Mitochondrial DNA copy number variation across human cancers.

Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA copy number variation across 22 tumor types profiled by The Cancer Genome Atlas project. We observe a tendency for some cancers, especially of the bladder, breast, and kidney, to be depleted of mtDNA, relative to matched normal tissue. Analysis of genetic context reveals an association between incidence of several somatic alterations, including IDH1 mutations in gliomas, and mtDNA content. In some but not all cancer types, mtDNA content is correlated with the expression of respiratory genes, and anti-correlated to the expression of immune response and cell-cycle genes. In tandem with immunohistochemical evidence, we find that some tumors may compensate for mtDNA depletion to sustain levels of respiratory proteins. Our results highlight the extent of mtDNA copy number variation in tumors and point to related therapeutic opportunities

Prosthetic Valve Thrombosis: Diagnosis and Management.

St. Jude mechanical prosthesis is the most commonly used prosthetic device with least valvular complications with excellent hemodynamics. However, prosthetic valve thrombosis is one of the serious complications, with rates between 0.03% and 0.13% per patient-year depending on the type of anticoagulation used and compliance to the therapy. Transthoracic echocardiography (TTE) is the initial screening tool (class I) that would provide clues for the assessment of valvular hemodynamics. Fluoroscopy is an alternate imaging modality for the assessment of mechanical leaflet motion, especially in patients when prosthetic valves are difficult to image on TTE or transesophageal echocardiography. A complete fluoroscopic evaluation of a prosthetic valve includes assessment of valvular motion and structural integrity. Opening and closing angles can be measured fluoroscopically to determine whether a specific valve is functioning properly. We discuss a case of a 91-year-old man with thrombosis of bileaflet mechanical mitral prosthesis that was demonstrated on real-time fluoroscopy (not evident on TTE). An algorithmic approach to diagnosis and management of prosthetic heart valve thrombosis is outlined

Renal vein tumor thrombus from metastatic anal gland adenocarcinoma

A 62-year-old female with a history of anal gland adenocarcinoma presents with metastatic disease to the kidney with renal vein tumor thrombus extending into the inferior vena cava (IVC). Metastatic disease to the kidney with renal vein tumor thrombus is extremely rare with only several cases described in the literature. We present the first reported case of metastatic anal gland adenocarcinoma to the kidney with renal vein tumor thrombus. Keywords: Tumor thrombus, Renal vein, Anal gland adenocarcinoma, Metastasi

Risk factors of laryngeal cryptococcosis: A case report

Cryptococcal infections are acquired by inhalation of encapsulated yeast cells or basidiospores. While Cryptococcus has a propensity to invade the lungs and central nervous system, other sites can be affected. Laryngeal cryptococcosis is rare with less than 30 previously reported cases, which commonly occurred in apparently immunocompetent hosts on inhaled corticosteroids. We present a case of laryngeal cryptococcosis with a long-term inhaled corticosteroid use, co-infection of pulmonary Mycobacterium avium-intracellulare, and mannose-binding lectin deficiency. Keywords: Cryptococcosis, Larynx, Endobronchial, Corticosteroid, Mycobacterium avium-Intracellulare (MAI), Mannose-binding lectin deficienc

Synchronous Bone Metastasis From Multiple Myeloma and Prostate Adenocarcinoma as Initial Presentation of Coexistent Malignancies

The radiographic appearance of bone metastases is usually determined by tumor histology and can be osteolytic, osteoblastic, or mixed. We present a patient with coexistent bone metastasis from multiple myeloma and prostate adenocarcinoma who exhibited synchronous bone involvement of both histologies within the same bone lesion, a rare phenomenon that has not been previously reported and led to atypical radiographic findings. The radiograph of a 71-year-old man with thigh swelling and pain demonstrated a lytic femoral lesion. Magnetic resonance imaging (MRI) confirmed a destructive process, but showed coexistent metaphyseal sclerosis. Multiple myeloma was suspected by demonstration of monoclonal gammopathy and confirmed by computed tomography (CT)-guided biopsy. Incidentally, CT demonstrated areas of sclerosis corresponding to T2 hypointensity on MRI. Further studies revealed osteoblastic spinal metastasis, prostate enhancement on CT and prostate-specific antigen (PSA) level of 90 ng/mL, concerning for concomitant prostate neoplasm. After endoprosthetic reconstruction, pathology of the femur identified both plasma cell neoplasm and metastatic prostate adenocarcinoma. An association between prostate cancer and multiple myeloma is hypothesized due to tumor microenvironment similarities and possible common genetic variations, however, coexisting bone metastases have never been reported. This unusual finding explains the discrepant imaging features in our patient and is evidenced that certain clinical situations merit contemplation of atypical presentations of common malignancies even if this leads to additional testing

Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma

While genomic sequencing routinely identifies oncogenic alterations for the majority of cancers, many tumors harbor no discernable driver lesion. Here, we describe the exceptional molecular phenotype of a genomically quiet kidney tumor, clear cell papillary renal cell carcinoma (CCPAP). In spite of a largely wild-type nuclear genome, CCPAP tumors exhibit severe depletion of mitochondrial DNA (mtDNA) and RNA and high levels of oxidative stress, reflecting a shift away from respiratory metabolism. Moreover, CCPAP tumors exhibit a distinct metabolic phenotype uniquely characterized by accumulation of the sugar alcohol sorbitol. Immunohistochemical staining of primary CCPAP tumor specimens recapitulates both the depletion of mtDNA-encoded proteins and a lipid-depleted metabolic phenotype, suggesting that the cytoplasmic clarity in CCPAP is primarily related to the presence of glycogen. These results argue for non-genetic profiling as a tool for the study of cancers of unknown driver