Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy.

BACKGROUND: Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory. METHODS: In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores. RESULTS: A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis. CONCLUSION: Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Microvessel density (Cluster of Differentiation-34 & Vascular Endothelial growth factor) in Nasopharyngeal Angiofibroma: Clinical correlation.

BACKGROUND: The literature on microvessel density (MVD) signifying neoangiogenesis/tumour-activity in juvenile nasopharyngeal angiofibroma (JNA) is limited. Accordingly, this study evaluates and correlates MVD characteristics with clinical parameters/aggressiveness/recurrence. MATERIAL AND METHODS: Sixty-two paraffin blocks of JNA were studied histopathologically and MVD was assessed following immunohistochemistry using VEGF and CD34 as vascular markers. A clinical correlation of MVD was undertaken in 43 cases. RESULTS: MVD scores of VEGF and CD34 showed strong inter-correlation. The 'age', 'duration of disease' and 'haemoglobin%' were the only clinical parameters that revealed significance with MVD. Significantly higher MVD scores were appreciated in recurrent cases as well as some other clinical differences from upfront cases. CONCLUSION: This is the first study of MVD with CD34 and VEGF simultaneously depicting clinical correlation. The strong correlation, supports a prognostic role of MVD scores in JNA and this can be better established in a larger multicentre study involving comprehensive examination of tumour dimensions.

A Comparative Analysis of Liquid-Based Cytology and Conventional Smears in Fine-Needle Aspirates of Thyroid Lesions.

Background Palpable nodules in the thyroid are present in 4-7% of the general population. Fine-needle aspiration cytology is a safe and cost-effective method of choice for evaluating thyroid nodules. Aspirated samples can be manually spread directly onto the slide and stained in the conventional smear method. The liquid-cased cytology method has been recently introduced, which is an automated machine-based method, yielding a single slide with a clean background and greater preservation of cells and consuming less time for screening. This study aimed to compare the cytomorphological features and diagnostic accuracy of conventional smears and liquid-based cytology smears. Methodology This prospective study comprised 250 cases of thyroid lesions. Fine-needle aspiration cytology using conventional smears and liquid-based cytology smears was reported per the Bethesda system of reporting thyroid cytopathology. Detailed cytomorphological features were evaluated and compared in both techniques. Results The cellularity of conventional smears was significantly higher for scores 2+ and 3+ than paired liquid-based cytology smears (paired t-test, p < 0.001). The overall diagnostic efficacy of conventional smears and liquid-based cytology smears was equivalent in the majority of cases (n = 171, 68.4%). Conventional smears were better than liquid-cased cytology smears in 34 (13.6%) cases, and liquid-based cytology smears were better than conventional smears in eight (3.2%) cases. Liquid-based cytology smears showed a higher unsatisfactory rate compared to conventional Smears (15.6% vs. 5.2%). The sensitivity and specificity of conventional smears were 84.6% and 94.4%, respectively, compared to 68.7% and 92.4%, respectively, of liquid-based cytology smears. Conclusions Conventional smears are a cost-effective and easy method for diagnosing thyroid nodules. Liquid-based cytology smears can be used in association with conventional smears to enhance the accuracy of the evaluation of malignant thyroid nodules.

BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer.

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George's Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (≥3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of "BRCAness" in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP-ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Immunohistochemical appraisal of epithelial mesenchymal transition type III in gall bladder cancer.

Background: Epithelial-mesenchymal transition (EMT) is the heart of invasion. EMT associated with cancer progression and metastasis is known as type III EMT. Beta-catenin, E-cadherin, and MMP9 markers of EMT are routinely employed for diagnostic purposes. Aims: We employed these markers to study EMT by immunohistochemistry (IHC) in gall bladder cancer (GBC) with respect to depth of tumor invasion, clinical outcome, and disease-free survival. Settings and Design: This was a prospective case-control study. Material and Methods: Seventy gall bladders were included (50 GBC and 20 CC). After detailed histology, immunoexpression was studied in terms of percentage and strength of expression. Statistics Analysis Used: Expression was compared between CC and GBC by Student t test and analysis of variance. Kaplan-Meier was used for survival analysis, and the extent of agreement ("Kappa") was calculated. Results and Conclusions: The age of incidence of GBC was 49.40 (+11.6) years with female predominance (F:M = 4:1). In 88% (44/50) of GBC, the fundus was involved. Moderately differentiated adenocarcinoma was most frequent [54%; 27/50]. Significant downregulation of E-cadherin (P = 0.022) and beta-catenin (P < 0.001) and upregulation in MMP9 (P < 0.001) were seen in GBC with respect to CC with significant association among them. MMP9 expression was significantly associated with higher tumor stage but with chemotherapeutic response. Our results display that epithelial-mesenchymal transition type III plays a role in GBC invasion. MMP9 overexpression and loss of membranous beta-catenin may be considered a marker for poor clinical outcomes and advanced disease.

Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein-Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis.

INTRODUCTION: Worldwide, breast cancer (BC)  is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world's population.  Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India. METHODOLOGY: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)- EBV PCR and Epstein-Barr virus latent membrane protein 1 (LMP1) IHC. RESULTS: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection. CONCLUSION: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.

Phosphatase and Tensin Homolog Immunohistochemical Expression and Promoter Methylation Status in Endometrioid Endometrial Carcinoma and Its Precursor Lesions.

BACKGROUND: Endometrioid endometrial carcinoma (EEC) is the most common invasive malignancy of the female genital tract. Despite advances in diagnosis and treatment, the incidence of EEC and mortality related to it have not decreased. Therefore, research is needed to explore the underlying molecular mechanisms of EEC and its precursors to reduce the mortality and societal burden associated with them. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene most commonly altered in endometrial carcinoma and its precursor lesions. Promoter methylation is a common mechanism for the inactivation of the PTEN tumor suppressor gene. METHODS: This was a prospective nested case-control study involving women aged 35 to 70 years old whose endometrial biopsy and resected samples were obtained for histological diagnosis. Before enrolling a person in the study, signed informed consent was obtained from each individual. The ethics committee for the institute gave its approval to the study protocol. Immunohistochemistry (IHC) was used to measure PTEN expression was measured, and methylation-specific PCR (MSP) was used to determine PTEN promoter methylation status (Bisulfite conversion). RESULTS: A total of 95 samples were assessed histopathologically, along withPTEN expression and PTEN promoter methylation status. PTEN immunoreactivity was observed in 79% (15/19) of normal proliferative endometrium, and loss of PTEN expression was observed in 73% (27/37) of endometrial hyperplasia with or without atypia and 90% (35/39) of EEC. Methylation analysis showed that the PTEN promoter was completely unmethylated in all normal proliferative endometria and endometrial hyperplasia without atypia. In contrast, the promoter region was methylated in 50% of endometrial hyperplasia with atypia cases and 38.5% of EEC cases. CONCLUSION: The loss ofPTEN expression was significantly associated with EEC and precancerous lesions of the endometrium compared to normal proliferative endometria. Methylation analysis also revealed that the frequency of methylation is significant in EEC and endometrial hyperplasia with atypia. Integration of PTEN protein expression along with promoter methylation status elucidates the underlying carcinogenic mechanism. This may help with personalized therapy for EECs and triaging cases of potential precancerous lesions.

Can dual staining with p16 and Ki67 be biomarkers of epithelial dysplasia in oral lesions?

Background: Oral carcinogenesis is a multistage process with epithelial dysplasia as a premalignant condition. There is a significant inter-observer variation in diagnosing and grading the oral epithelial dysplasia. As human papillomavirus (HPV) is believed to have à strong relationship with oral carcinogenesis, using P16 as a biomarker may help in identifying the cells which may be undergoing the malignant transformation. However, due to the low specificity of P16, dual staining test P16INK4/Ki67 might be a better promising marker for identifying the transformed cells. This study was designed to evaluate the dual expression of P16 and Ki67 as a promising biomarker for dysplasia and their correlation with clinicopathological factors. Materials and Methods: Immunohistochemical analysis for p16 and ki67 was performed on 30 premalignant oral lesions and 36 oral squamous cell carcinoma (OSCC) by dual staining using the CINtec PLUS kit. Results: CINtec positivity was observed only in leukoplakia with dysplasia (46.7%) and squamous cell carcinoma (25%). None of the cases of leukoplakia without dysplasia or oral submucosal fibrosis stained positive for CINtec plus staining. In leukoplakia with dysplasia, there was no significant association with any of the clinicopathological parameters studied. In OSCC cases, alcohol intake showed statistically significant association with CINtec positivity. Conclusion: P16INK4/Ki67 assessment by dual staining is a promising biomarker for identifying dysplasia in cases with diagnostic dilemmas.

Model for Early Prediction of Preeclampsia: A Nested Case Controlled Study in Indian Women.

Purpose: Preeclampsia (PE) affects 5-7% of the pregnancies worldwide, and is one of the most dreaded disorders of pregnancy contributing to maternal and neonatal mortality. PE is mostly presented in the third trimester of pregnancy. Here, we used serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to develop a model for predicting PE in Indian women in early second trimester. Methods: In this case-control study, a total 1452 healthy pregnant women were recruited. Blood samples were collected at the following gestational weeks (GWs), 12-20 (GW1), 21-28 (GW2) and 29-term (GW3), and post-delivery. Body mass index (BMI) was calculated by anthropometric measurements. Serum sFlt-1, PIGF and VEGF were analyzed by ELISA. A predictive model for PE was developed using multivariable logistic regression analysis. Results: In PE cases, serum PlGF and VEGF levels were significantly lower at each GW, while serum sFlt-1 was lower only at GW1, relative to age-matched controls, (n = 132/group). Age-matched comparison between PE cases and controls indicated that sFlt-1 was associated with decreased PE outcome (Odds ratio. OR = 0.988, CI = 0.982-0.993), whereas sFlt-1/PlGF ratio (OR = 1.577, CI = 1.344-1.920) and BMI (OR = 1.334, CI = 1.187-1.520) were associated with increased PE outcome. Logistic regression was used to develop a predictive model for PE at GW1. Using testing dataset, model was externally validated which resulted in 88% accuracy in predicting PE cases at 0.5 probability cutoff. Conclusion: Prediction model using sFlt-1, sFlt-1/PlGF ratio and BMI may be useful to predict PE as early as 12-20 weeks in women with optimal sensitivity and specificity.

Melanotic neuroectodermal tumor of infancy (MNTI) - A rare entity.

Melanotic neuroectodermal tumor of infancy is a rare pigmented pediatric tumor seen at craniofacial sites with the most common site being maxilla. This tumor arises from neural crest origin with a polyphenotypic expression of epithelial, neuroblastic, and melanotic markers. It is a locally aggressive tumor with rapid, expansile, and destructive growth. The tumor has fairly high chances of recurrence and malignant transformation, if not diagnosed and treated with time. There is no standard protocol for management owing to its rarity. Hereby, we present one such case of a 2-month-old male child with rapidly enlarging upper jaw swelling. The patient was treated with wide local excision, followed by two cycles of chemotherapy. The patient is in follow-up and doing well with no evidence of any local recurrence or metastasis till date.

Guided Needle Aspirations of Intra-Abdominal Masses: Analogy between Liquid-Based and Conventional Smear Preparation Methods.

OBJECTIVE: Image-guided fine needle aspiration cytology with conventional smear (CS) preparation offers onsite cellular adequacy evaluation; however, it still provides false negatives due to faulty smear preparations. Liquid-based cytology (LBC) can be advantageous in these scenarios. Hence, with an aim to investigate utility of LBC in these samples, we carried out the above study with objectives to find diagnostic accuracy of LBC and agreement of LBC with CS methods in guided aspiration samples from intra-abdominal masses. METHODS: A prospective observational study, of 113 patients with clinical or radiological diagnosis of intra-abdominal masses, was carried out. SurePath BD™ was used for LBC smear preparation, and the standard protocol was used for CS preparation. RESULTS: LBC alone was diagnostic in 80.8% of the cases, and CS alone was diagnostic in 71.2% cases (agreement was 83.7%, p = 0.03). Cellular morphology was better preserved in LBC; however, interpretation was easier in CS. CONCLUSION: CS may be complimented with LBC sample collection method to enhance the sensitivity of intra-abdominal FNA.

Frequent expression of a novel cancer testis antigen, protein kinase human monopolar spindle 1 (hMps1/TTK) in human urinary bladder transitional cell carcinoma.

Urothelial bladder cancer (UBC) is a frequently occurring malignancy of the urinary tract. The present study was undertaken to evaluate the mRNA and immunohistochemical (IHC) expression of protein kinase human monopolar spindle 1 (hMps1/TTK) gene in transitional cell carcinoma (TCC) of the bladder and correlate its expression with the clinicopathological characteristics of patients. In the present study, quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate TTK mRNA expression in TCC. IHC analysis of TTK was also evaluated. Independent Student's t, ANOVA and chi-square (χ2) tests were used to analyze the data statistically. The frequency of TTK mRNA over expression was detected in 50% of UBC (38/76) by qRT-PCR. Relative mean fold expression of TTK mRNA was found significantly (p < 0.05) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients (8.96 ± 4.51 vs. 5.64 ± 3.53, p = 0.03). Moreover, IHC reveals heterogenous immunostaining pattern of TTK in TCC tissues. The frequency of TTK protein over expression was detected in 56.9% (37 of 65) UBC patients. No significant IHC expression of TTK was detected among adjacent noncancerous tissues (ANCTs) and benign prostatic hyperplasia (BPH) used as control. Collectively our study observations conclude that TTK is a novel cancer/testis antigen (CTA) as a diagnostic marker for early diagnosis of UBC.

Nodular Hidradenocarcinoma, Trichelemmal Carcinoma and Squamous Cell Carcinoma with Clear Cell Changes: Pitfalls of Biopsy Diagnosis of Skin and Adnexal Tumours.

Skin and Adnexal tumours are a group of benign and malignant tumours whose basic diagnosis relies on histopathology. A single tumour may show more than 1 appendageal differentiation. Morphologic distinction between benign and its malignant counterpart is of utmost importance as it affects the treatment and prognosis of patient. We have described 3 cases who presented in our university hospital, in which final resection pathological diagnosis differed from initial core biopsy interpretation. The authors have made an attempt to provide a brief overview of diagnostic overlap existing between nodular hidradenocarcinoma and tumours of clear cell histology. Salient morphologic features differentiating cylindroma or trichilemmal carcinoma from squamous cell carcinoma have also been discussed. Final diagnosis is paramount for adjuvant management and prognostication of the patient in a clinical setting.

A rare case report of transitional urothelial carcinoma metastasizing to isolated upper cervical lymph node diagnosed on cytology.

Transitional urothelial carcinoma frequently metastasizes to pelvic and retroperitoneal lymph nodes usually within 2 years of primary diagnosis but isolated metastasis to upper cervical lymph node after 5 years of primary diagnosis is extremely rare. We report here a case of a 53-year-old male who presented with Level II cervical node enlargement after 5 years of being diagnosed and treated for urothelial carcinoma. The diagnosis of cervical metastasis from urothelial carcinoma was suggested by fine-needle aspiration cytology and confirmed by immunocytochemistry.

ALK-negative primary cutaneous T-cell anaplastic large cell lymphoma, myxoid variant; masquerading as sarcoma: unveiling the diagnostic dilemma.

We present a case of 50-year-old man with history of ulcerative right axillary mass for 6 months. Axillary lymphadenopathy and organomegaly were absent. Microscopic examination showed sheets of pleomorphic cells which were mitotically active. Distinctive myxoid change was seen throughout the tumor. These cells were strongly positive for CD30 and vimentin but were negative for CD3, CD5, CD20, CD15, anaplastic lymphoma kinase protein (ALK), CD56, cytokeratin, melan A, desmin, myogenin, CD68, S100, epithelial membrane antigen and CD34. The final diagnosis of primary cutaneous ALK-negative T-cell anaplastic large cell lymphoma (PCALCL), myxoid variant was made. Work-up revealed no systemic involvement. The patient received eight cycles of cyclophosphamide, doxorubicin, vincristine, prednisone and etoposide chemotherapy with complete resolution of disease. This case report highlights that a high index of suspicion is necessary in patients of PCALCL due to varied clinical presentation, and to discuss in brief the histopathologic and immunophenotypic features of this entity along with its differential diagnosis.

CASC5 is a potential cancer-testis gene in human urinary bladder transitional cell carcinoma.

Urinary Bladder cancer (UBC) is a diversified disease with an array of clinicopathological attributes. Several studies have shown that cancer susceptibility candidate 5 (CASC5) plays important roles in various types of malignancies; however its expression and clinical significance in human UBC remain largely unknown. This research study was intended to explore mRNA/protein expression pattern of CASC5 as a member of the cancer-testis (CT) gene family and assess its clinical utility in diagnostic management of patients with UBC. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) was employed to appraise the detailed expression profile of CASC5 in patients with UBC. The mRNA over expression of CASC5 was detected in testis tissue and relatively high frequency 59.2% (45 of 76) of CASC5 mRNA was detected in UBC tissues. CASC5 mRNA relative mean fold expression was also significantly (p < 0.01) higher in the muscle-invasive tumor tissues compared to non-muscle-invasive tumor tissues (12.26 ± 9.53 vs. 4.64 ± 2.50, p = 0.005). Heterogeneous staining pattern of CASC5 protein was exclusively detected using IHC. The frequency of CASC5 protein over expression was detected in 67.7% (44 of 65) UBC patients and negative in benign prostatic hyperplasia (BPH). Further, CASC5 protein expression was significantly (p < 0.001) associated with cigarette smoking habit in UBC patients. Our study findings testified that CASC5 over expression among patients with UBC as compared to controls and concludes that CASC5 is a potential CT gene in UBC.

Differentially expressed full-length, fusion and novel isoforms transcripts-based signature of well-differentiated keratinized oral squamous cell carcinoma.

Highly keratinized oral squamous cell carcinoma (OSCC) exhibits an improved response to treatment and prognosis compared with weakly keratinized OSCC. Therefore, we aimed to develop gene transcript signature and to identify novel full-length isoforms, fusion transcript and non-coding RNA to differentiate well-differentiated (WD) with Moderately Differentiated (MD)/Poorly Differentiated (PD)/WD-lymphadenopathy OSCC through, HTA, Isoform sequencing, and NanoString. Additionally, specific copy number gain and loss were also identify in WD keratinized OSCC through Oncoscan array and validated through Real-time PCR in histopathologically characterized FFPE-WD keratinized OSCC. Three-hundred-thirty-eight (338) differentially expressed full-length (FL) transcript isoforms (317 upregulated and 21 down-regulated in OSCC) were identified through Isoform Sequencing using the PacBio platform. Thirty-four (34) highly upregulated differentially expressed transcripts from IsoSeq data were also correlated with HTA2.0 and validated in 42 OSCC samples. We were able to identify 18 differentially expressed transcripts, 12 fusion transcripts, and two long noncoding RNAs. These transcripts were involved in increased cell proliferation, dysregulated metabolic reprogramming, oxidative stress, and immune system markers with enhanced immune rearrangements, suggesting a cancerous nature. However, an increase in proteasomal activity and hemidesmosome proteins suggested an improved prognosis and tumor cell stability in keratinized OSCC and helped to characterize WD with MD/PD/WD with lymphadenopathy OSCC. Additionally, novel isoforms of IL37, NAA10, UCHL3, SPAG7, and RAB24 were identified while in silico functionally validated SPAG7 represented the premalignant phenotype of keratinized (K4) OSCC. Most importantly we found copy number gain and overexpression of EGFR suggest that TKIs may also be used as therapeutics in WD-OSCCs.

The Multiple Cranial Nerve Palsies: A Prospective Observational Study.

BACKGROUND: Neurological presentation with isolated multiple cranial nerve palsies is common and its diverse causes include infectious, neoplastic, and inflammatory pathologies. The aetiological spectrum may depend upon geographical regions. We undertook this study to explore clinical spectrum and aetiological profile of multiple cranial nerve palsies. METHODS: This hospital-based prospective observational study was conducted from August 2015 to August 2017. All the consecutive patients of multiple cranial palsies presenting to the neurology department were included in the studies. Primary objectives were to define anatomical syndromes/cranial nerve combinations and to establish aetiology. Secondary objectives were to study associated factors. The multiple cranial nerve palsy was defined as involvement of two or more non-homologous nerves. Patients of neuromuscular junction disorders, anterior horn cell disorders, myopathies, brain stem syndromes were excluded. All patients underwent structured protocol of clinical evaluation, investigations and few specialized investigations in accordance with clinical suspicion to establish the diagnosis. RESULTS: Fifty-four patients with a mean age of 39.9 ± 14.2 years were included. Commonest cranial nerve involved was the abducens (75.9%) among all nerve combinations. The cavernous sinus syndrome (37%), orbital apex syndrome (22.2%) and jugular foramen syndrome (11.1%) were the most frequent anatomical patterns. Infections (40.7%) were the commonest aetiology followed by neoplastic and idiopathic in four patients. CONCLUSION: Cavernous sinus syndrome was the commonest anatomical syndrome of multiple cranial nerve palsies and infections were the commonest cause in this study.

Indian Academy of Cytologists National Guidelines for Cytopathology Laboratories for Handling Suspected and Positive COVID-19 (SARS-CoV-2) Patient Samples.

COVID-19, caused by the SARS-CoV-2 virus, has been declared a pandemic by the World Health Organization. This scenario has impacted the way we practice cytopathology. Cytology laboratories receive fresh and potentially infectious biological samples including those from the respiratory tract, from COVID-19 positive or suspected patients. Hence, the Indian Academy of Cytologists thought it necessary and fit to bring forth appropriate guidelines starting from transportation, receipt, processing, and reporting of samples in the COVID-19 era. The guidelines are prepared with the aim of safeguarding and protecting the health care personnel including laboratory staff, trainees and cytopathologists by minimizing exposure to COVID-19 so that they remain safe, in order to able to provide a continuous service. We hope that these national guidelines will be implemented across all cytopathology laboratories effectively.