Germline genetic contribution to the immune landscape of cancer.

Understanding the contribution of the host's genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling. Common variants of IFIH1, TMEM173 (STING1), and TMEM108 were associated with differential interferon signaling and variants mapping to RBL1 correlated with T cell subset abundance. Pathogenic or likely pathogenic variants in BRCA1 and in genes involved in telomere stabilization and Wnt-ß-catenin also acted as immune modulators. Our findings provide evidence for the impact of germline genetics on the composition and functional orientation of the tumor immune microenvironment. The curated datasets, variants, and genes identified provide a resource toward further understanding of tumor-immune interactions.

Monoarticular carcinomatous knee joint arthritis as an initial presentation of cervical carcinoma.

When it comes to cancer, one can expect the unexpected. The clinical presentations can be very bizarre. One of these uncommon presentations is monoarticular arthritis. The age group affected by cancer and arthritis are similar. However, the possibility of joint pain being secondary to metastatic involvement does not come to mind easily. In this report, a 65-year-old postmenopausal woman presented with complaint of pain and restricted movement of the right knee joint, in whom the clinical and magnetic resonance imaging features were suggestive of infective monoarthritis. However, synovial fluid aspirate showed presence of malignant cells. Hence, patient was evaluated with whole-body (18)F-fluorodeoxyglucose positron emission tomography computed tomography which detected primary malignancy of the cervix with regional nodal and right knee joint metastasis. To our knowledge, this is the first reported case of cervical malignancy with solitary skeletal metastasis involving the knee joint. The report also discusses overall incidence of malignant arthritis.

18-Fluorine-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in the Evaluation of the Great Masquerader Melioidosis: A Case Series.

Melioidosis is an emerging infectious disease in India. The disease has a crippling effect on the patient owing to its widespread dissemination and complications post bacteremia. The role of 18-fluorine-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is becoming increasingly important in terms of documenting the extent of disease and response to treatment. Herein, we present cases of two patients who were referred for a whole-body 18F-FDG PET-CT scan with a history of long-standing fever that went undiagnosed. 18F-FDG PET-CT scan was performed to evaluate pyrexia of unknown origin. A conclusion was reached after blood culture which showed the growth of Burkholderia pseudomallei - which is considered to be the cause of this rare but debilitating disease.

Silicone Implant Incompatibility Syndrome: Mimicking Metastases on Fluoro-Deoxy-Glucose Positron Emission Tomography-Computed Tomography in a Treated Case of Carcinoma Breast.

Silicone implant incompatibility syndrome (SIIS) has been identified as a cause of systemic symptoms such as lymphadenopathy, myalgia, and dyspnea in patients with silicone implants. We present a case of 76-year-old female patient, treated for carcinoma left breast with mastectomy and silicone breast implant, chemotherapy, and radiotherapy 42 years ago. There was a history of implant rupture and removal 2 years ago. The patient presented with right axillary swelling and dyspnea. 18-fluorine fluoro-deoxy-glucose positron emission tomography/computed tomography (F-18 FDG PET-CT) showed mildly FDG-avid left anterior chest wall and right rectus abdominis deposits, multiple lymph nodes, and low-grade FDG-avid pneumonitis changes in both lungs. Biopsy from the chest wall and rectus abdominis deposit was negative for malignancy and revealed foamy histiocytes and foreign-body giant cell reaction, indicative of SIIS. SIIS is a mimic for metastases and should be considered as a differential diagnosis in FDG PET-CT interpretation in patients with silicone breast implant.

A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-ß Superfamily.

We present an integromic analysis of gene alterations that modulate transforming growth factor ß (TGF-ß)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-ß signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-ß ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-ß superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-ß signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-ß superfamily.

Diagnostic importance of contrast enhanced (18)F-fluorodeoxyglucose positron emission computed tomography in patients with tumor induced osteomalacia: Our experience.

AIMS AND OBJECTIVES: To assess the diagnostic utility of contrast-enhanced (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-ceCT) in localization of tumors in patients with clinical diagnosis of tumor-induced osteomalacia (TIO), in correlation with histopathological results. MATERIALS AND METHODS: Eight patients (five male and three female) aged 24-60 (mean 42) years with a clinical diagnosis of TIO were included in this prospective study. They underwent whole body (head to toe) FDG PET-ceCT following a standard protocol on Philips GEMINI TF PET-CT scanner. The FDG PET-ceCT results were correlated with postoperative histology findings and clinical follow-up. RESULTS: All the patients had an abnormal PET-ceCT study. The sensitivity of PET-ceCT was 87.5%, and positive predictive value was 100%. The tumor was located in the craniofacial region in 6/8 patients and in bone in 2/8 patients. Hemangiopericytoma was the most common reported histology. All patients underwent surgery, following which they demonstrated clinical improvement. However, one patient with atypical findings on histology did not show any clinical improvement, hence, underwent (68)Gallium-DOTANOC PET-ceCT scan for relocalization of the site of the tumor. CONCLUSION: The tumors causing TIO are small in size and usually located in obscure sites in the body. Hence, head to toe protocol should be followed for FDG PET-ceCT scans with the inclusion of upper limbs. Once the tumor is localized, regional magnetic resonance imaging can be performed for better characterization of soft tissue lesion. Imaging with FDG PET-ceCT plays an important role in detecting the site of the tumor and thereby facilitating timely management.

Contrast-enhanced [18F] fluorodeoxyglucose-positron emission tomography-computed tomography as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin.

BACKGROUND: To evaluate the advantages of contrast enhanced F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-contrast enhanced CT [CECT]) when used as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin (MUO). MATERIALS AND METHODS: A total of 243 patients with fine needle aspiration cytology/biopsy proven MUO were included in this prospective study. Patients who were thoroughly evaluated for primary or primary tumor was detected by any other investigation were excluded from the analysis. Totally, 163 patients with pathological diagnosis of malignancy but no apparent sites of the primary tumor were finally selected for analysis. The site of probable primary malignancy suggested by PET-CECT was confirmed by biopsy/follow-up. RESULTS: PET-CECT suggested probable site of primary in 128/163 (78.52%) patients. In 30/35 remaining patients, primary tumor was not detected even after extensive work-up. In 5 patients, where PET-CECT was negative, primary was found on further extensive investigations or follow-up. The sensitivity, specificity, positive predictive value and negative predictive value of the study were 95.76%, 66.67%, 88.28% and 85.71% respectively. CONCLUSIONS: F-18 FDG PET-CECT aptly serves the purpose of initial imaging modality owing to high sensitivity, negative and positive predictive value. PET-CECT not only surveys the whole body for the primary malignancy but also stages the disease accurately. Use of contrast improves the diagnostic utility of modality as well as help in staging of the primary tumor. Although benefits of using PET-CECT as initial diagnostic modality are obvious from this study, there is a need for a larger study comparing conventional methods for diagnosing primary in patients with MUO versus PET-CECT.