Drug Resistance in Osteoarticular Tuberculosis: A Study From an Endemic Zone.

BACKGROUND: The present study was undertaken to determine the incidence of drug resistance against anti-tubercular drugs among patients from an endemic zone.  Methodology: Forty consecutive clinico-radiologically diagnosed patients of osteoarticular tuberculosis (29: spine, 11: extraspinal) were enrolled. Pus from needle aspiration was taken in 31 cases, tissue following spinal decompression in seven, synovial in one, and sinus edge biopsy in one. The pus/tissue was subjected to acid-fast bacilli (AFB) staining and liquid culture, sensitivity to 13 anti-tubercular drugs (Isoniazid (INH), rifampicin (RIF), kanamycin (KAN), amikacin (AMK,) capreomycin (CAP), ethionamide (ETH), levofloxacin (LEV), moxifloxacin (MOX), linezolid (LNZ), para-amino-salicylic acid (PAS), bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFO)) were checked, and histopathological/cytopathological examination and molecular tests were performed.   Results: The mean age of patients was 29.07(9-65) years; 21 were female and 19 were male. The diagnostic accuracy for tuberculosis was 20% by AFB smear, 65% by liquid culture, 82.5% by histopathology, and 90% by cartridge-based nucleic acid amplification testing (CBNAAT). All culture-positive isolates were identified as Mycobacterium tuberculosis with no non-tubercular Mycobacterium. The drug resistance detected on CBNAAT was 11.1%, line probe assay (LPA) first line was 15.4%, LPA second line was 4%, and liquid drug susceptibility testing (DST) 11.5%. We detected 15.4% INH resistance, 11.1% RIF, 7.6% LEV, 3.8% MOX and PAS. No resistance was detected against second-line injectable drugs (SLID), ETH, LNZ, BDQ, DLM, and CFO.    Conclusions: No single laboratory modality can ascertain the diagnosis in all cases; hence, samples should be sent for all tests in tandem. In the presence of insufficient samples, tissue may be subjected to CBNAAT and histopathology to arrive at tissue diagnosis. In this subset, overall drug resistance incidence was 12.5% (5/40) with one patient each of isolated INH and RIF resistance, one of multidrug-resistance (MDR), and two of pre-extensively drug-resistant (pre-XDR). Primary drug resistance came out to be 11.1% (4/36) with one patient each of isolated INH and RIF resistance, one of MDR, and one Pre-XDR.

Clinico-cytomorphological Spectrum of Calcinosis Cutis.

Introduction: The deposition of calcium in the skin is known as calcinosis cutis. It can affect any part of the body and can mimic soft tissue or bony lesions clinically. Aim: To describe the clinical and cytomorphologic features of calcinosis cutis on fine needle aspiration cytology smears. Materials and Methods: A total of 17 cases reported as calcinosis cutis on fine needle aspiration cytology were reviewed for the available clinical and cytological details. Results: The cohort included both adult and pediatric patients. Clinically, the lesions appeared as painless swellings of variable sizes. The common sites affected were the scrotum, iliac region, scalp, pinna, neck, axilla, elbow, arm, thigh, and gluteal region. Aspirate was chalky white, paste-like in all the cases. The cytologic evaluation revealed amorphous crystalline deposits of calcium along with histiocytes, lymphocytes, and multinucleated giant cells. Conclusions: Calcinosis cutis has a wide spectrum of clinical presentations. Fine needle aspiration cytology is a minimally invasive approach for diagnosing calcinosis cutis, thus eliminating the need for more extensive biopsy procedures.

Evaluation of hTERT Gene Expression and Chromosome 7 Copy Number Variation in Anal Squamous Intra-Epithelial Lesions: A Pilot Study.

Background: Akin to cervical squamous intra-epithelial neoplasia (CIN), anal squamous intra-epithelial lesion (a-SIL) is attributed to persistent infection with high-risk human papilloma virus infection. Amplification of human telomerase reverse transcriptase (hTERT) gene and aneuploidy are known to correlate with CIN evolution. It is plausible that the underlying genetic events in a-SIL are similar. We conducted this cross-sectional analytical study with the objective of determining expression of hTERT gene expression and chromosome 7, as marker of cell ploidy in a-SIL. Methods: Conventional anal cytology was performed in 86 adult consenting subjects with history of receptive anal intercourse (RAI) and 4 controls without history of RAI. Cases with a-SIL and controls were subjected to fluorescent in-situ hybridization (FISH) to evaluate hTERT gene and chromosome 7 expression, as marker of cell ploidy. Results were expressed as number of abnormal nuclei (≥3 respective signals), maximum degree of amplification, mean signals/nucleus and proportion of cases showing abnormal nuclei. Results: Twenty cases showed a-SIL; with 15 atypical squamous cells of undetermined significance (ASCUS), 3 low grade squamous intra-epithelial lesion (LSIL) and 2 cases of high-risk cytology. Expression of both hTERT gene and chromosome 7 increased from controls to ASCUS to LSIL with concomitant increase in proportion of cases having abnormal hTERT gene and chromosome 7 expression. Conclusions: Positive association of hTERT gene with a-SIL suggests its possible role in evolution of anal squamous abnormalities. Increase in chromosome 7 also correlated positively with a-SIL. These findings corroborate the similarities between squamous carcinogenesis in CIN and a-SIL.

Galectin-3 and CD117 immunocytochemistry in the diagnosis of indeterminate thyroid lesions: A pilot study.

BACKGROUND: Indeterminate thyroid lesions have always been a grey zone in the field of thyroid cytopathology. Immunocytochemistry (ICC) has emerged as a promising tool to correctly classify these indeterminate thyroid lesions into benign and malignant. Hence we planned to assess a panel of immune markers in the diagnosis of indeterminate thyroid lesions consisting of Galectin-3, considered positive for malignancy and CD117 which is positive in benign follicular epithelial cells and negative in malignant lesions. METHODS: All the thyroid aspirates reported as indeterminate lesions over a period of 3 years were evaluated. Galectin-3 and CD117 immunocytochemistry was done in 50 alcohol fixed Pap stained smears of AUS/FLUS, FN/SFN and SM category lesions. The expression of both immune markers was assessed by semi-quantitative method and ICC score was calculated. RESULT: Of 50 indeterminate lesions, 29 were positive for Galectin-3 and 21 were negative. CD117 was positive in 19 cases and rests 31 were negative. With the use of this ICC panel 29/30 indeterminate lesions in which histopathological correlation was available could be recategorized correctly into benign and malignant. The combined sensitivity and specificity of Galectin-3 and CD117 for categorising the indeterminate lesions into malignant category was 100%. CONCLUSION: The combined use of positive and negative immune markers for thyroid malignancy increases the sensitivity and specificity of ICC to categorise the indeterminate thyroid lesions into benign and malignant. In cases with discordant ICC results we propose that inclusion of one additional positive and/or negative marker may resolve the diagnostic dilemma.

Cytological diagnosis of juvenile xanthogranuloma: A rare histiocytic disorder.

Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhan cell histiocytic disorder, which is mostly confined to skin of head and neck. It is a self-limiting benign condition, which does not require surgery. We present a case of 8-month-old girl child with multiple yellowish brown colored papules over scalp, face, and neck. A clinical diagnosis of cutaneous mastocytosis was made. Fine-needle aspiration cytology (FNAC) smears showed foamy macrophages along with mixed inflammatory infiltrate and few touton giant cells. A diagnosis of JXG was rendered which was confirmed on histopathology and immunohistochemistry.Juvenile xanthogranuloma can be diagnosed on FNAC based on its characteristic cytologic features; however, it requires a high index of suspicion by cytopathologist. Cytological diagnosis of JXG can save the patient from unnecessary surgical biopsy or excision.

Implementation of the MILAN system for reporting salivary gland cytopathology: Interobserver concordance and cytohistological correlation of discordant cases.

BACKGROUND: Fine needle aspiration cytology (FNAC) plays a pivotal role in evaluating salivary gland (SG) tumors. Several studies have shown diagnostic utility of MILAN system for reporting salivary gland cytopathology (MSRSGC) by examining risk of malignancy but only an occasional study has focused on interobserver variability. Hence, the present study was undertaken to assess the agreement among cytopathologists with varying experience in SG cytopathology using MSRSGC and to re-evaluate discordant cytohistological diagnoses for possible causes of misinterpretation. METHODS: All SG lesions subjected to FNAC over a period of 3½ years were studied. The cases were critically reviewed by 2 pathologists with variable experience in cytopathology using MSRSGC and concordance level among them was calculated. Cytohistological discordant diagnoses were reclassified and possible causes of misinterpretation during routine reporting were evaluated. RESULTS: Of 150 SG aspirates categorized according to MSRSGC, diagnostic disagreement between 2 pathologists was found in 10. Unweighted Cohen's Kappa score between consultant and resident was 0.812 (high). Among 55 cases with histological correlation, cytohistological discordance was seen in 12. True pitfalls constituted 50% of discordant cases while rest 50% were attributed to practical issues (turnaround time and heavy case load) during routine reporting. CONCLUSION: MSRSGC can be used with good reproducibility between observers with variable cytopathology experience. Heterogeneous nature of SG neoplasm is a known pitfall in FNA diagnosis of SG neoplasms. During routine reporting turnaround time, heavy case load and reporting by cytopathologists with variable experience add on to challenges faced in reporting cytopathology of SG neoplasm.

Primary extraneural ependymoma of the broad ligament: A rare entity.

Extraneural broad ligament ependymoma is a rare entity. Herein, we present a case of unusually large broad ligament ependymoma in a 32-year-old female with pain and lump in the lower abdomen. Contrast-enhanced computed tomography abdomen revealed multiple heterogeneously enhancing pelvic masses with lobulated surface in bilateral adnexa along with multiple peritoneal nodules. Her relevant serum tumor markers were unremarkable. Core biopsy revealed tumor composed of elongated cells arranged predominantly in true and pseudoperivascular rosettes. The histopathological differentials included ependymoma, primitive neuroectodermal tumor, and teratoma with neural differentiation. Results of immunohistochemistry favored the diagnosis of ependymoma. Surgical exploration and optimal cytoreduction were done, and a final diagnosis of primary broad ligament ependymoma with peritoneal metastasis was made. The patient received six cycles of adjuvant chemotherapy and is doing well after 8-month follow-up. The present case highlights the diagnostic workup and management of a rare and an unusually large broad ligament ependymoma with peritoneal metastasis.

Current practice in handling and reporting needle biopsies: A hospital-based survey.

CONTEXT: Core-needle biopsy (CNB) is a minimally invasive screening and diagnostic tool which provides intact tissue fragments for histopathological examination. AIMS: This study was conducted to review the current practices of handling and reporting CNBs performed for core-needle biopsies from four organ systems which are frequently encountered in our institution. These include breast, prostate, soft tissues, and lymph nodes. SETTINGS AND DESIGN: This was a retrospective study conducted at a tertiary care hospital. MATERIALS AND METHODS: CNB reports of breast, prostate, soft tissue, and lymph nodes were accessed and categorized based on the site of biopsy, number, and average length of the cores. The CNB reports were categorized into diagnostic or nondiagnostic. In case of diagnosis of malignancy, reports were recorded as structured or nonstructured reports. STATISTICAL ANALYSIS USED: Fisher's exact test and Chi-square tests were applied to check the significance of the results obtained on comparing the number of cores and size of cores with the outcome of report. RESULTS: Out of 16,300 surgical pathology specimens received, 400 were CNBs comprising breast (n = 211), prostate (n = 108), soft tissue (n = 50), and lymph node (n = 31). Majority of the CNBs had 2-5 cores and the size of the core was ≥0.5 cm, which accounted for most of the reports which were diagnostic. There was a lack of clinical and radiological detail in many of the cases. Out of the malignant cases diagnosed, structured reports were given in 30% of breast, 79.3% of prostate, 41.7% soft tissue, and 60% of lymph node needle biopsies. CONCLUSIONS: The audit helped to identify areas of improvement in CNB services.

Intestinal GIST masquerading as an ovarian mass: Diagnosed on FNAC.

The preoperative diagnosis of metastatic intestinal gastrointestinal stromal tumors (GIST) on cytology can be quite difficult at times. The present case characterizes the cytomorphological and immunocytochemical features of GIST, emphasizing the utility of fine-needle aspiration cytology (FNAC) in the evaluation of spindle cell tumors of gastrointestinal tract. An accurate and early diagnosis of GIST affects the treatment, primarily allowing the use of tyrosine kinase inhibitors in unresectable or metastatic cases. Presence of highly cellular fragments of spindle-to-oval cells with variable degree of pleomorphism, atypia, and necrosis supplemented by immunocytochemistry can render a cytological diagnosis of GIST in dilemmatic clinical situations. Our case highlights the diagnostic role of FNAC in the evaluation of a pelvic mass, which was clinicoradiologically misdiagnosed as ovarian carcinoma.

Fine needle aspiration biopsy: An entrustable professional activity in cytopathology postgraduate training.

CONTEXT: In the context of competency-based medical education being advocated worldwide, fine needle aspiration biopsy (FNAB) is considered as an entrustable professional activity (EPA). There is no information regarding how much time and training are required to achieve a "competent level" for performing and documenting FNAB in the Indian context. AIM: To determine the time taken by an average postgraduate pathology trainee to become competent in performing FNAB with respect to history taking, clinical examination, and fine needle aspirate adequacy. SETTINGS AND DESIGN: A descriptive, retrospective, chart-based audit was conducted in the Department of Pathology. MATERIALS AND METHODS: FNAB chart records documented during 3 years of postgraduate training by a cohort of 13 postgraduate (PG) resident trainees admitted in 2010 were included in the study. Adequacy rates and criteria for adequacy were defined for the purpose of the study. STATISTICAL ANALYSIS: Data was entered in MS Excel and analyzed using the Statistical Package for the Social Sciences version 20.0. The adequacy rates are presented as percentages and time taken to achieve adequacy rates as median values. RESULTS: A total of 3272 charts were audited. Median time taken to achieve 85% adequacy rate for history taking, for clinical examination by the first and the second criteria, and for FNAB were 1 month, 1 month and 3.5 months, and 1 month, respectively. CONCLUSIONS: Although the mean time taken to achieve 85% adequacy rates for FNAB was 1 month, there was wide variation in the time durations between the residents to achieve this level.

Lymphoepithelioma-like carcinoma of cervix: Cytological Features on Conventional Cervical Smear.

Lymphoepithelioma-like carcinoma (LELC) is a rare neoplasm of the cervix. The importance of distinguishing this undifferentiated carcinoma with a predominant lymphocytic infiltrate lies in the fact that despite being poorly differentiated they have a better prognosis. The diagnosis however becomes more challenging when the pathologist is provided with a small cervical biopsy or a Papanicolaou smear. While the reports describing histology and their relation to Epstein-Barr virus (EBV) are many, there are only few case reports describing the cytology of these tumors. We describe the cytological features of LELC of cervix on conventional smear and correlate it with the histopathological findings of the same. A 67-year-old multiparous Hindu woman presented to the gynecology outpatient department with the history of postmenopausal bleeding for the past six months. The cytological examination of the cervical smear (Papanicolaou stain) was done followed by cervical and endometrial biopsy. Based on Papanicolaou smear and biopsy suggestive of a poorly differentiated carcinoma a radical hysterectomy with pelvic lymphadenectomy was performed. Hysterectomy specimen showed the morphology of LELC and was then correlated with the cervical smears retrospectively. On review of cytological smears it was seen that the tumor cell clusters had an abundant lymphoid background, which was overlooked earlier. Immunohistochemistry for EBV was negative. We conclude that the presence of undifferentiated tumor cell clusters with ill-defined cell borders and large number of lymphoid cells in the background suggest the diagnosis of LELC on cervical cytology. Diagn. Cytopathol. 2017;45:239-242. © 2016 Wiley Periodicals, Inc.

Neurocristic Hamartoma With Lymph Node Involvement: A Diagnostic Dilemma.

Neurocristic hamartoma (NH) is a rare dermal melanocytic lesion that is formed due to the aberrant development of neural crest-derived melanocytes during their course of migration through the dermis at the time of embryogenesis. Here, we describe a case of NH in a 6-year-old boy who clinically presented with diffuse plaque-type blue nevus on his scalp with a contiguous extension into the cervical region and lymph node involvement. A subcutaneous nodule displaying a marked histological heterogeneity with lymph node involvement is a very unusual and diagnostically challenging presentation of NH. The importance of an accurate diagnosis of NH lies in the fact that malignant transformation can rarely occur within these lesions over an unpredictable time course and remain undetected, rendering clinical management difficult. Although our child had a benign course after a follow-up of 5 years despite lymph node involvement, the possible risk of development of malignant melanoma in such a lesion warrants long-term surveillance. This case report highlights the unusual clinical presentation and histopathological features of this rare entity along with a relevant review of the literature. The present case also underscores the concept that sentinel lymph node involvement in certain melanocytic lesions in children must not be mistaken for malignant melanoma.

Implementation of the bethesda system for reporting thyroid cytopathology: interobserver concordance and reclassification of previously inconclusive aspirates.

Standardized diagnostic terminology was introduced by the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) in an effort to bring uniformity to the reporting of thyroid cytopathology, provide more defined categories to enable clinical management, and minimize the number of inconclusive cases. Previous studies indicate that the BSRTC is a reliable and valid reporting system for thyroid cytology. This study was conducted to compare the concordance between observers with varying cytopathology experience when using the BSRTC, and to assess the impact on the number of inconclusive reports. A retrospective study was conducted in two parts. In the first part 415 thyroid aspirates were reviewed independently by three observers with different experience levels. The aspirates were reclassified according to BSRTC and agreement scores were calculated using kappa statistics. In the second part 39 inconclusive aspirates signed out previously, were recategorized according to BSRTC. Agreement level between the three observers using the BSRTC was strong (Fleiss' kappa score = 0.6561). Inconclusive cases could be categorized further with BSRTC; there was significant reduction in the number of inconclusive diagnoses (P < 0.001). Strong interobserver agreement with BSRTC indicates the ease with which the new system can be applied in regular reporting. Significant reduction in the number of inconclusive diagnoses results in better communication with the clinician and improved risk assessment for thyroid aspirates.

Quinalphos induced oxidative stress and histoarcheitectural alterations in adult male albino rats.

Quinalphos is a synthetic organophosphate used as a broad spectrum insecticide and acaricide. The present study investigates the effect of three sub-lethal doses (0.52, 1.04, 2.6 mg/kg b.wt) of quinalphos for variable durations (15, 30 and 90 days) on oxidative stress and histopathological changes in adult male rats. Quinalphos treatment for 15 and 30 days resulted in a dose dependent significant increase in malondialdehyde (MDA) levels and glutathione-S-transferase (GST) activity together with a concurrent decrease in ferric reducing ability of plasma (FRAP) and glutathione (GSH) content. Quinalphos treatment for 90 days also induced a significant increase in MDA levels and GST activity but the effect was not dose-dependent. Histopathological examination of liver revealed architectural disarray and dilatation of sinusoids, focal fatty changes, accumulation of eosinophils and single cell necrosis with increasing doses. However, spleen and kidney did not show any histological changes. Administration of quinalphos resulted in oxidative stress and free radical induced injury as evidenced by increased lipid peroxidation, decreased FRAP and histopathological changes in liver.

Diagnostic usefulness of fragments of crushed cells in autoimmune thyroiditis.

Fine-needle aspiration cytology has emerged as an important diagnostic tool in cases of autoimmune thyroiditis. However, the patchy nature of this disease and its coexistence with other thyroid pathologies, with only subtle demonstrable cytologic features in many cases can lead to misdiagnosis. Of 313 thyroid aspirates, 62 were diagnosed as autoimmune thyroiditis. Fragments of crushed cells were observed in 51 (82.11%) of autoimmune thyroiditis (P < 0.001). The presence of "crush artifact" that can be easily picked up on low magnification should be used as an important criterion for the diagnosis of thyroiditis. It is particularly helpful in cellular smears from thyroiditis to avoid misdiagnosis of neoplasia.

Papillary cystadenocarcinoma of ovary presenting as obstructive jaundice: a rare presentation.

Obstructive jaundice resulting from malignancy of gastrointestinal tract and hepatobiliary tract has been reported in various studies. Ovarian malignancy leading to obstructive jaundice due to portal lymphadenopathy is of rare occurrence. We report a case presented with obstructive jaundice and on further evaluation, found to have ovarian papillary cyst adenocarcinoma with secondaries at porta hepatis which was managed successfully by neoadjuvant chemotherapy followed by cytoreductive surgery.

Clear cell adenosquamous carcinoma of the cervix: a case report with discussion of the differential diagnosis.

Clear cell adenosquamous carcinoma is an extremely rare and recently described variant of adenosquamous carcinoma of the cervix. It has a unique histologic appearance and has been shown to be associated with human papillomavirus-18. Its significance lies in the fact that it is associated with an aggressive clinical course and has to be differentiated microscopically from clear cell carcinoma and glassy cell carcinoma.

Pleural mesothelioma: an unusual case diagnosed on pleural fluid cytology and immunocytochemistry.

Mesothelioma is a rare neoplasm with relationship to occupational and environmental exposure to asbestos. Its accurate and early diagnosis is often difficult. We present an unusual clinical presentation and diagnostic dilemma in a 30-year-male, who presented with neck pain and diffuse edema of left upper limb. The color Doppler ultrasound revealed venous thrombosis. The right supraclavicular lymph node biopsy revealed a poorly differentiated carcinoma. The patient had mild bilateral pleural effusion, the characteristic cytomorphological features of mesothelioma on fluid cytology were helpful in establishing the diagnosis.