Pulmonary Mucoepidermoid Carcinoma Mimicking Carcinoid Lung on 18 F-FDG and 68 Ga-DOTANOC PET/CT.

ABSTRACT: Pulmonary mucoepidermoid carcinoma (PMEC) is a rare pulmonary neoplasm. Although 18 F-FDG PET/CT has been shown to present with increased metabolic activity in PMEC, literature does not report increased somatostatin receptor expression in these tumors. We present the case of a 15-year-old boy where PMEC mimicked a typical carcinoid of the lung on DOTANOC PET/CT by showing significant uptake on 68 Ga-DOTANOC.

99mTechnetium-Ubiquicidin Scan with Single-Photon Emission Computed Tomography/Computed Tomography in Skull Base Osteomyelitis.

Malignant otitis externa (MOE) with skull base osteomyelitis (SBO) is an aggressive infection that predominantly affects elderly, diabetic, or immunocompromised patients, and is associated with high disease-specific mortality. Pseudomonas aeruginosa is the most isolated microorganism. External otitis associated with granulation tissue and pain is the most common presenting feature; a biopsy is obtained to rule out malignancy. A proper consensus is lacking regarding the best imaging modality for early initial diagnosis and follow-up. 99mTechnetium (99mTc)-labeled ubiquicidin (UBI) 29-41 is a bacterial attaching peptide that does not bind to activated leukocytes. We report a case of SBO initially misdiagnosed as a chronic otitis media, but later proved to be a case of MOE. 99mTc methylene diphosphonate bone scan and 99mTc-UBI 29-41 scan with single-photon emission computed tomography/computed tomography scans were performed to corroborate the clinical diagnosis. SBO remains a great challenge due to its increasing prevalence and high morbidity are difficult to diagnose and are often confused with cholesteatoma and neoplastic process. The UBI scan could be an auxiliary noninvasive diagnostic alternative in early diagnosis.

Unusual Male Breast Involvement in Burkitt Lymphoma Detected on Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Burkitt lymphoma (BL) is a poorly differentiated, aggressive form of B-cell non-Hodgkin's lymphoma. The clinical presentation of this disease is varied and may be nodal, extranodal, or both. BL of the breast, either primary or secondary, with bilateral breast involvement, is extremely rare. Herein, we present a case of BL in a 27-year-old male with unusual bilateral breast involvement.

Multi-time point imaging in 99m Tc-pertechnetate scintigraphy of ectopic gastric mucosa in duplication cysts: value-added services.

OBJECTIVES: The aim of our study was to describe the scintigraphic patterns of 99m Tc-pertechnetate uptake in patients who were referred to the department of nuclear medicine for evaluating and diagnosing ectopic gastric mucosa in foregut and midgut duplication cysts. MATERIALS AND METHODS: This hospital-based, retrospective cum prospective research spans a period of 8 years from April 2014 to January 2022. Previous hospital medical records were analyzed and subsequently, a database was prepared which included the age, sex, clinical indication of a 99m Tc-pertechnetate scan, and the planar and SPECT-computed tomography (CT) imaging findings. Postoperative histopathological reports were available for 21 patients. Dynamic and planar static imaging was performed. We included SPECT-CT in suspected duplication cysts to increase the sensitivity and specificity which is a tradeoff for a small amount of additional radiation exposure. A total of 69 patients were subjected to a 99m Tc-pertechnetate scan for suspected foregut or midgut duplication cysts. All were subjected to dynamic planar and delayed static images up to 24 h or until focal uptake of radiotracer was noted which corroborated the anatomical findings, whichever was earlier. SPECT-CT was performed along with the planar study in 31 patients which confirmed the findings. Previously performed CT scans were used for anatomical correlation in the remaining ones. RESULTS: Duplication cysts were localized in a total of 28 patients (19 foregut duplication cysts and 12 small bowel duplications - 3 patients had dual duplication cysts, both foregut, and midgut). Forty-one patients had no scintigraphic evidence of ectopic gastric mucosa. Of these 69 patients, histopathological diagnosis was available for 21 patients (22 lesions). The report was concordant with the scan findings in 15 patients (16 lesions) and 6 patients showed discordance in histopathological diagnosis and scan findings. CONCLUSION: In conclusion, multi-time point imaging is the key to diagnosing ectopic gastric mucosa of various sizes and in various locations. An abnormal radiotracer uptake in dynamic sequences, even before the appearance of the stomach in the region of the small bowel is indicative of intestinal duplication, and delayed radiotracer visualization in the region of the thorax is characteristic of intrathoracic foregut duplication cyst.

Single HER2-positive tumor cells are detected in initially HER2-negative breast carcinomas using the DEPArray™-HER2-FISH workflow.

BACKGROUND: In breast cancer (BC), overexpression of HER2 on the primary tumor (PT) is determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) to stratify samples as negative, equivocal and positive to identify patients (pts) for anti-HER2 therapy. CAP/ASCO guidelines recommend FISH for analyzing HER2/neu (ERBB2) gene amplification and for resolving equivocal HER2 IHC results. However, pre-analytical and analytical aspects are often confounded by sample related limitations and tumor heterogeneity and HER2 expression may differ between the PT and circulating tumor cells (CTCs), the precursors of metastasis. We used a validation cohort of BC patients to establish a new DEPArray™-PT-HER2-FISH workflow for further application in a development cohort, characterized as PT-HER2-negative but CTC-HER2/neu-positive, to identify patients with PT-HER2 amplified cells not detected by routine pathology. METHODS: 50 µm FFPE tumor curls from the validation cohort (n = 49) and the development cohort (n = 25) underwent cutting, deparaffinization and antigen retrieval followed by dissociation into a single-cell suspension. After staining for cytokeratin, vimentin, DAPI and separation via DEPArray™, single cells were processed for HER2-FISH analysis to assess the number of chromosome 17 and HER2 loci signals for comparison, either with available IHC or conventional tissue section FISH. CTC-HER2/neu status was determined using the AdnaTest BreastCancer (QIAGEN, Hilden, Germany). RESULTS: Applying CAP/ASCO guidelines for HER2 evaluation of single PT cells, the comparison of routine pathology and DEPArray™-HER2-FISH analysis resulted in a concordance rate of 81.6% (40/49 pts) in the validation cohort and 84% (21/25 pts) in the development cohort, respectively. In the latter one, 4/25 patients had single HER2-positive tumor cells with 2/25 BC patients proven to be HER2-positive, despite being HER2-negative in routine pathology. The two other patients showed an equivocal HER2 status in the DEPArray™-HER2-FISH workflow but a negative result in routine pathology. Whereas all four patients with discordant HER2 results had already died, 17/21 patients with concordant HER2 results are still alive. CONCLUSIONS: The DEPArray™ system allows pure tumor cell recovery for subsequent HER2/neu FISH analysis and is highly concordant with conventional pathology. For PT-HER2-negative patients, harboring HER2/neu-positive CTCs, this approach might allow caregivers to more effectively offer anti-HER2 treatment.

Lower Gastrointestinal Bleed Playing Hide and Seek.

A 13-year-old adolescent male presented with an episode of rectal bleed. He has had five such episodes in the past year where he witnessed black tarry stools mixed with fresh blood, painless, not associated with fever or hematemesis. Clinical examination revealed pallor and a soft, non-tender abdomen. Vitals were stable. Blood investigations revealed haemoglobin of 102g/L, WBC count of 10 X 109/L and platelet count of 165 × 109/L. The clotting screen was normal. Upper GI endoscopy and colonoscopy revealed no abnormality. The patient underwent Tc-99m pertechnetate scintigraphy to look for Meckel's Diverticulum in view of painless lower GI bleed.

Multiparametric liquid biopsy analysis in metastatic prostate cancer.

Molecular profiling of prostate cancer with liquid biopsies, such as circulating tumor cells (CTCs) and cell-free nucleic acid analysis, yields informative yet distinct data sets. Additional insights may be gained by simultaneously interrogating multiple liquid biopsy components to construct a more comprehensive molecular disease profile. We conducted an initial proof-of-principle study aimed at piloting this multiparametric approach. Peripheral blood samples from men with metastatic castrate-resistant prostate cancer were analyzed simultaneously for CTC enumeration, single-cell copy number variations, CTC DNA and matched cell-free DNA mutations, and plasma cell-free RNA levels of androgen receptor (AR) and AR splice variant (ARV7). In addition, liquid biopsies were compared with matched tumor profiles when available, and a second liquid biopsy was drawn and analyzed at disease progression in a subset of patients. In this manner, multiparametric liquid biopsy profiles were successfully generated for each patient and time point, demonstrating the feasibility of this approach and highlighting shared as well as unique cancer-relevant alterations. With further refinement and validation in large cohorts, multiparametric liquid biopsies can optimally integrate disparate but clinically informative data sets and maximize their utility for molecularly directed, real-time patient management.

Reference Size Matching, Whole-Genome Amplification, and Fluorescent Labeling as a Method for Chromosomal Microarray Analysis of Clinically Actionable Copy Number Alterations in Formalin-Fixed, Paraffin-Embedded Tumor Tissue.

Cancer genome copy number alterations (CNAs) assist clinicians in selecting targeted therapeutics. Solid tumor CNAs are most commonly evaluated in formalin-fixed, paraffin-embedded (FFPE) tissue by fluorescence in situ hybridization. Although fluorescence in situ hybridization is a sensitive and specific assay for interrogating preselected genomic regions, it provides no information about coexisting clinically significant copy number changes. Chromosomal microarray analysis is an alternative DNA-based method for interrogating genome-wide CNAs in solid tumors. However, DNA extracted from FFPE tumor tissue produces an essential, yet problematic, sample type. The College of American Pathologists/American Society of Clinical Oncology guidelines for optimal tumor tissue handling, published in 2007 for breast cancer and in 2016 for gastroesophageal adenocarcinomas, are lacking for other solid tumors. Thus, cold ischemia times are seldom monitored in non-breast cancer and non-gastroesophageal adenocarcinomas, and all tumor biospecimens are affected by chemical fixation. Although intended to preserve specimens for long-term storage, formalin fixation causes loss of genetic information through DNA damage. Herein, we describe a reference size matching, whole-genome amplification, and fluorescent labeling method for FFPE-derived DNA designed to improve chromosomal microarray results from suboptimal nucleic acids and salvage highly degraded samples. With this technological advance, whole-genome copy number analysis of tumor DNA can be reliably performed in the clinical laboratory for a wide variety of tissue conditions and tumor types.

Striatal "function-metabolism" mismatch on F-18 FDG/F-18 FDOPA PET/CT.

Decrease in gray matter metabolism following cranial irradiation has been documented, but the functional relevance of this finding has not been documented. This case of "function-metabolism" mismatch in the striatum following radiation for a grade III frontoparietal glioma demonstrates that the down-regulation of glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography/computed tomography is associated with preservation of presynaptic dopaminergic function by the striatal neurons which was demonstrated on a correlative l-3,4-dihydroxy-6-F-flurophenylalanine (F-18 FDOPA) study. The reversibility of this down-regulation is demonstrated in a follow-up scan further proving that there is no neurodegeneration involved.

Minimum diagnostic criteria for plasmablastic lymphoma of oral/sinonasal region encountered in a tertiary cancer hospital of a developing country.

BACKGROUND: Haematolymphoid tumours other than plasmablastic lymphoma (PBL) may reveal plasmablastic differentiation with overlapping immunoreactivity causing diagnostic dilemma. Elaborate ancillary diagnostic techniques can make the process expensive, tedious and out of reach for pathology laboratory in a developing country. METHODS: Out of 98 total cases of primary non-Hodgkin's lymphoma and plasmacytoma of oral-sinonasal region recorded in our institute over 4 years, 39 cases showing varied plasmablastic differentiation were selected. Morphological and immunohistochemical criteria were applied to identify minimum diagnostic criteria for PBL. Human Immunodeficiency Virus (HIV) correlation and Epstein-Barr virus expressed RNA (EBER) in-situ hybridisation studies were also performed. RESULTS: Minimum morphological criteria required to diagnose PBL were: (1) predominant population of plasmablasts which are large monomorphic cells with high nuclear-cytoplasmic ratio, moderate amount of amphophilic cytoplasm and round nucleus with prominent central nucleolus, (2) high mitotic and/or apoptotic index and (3) absence of neoplastic plasma cells in the background. Essential diagnostic immunophenotype consisted of CD20 negativity, LCA +/-, CD138/VS38c diffuse positivity, light chain restriction and high MIB-1 index (>60 %). Twenty-five of the total 32 PBL cases thus identified, involved oral cavity. Of these, 84% affected gingivo-buccal complex. Twenty-eight cases were HIV positive. EBER positivity confirmed the diagnosis in all the HIV-negative cases. CONCLUSIONS: A triad of 'rapidly growing lesion with predilection for oral mucosa, classical plasmablastic morphology and limited immunohistochemical panel' can render a reliable diagnosis of PBL, irrespective of HIV and EBV status, especially in developing countries with limited resources.