Reporting Pancreatic FNAC using the Papanicolaou System: Still a Diagnostic Challenge.

Introduction: The Papanicolaou Society of Cytopathology System for reporting Pancreaticobiliary Cytology (PSCPC) is a reliable method to classify pancreatic fine needle aspiration cytology (FNAC) smears. However, it is not without practical problems which can diminish the diagnostic accuracy of the cytological diagnosis. Aims and Objectives: To determine the diagnostic pitfalls while reporting cytomorphology of pancreatic lesions according to PSCPC on correlating FNAC findings with histopathology. Materials and Methods: Retrospective analysis of pancreatic FNAC smears received in the Department of Pathology of our tertiary care institute over a period of 2 years was done. The cytological diagnoses were classified according to the Papanicolaou Society of Cytopathology system of reporting pancreaticobiliary cytology and correlated with histopathology. The reasons of cyto-histological discordance were analyzed. Results: Out of 50 cases in which both FNAC and biopsy of pancreatic lesions were done, 34 cases were positive/malignant (Category VI), eight cases were suspicious for malignancy (Category V), three cases were neoplastic (Category IV), two cases were atypical (Category III), two cases were negative for malignancy (Category II), and one case was non-diagnostic (Category I). Out of 50 cases, histopathology was non-diagnostic due to inadequate material in six cases. The cytological diagnoses were compared with histopathology in the remaining 44 cases. Categories III, IV V, and VI were considered as positive for neoplastic pathology. The sensitivity of FNAC to predict neoplastic pathology was 97.5%, while the specificity was 25%. The positive predictive value was 92.9%. Two cases reported as atypical (Category III) turned out to be adenocarcinoma on histopathology. One case reported as neuroendocrine tumor and two cases reported as adenocarcinoma on cytology displayed features of chronic pancreatitis on histology. One case reported as neoplastic mucinous cyst (Category IV) turned out to be adenocarcinoma on histology (limited concordance). Conclusion: The cytopathologist needs to be wary of the potential pitfalls to improve the diagnostic accuracy of FNACs.

Reticular Skin Rash as an Adverse Effect of 5-Azacitidine.

Azacitidine is a hypomethylating agent used for the treatment of patients with myelodysplastic syndrome (MDS). It has been approved by the Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of MDS and is also indicated for the treatment of acute myeloid leukemia (AML). Injection site erythema, ecchymosis, and petechiae are some of the common cutaneous adverse reactions associated with azacitidine. This article describes a rare adverse cutaneous drug reaction with azacitidine in the form of a reticular generalized skin rash in a 28-year-old female with AML.

Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer's disease.

Background: Neuronal- and circuit-level abnormalities of excitation and inhibition are shown to be associated with tau and amyloid-beta (Aß) in preclinical models of Alzheimer's disease (AD). These relationships remain poorly understood in patients with AD. Methods: Using empirical spectra from magnetoencephalography and computational modeling (neural mass model), we examined excitatory and inhibitory parameters of neuronal subpopulations and investigated their specific associations to regional tau and Aß, measured by positron emission tomography, in patients with AD. Results: Patients with AD showed abnormal excitatory and inhibitory time-constants and neural gains compared to age-matched controls. Increased excitatory time-constants distinctly correlated with higher tau depositions while increased inhibitory time-constants distinctly correlated with higher Aß depositions. Conclusions: Our results provide critical insights about potential mechanistic links between abnormal neural oscillations and cellular correlates of impaired excitatory and inhibitory synaptic functions associated with tau and Aß in patients with AD. Funding: This study was supported by the National Institutes of Health grants: K08AG058749 (KGR), F32AG050434-01A1 (KGR), K23 AG038357 (KAV), P50 AG023501, P01 AG19724 (BLM), P50-AG023501 (BLM and GDR), R01 AG045611 (GDR); AG034570, AG062542 (WJ); NS100440 (SSN), DC176960 (SSN), DC017091 (SSN), AG062196 (SSN); a grant from John Douglas French Alzheimer's Foundation (KAV); grants from Larry L. Hillblom Foundation: 2015-A-034-FEL (KGR), 2019-A-013-SUP (KGR); grants from the Alzheimer's Association: AARG-21-849773 (KGR); PCTRB-13-288476 (KAV), and made possible by Part the CloudTM (ETAC-09-133596); a grant from Tau Consortium (GDR and WJJ), and a gift from the S. D. Bechtel Jr. Foundation.

Perineal warty plaques: A case of verrucous porokeratosis.

Nonvenereal genital dermatoses form an important category of disorders, and verrucous porokeratosis is a rare and less recognized entity among the same. We present the case of a young adult male with warty growths over scrotum and buttocks for a year. Characteristic cornoid lamellae with typical differentiating features were seen in the histopathology, establishing the diagnosis. This case emphasizes the rare nonvenereal cause for a condition clinically mimicking condyloma acuminata.

Plantar Lichen Planus: An Atypical Presentation at a Young Age.

Lichen planus is a chronic lichenoid dermatosis commonly encountered by dermatologists worldwide, affecting skin, mucosa, and scalp. The current case describes a rare variant of lichen planus, plantar lichen planus, in a 17-year-old male who presented with erythematous scaly plaques on the sole for two years associated with walking discomfort. The lesion was subjected to skin biopsy and a diagnosis of lichen planus was made considering the histopathological and clinical findings. Plantar lichen planus can often be misdiagnosed. Treating plantar lichen planus can be a therapeutic challenge and, thus, more insight is needed regarding treatment protocol or outcome of such cases.

Computational analysis of a 9D model for a small DRG neuron.

Small dorsal root ganglion (DRG) neurons are primary nociceptors which are responsible for sensing pain. Elucidation of their dynamics is essential for understanding and controlling pain. To this end, we present a numerical bifurcation analysis of a small DRG neuron model in this paper. The model is of Hodgkin-Huxley type and has 9 state variables. It consists of a Nav1.7 and a Nav1.8 sodium channel, a leak channel, a delayed rectifier potassium, and an A-type transient potassium channel. The dynamics of this model strongly depend on the maximal conductances of the voltage-gated ion channels and the external current, which can be adjusted experimentally. We show that the neuron dynamics are most sensitive to the Nav1.8 channel maximal conductance ([Formula: see text]). Numerical bifurcation analysis shows that depending on [Formula: see text] and the external current, different parameter regions can be identified with stable steady states, periodic firing of action potentials, mixed-mode oscillations (MMOs), and bistability between stable steady states and stable periodic firing of action potentials. We illustrate and discuss the transitions between these different regimes. We further analyze the behavior of MMOs. As the external current is decreased, we find that MMOs appear after a cyclic limit point. Within this region, bifurcation analysis shows a sequence of isolated periodic solution branches with one large action potential and a number of small amplitude peaks per period. For decreasing external current, the number of small amplitude peaks is increasing and the distance between the large amplitude action potentials is growing, finally tending to infinity and thereby leading to a stable steady state. A closer inspection reveals more complex concatenated MMOs in between these periodic MMO branches, forming Farey sequences. Lastly, we also find small solution windows with aperiodic oscillations which seem to be chaotic. The dynamical patterns found here-as consequences of bifurcation points regulated by different parameters-have potential translational significance as repetitive firing of action potentials imply pain of some form and intensity; manipulating these patterns by regulating the different parameters could aid in investigating pain dynamics.

A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy.

Vincristine is a core chemotherapeutic drug administered to pediatric acute lymphoblastic leukemia patients. Despite its efficacy in treating leukemia, it can lead to severe peripheral neuropathy in a subgroup of the patients. Peripheral neuropathy is a debilitating and painful side-effect that can severely impact an individual's quality of life. Currently, there are no established predictors of peripheral neuropathy incidence during the early stage of chemotherapeutic treatment. As a result, patients who are not susceptible to peripheral neuropathy may receive sub-therapeutic treatment due to an empirical upper cap on the dose, while others may experience severe neuropathy at the same dose. Contrary to previous genomics based approaches, we employed a metabolomics approach to identify small sets of metabolites that can be used to predict a patient's susceptibility to peripheral neuropathy at different time points during the treatment. Using those identified metabolites, we developed a novel strategy to predict peripheral neuropathy and subsequently adjust the vincristine dose accordingly. In accordance with this novel strategy, we created a free user-friendly tool, VIPNp, for physicians to easily implement our prediction strategy. Our results showed that focusing on metabolites, which encompasses both genotypic and phenotypic variations, can enable early prediction of peripheral neuropathy in pediatric leukemia patients.

Micronuclei in Exfoliated Cells: A Biomarker of Genotoxicity in Tobacco Users.

AIMS: The aim of this study was to analyze the tobacco-related genotoxic effects in individual with habit of smoking and chewing tobacco. MATERIALS AND METHODS: The present study sample consisted of 120 individuals attending the outpatient department of D. J. College of Dental Sciences and Research, Modinagar, Uttar Pradesh (UP). The sample was divided into four groups as follows: Group I (individuals with habit of smoking tobacco), Group II (individuals with habit of chewing tobacco), Group III (individuals with habit of smoking and chewing tobacco), and Group IV control group (nontobacco-exposed individuals). Patients were asked to rinse their mouth gently with water. The exfoliated cells were obtained by scraping the buccal mucosa of individuals with a wooden spatula. The scraped cells were placed on the precleaned slides. The smears were then stained with RAPID-PAP™ and analyzed under the microscope. Data were analyzed using SPSS statistical software. RESULTS: In the present study, an arbitrary unit was obtained using frequency/day multiplied by the duration of years (risk multiplication factor [RMF], a positive and significant correlation were observed between the RMF and the mean percentage of micronucleated cell count in smokers, chewers, and in individuals with both smoking and chewing habit, respectively. A weak positive and nonsignificant correlation were observed between age and mean percentage of micronucleated cells in smokers and smokers + chewers, respectively, while it was weak negative and nonsignificant in chewers. In control group, correlation between age and percentage of micronucleated cells was weak positive and nonsignificant at 5% level of significance. CONCLUSION: The micronuclei in exfoliated mucosal cells from buccal mucosa can be used as a biomarker of genotoxicity in predicting the effects of carcinogens.

Quantitative analysis of AgNOR counts and pap stain in exfoliative cytology specimens of oral mucosa in bidi smokers and nonsmokers.

Background: Bidi smoking is a serious health hazard which is common throughout South Asia and parts of the Middle East. It has been strongly implicated to various benign and malignant lesions of oral cavity and oropharynx. These tobacco-filled leaves deliver more than three times the amount of nicotine, carbon monoxide, and tar as cigarettes which exert injurious effects on cells reflected in terms of accelerated proliferative activity in normal oral mucosal cells. Aim: This study aimed to compare the exfoliated cells from the oral mucosa of bidi smokers and nonsmokers, with emphasis on proliferative activity. Materials and Methods: Exfoliative smears were obtained from the oral mucosa of forty participants (twenty nonsmokers and twenty smokers) with age group ranging from 30-80 years, in and around Barwala (Haryana). The cytologic smears were evaluated using Papanicolaou (PAP) stain and AgNOR in order to evaluate the presence of cytological alterations suggestive of inflammation, dysplasia, keratinization, and proliferative activity of epithelial cells. Only PAP Class I and Class II smears were observed. Results: Comparison of the mean number of AgNORs showed a significant difference between nonsmokers and smokers. Inflammatory alterations were found in 70% of smokers and 55% of nonsmokers. A significant difference in proliferative activity was observed between smokers and nonsmokers classified as PAP Class II. Conclusion: A significant difference of AgNORs/nucleus was observed between bidi smokers and nonsmokers.

RésuméContexte: Bidi fumeurs est un grave danger pour la santé qui est commune dans toute l'Asie du Sud et certaines parties du Moyen-Orient. Il a été fortement impliqué dans diverses lésions bénignes et malignes de la cavité buccale et l'oropharynx. Ces feuilles de tabac offrent plus de trois fois la quantité de nicotine, monoxyde de carbone et de goudron que les cigarettes qui exercent des effets préjudiciables sur les cellules reflétés sous la forme d' une accélération de l'activité proliférative des cellules de la muqueuse buccale normale. Objectif: Cette étude visait à comparer les cellules exfoliées de la muqueuse orale des bidis fumeurs et non fumeurs, avec l'accent sur l'activité proliférative. Matériels et méthodes: frottis Exfoliative ont été obtenus à partir de la muqueuse orale de 40 participants (20 non-fumeurs et fumeurs) avec 20 Groupe d'âge allant de 30-80 ans, dans et autour de Barwala (Haryana). Le frottis cytologique ont été évalués à l'aide de la coloration de Papanicolaou (PAP) et d'AgNOR afin d'évaluer la présence d' altérations cytologiques évocateurs d'infl ammation, dysplasie, la kératinisation, et l'activité proliférative des cellules épithéliales. PAP uniquement les catégories I et II de Papanicolaou n'a été observé. Résultats: comparaison du nombre moyen d'AgNORs ont montré une différence entre les non-fumeurs et les fumeurs. Des modifications ont été trouvés infl ammatory dans 70% des fumeurs et 55% des non-fumeurs. Une différence dans l'activité proliférative a été observée entre les fumeurs et les non-fumeurs PAP, le niveau d'emploi de la classe II. Conclusion: une différence de AgNORs/noyau a été observée entre fumeurs et non-fumeurs bidi. Mots-clés: AgNOR, frottis exfoliative, les fumeurs.

A case of antiepiligrin cicatricial pemphigoid with extensive cutaneous erosions mimicking pemphigus vulgaris.

Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepidermal blistering disease with predominant mucosal involvement. In this article, we report a young patient with mucosal and extensive cutaneous involvement in the form of large erosions mimicking those of pemphigus vulgaris thus leading to diagnostic dilemma. We were unable to find any other previous reports with such extensive cutaneous erosions mimicking those of pemphigus vulgaris. Laminin 5 was the antigen found on knockout substrate testing. Antiepiligrin CP is a distinct subtype of CP with antibodies against laminin 5. This subtype is mostly associated with malignancy but no underlying malignancy was found in our case. Present report also highlights the importance of knockout substrate testing when immunoblot is not available.

Management of refractory trigeminal neuralgia using extended duration pulsed radiofrequency application.

Trigeminal neuralgia (TN) produces incapacitating facial pain that reduces quality of life in patients. Thermal radiofrequency (RF) ablation of gasserian ganglion (GG) is associated with masseter weakness and unpleasant sensations along the distribution of the ablated nerve. Pulsed radiofrequency (PRF) of GG has minimal side effects but literature is inconclusive regarding its benefit in refractory TN. Increasing the duration of PRF application to 6 minutes in TN produced encouraging results. PRF application to the saphenous nerve for 8 minutes reported improved pain relief and patient satisfaction. We report successful management of two patients of classic TN, which were refractory to medical management and interventional nerve blocks. The lesion site were confirmed with motor and sensory stimulation through a 22 G, 10 cm RF needle with 5 mm active tip. Both the patients received four cycles of PRF at 42 °C with each cycle of 120 seconds (8 minutes). The visual analogue scale (VAS) in case 1 reduced from pre-block score of 80 to score 10 post-block, while in case 2 the VAS reduced from pre-block score of 85 to score 15 post-block. During follow up both the patients are now pain free with minimal dose of carbamazepine at 12 and 6 months respectively. We used PRF for longer duration (8 minutes) in these patients, which resulted in improved VAS and WHOQOL-BREF score in these patients. PRF of mandibular division of GG for extended duration provided long-term effective pain relief and quality of life in patients of refractory classic TN.

Emergence of micronuclei as a genomic biomarker.

The presence of micronuclei (MN) in mammalian cells is related to several mutagenetic stresses. MN are formed as a result of chromosome damage and can be readily identified in exfoliated epithelial cells. MN is chromatin particles derived from acentric chromosomal fragments, which are not incorporated into the daughter nucleus after mitosis. It can be visualized by chromatin stains. A variety of factors influences the formation of MN in cells such as age, sex, genetic constitution, physical and chemical agents, adverse habits such as tobacco, areca nut chewing, smoking, and alcohol consumption. Micronucleation has important implications in the genomic plasticity of tumor cells. The present paper reviews the origin, fate and scoring criteria of MN that serves as a biomarker of exposure to genetic toxins, and for the risk of cancer.

Psoriasiform type of lichen scrofulosorum: clue to disseminated tuberculosis.

We present a 16-year-old girl with tuberculosis of the lungs, lymph nodes, and liver, who had extensive inflammatory lesions with pustules, which resembled psoriasis. A skin biopsy showed extensive tuberculoid granulomas surrounding hair follicles, consistent with lichen scrofulosorum. Antitubercular therapy led to resolution of skin lesions. This severe inflammatory type of lichen scrofulosorum is extremely rare.

Disseminated cutaneous histoplasmosis in an immunocompetent child, relapsed with itraconazole, successfully treated with voriconazole.

We present a rare case of disseminated cutaneous histoplasmosis in an immunocompetent child who relapsed after treatment with amphotericin B followed by itraconazole and was successfully treated with voriconazole.