of the nerve sheath. They may arise anywhere in the course of the nerves in the body. The clinical presentations are non-specific, and when present in rare locations such as lungs, the diagnosis becomes difficult. The present case series describes the clinical presentation and diagnosis of five cases of lung schwannoma. The diagnosis was mainly assisted by the immuno-histochemical examination comprising markers such as S-100, Calretinin, CD34, CD56, Desmin, and EMA. A definitive diagnosis of benign nerve tumours in such rare locations may help in better pre-operative assessment and surgery for complete recovery of the patients.

Spinal aspergillosis: a rare complication of COVID-19 infection.

BACKGROUND: Several complications have been reported in COVID-19 infection. Most of the complications include secondary infection. CASE PRESENTATION: We report an 85-year-old male who presented with cauda equina syndrome 7-months after contracting COVID-19 infection. We excised an extradural mass which on examination proved to be Spinal Aspergillosis. CONCLUSIONS: Spinal Aspergillosis should be kept in mind in patients who present with local spinal pain with or without neurological deficit after COVID-19 infection.

Papillary Tumor of Pineal Region in a 5-Year-Old Male Child: A Rare Entity.

Papillary tumor of the pineal region (PTPR) is a rare grade II to III pineal lesion. These tumors mostly occur in adults, only rarely in children, with six cases in children under the age of 16 years (10.2%) up to now. We report the case of a 5-year-old male child presenting with worsening headaches, abnormally enlarged head since birth and visual disturbances. Imaging reveals a mass in the region of the pineal gland. The third and lateral ventricles were enlarged. The patient underwent a gross-total surgical resection of pineal mass through a suboccipital supracerebellar approach and tissue sent for histopathological examination and an available immunohistochemical workup has been done which confirmed the diagnosis of papillary tumor pineal region. This case highlights the histopathological features, imaging along clinical presentation similar to those in the original description of this rare entity PTPR. More studies are required to determine the prognosis and standard treatment protocol of this rare entity.

Role of Diffusion and Perfusion Magnetic Resonance Imaging in Predicting the Histopathological Grade of Gliomas - A Prospective Study.

CONTEXT: Gliomas are the most common brain tumors. In addition to conventional magnetic resonance imaging (MRI) techniques, a variety of new techniques offers more than the anatomic information. The new MRI techniques include perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). AIMS: The aim of this study is to assess the sensitivity, specificity, predictive value, and accuracy of diffusion- and perfusion-weighted MRI in the preoperative grading of gliomas. SETTING/DESIGN: The study was conducted in the Department of Neurosurgery, Pathology, and Radiodiagnosis, Sher-e-Kashmir Institute of Medical Sciences, Kashmir, India, which is the only tertiary care neurosurgical center in the state. It was a prospective study. PATIENTS AND METHODS: Thirty-one consecutive patients with gliomas were included in the study. All the patients were evaluated by a standard conventional contrast-enhanced study on Siemens 1.5 Tesla MRI. In addition to the standard MRI, diffusion- and perfusion-weighted MRI were also performed. The histopathological grading of the tumor was done as per the WHO classification of 2007. The sensitivity, specificity, predictive value, and accuracy of diffusion- and perfusion-weighted MRI in determining tumor grade were calculated. Comparison was done between PWI, DWI findings, and WHO histopathological grading. ANALYSIS METHOD: The statistical analysis was done using the Statistical Package for the Social Sciences, and receiver operating characteristic curves were used to estimate sensitivity, specificity, and accuracy. RESULTS: The overall sensitivity of PWI (with regional cerebral blood volume cutoff of 1.7) in the preoperative assessment of high-grade gliomas was 82.6% and specificity was 75%, the positive predictive value (PPV) was 90.48%, and the negative predictive value (NPV) was 60%. The overall accuracy was 80.65%. In case of DWI, the sensitivity was 69.57% and the specificity was 75%, and the PPV and NPVs were 88.8% and 46.15%, respectively. The overall accuracy was 71%. CONCLUSION: Our results clearly show higher accuracy of diffusion- and perfusion-weighted MRI in assessment of glioma grade as compared to conventional MRI. This information can prove very useful for the operating neurosurgeon in preoperative assessment and surgical planning. Postoperatively, the neuropathologist can also benefit from such information.

Clinicopathological Characteristics of Meningiomas: Experience from a Tertiary Care Hospital in the Kashmir Valley.

BACKGROUND: Meningiomas comprise 15%-20% of all primary intracranial tumors. They are generally benign tumors, and most patients are cured after surgery and remain free of recurrence. However, some tumors behave in an aggressive manner, and patients develop local recurrence or metastasis. Overall prognosis is good. PATIENTS AND METHODS: This is an 11-year retrospective study conducted in the Departments of Pathology and Neurosurgery at Sheri-I-Kashmir Institute of Medical Sciences, Kashmir, India. Besides the demographic profile, the parameters analyzed were location of tumor on imaging, histopathological subtype, and grade of tumor according to the 2007 WHO classification and recurrence at follow-up. RESULTS: A total of 254 patients were included in our study, of which 205 (80.7%) were brain meningiomas and 49 (19.3%) were spinal, with an overall female: male ratio of 2:1. Female: male ratio was more in spinal meningiomas, 15.3:1. Most of our patients were in the 4-6th decade of life with a mean age of 48 years (range: 5-73 years). Meningothelial meningioma was the most common histological type. Of ten patients who showed recurrence, seven cases showed only recurrence, but no progression to higher grade and three cases showed recurrence with progression by one WHO-grade. We also noticed that recurrence was higher in Simpson Grades II and III. CONCLUSION: Meningiomas are common in females and most of the meningiomas do well after surgery. The recurrence rate was 3.93% in our study and Simpson grade of tumor excision and histopathological grade contribute significantly to the recurrence of the tumor.

Utility of Computed Tomography-guided Biopsy in Evaluation of Metastatic Spinal Lesions.

INTRODUCTION: Computed tomography (CT)-guided biopsy of spine is currently a valuable diagnostic tool and effective technique for diagnosing and planning a proper therapeutic strategy for certain spinal lesions. The reported diagnostic accuracy of core biopsy ranges from 77% to 97%. MATERIALS AND METHODS: We included all patients with spinal lesions suspicious of metastasis on magnetic resonance imaging, who presented between May 2012 and April 2014 and underwent CT-guided biopsy in our study. A total of thirty patients with spinal lesions were evaluated. RESULTS: Majority presented in the seventh decade of their life (average age = 53.93; age range = 10-72 years). Male:female ratio was 1.5:1. Pain was the most common presenting symptom (100%). Lumbar spine was the most common site of lesion followed by dorsal spine. Biopsy is the gold standard in histopathological evaluation of spinal lesions. Metastatic lesion was diagnosed in 12 (40%) cases, plasmacytoma in 12 (40%) cases, non-Hodgkin's lymphoma in 2 (6.66%) cases, small round cell tumor in 1 (3.33%) case, nonspecific chronic inflammation in two patients, and necrosis with no viable cells in one patient. The most common malignancy to metastasize to spine was adenocarcinoma. The most common primary tumor of spine was plasmacytoma - multiple myeloma. CONCLUSION: CCT-guided biopsy is a safe procedure, and no procedure-related complication was seen in any patient.

Primary Hypothalamic Lymphoma in an Adult Male: A Case Report and Literature Review.

Primary central nervous system lymphoma is a well-known entity. However, the hypothalamus is a rare location, especially in adults. Few cases of secondary lymphomas have been reported. We report a case of primary hypothalamic lymphoma in an adult male with normal pituitary functions. Lymphoma should be considered as one of the differential diagnosis of lesions involving the hypothalamic/third ventricular area.

Combination of needle aspiration and core needle biopsy: A new technique of stereotactic biopsy.

AIM: The study aims at describing the results of using a new technique to acquire the tissue sample in stereotactic biopsy of brain lesions. MATERIALS AND METHODS: The study was performed in 19 patients over a period of 5 years in which we used the new technique, i.e., Abrar and Afzal technique (AT) of obtaining tissue biopsy. It is a combination of core tissue biopsy and needle aspiration techniques. The technique was devised to acquire greater amount of tissue for pathologic study. RESULTS: While we could give pathologic diagnosis in 18 patients out of 19 (94.7%), in one patient, the tissue sample revealed only inflammatory cells and definitive diagnosis could not be reached. There was no significant morbidity or any mortality in the series. CONCLUSION: Abrar and Afzal technique is a reasonably accurate technique of acquiring larger tissue sample in stereotactic brain biopsy without any additional risks. It can be done with little modification of the conventional equipment available with the stereotactic system.

Compressive Myelopathy due to Osteochondroma of the Atlas and Review of the Literature.

We report a case of vertebral osteochondroma arising from the posterior C1 arch that presented with features of compressive myelopathy. Osteochondromas are usually found in extremities and are rarely seen in the spine. They are most commonly found in posterior elements in the spine, and intraspinal extension is uncommon. The most common presentation is incidental finding during routine imaging followed by palpation of painless swelling. Compressive myelopathy as a presentation of vertebral osteochondroma in a child is a rare entity. Surgical excision is the treatment of choice. Spinal osteochondromas should also be kept in mind as a cause of spinal cord or nerve root compression in children.

Metastatic Ameloblastoma to Brain: A Rare Entity.

Ameloblastoma is a rare odontogenic tumor of the jaw. It is a benign neoplasm but local recurrence is common. Metastasis from this tumor is all the more rare. The commonest site for metastasis is lung. Brain is a very uncommon site of involvement. Overall prognosis is good. We hereby discuss ameloblastoma of lower jaw in a young adult which had metastasized to brain. Patient was operated for the metastatic lesion of brain and is doing well on follow-up.

Nodular Graves' disease with medullary thyroid cancer.

Co-existence of thyroid nodules with Graves' disease has been reported in various studies. 10-15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves' disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves' disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC.

Primary pulmonary synovial sarcoma: Diagnosis on squash smears.

Synovial sarcomas are rare tumors accounting for approximately 5-10% of soft tissue sarcomas. They occur predominantly in the extremities, followed by head and neck. Primary pulmonary sarcomas are very rare and comprise only 0.5% of all primary lung malignancies. The diagnosis is established only after sarcomas like primary lung malignancies, and metastatic sarcomas have been excluded. For synovial sarcomas that arise at unusual locations, a definitive diagnosis is challenging and requires the use of ancillary diagnostic procedures such as immunohistochemistry (IHC) and molecular genetic techniques for confirmation of diagnosis. We report a case of 29-year-old male who had right lower lobe lung mass. He underwent right lower lobectomy. Intraoperative squash smears revealed spindle cell sarcoma. Subsequent histopathology and IHC confirmed the diagnosis as synovial sarcoma. We report this case on account of its rarity and to emphasize the utility of intraoperative squash smears in the diagnosis of such cases, which has been under-utilized in clinical practice.

Intraparenchymal anaplastic meningioma in a child: A rare entity.

Brain tumors are not rare in children. The common brain tumors in children are medulloblastomas and craniopharyngiomas. Intraparenchymal meningiomas are very rare. We report a case of intraparenchymal meningioma in a child who was operated with a preoperative impression of a primitive neuroectodermal tumor.

Squamous cell carcinoma of lung with osteo-cartilaginous metaplasia - a case report and review of the literature.

Calcification and ossification are very rare in primary squamous cell carcinoma of the lung. We report a 55-year-old male with primary squamous cell carcinoma of the lung who on histopathological examination was seen to have extensive calcification and ossification. Squamous carcinoma of the lung rarely presents with osteocartilaginous metaplasia. The case is presented here for its unique presentation.