Implications of Corona Virus Disease-19 pandemic on cytopathology laboratory-Challenges and solutions in resource-limited settings.

Background: Corona Virus Disease-19 (COVID-19) disease which is still showing peaks and plateau with emerging new mutational viral variants has led to the modification of working of hospitals and medical institutes. Cytopathology laboratories geared up with the changing situation to cope up with not only the COVID-19 patients but also patients of other diseases, particularly oncology patients. It was also important to adopt changes in the cytopathology residency program so as to cope up with the changing scenario. Aim: The present study was conducted to study the various measures adopted and the changes made in the cytopathology laboratory during COVID-19 infection in a resource-limited setting while catering to a large population of COVID-19-positive patients in the north Himalayan region of India. It was also intended to study the methods adopted for effective cytopathology residency training during corona times. Setting and Design: The study was conducted from March 2020 to December 2021 in the cytopathology lab, and all the samples were analyzed and compared with the samples received in pre-corona times from March 2018 to December 2019. The different methods adopted during corona times for effective cytopathology residency training were also analyzed. Results: The total number of samples received in the cytopathology laboratory in pre-corona times from March 2018 to December 2019 were 6822, and samples received from March 2020 to December 2021 were 6567 with decrease of 1.9% of cases. There was increase in 17.4% for the samples of the respiratory tract received in the lab with an increase in cases of infections including aspergillosis, mucormycosis, and tuberculosis. There was 10.3% increase in cytological diagnosis of malignant cases during corona times. Use of 90% alcohol for fixation rather than air drying of smears, avoiding of pneumatic tubes, judicious use of personal protective equipment (PPE) kits along with access to the digital cytology slide database were included in the changes made in the lab. Conclusions: There was a marginal decrease in cytopathological diagnosis during COVID-19 with substantial increase in the malignancy rate of 10.3% in cytological diagnosis of different organs. Diagnosis of mucormycosis, aspergillosis, and tuberculosis infections of respiratory tract cytology increased during this period. Judicious use of limited available resources led not only to smooth functioning of the cytopathology lab but also prevented any infection in the working health personals. Newer online resources were explored and modified for continuous training of the cytopathology residents. Emotional support with effective communication was the key to alleviate any psychological stress among all health professionals in the cytopathology laboratory.

A controversial ER negative PR positive molecular subtype of breast carcinoma-Report of two cases.

ER-/PR+ is a controversial subtype and is not formally recognised as molecular subtype of breast carcinoma. Few studies concluded that this subtype does not exist and is due to technical errors, however, in contrast others consider it to be distinct entity with different response to therapy and clinical outcome. It is also essential to know whether this subtype shows any distinct histomorphological features or prognosis.Therefore, the present two cases of controversial subtype ER-/PR+ breast cancer is being reported with both the cases showing neuroendocrinal differentiation.

Expression of PD-L1 in Lung Carcinoma and Its Correlation with Histopathological Grade, Stage, and Survival of Patients.

Objective PD-L1, a 40 kDa type 1 transmembrane protein, suppresses the adaptive arm of the immune system. The interaction of PD-1 with the ligand PD-L1 inhibits cytokine production and plays a role in the progression of lung cancer. The present study was performed to observe the expression of PD-L1 in lung carcinoma patients and its correlation with histopathological grade, stage, and survival of patients. Materials and Methods This prospective study included all new cases of lung carcinoma diagnosed on histopathological or cytopathological examination over a period of 1 year. PD-L1 immunoexpression was statistically analyzed and graded according to the Tumor Proportion Score in all cases and correlated with histopathological grade, stage, and survival of patients. Results This study included 56 cases of lung carcinoma with 64.2% cases showing PD-L1 positivity, out of which 44.6% were non-small cell and 19.6% were small cell lung carcinoma. In all, 32.1% cases with lymphovascular invasion, 53.5% with necrosis, and 37.5% cases with greater than 5/10 HPF mitotic figures showed positive PD-L1 expression. Paired cell blocks and histopathology showed 70% concordance for PD-L1 expression. 16.1% cT3N1M0 cases and 25% stage IIIA cases showed PD-L1 positivity. In all, 60.7% patients with positive PD-L1 expression did not survive for 12 months following diagnosis. Conclusion PD-L1 immunoexpression was increased in lung carcinoma cases and was associated with poor histomorphological features including lymphovascular invasion, necrosis, and increased mitotic activity. PD-L1 correlated with cases having decreased 12-month survival and stage IIIA carcinoma. Thus, it may be useful in the stratification of patients who benefit from the PD-L1 targeted therapy.

Study of PD-L1 Expression with Association of Pathological Factors and Molecular Subtypes in Breast Carcinoma.

Background Programmed death ligand 1 (PD-L1), expressed on cancer cells, shows varied results in the prognosis of breast cancer. This study was conducted to study the expression of PD-L1 in breast carcinoma and to correlate it with pathological, molecular classification and prognostic factors. Materials and Methods PD-L1 expression was correlated with tumor size, histopathological grade, necrosis, lymphovascular, perineurial invasion, lymph node metastasis, molecular classification, and survival in breast carcinoma cases. Results Fifty cases were included which showed statistically significant difference of PD-L1 with mean age, tumor size, histopathological grade, lymphovascular emboli, and lymph node metastasis ( p < 0.05). Estrogen receptor was strongly positive in 46%, progesterone receptor in 42%, and PD-L1 in 6% of cases. No statistically significant difference between pathological tumor-node-metastasis (TNM) staging and PD-L1 expression ( p = 0.354) was observed. Receptor operating characteristic curve analysis showed that at the cutoff of PD-L1 greater than 120, specificity was 56.1%, sensitivity 66.7%, negative predictive value 88.5%, and positive predictive value 25% for predicting living status. Conclusion PD-L1 is associated with poor prognostic factors including tumor size, histopathological grade, lymphovascular emboli, and lymph node metastasis in breast carcinoma. However, no significant association was observed between PD-L1 and pathological TNM stage or molecular subtypes of breast carcinoma. It is suggested that immunohistochemical reporting of PD-L1 should be standardized so that it is reproducible and reliable for the evaluation of breast carcinoma. Further, larger studies with extended follow-ups are recommended so that the exact role of PD-L1 as a prognostic marker in breast carcinoma could be ascertained.

Clinical, radiological and histopathological profile of patients with endobronchial lesions on fibreoptic bronchoscopy.

Various pulmonary diseases, both benign as well as malignant, manifest in the form of endobronchial lesions on bronchoscopy. Malignancy is frequently the provisional diagnosis in the mind of a chest physician undergoing an endobronchial biopsy. Other benign diseases, however, may present similarly on bronchoscopy and computerized tomography (CT) scan. This observational study was conducted to better understand why there is such a wide range of endobronchial lesions with even more diverse radiological and pathological presentations. The research was carried out at the Department of Respiratory Medicine, Himalayan Institute of Medical Science (HIMS), Swami Ram Nagar, Dehradun. Subjects were recruited from HIMS, Dehradun patients over a 12-month period (August 2020 to July 2021). The study included patients (over the age of 18) who had a fibreoptic bronchoscopy and were found to have an endobronchial lesion. After a thorough history, examination, and application of the inclusion and exclusion criteria, 120 patients were enrolled. The majority of patients were between the ages of 56 and 65, with males outnumbering females. The majority of the patients were smokers, and the most common complaint was shortness of breath. Poorly differentiated carcinoma and squamous cell carcinoma were the most common endobronchial lesions in men, while small cell carcinoma was the most common in women. A mass lesion was the most common radiological finding, followed by mediastinal lymphadenopathy, and an exophytic lesion was the most common endobronchial lesion detected in bronchoscopy. We looked at the diseases that cause endobronchial lesions and their clinico-radiological and histopathological profiles. This study clearly demonstrates the importance of studying the histopathological profiles of patients with endobronchial growth, which can mimic malignancy in rare cases.

Analytical and Post Analytical Phase of an ISO 15189:2012 Certified Cytopathology Laboratory-A Five Year Institutional Experience.

Objective: Analytical and post analytical phase are integral part of total quality management system and include steps from submission of slides till reports are dispatched. The present study was conducted to analyze the analytical and post analytical phase of the ISO15189:2012 certified cytopathology laboratory. It was also intended to study the various errors which were encountered and steps taken to reduce these discrepancies. Methods: The study included all documents of quality program from 1 November 2014 till 31 Oct 2019 in medical institute situated in north Himalayan region of India. All the data was recorded and analyzed for analytical and post analytical phase. Results: The number of samples received in cytopathology lab was 21,566 with total quality errors of 5.19%. Out of these pre-analytical errors were 55%, analytical 10.5% and post analytical errors constituted 34.4%. The maximum errors detected were due to typographical errors followed by delayed turnaround time. Cyto-histopathological discordance was 10.5% in non-gynecological cases and 2.2% in gynecological cases. Conclusion: Analytical and post analytical phase analysis is essential to minimize the errors and improve the quality of cytopathology lab. Cyto-histopathological correlation is valuable for continuous data tracking in the cytopathology with analytical errors analysis. Maintenance of external, internal quality program, turnaround time with documentation, continuous training and communication with clinician is fundamental for quality improvement in any cytopathology lab. Acknowledgement of nonconformance with root cause analysis and sincere efforts to minimize them is the basic key for successful quality management.

C5: A Step Towards Smart World with Enhanced Holistic Wellbeing.

Today our life without smart gadgets is beyond imagination. In fact, smart apps are now the inseparable part of a human life. The use of technology has provided more comfortable and easier life than ancient times, but the overuse of social media and mobile devices may lead to numerous Psychological, Physical and Psychosomatic (P3) disorders, such as eyestrain, anxiety, fatigue, and difficulty focusing on important tasks. They may also create serious health malfunctions, such as depression and hypertension. Social media may be the first solution that comes to mind when we are lonely; it seems to be a quick and easy access to number of people. However, many studies have shown that our online networks, although they may offer an illusion of connectedness, rather make us even lonelier and more segregated. The overuse of technology may have a significant impact on developing children and teenagers. Mind is the powerhouse of a human body, and the activity level determines the overall health of a person. Hyperactive or hypoactive minds, both are the signs of abnormality and to avoid such conditions C5 (Creativity, Contentment, Confidence, Calmness, Concentration) concept is being practiced. In this paper, we present a novel idea of using C5 concept for overall harmonical holistic development. A good relationship is established between C5 growth along with HEALTH (Harmony, Energy, Aesthetics, Limberness, Tranquility & Happiness). The convenience of C5 concept to assess anxiousness and stressed mental state of a person through empathetic intelligence by applying haptic Aps via tactile internet makes our world smarter than present times to dwell in with a proper care of ourselves and our related people giving better outcomes in our personal and professional fronts.

Expression of CD10 in urothelial carcinoma of the bladder and its correlation with histopathological grade, pathological stage, and survival of patients.

BACKGROUND: CD10 plays a role in signal transduction pathway and regulation of cell growth apoptosis, and therefore, it has been evaluated in different malignancies. The present study was conducted to study the immunoexpression of CD10 in urothelial carcinoma and to correlate it with histological grade, pathological stage, and survival of patients. MATERIALS AND METHODS: The study included 51 cases of urothelial carcinoma diagnosed on histopathology along with 50 controls having nonneoplastic urothelium. All the cases and controls were subjected to CD10 immunostaining. The CD10 expression was compared between the cases and controls and was also correlated with histological grade, pathological stage, histomorphological features, and 1-year survival. RESULTS: The study included 78.4% of high-grade urothelial carcinoma (HGUC) and 21.6% of low-grade urothelial carcinoma. The positive score of CD10 expression was observed in 68.6% of cases, while 96% of controls observed negative immunostaining. About 90.9% of low-grade carcinoma observed score 0, while 83.7% of high grade observed positive score of 1 and 2. Although there was statistical significant difference between CD 10 score and stage of tumor, its expression did not correlate with 1-year survival of cases. CONCLUSION: CD10 expression increases with the grade of tumor and thus may be helpful in differentiating low grade from HGUC. Its expression also increases with stage and poor prognostic factors suggesting its possible role in pathogenesis and progression of urothelial carcinoma. CD 10 may be further analyzed for molecular targeted therapy against urothelial carcinoma.

Isolated cerebral mucormycosis masquerading as a tumor in an immunocompetent patient.

Mucormycosis is an opportunistic fungal disease that commonly presents as cutaneous or rhinocerebral infections associated with immunocompromised states. It may exceptionally present as isolated involvement of the brain with a varied clinical presentation, which may be difficult to diagnose early, leading to increased mortality. Herein, we report the case of a 42-year-old immunocompetent female with left-sided limb weakness and a history of recurrent vomiting and headache for the last two years. Clinically, glioma was suspected, but histopathological examination revealed a few broad aseptate fungal hyphae. As no other organ was involved, the diagnosis of isolated cerebral mucormycosis was rendered. Reporting this case, we show an unusual presentation of a central nervous system mucormycosis masquerading a tumor in an immunocompetent patient. The case also highlights the importance of a careful histopathological examination to avoid missing the presence of occasional fungal hyphae. Ideally, recognition of fungal hyphae in the brain, during intraoperative consultation, can prompt brain tissue culture for definitive diagnosis and early empirical antifungal therapy, which may prove life-saving.

Isolated cerebral mucormycosis masquerading as a tumor in an immunocompetent patient

Mucormycosis is an opportunistic fungal disease that commonly presents as cutaneous or rhinocerebral infections associated with immunocompromised states. It may exceptionally present as isolated involvement of the brain with a varied clinical presentation, which may be difficult to diagnose early, leading to increased mortality. Herein, we report the case of a 42-year-old immunocompetent female with left-sided limb weakness and a history of recurrent vomiting and headache for the last two years. Clinically, glioma was suspected, but histopathological examination revealed a few broad aseptate fungal hyphae. As no other organ was involved, the diagnosis of isolated cerebral mucormycosis was rendered. Reporting this case, we show an unusual presentation of a central nervous system mucormycosis masquerading a tumor in an immunocompetent patient. The case also highlights the importance of a careful histopathological examination to avoid missing the presence of occasional fungal hyphae. Ideally, recognition of fungal hyphae in the brain, during intraoperative consultation, can prompt brain tissue culture for definitive diagnosis and early empirical antifungal therapy, which may prove life-saving.

Cytological diagnosis of primary cutaneous histoplasmosis with hemophagocytosis in immunocompetent patient - A rare case from non endemic region.

Histoplasma capsulatum is an opportunistic dimorphic fungus caused by inhalation of spores present in the soil. It is extremely rare in the northern Himalayan region of India and is usually asymptomatic. It may rarely progress to disseminated histoplasmosis which is usually observed in immunocompromised patients associated with malignancy, acquired immunodeficiency syndrome or diabetes. The present case is being reported because of unusual cutaneous presentation of disseminated histoplasmosis in an immunocompetent patient of non-endemic region. The case also highlights the importance of fine needle aspiration cytology for its precise early diagnosis and avoiding of further complications.

Fine-needle aspiration cytology of gallbladder with an attempt of cytomorphological classification.

BACKGROUND: Image-guided fine-needle aspiration has emerged as an effective diagnostic tool for precise diagnosis of deep-seated lesions. Although occasional studies have made an attempt to classify the gallbladder carcinoma on cytology, literature lacks the standardized cytological nomenclature system used for it. The present study was conducted to study the role of fine-needle aspiration cytology (FNAC) in diagnosis of gallbladder lesions with an attempt of cytomorphological classification. METHODS: The study included cases of image-guided FNAC of the gallbladder over a period of 3½ years. An attempt was made to categorize gallbladder lesions on basis of architectural and cytomorphological features along with analysis of management. RESULTS: The study included 433 cases and lesions were categorized on FNAC into five categories ranging from Category 1 (inadequate), Category 2 (negative for malignancy), Category 3 (atypical cells), Category 4 (highly atypical cells suggestive of malignancy), and Category 5 (positive for malignancy). The most common architectural pattern observed on FNAC of neoplasm was sheets and acini with predominance of columnar cells and adenocarcinoma being the most common malignancy. The histopathological diagnosis was available in 93 cases with cytohistopathological concordance of 94.4% in malignant cases. CONCLUSIONS: Image-guided FNAC plays an important role in diagnosis of gallbladder lesions with minimal complications. The cytomorphological classification of gallbladder lesions provides an effective base for accurate diagnosis and management. Category 3 and 4 are the most ambiguous category on FNAC which should be managed by either repeat FNAC or surgery in the light of worrisome radiological features. The vigilant examination of architectural pattern and cytomorphological features of the smears may be helpful in clinching the diagnosis and precisely subtyping malignant tumors along with prognostication of these tumors.

Serum Interleukin-6 is Not Linked with Sleep-Quality, Restless Legs Syndrome, and Depression, But with 6-Month Survival in Hematological Malignancies.

BACKGROUND: Serum interleukin (IL)-6 has been found to be associated with sleep quality, mood, and survival in patients with solid tumors. Results in these studies were confounded by knowledge of diagnosis to study subjects. Moreover, such data among subjects with hematological malignancies and data regarding restless legs syndrome is limited. The present study was, therefore, conducted to assess the sleep quality, depression, and restless leg syndrome in hematological malignancies and to study if there is any role of IL6 associated with it. METHODS: Sixty-six subjects having hematological malignancy were included in this study after excluding the potential confounders. Sleep quality was examined using Pittsburg Sleep Quality Index, depression by the Patient Health Questionnaire-9. Diagnosis of RLS was made through clinical examination. Serum for measurement of IL-6 was collected at baseline and after 1 month of initiation of chemotherapy. Patients were followed up for 6 months. RESULTS: Average age of study subjects was 50.16 years with male predominance. Nearly 22.7% had clinical depression, 28.8% had poor quality sleep, and restless legs syndrome (RLS) was reported in 6.1% cases. Nearly 22.7% patients died at 6 months. Disturbed sleep at baseline was associated with depression (odds ratio [OR] =7.89) and poor 6 months survival. Serum IL-6 did not show any association with sleep quality, restless-legs-syndrome, and depression. However, baseline high level of serum IL-6 (OR = 26.06) and low level after chemotherapy (OR = 0.03) were associated with poor survival at 6 months. CONCLUSION: Poor quality sleep, depression, and RLS are prevalent among adult subjects with hematological malignancies. Sleep disturbance, high pretreatment inflammatory and lowering of inflammatory load after chemotherapy increase likelihood for poor prognosis. Serum IL-6 did not show any association with sleep quality, restless legs syndrome and depression.

Von Meyenburg complex clinically presenting as metastatic liver nodule: A rare finding in an elderly male.

Von Meyenburg complex is a benign biliary hamartoma observed in approximately 3% of the autopsies conducted. These hamartomas are small, multiple and can be seen anywhere in the liver. There is usually no abnormality in liver function tests, and the patient is mostly asymptomatic. They serve as a diagnostic dilemma, particularly during metastatic workup in suspected cancer patients. Imaging studies are usually noncontributory, and biopsy is necessary for a definite diagnosis. We present here a middle-aged North Indian male who underwent liver biopsy to rule out metastasis.

Titanium Dioxide Nanoparticles and Cetylpyridinium Chloride Enriched Glass-Ionomer Restorative Cement: A Comparative Study Assessing Compressive Strength and Antibacterial Activity.

OBJECTIVE: To evaluate the addition of titanium dioxide (TiO2) nanoparticles and cetylpyridinium chloride (CPC) on the compressive strength and antibacterial activity of conventional glass-ionomer cement (GIC). STUDY DESIGN: TiO2 nanoparticles enriched GIC was prepared by adding 3% TiO2 nanoparticles (w/w) into the powder component of conventional GIC. CPC containing GIC was developed by incorporating 1% CPC (w/w) into conventional GIC powder. Samples were segregated into three groups: GIC with 3% TiO2 nanoparticles, GIC with 1% CPC and unmodified conventional GIC. Compressive strength was assessed using the universal testing machine on cylindrical specimens made from each material. Antibacterial activity was assessed by measuring inhibition zones on Mitis Salivarius Bacitracin (MSB) agar inoculated with pure strain of Streptococcus mutans (S. mutans). RESULTS: GIC containing TiO2 nanoparticles exhibited significantly greater compressive strength as compared with CPC and conventional GIC groups (P < 0.01). However, there was no significant difference between the compressive strengths of CPC and conventional GIC group (P >0.05). Antibacterial activity was significantly greater for TiO2 group than conventional GIC (P <0.05). CPC increased the antibacterial activity of conventional GIC, though not significantly. CONCLUSION: The addition of 3% TiO2 nanoparticles improves the compressive strength of GIC as well as its antibacterial activity against S. mutans.

Study of the Pre-Analytical Phase of an ISO 15189: 2012-Certified Cytopathology Laboratory: A 5-Year Institutional Experience.

OBJECTIVE: Total quality management, which basically involves pre-analytical, analytical, and postanalytical phases, is relatively more difficult in cytopathology due to descriptive reports and subjective variability. The pre-analytical phase of total quality management constitutes a major burden of errors in the laboratory and it has not been widely studied in cytopathology except in cervical Pap smears. The present study was therefore conducted to study the pre-analytical phase over 5 years from April 2013 until May 2018 at an ISO 15189: 2012-certified cytopathology laboratory, in a resource-limited setting. It was also intended to study the level of satisfaction of the patients and the training of the professionals provided in the cytology lab so as to improve and maintain high quality standards. METHODS: The study included all the documents relating to the quality program used in the last 5 years in a medical institute situated in the north sub-Himalayan region of India. All the data were recorded and analysed for pre-analytical analysis of the total quality management system. RESULTS: In total, 20,130 samples were received for cytological investigation. The total number of errors which were detected in the cytopathology lab were 1,430, constituting 7.1% of the total investigations done. The pre-analytical phase errors comprised 57% of the total errors (815/1,430), analytical errors constituted 11% (157/1,430), while postanalytical errors represented 32% (458/1,430). Incompletely filled requisition forms constituted the most common pre-analytical error (38%). There was a gradual decrease in the errors with time, but with a sudden increase between January to June 2015 due to new technicians joining during that period. CONCLUSION: Pre-analytical quality management is an essential component for maintaining the quality and reducing the errors in the cytopathology lab. Documentation, continuous training, and maintenance of internal and external quality control with quality charts are the key for successful quality management. The identification of non-conformance with root-cause analysis and provision of scope for continuous improvement is vital for quality improvement in the lab. Patient satisfaction is an important aspect of quality in the lab, which should be combined with the satisfaction of the personnel working in the lab.

Expression of p16INK4a and human papillomavirus 16 with associated risk factors in cervical premalignant and malignant lesions.

INTRODUCTION: Human papilloma virus (HPV) which is causative factor for cervical cancer may interact with p16 leading to malignant transformation of cervical epithelial cells. The present study was conducted to assess the immunoexpression of p16 INK4a in premalignant and malignant lesions of cervix and to correlate it with HPV 16 expression. It was also intended to study the various risk factors which may be associated with cervical cancer in this north Himalayan region of India. MATERIAL AND METHODS: The study included 50 cases of premalignant and malignant cervical lesions and 50 controls diagnosed on histopathology over a period of one year. All the relevant clinical details were noted and both cases and controls were subjected to HPV 16 and p16 INK4a immunohistochemical staining. RESULTS: 67% of subjects (including cases and controls) and 94% of the cases were positive for HPV 16 expression. p16 INK4a expression was negative in all the controls, positive in 96% of invasive cancer, 66.6% in HSIL and 37.5% in LSIL. CONCLUSION: Cervical cancer is associated with low socio economic status, illiteracy, smoking, early age of marriage and conception in north Himalayan region of India. HPV 16 infection is positive in both cases and controls indicating high prevalence of HPV 16 in this region. Neoplastic transformation by HPV is identified by over expression of p16 INK4a in premalignant and malignant cases. The immunopositivity of p16 INK4a increases with the severity of cervical lesions and thus may play an important role in stratification of premalignant and malignant lesions.

Cytological diagnosis of osteoblastoma of the talus: Case report with unusual presentation and diagnostic pitfalls.

Osteoblastoma is a rare bone tumor mostly affecting the young adults and commonly involving the spinal cord and long bones. Talus is the uncommon site of presentation, and if involved, then the neck is more commonly involved than the body of talus. The cytological diagnosis of osteoblastoma is limited, and to the best of our knowledge, its fine-needle aspiration (FNA) in the talus has still not been reported in the literature. The present case of osteoblastoma is, therefore, being reported due to the unusual presentation in elderly male in the body of talus and showing extensive involvement on X-ray. The case was initially diagnosed on FNA cytology excluding the possibility of giant-cell tumor and osteosarcoma. The case also highlights the importance of vigilant observation of subtle cytological features of this rare tumor which may be helpful in avoiding diagnostic pitfalls, especially at an uncommon site and with unusual presentation. An early precise diagnosis by cytology may be followed by appropriate treatment and thus avoiding any further complications.

Malignancy rate in thyroid nodules categorized as atypia of undetermined significance or follicular lesion of undetermined significance - An institutional experience.

INTRODUCTION: Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) of Bethesda system for reporting thyroid cytopathology has emerged as most controversial category due to its heterogeneity and inconsistent usage. Initially associated risk of malignancy was estimated to be about 5-15%, but eventually different results have been obtained across institutions due to variable follow-ups and interpretation. The present study was conducted to evaluate the rate of malignancy along with appropriate management in this category. MATERIALS AND METHODS: The study included AUS/FLUS cases diagnosed over period of 4 years on thyroid fine needle aspiration cytology (FNAC). Detailed clinical history and radiological examination were recorded along with follow-ups and management of all cases. Histopathology was available for cases which underwent surgery due to high clinical suspicion, worrisome radiological features or two consecutive AUS/FLUS reports. RESULTS: The incidence of AUS/FLUS was 6.4% with repeat FNAC done in 39.6%, immediate surgery in 49.2% and follow-up without intervention in 11.1% cases. The overall malignancy rate was 28.5% with most common malignancy being follicular variant of papillary carcinoma (FVPC). Malignancy rate was more in cases (24.1%) which morphologically showed atypical nuclear features in comparison to architectural atypia. CONCLUSION: AUS/FLUS is associated with higher risk of malignancy than previously anticipated. Surgical intervention may have greater implication than repeat FNAC in appropriate management of this category. Substratification of this category according to nuclear features and architecture may be more useful in predicting malignancy risk and reducing the variability in the group.