Determining the Best Thyroid Imaging Reporting and Data System: A Prospective Study Comparing the Diagnostic Performance of ACR, EU, and K TIRADS in the Evaluation of Thyroid Nodules.

Background Many different risk stratification systems have been formulated for thyroid nodules, differing in their fine-needle aspiration cytology (FNAC) indication, suggesting a lack of consensus around the world. Purpose This prospective study was conducted to find the best guideline for risk stratification, for a better malignancy yield, and with reduced rates of negative FNACs among three Thyroid Imaging, Reporting, and Data System (TIRADS) guidelines. Materials and Methods A total of 625 thyroid nodules with conclusive FNAC or histopathological diagnosis were included in the study. Various sonographic parameters were recorded. They were classified into categories as per the three guidelines and compared with FNAC diagnosis. The guidelines were evaluated in terms of sensitivity, specificity, predictive values, and diagnostic accuracy. Sensitivity and specificity were compared by McNemar's test. Results American College of Radiology (ACR) TIRADS had the highest diagnostic accuracy (56.8%), specificity (50.75%), positive predictive value (23.92%), lowest rates of negative FNACs (76.08%), and high negative predictive value (97.84 %). Korean (K) TIRADS had the maximum sensitivity (97.75%), highest negative predictive value (98.44%), and gross malignancy yield. European TIRADS was between the two other guidelines in most parameters with specificity like K TIRADS. Conclusion All the three guidelines are very good screening tools, with comparable high sensitivity. ACR TIRADS is better in terms of specificity and reduced rates of negative FNACs. Including the presence of a suspicious cervical lymph node as a criterion and more frequent follow-up might further improve the diagnostic performance of the guideline.

Accidental fatal poisoning in a child due to ingestion of Nerium oleander leaf.

Nerium oleander is an ornamental plant that belongs to the family Apocynaceae. It contains a cardiac glycoside named oleandrin, which is present in all parts of the oleander plant. Suicidal and medication-related deaths due to Nerium oleander poisoning are not uncommon. However, accidental deaths due to oleander leaf ingestion are most commonly encountered. We are reporting a case of an accidental ingestion of Nerium oleander leaf in a child by mistaking it for a guava leaf. The child presented to the casualty with vomiting, poor sensorium, hypotension, and shock. The child developed hyperkalemia, acute kidney injury, myocardial dysfunction, and bleeding manifestations. The urine output was decreased (< 0.5 ml/kg/h). Later, the child died after 36 h. On autopsy examination, periorbital puffiness and bluish discoloration of the nail beds were present. Petechial hemorrhages were present in the heart, kidney, and mesentery. The stomach mucosa was hemorrhagic. Histopathologically, the lung showed interstitial congestion, the liver showed centrilobular necrosis, and the kidney showed acute tubular necrosis. Toxicology analysis was positive for oleander poisoning. This case highlights the toxic nature of Nerium oleander ingestion and the importance of avoiding such plants around residential areas.

Primary Pediatric Yolk Sac Tumor of Liver With Lung Metastasis: An Unusual Presentation With Diagnosis Aided by LIN28 Immunohistochemistry.

Yolk sac tumor is a malignant germ cell tumor, which typically occurs in the gonads with elevated serum alpha-fetoprotein (AFP). Among extragonadal sites, the liver is an uncommon location for primary pediatric yolk sac tumors. Other common hepatic tumors in this age group presenting with elevated serum AFP like hepatoblastoma and hepatocellular carcinoma must be differentiated from yolk sac tumors for initiating appropriate treatment and accurate prognostication. Lung metastasis with refractoriness to chemotherapy is an extraordinary presentation that has never been documented in the literature. We report our experience with a 2-year-old female child initially misdiagnosed as hepatoblastoma. It was found that LIN28 positivity by immunohistochemistry aided in confirmation of the histopathological diagnosis of primary yolk sac tumor of the liver.

Plasma Cell Granuloma of the Maxillary Sinus-A Case Report and Review.

Plasma cell granuloma is a rare, benign, space occupying lesions occurring after recurrent infections. It most commonly involves young adults with lungs being the most common site. They are usually rounded masses with bony expansion and destruction without any life threatening complications and surgery being the best choice of treatment. Here we reported a 33 year-old female with plasma cell granuloma of the maxillary sinus treated with surgery and no recurrence has been noted.

Primary pulmonary T-cell lymphoma.

Primary pulmonary lymphoma (PPL) is a rare clonal proliferation of lymphoid tissue involving one or both lungs. It is of two types, B-cell and T-cell lymphomas among which T-cell lymphoma is a rare entity and it is sparsely considered as a differential diagnosis in neoplastic lesions of the lung. Here, we are reporting a case of primary pulmonary T-cell lymphoma. PPL is a rare disease and can present with nonspecific symptoms. Radiologically, it can easily be confused with more common malignancies such as bronchogenic carcinoma with or without metastases. PPL carries different therapeutic and prognostic implications. Therefore, physicians should make every effort to achieve histopathological diagnosis before prognosticating a patient presenting with lung cancer.

A Giant Right Atrial Hemangioma- Case Report.

A primary cardiac tumor is sporadic. Most cardiac tumors are benign, with cardiac myxoma being the most common tumor. The incidence of cardiac hemangioma is extremely low. We report a 55-year-old female patient admitted for chest pain and breathlessness and, on evaluation by Echocardiography and Computed tomography, was diagnosed with a right atrial mass. The patient was taken up for surgery. The excised right atrial mass was confirmed as atrial hemangioma by postoperative histopathology. Cardiac hemangioma should be suspected when imaging shows a homogenous mass with vascularity. We present this case as the tumor is sporadic and illustrate the technical difficulties we encountered during the surgery.

Evaluation of change in tumor stiffness measured by acoustic radiation force impulse imaging for early prediction of response to neoadjuvant chemotherapy in breast cancer.

OBJECTIVES: In this study, the role of change in tumor stiffness between pre- and post-two cycles of neoadjuvant chemotherapy (NACT) measured by Acoustic Radiation Force Impulse (ARFI) imaging for predicting the response to NACT in breast cancer was analyzed. METHODS: Fifty-two adult women with biopsy-proven locally advanced breast cancer and early-stage breast cancer who received NACT followed by either modified radical mastectomy or breast conservation surgery were included in the study. Tumor stiffness represented by shear wave velocity (SWV) in meter per second by ARFI imaging was measured before and after two cycles of NACT. Participants were categorized into responders and nonresponders based on pathological response assessment from the postoperative specimen. The association of change in tumor stiffness between pre- and post-two cycles of NACT with final pathological response status was assessed. RESULTS: The mean change in SWV before and after completion of two cycles of NACT was 0.42 ± 0.16 and 0.17 ± 0.11 m/s in responders and nonresponders, respectively, and this difference was proven to be statistically significant (p < 0.001) suggesting that tumors that exhibit a larger reduction in tumor stiffness, respond better. An SWV reduction cut-off of 0.295 m/s between baseline and post-two cycles of NACT was also arrived at, which can discriminate between responders and nonresponders with a sensitivity and specificity of 88% and 83%, respectively. CONCLUSION: Difference in tumor stiffness measured by ARFI imaging before and after two cycles of chemotherapy can be used as a reliable early predictor of response to chemotherapy in breast cancer.

Disseminated histoplasmosis as a presenting manifestation in an HIV patient - A case report from South India.

Histoplasmosis has heterogenous clinical presentation ranging from mild and self-limiting respiratory disease to disseminated forms with high mortality. In progressive disseminated histoplasmosis (PDH), patient presents with fever, lymphadenopathy, hepatosplenomegaly, adrenal enlargement, hemophagocytic lymphohistiocytosis and non-specific mucocutaneous lesions, usually in late stage of HIV. Cutaneous involvement is upto 25% in PDH which are papules, plaques, nodules and ulcers. Forty-two year old male, recently diagnosed as HIV positive presented with complaints of multiple painful ulcerated lesions over face, neck, tongue, arms, trunk & genitalia. Skin Biopsy was suggestive of histoplasmosis. Patient showed excellent response with amphotericin B and itraconazole. Since histoplasmosis is relatively uncommon, there should be a high-index of suspicion when an HIV patient presents with disseminated skin lesions.

Challenges in the Management of Lung Cancer: Real-World Experience from a Tertiary Center in South India.

Lung cancer is one of the most common cancers and an important cause of cancer-related mortality. Recent advances in targeted therapy and immunotherapy have improved outcomes, but these have limited penetration in resource-constrained situations. We report the real-world experience in treating patients with lung cancer in India. A retrospective analysis of baseline characters, treatment and outcomes of patients with lung cancer seen between January 2015 to December 2018 ( n = 302) at our center was carried out. Survival data were censored on July 31, 2019. A total of 302 patients (median age: 57 years [range, 23-84 years]; males [ n = 203; 67.2%]) were registered. Adenocarcinoma was the most common histology ( n = 225, 75%). The testing rate of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutation analysis in stage IV adenocarcinoma ( n = 191) was 67% and 63%, respectively. Systemic therapy (chemotherapy/gefitinib) was started after a median of 62 days (range, 1-748) from presentation and 38 days (range, 1-219 days) from diagnosis. The median progression-free survival (PFS) and overall survival (OS) were 4.3 months (95% CI, 3.2-5.4) and 9.0 months (95% CI, 7.6-10.5), respectively in the 141 patient without targetable mutations who started palliative chemotherapy. Of the 58 patients who tested positive for EGFR mutation, 41 (71%) started an EGFR tyrosine kinase inhibitor (TKI), and the median PFS and OS in these patients were 8.5 months (95% CI, 5.6-11.4) and 18.4 months (95% CI, 12.2-24.6), respectively. Only 1 out of 10 patients with stage IV ALK -positive adenocarcinoma was started on ALK inhibitor. On multivariate analysis of OS for patients who started on palliative chemotherapy, response to first-line treatment, long distance from the center, use of second line therapy, and a delay of > 40 days from diagnosis to treatment predicted improved survival. Despite providing free diagnostic and treatment services, there was considerable delay in therapy initiation, and a significant proportion of treatment noninitiation and abandonment. Measures should be taken to understand and address the causes of these issues to realize the benefits of newer therapies The apparent paradox of improved survival in those with long delay in initiation of treatment could be explained based on a less aggressive disease biology.

Clinical and Dermoscopic Features of a Case of Idiopathic T-Cell Pseudolymphoma.

Cutaneous pseudolymphomas are a group of benign lymphocyte-rich infiltrates that can mimic cutaneous lymphomas either clinically and/or histologically. Idiopathic T-cell pseudolymphoma (TCPL) usually presents as a solitary nodule or plaque on the trunk or head. A clinicopathologic correlation is mandatory to arrive at a final diagnosis and rule out true lymphomas. There are only sparse dermoscopic reports on cutaneous pseudolymphomas. Hereby, we describe the clinical and dermoscopic features of a case of idiopathic TCPL in a 26-year-old man who presented with an asymptomatic thin reddish-brown "table tennis racquet"-shaped plaque on the right inframammary area.

Dilemma in diagnosis and management of rare primary pleural Ewing's sarcoma with synchronous limited metastatic disease.

We present a case of a 34-year-old woman who presented with complaints of fever, cough and dyspnoea of 2 months' duration. On evaluation, she was diagnosed with a rare entity primary pleural Ewing's sarcoma with synchronous metastases to mediastinal, supraclavicular nodes and single vertebra. Due to the rarity of this entity and lack of treatment guidelines on extraosseous Ewing's sarcoma, the patient was managed with a combination of multiagent chemotherapy, surgery and radiotherapy as per standard guidelines for skeletal Ewing's sarcoma. We present this case to discuss differential diagnoses and management dilemmas encountered on the use of local modalities such as surgery and radiotherapy for control of primary and metastatic sites.

The strength of cytomorphology and efficacy of immuno-cytochemistry in distinguishing hepatocellular carcinoma from its mimics on fine-needle aspiration cytology.

BACKGROUND: Cytomorphologic distinction of hepatocellular carcinoma (HCC) from its mimics on fine-needle aspiration cytology (FNAC) is often problematic. The present study evaluates the strength of cytomorphology and the utility of an immuno-panel of arginase-1, glypican-3, HepPar-1, thyroid transcription factor (TTF-1) and CK-19 in resolving this diagnostic issue. METHODS: FNAC features of 71 nodular hepatic lesions were studied with an immunocyto/ histochemical (ICC/IHC) panel of arginase-1, glypican-3, HepPar-1, TTF-1 taking 10% positivity as "cut-off." Cytomorpholologic diagnoses were compared with diagnoses made on combined cytomorphologic and ICC/IHC approach. RESULTS: Of 71 cases, 32, 10 and 29 had histopathologic, cell block and clinico-radiologic correlation respectively with 55 metastatic adenocarcinomas (MAC), 13 HCCs and one case each of hepatic adenoma (HA), cirrhotic nodule (CN) and intrahepatic cholangiocarcinoma (CC). Cytoplasmic positivity of HepPar-1 and glypican-3 were noted in 11/13 and 8/13 HCCs respectively; while only 3/13 and 1/13 HCCs revealed cytoplasmic positivity for arginase-1 and TTF-1 respectively. Benign hepatic lesions were negative for glypican-3 and TTF-1, but expressed both arginase-1and HepPar-1. Twenty-one of 55 MACs and the lone case of CC were positive for CK-19; however, all MACs and CC cases were negative for HepPar-1, arginase-1, glypican-3 and TTF-1. The immune-panel had sensitivity, specificity and diagnostic accuracy of 100%, 88.9% and 90.6%, respectively, for differentiating HCC from its morphologic mimics. CONCLUSION: Though a meticulous cytologic evaluation in conjunction with clinicoradiologic profile helps in distinguishing HCC from its benign and malignant mimics; an immunopanel of arginase-1, glypican-3, HepPar-1, TTF-1 and CK-19 drastically improves the diagnostic accuracy.

Evaluation of real time polymerase chain reaction targeting mpb64 gene for diagnosis of extrapulmonary tuberculosis.

BACKGROUND: Paucibacillary nature of extrapulmonary tuberculosis (EPTB) has paved way for molecular methods increasingly being used for diagnosis. We undertook a study for evaluation of sensitivity and specificity of real-time polymerase chain reaction (RT-PCR) targeting mpb64 gene for diagnosis of EPTB. METHODS: A total of 152 clinical samples from suspected cases of EPTB were included in this study. All samples were extracted using spin column based commercial DNA extraction kit and were subjected to RT-PCR targeting mpb64 and IS6110. Smear and culture was also done for samples whenever quantity was sufficient. Cytology report was noted from hospital information system. Receiver operating characteristic (ROC) curve analysis was done for determining cut-off Ct value for mpb64 RT-PCR. Melt curve analysis was done for samples whose cycle threshold (Ct) value was more than 37. The sensitivity and specificity of the mpb64 RT-PCR was calculated using a composite gold standard i.e., positive for one or more of the following: microscopy (including fine needle aspiration cytology (FNAC), acid-fast bacilli positivity), culture and IS6110 RT-PCR. RESULTS: Out of the 152 samples, 72 (47.4%) were positive for tuberculosis by composite gold standard. Samples consisted of ascitic fluid (12), CSF (35), pus (23), lymph node aspirate (35), pleural fluid (37), synovial fluid (4), urine (1), pericardial fluid (1) and tissue bits (4). Microscopy (AFB smear including lymph node aspirate) was done for 124 samples of which 43 (34.7%) were positive. Culture results were available for 79 samples, 25 (31.6%) of which were positive and 42 (27.6%) of the 152 samples were positive by IS6110 PCR. Based on ROC and melt curve analysis, mpb64 RT-PCR was able to detect 38 (52.8%) of the 72 positive samples. In comparison to IS6110 RT PCR, 4 additional cases were detected by mpb64 RT-PCR. Compared to composite gold standard mpb64 showed overall sensitivity of 52.8%. CONCLUSION: The mpb64 RT-PCR is highly specific or MTB and can be used as a supplemental test for diagnosis of EPTB along with other diagnostic tests. However the overall sensitivity of mpb64 RT-PCR is too low to be used as an independent test for diagnosis of EPTB. Combining the results of IS6110 RT PCR and mpb64 RT PCR improved the overall sensitivity and hence mpb64 can be used as an additional target for diagnosis of EPTB.

Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar Rats.

OBJECTIVES: Anti-TB drugs-isoniazid and rifampicin induced hepatotoxicity present a significant clinical problem. We aimed to evaluate the beneficial effect of gallic acid in anti-TB drug-induced liver injury in vivo and for the mechanism of action, we explored the influence of gallic acid on Nrf2 and NF-κB pathways. METHODS: We assessed serum liver function tests and histopathological analysis for the preventive effect of gallic acid on liver injury. For exploring the beneficial mechanism, we studied Nrf2 and NF-κB signalling pathways using molecular assays. Subsequently, we conducted in vitro cytotoxicity assays with Nrf2(ML385) and NF-κB(BAY 11-7085) antagonists. KEY FINDINGS: Gallic acid co-administration attenuated the elevation of liver function enzymes, hepatic necrosis and inflammation compared to the anti-TB drug treatment alone. Mechanistic investigations reveal that gallic acid increased Nrf2 activation and induction of its downstream targets, preventing cytotoxicity by isoniazid and rifampicin. The protective effect of gallic acid diminished in the presence of Nrf2 antagonists in vitro. Furthermore, we found that gallic acid treatment inhibited NF-κB/TLR-4 axis upregulated by the anti-TB drugs. CONCLUSIONS: Gallic acid is effective in preventing isoniazid and rifampicin induced hepatotoxicity in vivo by improving the redox homeostasis by activating Nrf2 and inhibiting NF-κB signalling pathways.

Quercetin modulates NRF2 and NF-κB/TLR-4 pathways to protect against isoniazid- and rifampicin-induced hepatotoxicity in vivo.

Isoniazid and rifampicin are crucial for treating tuberculosis (TB); however, they can cause severe hepatotoxicity leading to liver failure. Therapeutic options are limited and ineffective. We hypothesized that prophylaxis with quercetin attenuates isoniazid- and rifampicin-induced liver injury. We randomly divided Wistar rats into seven groups (n = 6). The animals received isoniazid and rifampicin or were co-treated with quercetin or silymarin for 28 days. The protective effect of quercetin was assessed using liver function tests and liver histology. Nuclear factor erythroid 2-related factor 2 (NRF2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways were explored to elucidate the mechanism of action. Quercetin co-administration prevented the elevation of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and bilirubin compared with isoniazid and rifampicin treatment alone. In the histological analysis, we observed that quercetin prophylaxis lessened the severity of hepatic necrosis and inflammation compared with the anti-TB drug-treated group. Quercetin attenuated anti-TB drug-induced oxidative stress by increasing NRF2 activation and expression, boosting endogenous antioxidant levels. Additionally, quercetin blocked inflammatory mediators high mobility group box-1 (HMGB-1) and interferon γ (IFN-γ), inhibiting activation of the NF-κB/ toll like receptor 4 (TLR-4) axis. Quercetin protects against anti-TB liver injury by activating NRF2 and blocking NF-κB/TLR-4.

Leiomyosarcoma of the inferior vena cava posing as an adrenal incidentaloma.

Adrenal incidentalomas are incidentally detected adrenal lesions on imaging, which have a variety of differential diagnoses, the most common being a non-functioning adenoma. Surgical intervention for these lesions is needed when there is hypersecretion, for lesions larger than 4 cm and smaller lesions with suspicious characteristics. Here we present a young woman who was incidentally found to have a right suprarenal mass with loss of fat planes with the inferior vena cava (IVC). She underwent resection of the tumour along with the posterior wall of IVC, which was primarily repaired. Her postoperative biopsy was suggestive of leiomyosarcoma arising from the IVC. In the absence of distant metastasis, the sole prognostic factor for this tumour is achieving negative margins through radical resection of the tumour with IVC resection. Retroperitoneal leiomyosarcomas should be considered as a differential diagnosis for larger lesions, especially those more than 10 cm.

Tuberculosis heralding connective tissue disorder.

Connective tissue diseases and infections are amongst the causes for organising pneumonia. However, organising pneumonia preceding other connective tissue disease manifestations is rare. Mycobacterium tuberculosis is rarely associated with organising pneumonia. We report such a case. A 50-year-old diabetic male, a roadside shop keeper, a current smoker presented with fever, breathlessness, cough and weight loss for four months. Chest radiography demonstrated areas of consolidation with halo signs. Anti-nuclear antibody blot was positive for Scl-70 and Jo-1 suggestive of a syndrome of systemic sclerosis and polymyositis overlap. Fibre-optic bronchoscopy guided lung biopsy was suggestive of organising pneumonia, and broncho-alveolar lavage detected Mycobacterium tuberculosis. Mycobacterium tuberculosis should be investigated as an aetiology of organising pneumonia, as this may occur in unestablished cases of connective tissue disease even before clinical and radiological manifestations appear, as response can be achieved with anti-tuberculosis therapy alone, without additional use of systemic steroids.

Cystic Uterine Endosalpingiosis in a Patient with Carcinoma Endometrium.

Endosalpingiosis is a benign condition characterized by the presence of tubal-type epithelial cells outside the Fallopian tube. It may rarely involve the uterus and present as a cystic or tumor-like mass. We report an unusual case of cystic uterine endosalpingiosis in a postmenopausal female with carcinoma endometrium. Preoperative and intraoperative diagnosis of this condition is challenging. Awareness about this condition in clinicians may help in preventing misdiagnosis and overtreatment.