Methylation study of tumor suppressor genes in human aberrant crypt foci, colorectal carcinomas, and normal colon.

BACKGROUND: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. METHODS: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. RESULTS: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear ß-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. CONCLUSIONS: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Rare Case of Epithelioid Hemangioendothelioma - A Diagnostic Challenge.

Our case highlights the 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan findings in a rare case of biopsy-proven epithelioid hemangioendothelioma (EHE) in a 66-year-old woman with multi-organ involvement (lung, liver, and bone) who was subsequently treated with palliative radiation therapy and oral pazopanib. Furthermore, follow-up 18F-FDG PET/CT findings are detailed. EHE is a rare malignant vascular neoplasm (<1% of all vascular tumors) with an epithelioid and histiocytoid appearance arising from the vascular endothelial and preendothelial cells.

Metastases to the Parotid Gland: Study from a Tertiary Care Centre.

BACKGROUND: Metastases account for 6-25% of parotid tumors, often presenting dilemmas in their diagnosis. METHODS: Parotid metastases diagnosed on histology/cytology were retrieved. MUC2, MUC5AC, androgen receptor immunohistochemistry was performed in select cases. RESULTS: Fifty-one samples were identified from 42 patients, including 14 aspirates, 7 biopsies and 30 parotidectomies. Previous history was available in 17 cases, 13 parotidectomies accompanied excision of the primary, and relevant clinical data was unavailable for 12 patients. Majority (81%) had head and neck primaries; eye and ocular adnexa were the commonest subsite (52.4%), and sebaceous carcinoma the commonest histology (33%). When history was unavailable, most metastases were initially diagnosed as poorly differentiated carcinoma/malignant tumor, or mucoepidermoid carcinoma on cytology. CONCLUSIONS: Intraparotid metastases encompass a wide spectrum, often mimicking primary salivary gland neoplasms, particularly on limited samples. Metastases should be considered when histological/cytological features are unusual; detailed clinical information and ancillary techniques aid in arriving at an accurate diagnosis.

Endocrine Mucin Producing Sweat Gland Carcinoma with Metastasis to Parotid Gland: Not as Indolent as Perceived?

Endocrine mucin-producing sweat gland carcinoma (EMPSCG) is a rare, low-grade cutaneous adnexal neoplasm with evidence of neuroendocrine differentiation, predominantly involving the eyelids of elderly. It has a striking resemblance to solid papillary carcinoma of breast which similarly displays neuroendocrine features. EMPSGC is considered a precursor of cutaneous mucinous carcinoma, and the term "mucinous carcinoma" is also recommended for hybrid lesions which reveal an invasive mucinous component associated with EMPSGC. While local recurrences are well- documented in EMPSGC, metastases had not been encountered until very recently; two reports in the past year have described metastases from eyelid EMPSGC to the parotid gland after a prolonged interval from the primary presentation. We report the case of a 78-year-old male with eyelid EMPSGC metastatic to the parotid gland nine years after excision of the primary tumor, which had initially been diagnosed as a poorly differentiated carcinoma. Development of metastasis after a prolonged interval is similar to both the previously described cases, and emphasizes the need to reevaluate the stated indolent nature of this neoplasm. It also aims to draw attention of pathologists to this uncommon tumor of the eyelid which is often misdiagnosed on primary presentation.

Multiparametric Magnetic Resonance Imaging, 68Ga Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography, and Respective Quantitative Parameters in Detection and Localization of Clinically Significant Prostate Cancer in Intermediate- and High-Risk Group Patients: An Indian Demographic Study.

OBJECTIVES: The objective of this study was to evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) and 68Ga prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET-CT) and respective quantitative parameters (Ktrans - influx rate contrast, Kep - efflux rate constant, ADC - apparent diffusion coefficient, and SUVmax ratio - prostate SUVmax to background SUVmax ratio) in detection and localization of clinically significant prostate cancer (CSPCa) in D'Amico intermediate- and high-risk group patients (prostate-specific antigen [PSA] >10 ng/ml). METHODOLOGY: The study included thirty-three consecutive adult men with serum prostate specific antigen >10ng/ml, and systematic 12 core prostate biopsy proven prostate cancer. All the 33 patients, were evaluated with mpMRI, and 68Ga PSMA PET-CT. The biopsy specimens and imaging were evaluated for 12 sectors per prostate by a predetermined scheme. RESULTS: MpMRI Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score ≥3 showed higher sensitivity than 68Ga PSMA PET-CT (96.3% vs. 82.4%), with similar specificity (54.5% vs. 54.5%) (n = 33 patients, 396 sectors). Combined use of MRI and 68Ga PSMA PET-CT in parallel increased sensitivity (99.5%) and NPV (98.7%) for detection of CSPCa and combined use of MRI and 68Ga PSMA PET-CT in series increased specificity (71.8%) and PPV (71.5%) (n = 33 patients, 396 sectors). ADC showed a strong negative correlation with Gleason score (r = -0.77), and the highest discriminative ability for detection and localization of CSPCa (area under curve [AUC]: 0.91), followed by Ktrans (r = 0.74; AUC: 0.89), PI-RADS (0.73; 0.86), SUVmax ratio (0.49; 0.74), and Kep (0.24; 0.66). CONCLUSION: MpMRI PI-RADS v2 score and 68Ga PSMA PET-CT (individually as well as in combination) are reliable tool for detection and localization of CSPCa. Quantitative MRI and 68Ga PSMA PET-CT parameters have potential to predict Gleason score and detect CSPCa.

Ocular non-teratoid medulloepithelioma with teratoid metastases in ipsilateral intraparotid lymph nodes.

PURPOSE: To describe a rare presentation of a case of intraocular non-teratoid medulloepithelioma with teratoid metastases in ipsilateral intraparotid lymph nodes. CASE DESCRIPTION: A 9-year-old male child with previous history of ciliary body non-teratoid medulloepithelioma presented with a swelling in the right pre-auricular region for 1 month. Magnetic resonance imaging and positron emission tomography-computed tomography showed a right intraparotid mass with enlarged ipsilateral cervical lymph nodes. A core biopsy was taken from the lesion, which on microscopy showed a tumor composed of small round cells arranged in cords, tubules lined by multilayered cells, and in cribriform pattern. These cells were embedded in a hypocellular, loose myxoid matrix. Based on the histopathological characteristics and previous history, a diagnosis of medulloepithelioma metastastic to ipsilateral parotid gland was made. The patient underwent right total conservative parotidectomy and bilateral neck dissection. Histopathological examination revealed metastatic medulloepithelioma in five out of eight intraparotid lymph nodes, with extranodal extension into the adjacent parotid parenchyma. Foci of hyaline cartilage were identified within the tumor, leading to a diagnosis of metastatic teratoid medulloepithelioma. CONCLUSION: Intraparotid lymph node metastases from intraocular medulloepithelioma is a rare possibility and we recommend that the parotid should be evaluated in cases of intraocular medulloepithelioma at initial presentation as well as during the follow-up period. Also, metastasis should be considered in all pediatric patients with solitary mass lesions showing unconventional histology for a primary parotid neoplasm.

Wall-mounted Versus Handheld Syringe Suction for Pediatric Bronchoalveolar Lavage: A Randomized Controlled Trial.

BACKGROUND: Bronchoalveolar lavage (BAL) via flexible bronchoscopy is a valuable diagnostic technique in children. The quality of BAL is directly related to the volume of the fluid recovered. Continuous wall suctioning and handheld syringe suctioning are the 2 commonly used methods, but they are rarely compared in children. We aimed to compare the above 2 suctioning techniques for BAL in the pediatric age group. METHODS: This randomized controlled study enrolled children from 1 month to 18 years of age undergoing flexible bronchoscopy and BAL. We compared continuous wall suctioning and the handheld syringe suctioning technique. The primary outcome was the percentage of BAL fluid recovery in 2 different suctioning techniques. Secondary outcomes included technical acceptable BAL and yield of various diagnostic tests in BAL. RESULTS: The study included 73 children (48 boys) with a median (interquartile range) age of 30 (8, 108) months. There were 37 children in the wall mount group and 36 children in the syringe suction group. Baseline characteristics of the groups were similar. The wall mount suction had more recovery of BAL fluid compared with the syringe method (43.6±8.4% vs. 37.8±8.5%, P=0.004). The proportion of BAL having a fluid recovery of ≥40% was also high in the wall mount suction [31 (83.8%) vs. 17 (47.2%); P=0.001]. There was no difference in diagnostic yield between the groups. CONCLUSION: Wall mount suction had better BAL fluid recovery compared with handheld syringe suction in children undergoing flexible bronchoscopy. The diagnostic yield was similar in both groups.

Microfilaria in urine cytology: Report of three cases with review of literature.

Lymphatic filariasis is a major public health problem in the developing countries. In India, around 90% of the cases are attributed to Wuchereria bancrofti species morphologically identified as sheathed parasites with tail tip free of nuclei. Microfilariae have been described in urine specimens from patients with chylous and achylous hematuria as well as in a spectrum of other body fluids. Case reports describe their presence in aspirates from numerous neoplasms. However, their association with urothelial carcinoma in urine sediment has been rather rare with only three cases described previously. We report three cases of filariasis in urine cytology, one of which was associated with atypical urothelial cells. Our aim is to stress on the possibility of concomitant filariasis in body fluids and aspirates with other significant findings, especially in endemic areas. Identification of the same renders complete diagnosis and proper treatment to the patient.

SMARCB1 (INI1)-deficient thyroid carcinoma: A novel entity expanding the spectrum of tumors with INI1 loss.

BACKGROUND: Biallelic loss of SMARCB1/INI1 is associated with highly aggressive malignancies, namely renal and extra-renal malignant rhabdoid tumors, and atypical teratoid/ rhabdoid tumor. Increasing availability of molecular testing and immunohistochemical stains acting as surrogate tools to genetic analysis has led to an increasing recognition of SMARCB1 loss in a variety of neoplasms. Interestingly, many of these lack the typical rhabdoid features ascribed to this group of tumors, making their identification difficult. CASE PRESENTATION: We describe the cytological, histological, immunohistochemical and molecular features of the first case of primary SMARCB1 (INI1)-deficient carcinoma of the thyroid gland in literature. The tumor was unique in various aspects; apart from never having been documented at this location, it showed extensive glandular differentiation, mimicking metastatic adenocarcinoma. CONCLUSION: Awareness of this novel entity is essential to avoid misdiagnosis, and for appropriate management, especially in an era of increased feasibility of targeted therapy.