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.

The Role of Cartridge-Based Nucleic Acid Amplification Test (CBNAAT), Line Probe Assay (LPA), Liquid Culture, Acid-Fast Bacilli (AFB) Smear and Histopathology in the Diagnosis of Osteoarticular Tuberculosis.

BACKGROUND: There is a paucity of data on the role of molecular methods in the diagnosis of osteoarticular tuberculosis. The present study was conducted to define the role of molecular (CBNAAT, LPA), phenotypic (AFB smear and culture) and histopathological evaluation in the diagnosis of osteoarticular TB. METHODS: Seventy-seven consecutive cases of osteoarticular tuberculosis were grouped into presumptive TB cases (group A) and presumptive drug-resistant cases (group B). Tissue samples obtained were submitted for CBNAAT, LPA, AFB smear, liquid culture and histological examinations. The diagnostic accuracy of each test was reported against histologically diagnosed cases and in all tests in tandem. RESULTS: Group A and group B had 65 and 12 cases, respectively. The diagnostic accuracy for tuberculosis was 84.62% by CBNAAT, 70.77% by LPA, 86.15% by molecular tests (combined), 47.69% by AFB smear, 50.77% by liquid culture and 87.69% by histology in group A, and 91.67% for CBNAAT, 83.33% for LPA, 91.67% for molecular tests (combined), 25% for AFB smear, 16.67% for liquid culture and 83.33% for histology in group B. The drug resistance detection rate was 4.62% on CBNAAT, 3.08% on LPA, 6.15% on molecular tests (combined) and 1.54% on DST in group A, while it was 33.33% on CBNAAT, 58.33% on LPA, 58.33% on molecular tests (combined) and 16.67% on DST among group B cases. Similar sensitivity rates for the various tests were obtained among both the groups on comparison with histology (taken as denominator). The addition of molecular methods increased the overall diagnostic accuracy (all tests in tandem) from 93.8 to 100% in group A and from 83.3 to 100% in group B cases. CONCLUSION: No single tests could diagnose tuberculosis in all cases; hence, samples should be evaluated by molecular tests (CBNAAT and LPA), AFB smear, culture and histological examinations simultaneously. The molecular tests have better demonstration of drug resistance from mycobacterial culture. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43465-020-00326-w.

Transgenders are the most vulnerable amongst individuals engaging in receptive anal intercourse: A cross-sectional study from North India.

Background: In India, sexuality not confirming to hetero-conjugal and peno-vaginal norm is abhorred and discriminated against. Individuals engaging in Receptive Anal Intercourse (RAI) are marginalized. Reappraisal of their sexual health conditions is likely to promote inclusive health care. Methods: Eighty-five consenting adults with RAI history were recruited from a tertiary care hospital in Delhi. Clinico-demographic data was noted and anal cytology samples were reported by Bethesda 2014 terminology. Results: There were 29 transgenders (TGs), 51 males (31 bisexual) and five females. Fifty-four subjects were Human Immunodeficiency Virus (HIV) infected (22 TGs, 31 males (17 bisexual) and one female) and 52 were receiving anti-retroviral treatment (ART). Thirty-one subjects had anal warts (6 TGs, 20 males, five females). Anal cytology revealed squamous intra-epithelial lesions (SIL) in 20 (5 TGs, 13 males, two females). TGs had significantly risker sexual practices than homosexual males, bisexual males and females, with consistently earlier age of first RAI exposure and frequent childhood (≤16 years) RAI experience compared to homosexual males, bisexual males and females, even after stratification by HIV status, warts and SIL. Conclusions: TGs had the highest sexual health risk profile including higher frequency of HIV infection compared to other subjects with RAI history. Bisexuality was common; their risk profile was variably lower than homosexual males. Mindfulness of above is likely to help overcome barriers to health care access and promote compassionate approach at all levels including primary care physicians.

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.

Lichen Nitidus Associated with Onychodystrophy and Response to Therapy: Report of Two Cases.

Lichen nitidus (LN) is a chronic inflammatory condition characterised by multiple asymptomatic shiny, flat-topped, pale to skin-coloured tiny papules. LN occurs most often in children and young adults with limbs, abdomen, chest, and penile shaft as common sites of predilection. Nail involvement is rare and includes irregular longitudinal grooving and ridging of the nail plate. We report two cases of generalised LN with nail dystrophy in 8- and 12-year-old boys along with the treatment response and review the pertinent literature.

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.

Tuberculosis of the glans penis: an important differential diagnosis of genital ulcer disease.

We report a 45-year-old, apparently healthy sero-negative man, presenting with multiple ulcers on the glans penis for a duration of three months. There was no significant inguinal lymphadenopathy. He showed no improvement on systemic antibiotics and acyclovir. Histopathology revealed the diagnosis of genital tuberculosis (TB), and polymerase chain reaction for Mycobacterium tuberculosis tested positive. The patient responded well to category I anti-tubercular treatment with complete resolution of lesions in six months. It is important to consider a differential diagnosis of penile TB in patients with non-healing genital ulcers.

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.