Aflatoxin exposure is associated with an increased risk of gallbladder cancer.

Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3-8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4-17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5-16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3-35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3-14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2-12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8-100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6-17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.

Dual-energy CT in differentiating benign gallbladder wall thickening from wall thickening type of gallbladder cancer.

OBJECTIVE: To evaluate the performance of dual-energy computed tomography (DECT) in differentiating non-acute benign from malignant gallbladder wall thickening (GBWT). METHODS: This prospective study comprised consecutive adults with GBWT who underwent late arterial phase (LAP) and portal venous phase (PVP) DECT between January 2022 and May 2023. The final diagnosis was based on histopathology or 3-6 months follow-up imaging. DECT images in LAP and PVP were assessed independently by two radiologists. The demographic, qualitative, and quantitative parameters were compared between two groups Multivariate logistic regression was performed to determine the association between the aforementioned factors and malignant GBWT. RESULTS: Seventy-five patients (mean age 56 ± 12.8 years, 46 females) were included. Forty-two patients had benign, and 33 had malignant GBWT. In the overall group, female gender (p = 0.018), lymphadenopathy (p = 0.011), and omental nodules (p = 0.044) were significantly associated with malignant GBWT. None of the DECT features differed significantly between benign and malignant GBWT in overall group. In the xanthogranulomatous cholecystitis (XGC, n = 9) vs. gallbladder cancer (GBC) (n = 33) subgroup, mean attenuation value at 140 keV LAP VMI was significantly associated with malignant GBWT [p = 0.023, area under curve 0.759 (95%CI 0.599-0.919)]. CONCLUSION: DECT-generated quantitative parameters do not add value in differentiating non-acute benign from malignant GBWT. However, DECT may have a role in differentiating XGC from GBC in a selected subgroup of patients. Further, larger studies may be necessary to confirm these findings. CLINICAL RELEVANCE STATEMENT: In patients with non-acute gallbladder wall thickening in whom there is suspicion of xanthogranulomatous cholecystitis (XGC), DECT findings may allow differentiation of XGC from wall thickening type of gallbladder cancer. KEY POINTS: Differentiation of benign and malignant gallbladder wall thickening (GBWT) at CT is challenging. Quantitative dual energy CT (DECT) features do not provide additional value in differentiating benign and malignant GBWT. DECT may be helpful in a subgroup of patients to differentiate xanthogranulomatous cholecystitis from gallbladder cancer.

The Great Impostor: A challenging case of small-cell melanoma with isolated adrenal metastasis.

Small-cell melanoma masquerading as an adrenal non-Hodgkin lymphoma. The index report illustrates the deceptive cytomorphologic features of a small cell type malignant melanoma metastatic to the adrenal gland. The diagnosis was confirmed by performing immunocytochemistry on the cell block sections. The key cytomorphologic mimics and their distinctive features have also been highlighted.

A sub-hepatic nodule in a young female: Chase the case.

Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female. Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female.

Bugs' eyes and black monsters: Ascitic fluid cytology in an elderly male with hematochezia.

Anorectal malignant melanomas are rare, accounting for less than 2% of all melanomas. Malignant effusions developing secondary to malignant melanoma are highly uncommon. Herein, we present the cytomorphological features of a metastatic anorectal malignant melanoma presenting with ascites at the initial clinical presentation.

Extragonadal Germ Cell Tumor with Hepatic Infiltration in a Child: Aberrant Somatostatin Receptors and the Diagnostic Conundrum.

Extragonadal germ cell tumors (GCTs) are challenging to diagnose. We present a case of suprarenal GCT, with hepatic infiltration where differential diagnosis included neuroblastoma and hepatoblastoma. The positive positron emission tomography scan further obfuscated the situation. The diagnosis was clinched by fine-needle aspiration cytology and cell block immunohistochemistry.

Multiparametric MR imaging with diffusion-weighted, intravoxel incoherent motion, diffusion tensor, and dynamic contrast-enhanced perfusion sequences to assess gallbladder wall thickening: a prospective study based on surgical histopathology.

OBJECTIVE: To investigate the diagnostic performance of a multiparametric magnetic resonance imaging (MRI) protocol comprising quantitative MRI (diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and dynamic contrast-enhanced (DCE) perfusion MRI) and conventional MRI in the characterization of gallbladder wall thickening (GWT). METHODS: This prospective study comprised consecutive adults with GWT who underwent multiparametric MRI between July 2020 and April 2022. Two radiologists evaluated the MRI independently. The final diagnosis was based on surgical histopathology. The association of MRI parameters with malignant GWT was evaluated. The area under the curve (AUC) for the quantitative MRI parameters and diagnostic performance of conventional, and multiparametric MRI were compared. The interobserver agreement between two radiologists was calculated. RESULTS: Thirty-five patients (mean age, 56 years, 23 females) with GWT (25 benign and ten malignant) were evaluated. The quantitative MRI parameters significantly associated with malignant GWT were apparent diffusion coefficient on DWI (p = 0.007) and mean diffusivity (MD) on DTI (p = 0.013), perfusion fraction (f) on IVIM (p = 0.033), time to peak enhancement (TTP, p = 0.008), and wash in rate (p = 0.049) on DCE-MRI. TTP had the highest AUC of 0.790, followed by MD (0.782) and f (0.742) (p = 0.213) for predicting malignant GWT. Multiparametric MRI had significantly higher sensitivity (90% vs. 80%, p = 0.045) than conventional MRI for diagnosing malignant GWT. The two radiologists' reading had substantial to near-perfect agreement (kappa = 0.639-1) and moderate to strong correlation (interclass correlation coefficient = 0.5-0.88). CONCLUSION: Multiparametric protocol incorporating advanced sequences improved the diagnostic performance of MRI for differentiating benign and malignant GWT. KEY POINTS: • Multiparametric MRI had 90% sensitivity and 88% specificity for diagnosing malignant GWT, compared to 80% sensitivity and 88% specificity for conventional CE-MRI. • Among the quantitative MRI parameters, TTP (perfusion-MRI) had the highest AUC of 0.790, followed by MD (0.782) and IVIM-f (0.742). • For most quantitative MRI parameters, there was moderate to strong agreement (ICC = 0.5-0.88).

Liquid-based cytology and immunocytochemistry in the evaluation of a vault lesion in a postmenopausal woman.

Cytological features of small cell neuroendocrine carcinoma of the cervix in a liquid-based preparation from a vault lesion.

Fine needle aspiration cytology of metastatic tumours to the thyroid.

BACKGROUND: Metastasis to the thyroid gland from non-thyroid sites is relatively rare and often poses a diagnostic difficulty on fine-needle aspiration cytology, as it often mimics primary thyroid neoplasms. METHODS: All cases of fine needle aspiration cytology (FNAC) of metastasis to the thyroid gland (2014-2022) were selected from the pathology database. The detailed cytopathological features and histopathology of the cases were studied. RESULTS: There was a total of 18 cases of secondary tumours of the thyroid. All cases had confirmed histopathological data. The most common primary tumours in our study were squamous cell carcinoma of the oesophagus (nine cases) followed by infiltrating ductal carcinoma of the breast (four cases), and one case each of renal cell carcinoma, neuroendocrine carcinoma of the lung, adenocarcinoma stomach and malignant melanoma and squamous cell carcinoma from vallecula. CONCLUSION: Metastasis to thyroid carcinoma is relatively uncommon. A history of malignancy, the presence of malignant cells amid benign thyroid follicular cells, unusual malignancy in a FNAC smear and immunocytochemistry are helpful in diagnosing such cases.

Unravelling the mysteries of Xp11.2 translocation-associated renal cell carcinoma: A case report with a review of the literature.

Cytomorphologic and immunocytochemical features of TFE3 translocation-associated renal cell carcinoma.

Cerebrospinal fluid infiltration by chronic myeloid leukaemia: Evaluation of cytomorphological features.

BACKGROUND AND AIM: To describe the cytomorphological findings of all cerebrospinal fluid (CSF) cytology samples showing infiltration by chronic myeloid leukaemia (CML) and their correlation with haematological findings. MATERIALS AND METHODS: A retrospective analysis of all CSF samples reported as showing infiltration by CML on cytology from January 2014 to December 2021 was performed. RESULTS: A total of 10 cases with positive CSF cytology were evaluated. The mean age of the patients was 34.1 years (range 17-70 years). There were more males than females. All cases were pre-diagnosed cases of CML on haematological investigations. On cytology, the smears showed atypical/immature blast-like cells, with a high nucleo-cytoplasmic ratio, opened-up chromatin, 1-2 conspicuous nucleoli and a scant to moderate amount of agranular to fine granular cytoplasm along with occasional granulocytic precursors. The shortest time interval for CSF positivity in a known case of CML was 5 months, and the longest interval was 11 years. CONCLUSION: It is extremely uncommon to encounter CML infiltration in CSF. Timely analysis of CSF cytology samples can allow quick diagnosis and alter the patient management protocol.

The utility of WhatsApp-based off-site evaluation for rapid cytology of EBUS-TBNA samples.

BACKGROUND: Whether off-site evaluation of slides by a cytologist viewing the images shared by WhatsApp improves the on-site evaluation by a pulmonologist (P-ROSE) remains unknown. This study's objective was to compare the sensitivity of P-ROSE and WHOSE for adequacy and diagnosis of cytology specimens obtained by endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA). MATERIALS AND METHODS: We retrospectively reviewed our bronchoscopy database to identify subjects who underwent EBUS-TBNA for lymph node sampling and had reports of P-ROSE and WHOSE. We collected data on the adequacy of samples as reported by the pulmonologist (P-ROSE), remotely by the cytologist (WHOSE), and finally after detailed cytologic evaluation. The study's primary outcome was to assess the increment in sensitivity for adequacy and diagnostic category (using the final cytology report as reference) by incorporating WHOSE. RESULTS: We included 264 (P-ROSE, n = 184; WHOSE, n = 80) subjects. The sensitivity (95% CI) for sample adequacy by P-ROSE and WHOSE was 65.3% (57.9%-72%) and 92% (83.6%-96.2%), respectively. There was a 26.6% (95% CI, 16%-35.2%) increment in the sensitivity for adequacy. The sensitivity (95% CI) for diagnosis by P-ROSE and WHOSE was 53.9% (46%-61.1%) and 89.8% (79.5%-95.3%), respectively. There was a 35.9% (95% CI, 23.4%-45%) increment in the sensitivity for diagnosis with WHOSE. The agreement between P-ROSE and final cytology in adequacy was poor (κ = -0.023, p = 0.616). The agreement between WHOSE and final cytology was moderate for adequacy (κ = 0.491, p = <0.001). CONCLUSION: We found WHOSE significantly improves the performance of P-ROSE for rapid assessment of cytology specimens obtained by EBUS-TBNA.

Cytomorphological and immunocytochemical diagnosis of an oesophageal mass in a 62-year-old female with dysphagia.

Oesophageal schwannoma is an extremely rare benign neoplasm. Cytological diagnosis of oesophageal schwannoma has been sporadically reported in the literature. Presented here is a case of oesophageal schwannoma in an older woman that could be accurately diagnosed based on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology accompanied by cell block immunocytochemistry.

Flow cytometric immunophenotyping in a liquid-based cytology sample of pleural fluid: Connecting the dots.

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon non-Hodgkin lymphoma that is rarely described in cytology samples. The present study highlights the importance of flowcytometric immunophenotyping and immunocytochemistry in an effusion sample of an uncommon case of PMBCL.

Cytodiagnosis of bilateral abdominopelvic masses in a postmenopausal woman.

Cytologic diagnosis of ovarian low-grade serous carcinoma.

Cerebrospinal fluid cytology in a toddler with a posterior fossa space-occupying lesion.

An atypical teratoid rhabdoid tumour (AT/RT) is an extremely rare malignant neoplasm. Cerebrospinal fluid (CSF) involvement at presentation indicates intracranial dissemination and is associated with an aggressive course and worse outcomes. We present the characteristic cytomorphological features of AT/RT in the cerebrospinal fluid from a toddler presenting with a posterior fossa space-occupying lesion.

Cervical cytology in the detection of uterine clear cell carcinoma: Diagnostic predictors from a case-control study.

INTRODUCTION: Uterine clear cell adenocarcinoma (CCC) is a rare, aggressive malignancy with poor prognosis. The present study aimed to identify and describe its characteristic morphological features in cervical cytology. METHODS: This was a 3-year retrospective case-control study. Cases included cervical samples of histopathologically proven endometrial and cervical CCC. Controls included cervical samples of histopathologically proven endometrial serous carcinoma (n = 15), endometrioid adenocarcinoma (n = 20), and endocervical adenocarcinoma (n = 15). Twenty-eight cytomorphological features were evaluated; the strength of association was determined by odds ratio (OR) and Cramer's V, and the diagnostic accuracy of statistically significant features was assessed. RESULTS: Cases consisted of histopathologically proven 25 (34.7%) endometrial and 13 (18.0%) cervical CCC. Corresponding cervical samples were available for a total of 14 (36.8%) patients, of which 13 (92.8%) were positive for epithelial cell abnormality. On univariate analysis, three cytomorphological variables were significant predictors of uterine CCC: presence of dense cytoplasm (OR = 88; V = 0.72), deep nuclear membrane irregularities (OR = 17.5; V = 0.55), and coarse chromatin (OR = 21.3; V = 0.46). Dense cytoplasm had the highest positive predictive value (92%) and high specificity (97.8%), whereas coarse chromatin had the highest sensitivity (92.3%) and negative predictive value (96.7%). CONCLUSIONS: The presence of dense cytoplasm and deep nuclear membrane irregularities in the tumour cells were strong predictors, and coarse chromatin a moderate predictor, of uterine CCC compared to its close cytological mimics.

Sequential small cell transformation and T790M mutation in an epidermal growth factor-mutant lung adenocarcinoma: A rare occurrence with significant management implications.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance may be acquired via genotypic and/or phenotypic transformations. Herein, we report an extremely uncommon case with sequential small cell transformation and EGFR T790M mutation, in an elderly female with EGFR exon 21 L858R-mutant lung adenocarcinoma, following treatment with a first-generation EGFR-TKI. CASE: A 67-year-old female never-smoker presented with a cough and dyspnoea of 2 months' duration. Computerised tomography revealed a 39 mm lesion in the upper lobe of the right lung with pleural effusion. Pleural fluid cytology revealed metastatic lung adenocarcinoma, and EGFR testing revealed exon 21 L858R mutation. She was started on gefitinib. After a progression-free survival of 31 months, she presented with disease progression and multiple extra-thoracic metastases. Fine needle aspiration cytology of a chest wall lesion revealed metastatic small cell carcinoma. EGFR testing on this aspirate revealed persistent L858R mutation only. In view of small cell transformation, chemotherapy (etoposide and carboplatin) was administered. After 4 months, ascitic fluid cytology revealed metastatic adenocarcinoma with persistent L858R mutation and an acquired T790M mutation (both detected on liquid biopsy as well) indicating amplification of the adenocarcinoma clone and regression of the small cell carcinoma clone. She was then initiated on osimertinib. CONCLUSIONS: The index case highlights the significance of serial EGFR genotyping along with repeated tissue and/or blood sampling in the prompt detection of genetic and phenotypic resistance mechanisms to EGFR-TKIs. Furthermore, it lends evidence in support of the upfront treatment approaches targeting the heterogeneity of acquired EGFR-TKI resistance mechanisms.

Metastatic germ cell tumour in effusion cytology.

BACKGROUND: Germ cell tumours infrequently metastasise to body cavities, where early detection on fluid samples is possible and can spearhead early treatment and survival. MATERIALS AND METHODS: A total of seven cases of metastatic germ cell tumours were retrieved out of 7500 effusion samples received for cytopathological examination from 2015 to 2021. Detailed cytological features of metastatic germ cell tumours in effusion samples were studied, along with a correlation between clinical, radiological, and histopathological features. RESULTS: A total of seven cases of metastatic germ cell tumours were analysed in effusion samples which included dysgerminoma (2), immature teratoma (2), yolk sac tumour (1), embryonal carcinoma (1), and mixed germ cell tumour (1). The smears showed predominantly discrete or loose clusters of cells. The cells with round nuclei and prominent nucleoli were helpful in detecting dysgerminoma and yolk sac tumours. Immature teratoma showed tiny groups of small cells and mature squamous cells. Serum tumour markers were raised in the majority of cases. CONCLUSION: Metastatic germ cell tumours in effusion are uncommon, but detailed clinical history, including serum markers and characteristic cytological features, are helpful in their diagnosis.

Identifying the primary site of malignancy in carcinomatous serous effusions using immunocytochemistry.

INTRODUCTION: Malignant effusions are commonly encountered in day-to-day cytology practice. Determining the primary site of malignancy in carcinomatous effusions is a Herculean task. Cytology coupled with immunocytochemistry (ICC) is often found to be helpful in this context. MATERIALS AND METHODS: This study was conducted to evaluate the diagnostic utility of ICC on sections from cell blocks (CBs) in the detection of the primary site of origin in cases of metastatic carcinomatous effusions. To determine the origin of the primary tumour, TTF1 (lung), PAX-8 (ovary), CDX2 (colorectal), GATA3 (breast), and CK19 (pancreaticobiliary) were employed, depending on the clinical and radiological findings, and serum tumour markers. RESULTS: A total of 13,459 serous effusion samples were received for cytological evaluation from January 2017 to December 2021, of which 2708 (20.1%) were carcinomatous effusions. Out of these, 1044 (38.5%), 1611 (59.5%), and 53 (2.0%) were from pleural, peritoneal and pericardial cavities, respectively. Of these, the majority were adenocarcinoma. ICC was performed in 309 (11.4%) cases. The ovary was the most common primary site in 179 cases (57.9%), followed by the lung (75, 24.3%), pancreaticobiliary system (12, 3.9%), colon/rectum (8, 2.6%), breast (6, 1.9%), prostate (2, 0.6%) and kidney (1, 0.3). The lung was the most common primary site in pleural (67/113, 59.3%) and pericardial (6/8, 75%) effusions. The ovary (168/188, 89.4%) was the most common primary site for carcinomatous effusions in the peritoneal cavity. However, in 17 (5.5%) cases, the exact primary site could not be established. CONCLUSIONS: Judicious and methodical use of ICC on CBs helps to identify the primary site of the tumour in most carcinomatous effusions. This is of immense help to the treating clinician in directing appropriate therapy.