Oncofetal protein IMP3, a new cancer biomarker.

IMP3 is a member of a family of RNA-binding proteins that consists of IMP1, IMP2 and IMP3. These proteins contain 2 RNA recognition motifs and 4 K-homology domains that allow them to bind RNAs strongly and specifically. IMP3 is an oncofetal protein involved in embryogenesis and its expression is associated with a number of malignant neoplasms. IMP3 is associated with aggressive and advanced cancers and is specifically expressed in malignant tumors but is not found in adjacent benign tissues. Moreover, in vitro studies have shown that IMP3 promotes tumor cell proliferation, adhesion, and invasion. This review focuses on the studies of IMP3 expression in different cancers and emphasizes the potential utility of IMP3 in routine surgical pathology practice. We also discuss IMP3 as a prognostic biomarker for cancer patients' outcomes.

Unresectable Metastatic Solid Pseudopapillary Pancreatic Neoplasm Treated With Liver Transplantation.

We present a 49-year-old woman requiring living donor liver transplantation after liver metastasis from a pancreatic solid pseudopapillary tumor. After identifying a pancreatic mass and liver lesions, she underwent extensive surgical resection. Pathology revealed a solid pseudopapillary neoplasm of the head and body of the pancreas, extending into the peripancreatic soft tissues and confirmed to have spread to the liver. Subsequently, she underwent adjuvant chemotherapy and radiofrequency ablations of the new liver lesions. Despite immunotherapy and chemotherapy, there was a progression of the lesions. With interval growth of liver lesions, without evidence of extrahepatic disease, she underwent living donor liver transplantation.

Hepatitic Variant of Graft-vs-Host Disease.

OBJECTIVES: Graft-vs-host disease (GVHD) of the liver is a complication of allogeneic hematopoietic stem cell transplantation with hepatitic and classic variants. We determined the percentage of hepatitic variant cases, compared clinicopathologic features of the two groups, and assessed prognostic factors. METHODS: Fifty liver biopsy specimens from 40 patients with GVHD were studied. RESULTS: Fifteen (30%) cases had moderate to marked lobular inflammation and were classified as a hepatitic variant. Bile duct damage was present in all cases. Ductular reaction, apoptosis. and endotheliitis were more commonly seen in the hepatitic variant. Hepatocyte ballooning was an independent poor prognostic factor. The median aspartate aminotransferase and alanine aminotransferase were higher in the hepatitic variant while alkaline phosphatase and bilirubin were higher in the classic group. Forty (80%) GVHD cases were more than 100 days after transplant, correlating to immunosuppression taper. There was response to treatment with increased immunosuppression in both groups, but time to normalization of liver function tests was higher in the hepatitic variant. CONCLUSIONS: Bile duct damage was the most consistent pathologic finding in our cohort and was present in all cases of GVHD. Moderate to marked lobular inflammation can be seen in GVHD in up to 30% of cases without any other coexisting cause. Hepatocyte ballooning is an independent poor prognostic factor.

Diagnosis of Focal Nodular Hyperplasia (FNH) after Liver Transplantation.

Following liver transplantation (LT), recipients can develop benign and malignant hepatic masses just like any other patient. Patients transplanted for hepatocellular carcinoma (HCC) undergo surveillance imaging, and any new mass seen on imaging must be carefully evaluated to rule out recurrent cancer. Focal nodular hyperplasia (FNH) is a benign tumor of the liver that most often occurs in women and is rarely symptomatic. It is important to distinguish FNH from more serious etiologies, such as recurrent HCC and other malignancies, since the treatments differ greatly. To date, there have been very few reports of FNH occurring in a liver allograft. We present a case of a patient with a history of a carcinoid tumor who underwent LT for HCC. Several years posttransplant, the patient was found to have a liver mass with classic features of HCC on imaging. The liver biopsy revealed the unexpected diagnosis of FNH. This finding avoided unnecessary treatment for HCC, which is associated with morbidity, especially in the posttransplant setting. We present our diagnostic approach, discuss the clinicopathologic and imaging findings of FNH, and review the literature on FNH in the posttransplant setting.

The diagnostic value of FNA biopsy in grading pancreatic neuroendocrine tumors.

BACKGROUND: There has been much controversy regarding the accuracy of grading pancreatic neuroendocrine tumors (PNETs) on fine-needle aspiration (FNA) biopsy. The objectives of this study were to evaluate whether grading according to the fraction of Ki-67-positive tumor cells (the Ki-67 proliferation index) on material from endoscopic ultrasound-guided FNA biopsies correlated with grading on surgical resection specimens and to evaluate the minimum amount of FNA material needed. METHODS: A case series of 27 PNETs with FNA biopsies and corresponding surgical resection specimens at the authors' institution were evaluated. Tumors were graded on FNA and surgical specimens with an evaluation of Ki-67 index according to 2010 World Health Organization criteria. Chart reviews were conducted to evaluate recurrence or clinical progression in patients who were being managed conservatively with observation. RESULTS: The evaluation of grading between FNA and tumor resection specimens revealed that 22 of 26 FNA specimens (84.6%) had Ki-67 results comparable to those in the corresponding surgical resection specimens, thus allowing for accurate grading. Correct FNA diagnosis with the ability to distinguish between grade 1 and 2 tumors had a positive predictive value of 88.9%, with 72.7% sensitivity, 93.3% specificity, and a P value of .00081. In addition, 24 of 26 cases contained less than 2000 cells, of which 20 were correctly graded on FNA material. Seven of 26 FNA samples had less than 1000 cells, of which 6 were correctly graded, including 2 that had only 50 cells. CONCLUSIONS: The current results exhibit good correlation between FNA grade and final grade on surgical resection specimens using Ki-67 index, even in samples with less than the recommended total cell count. Therefore, grading of PNETs on FNA with the Ki-67 proliferation index should be assessed and is a practical parameter to report to clinicians. Cancer Cytopathol 2018;126:170-8. © 2017 American Cancer Society.

Inflammatory fibroid polyp of the gastric antrum presenting as hypovolemic shock: Case report and literature review.

Inflammatory fibroid polyps (IFP) are an extremely rare entity that arise within the submucosa of the gastrointestinal tract, and represent less than 0.1% of all gastric polyps. They are most commonly localized to the gastric antrum, small intestines and recto-sigmoid colon. IFPs are most commonly found incidentally upon endoscopic evaluation in the absence of symptoms. Presenting symptoms depend on the location of the tumor, although polyps located in the stomach most commonly present with epigastric pain and early satiety. Classic histologic features include perivascular onion skinning of spindle cells with an abundance of eosinophilic infiltration. The prompt diagnosis and management of IFP is essential due to its underlying risk for intussusception, outlet obstruction and acute hemorrhage. In addition, recent evidence has shown that IFP is driven by an activating mutation in the platelet derived growth factor receptor alpha (PDGFRA) gene, suggesting a neoplastic etiology. Herein, we discuss a case of a 65-year-old woman with an inflammatory fibroid polyp of the gastric antrum who initially presented with early hypovolemic shock and melena. Diagnosis was made by endoscopic visualization, biopsy and immunohistochemical analysis.

A 66-Year-Old Man With a Past History of Relapsing Polychondritis Presented With Right Upper Lobe Consolidation, Nodular Airway Lesions, and a Corticosteroid-Responsive Chronic Cough.

A 66-year-old male nonsmoker from Arizona was referred to our practice for evaluation of chronic cough. He had a history of biopsy-proven relapsing polychondritis manifesting as right auricular and nasal pain and swelling 9 months prior to presentation. The onset of his cough coincided with the diagnosis of relapsing polychondritis, and he was prescribed prednisone 90 mg/d, which promptly relieved his rheumatologic and respiratory symptoms. A chest radiograph, obtained prior to the initiation of therapy, was normal. Any attempts at decreasing the dose of the glucocorticoid to < 30 mg/d resulted in recurrence of the cough but not of the auricular or nasal symptoms. A second chest radiograph done 6 months before presentation, while the patient was receiving prednisone 20 mg/d, was normal as well. In anticipation of our evaluation, he stopped all glucocorticoids for 7 days. He was not receiving any other medications, and he had no history of an atopic diathesis.

Chronic nicotine exposure during adolescence differentially influences calcium-binding proteins in rat anterior cingulate cortex.

We have recently shown that chronic amphetamine exposure selectively up-regulates parvalbumin (PV) calcium-binding proteins in the anterior cingulate cortex (ACC). In this study, we evaluated the effects of chronic nicotine (NIC) exposure on PV, calbindin D28k (CB) and calretinin (CR) calcium-binding protein immunostaining in ACC GABAergic interneurons. Chronic NIC exposure for 3 weeks in adolescent rats, either via drinking water (the oral group) or by twice daily subcutaneous injections (the injection group), resulted in the expression of high levels of CR proteins in the ACC but not in the parietal cortex. Larger increases in the density of CR-immunoreactive (ir) neurons were noted in the NIC-injected rats at 0-day withdrawal (45% increase) compared with the oral group (26% increase). The larger increases in CR-ir neuron density in the NIC-injected rats were also reflected by prominent CR-ir processes across cortical layers. The density of PV-ir neurons was also increased (37%) at 0-day withdrawal but only in the oral NIC group and no changes in CB-ir neuron density were observed in either NIC group. Combined dual-immunofluorescence and confocal microscopy revealed that somatodendritic alpha4 nicotinic acetylcholine receptors colocalized with cortical neurons stained positively for CR, PV or CB. These results suggest that CR- and/or PV-ir-containing GABA interneurons may be involved in channeling the effects of NIC in the ACC, which is closely associated with the ventral basal ganglia circuit that is linked to brain reward function.