Squamous cell carcinoma (SCC) from an unknown primary tumor (SCCUP) accounts for 2.0%-5.0% of all head and neck cancers. SCCUP presents as enlarged cervical lymph nodes without evidence of a primary tumor upon physical examination. Primary site detection is important to target treatment and avoid treatment-related morbidity. In this review, we discuss updates in SCCUP management. Diagnostic workup should focus on localization of the primary tumor in SCCUP. Initial workup centers on neck biopsy to confirm the presence of SCC. Given the increasing incidence of HPV-related SCC in the oropharynx, HPV testing is crucial. An HPV-positive status can localize the tumor to the oropharynx, a common site for occult tumors. Imaging includes neck CT and/or MRI, and PET/CT. After imaging, panendoscopy, palatine tonsillectomy or diagnostic transoral robotic surgery can facilitate high rates of primary tumor localization. Primary tumor localization influences treatments administered. SCCUP has traditionally been treated aggressively with large treatment fields to all potential disease sites, which can induce weight loss and swallowing dysfunction. As a result, primary localization can reduce radiation fields and provide possible de-escalation to primary surgical management. Advances in intensity-modulated radiation therapy and dose management also have the potential to improve functional outcomes in SCCUP patients. Given the improved prognosis associated with HPV-positive SCCs, HPV tumor status may also inform future treatment de-intensification to reduce treatment-related toxicity.

Background

Cytomegalovirus (CMV) infection can be asymptomatic in healthy individuals but may cause serious complications in immunocompromised patients. We investigated the clinicopathological correlation of CMV in gastrointestinal (GI) biopsies at our institute between January 1, 2013 and December 31, 2015.

Methods

A total of 105 non-neoplastic GI biopsies tested positive for CMV by immunohistochemistry (IHC). The IHC results were stratified as "true positive" if > 2 cells stained, or "rare positive" if only 1 - 2 cells stained. Clinical information including comorbidities, serum CMV viral loads, and treatment was reviewed and correlated.

Results

Overall 1% of all GI biopsies were positive for CMV by immunostaining. The most frequently involved organ was colon, followed by esophagus, stomach, ileum and duodenum. When > 2 cells were stained positive, serum CMV viral loads were positive in 52.2%, negative in 17.2%, and not tested in 27.6% of cases. When only 1 - 2 cells stained positive, CMV viral loads were positive in 23.4%, negative in 25.5%, and not tested in 51.1% of cases. We further showed that clinical management of CMV differs based on both pathological findings and underlying diseases.

Conclusions

The role of CMV in GI biopsies remains controversial. We propose an algorithm of performing CMV immunostaining based on clinicopathological correlation.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by xanthogranulomatous infiltration of foamy histiocytes frequently involving bone and other organ systems. We herein report a unique case of ECD discovered incidentally in an explanted liver in a 65-year-old male with end-stage liver disease secondary to hepatitis C cirrhosis. Histological examination and immunohistochemical studies in the explanted liver revealed prominent foamy histiocytes that were CD68 positive, but CD1a and S100 negative. Mutational hotspot analysis of the explanted liver using a panel of 47 most common cancer-related genes performed by next generation sequencing (NGS) revealed likely somatic mutations in the PDGFRA, PTEN, and HNF1A genes, but no BRAF codon 600 mutations were detected. The bone marrow showed similar findings as in the liver. Whole body PET and bone scans demonstrated increased heterogeneous uptake in bilateral humeral and femoral diaphysis, most compatible with ECD. To our knowledge, this is the first case report of ECD that involves mainly bone marrow and liver with novel genomic alterations. Our case highlights the diversity and complexity of this disease entity and the importance of multi-modality approach integrating clinical and radiologic features with histopathologic and molecular/genomic findings.

We present a case of intussusception with complete small bowel obstruction caused by intestinal anisakidosis requiring surgical resection. A 30-year-old man presented with acute onset of severe abdominal pain 3 days after eating home-cured salmon gravlax. Despite surgery, the patient developed recurrent abdominal pain on two occasions with evidence of continued inflammation proximal to the surgical anastomosis. He was then treated with albendazole and prednisone, and symptoms improved. A decision was made to prophylactically treat two asymptomatic family members who also consumed home-cured gravlax with albendazole, resulting in one individual passing an intact Anisakis worm in her stool. We suggest that albendazole therapy could be considered as a therapy for continued symptoms of anisakidosis and postexposure prophylaxis of Anisakis larvae ingestion from a common source.

Abstract

There are reports of AA amyloidosis associated with intravenous and/or subcutaneous injection of street drugs, such as heroin and cocaine. Most reports describe patients with substance use disorder, renal amyloidosis and concurrent viral infections, such as hepatitis and/or human immunodeficiency virus. Herein, we present a case of systemic AA amyloidosis and sepsis in a 34-year-old woman with a history of intravenous injection of oral prescription medications (as evidenced by excipient lung disease) who had no known history of human immunodeficiency virus nor of hepatitis B or C. Our case shows the broader spectrum of pathology that can occur with the misuse of prescription medications.

Background

Malignant mesothelioma (MM) arises from mesothelial cells that line the pleural, peritoneal and pericardial surfaces. The majority of MMs are pleural and have been associated with asbestos exposure. Previously, pleural MMs have been genetically characterized by the loss of BAP1 (40-60%) as well as loss of NF2 (75%) and CDKN2A (60%). The rare peritoneal form of MM occurs in ~10% cases. With only ~300 cases diagnosed in the US per year, its link to asbestos exposure is not clear and its mutational landscape unknown.

Methods

We analyzed the somatic mutational landscape of 12 peritoneal MM of epitheloid subtype using copy number analysis (N = 9), whole exome sequencing (N = 7) and targeted sequencing (N = 12).

Results

Peritoneal MM display few copy number alterations, with most samples having less than 10 Mbp total changes, mostly through deletions and no high copy number amplification. Chromosome band 3p21 encoding BAP1 is the most recurrently deleted region (5/9), while, in contrast to pleural MM, NF2 and CDKN2A are not affected. We further identified 87 non-silent mutations across 7 sequenced tumors, with a median of 8 mutated genes per tumor, resulting in a very low mutation rate (median 1.3 10(-6)). BAP1 was the only recurrently mutated gene (N = 3/7). In one additional case, loss of the entire chromosome 3 leaves a non-functional copy of BAP1 carrying a rare nonsense germline variant, thus suggesting a potential genetic predisposition in this patient. Finally, with targeted sequencing of BAP1 in 3 additional cases, we conclude that BAP1 is frequently altered through copy number losses (N = 3/12), mutations (N = 3/12) or both (N = 2/12) sometimes at a sub-clonal level.

Conclusion

Our findings suggest a major role for BAP1 in peritoneal MM susceptibility and oncogenesis and indicate important molecular differences to pleural MM as well as potential strategies for therapy and prevention.

Background & aims

The association between quantity of liver fat and the presence of metabolic syndrome needs to be assessed systematically. We aimed to determine the association between the quantity of liver fat and the presence of the metabolic syndrome in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), independent of nonalcoholic steatohepatitis (NASH).

Methods

We recruited 146 patients with well-characterized biopsy-proven NAFLD and 50 individuals without NAFLD (controls) to participate in a case-control study at the NAFLD Translational Research Unit at the University of California San Diego. Liver fat was quantified in patients with NAFLD and controls using an advanced magnetic resonance imaging-based biomarker, the proton-density-fat-fraction (MRI-PDFF). Patients with NAFLD were divided into groups based on whether they were above or below the median MRI-PDFF value (15.4% in patients with NAFLD); the MRI-PDFF value for controls was less than 5%. The primary outcome was the presence of the metabolic syndrome using Adult Treatment Panel III criteria without and with adjustment for the presence of NASH.

Results

Compared with NAFLD patients with MRI-PDFF values below the median, and compared with controls, NAFLD patients with MRI-PDFF values above the median were more likely to have abdominal obesity (P < .0001), lower levels of high-density cholesterol (P < .0001), higher levels of triglycerides (P < .0001), and higher fasting glucose levels (P < .001). Compared with NAFLD patients with MRI-PDFF values below the median, NAFLD patients with MRI-PDFF above the median were more likely to have the metabolic syndrome (60.3% vs. 44.4%; P < .04), independent of biopsy-detected NASH.

Conclusions

Increased liver fat content in patients with NAFLD is associated with increased rates of the metabolic syndrome, independent of NASH. There appears to be an association between the quantity of liver fat and the risk for cardiovascular disease in patients with NAFLD.

Background. Ectopic fat deposition in the pancreas and its relationship with hepatic steatosis and insulin resistance have not been compared between patients with nonalcoholic fatty liver disease (NAFLD) and healthy controls. Aim. Using a novel magnetic resonance imaging (MRI) based biomarker, the proton-density-fat-fraction (MRI-PDFF), we compared pancreatic fat content in patients with biopsy-proven NAFLD to healthy controls and determined whether it is associated with insulin resistance and liver fat content. Methods. This nested case-control study was derived from two prospective studies including 43 patients with biopsy-proven NAFLD and 49 healthy controls who underwent biochemical testing and MRI. Results. Compared to healthy controls, patients with NAFLD had significantly higher pancreatic MRI-PDFF (3.6% versus 8.5%, P value <0.001), and these results remained consistent in multivariable-adjusted models including age, sex, body mass index, and diabetes (P value =0.03). We found a strong correlation between hepatic and pancreatic MRI-PDFF (Spearman correlation, P = 0.57, P value <0.001). Participants with increased insulin resistance determined by homeostatic-model-of-insulin-resistance (HOMA-IR) greater than 2.5 had higher pancreatic (7.3% versus 4.5%, P value =0.015) and liver (13.5% versus 4.0%, P value <0.001) MRI-PDFF. Conclusion. Patients with NAFLD have greater pancreatic fat than normal controls. Insulin resistance is associated with liver and pancreatic fat accumulation.

Objective

The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD).

Subjects and methods

In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed.

Results

CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all).

Conclusion

Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD.

Inflammatory pseudotumor (IPT), also known as plasma cell granuloma, is a rare lesion of unknown etiology that occurs in many organs, especially in the lung. Here we report five cases of IPT arising in pulmonary artery mimicking chronic thromboembolic disease, not previously documented in the literature. Those cases were identified at our institute among over 2500 pulmonary endarterectomy (PEA) specimens acquired from 2000 to 2017. The cohort included three men and two women with a median age of 41 years (range: 23-54). All patients presented with dyspnea and radiologic findings of pulmonary artery thromboembolism, some concerning for intimal sarcoma. The duration between disease onset and PEA ranged from 6 months to approximately 3 years. Histologically, all cases showed proliferation of spindle cells with marked inflammatory infiltrates composed predominantly of plasma cells, histiocytes, and small lymphocytes. Ancillary studies were performed in each case and ruled out other possibilities, such as sarcoma, lymphoma, plasmacytoma, IgG4-related disease, and infection. IPT arising in pulmonary artery presenting clinically as acute or chronic thromboembolic disease is very unusual, in which clinical data, radiographic findings, and histopathologic features have to be integrated for reaching the proper diagnosis.