The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.¹.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.¹.

Background and aims

Prompt and accurate differentiation of benign and malignant strictures in primary sclerosing cholangitis (PSC) is crucial. ERCP with brush cytology, the most common modality to achieve this, is hindered by a low diagnostic yield. Cholangioscopy can overcome this limitation by establishing a visual diagnosis based on the characteristic morphologic features of cholangiocarcinoma (CCA) and can aid in targeted biopsies of suspicious lesions. However, its role in PSC remains unclear. This case series demonstrates the performance of the latest generation of single-operator cholangioscope for this indication.

Methods

A single experienced endoscopist performed cholangioscopy for PSC cases referred for ERCP.

Results

Cholangioscopies of patients 1 to 3 demonstrate the features of extrahepatic duct dominant strictures (DS) and the cholangioscopic maneuvers undertaken in these cases, including advancement across the DS after balloon dilation, biopsy of the DS, and electrohydraulic lithotripsy of impacted stones. Cholangioscopies of patients 4 to 6 demonstrate the varied features of CCA ranging from focal stricture with tumor vessels, papillary frond-like projections, and features of an intraductal papillary biliary neoplasm. Also shown are the radiographic and histopathologic features of the disease.

Conclusions

Cholangioscopy allowed us to identify morphologic features of both malignancy and benign disease in PSC in the setting of extrahepatic duct strictures, and we were able to obtain adequate targeted tissue samples for histopathologic confirmation.

Background and aims

Cholangioscopy is useful in establishing a visual diagnosis of cholangiocarcinoma (CCA), but this is harder to achieve in primary sclerosing cholangitis (PSC) because of the stricture-forming nature of the disease. Furthermore, it can be harder to differentiate malignant from benign features of the underlying inflammation. This case series demonstrates the varied features of nonmalignant inflammatory findings in PSC.

Methods

A single experienced endoscopist performed cholangioscopy for PSC cases referred for ERCP.

Results

Cholangioscopy in these 5 cases without CCA demonstrated the features of acute and chronic inflammation, acute inflammatory mass, dominant stricture, acute cholangitis in a duct with features of chronic inflammation with a large pigmented stone, and fibrostenotic disease. Cholangioscopic maneuvers such as advancement across strictures after balloon dilation, targeted mucosal biopsy, and electrohydraulic lithotripsy (EHL) of impacted stones are demonstrated. The relevant radiographic and histopathologic features of the disease accompany each case description. Regarding long-term prognosis, 1 case of acute inflammatory mass and a case of worsening liver function required a liver transplant evaluation, whereas the other 3 cases remain stable.

Conclusions

Cholangioscopic features of benign disease in PSC are varied. Knowledge of these features is essential in differentiating between benign and malignant findings. These features, combined with biopsy and cytology evaluation, can help in tailoring management in patients with benign PSC.

Abdominal ascites is most commonly caused by portal hypertension from liver cirrhosis. When present, portal hypertension is associated with an elevated serum-ascites albumin gradient (SAAG) ≥1.1 g/dL. In contrast, a SAAG < 1.1 g/dL suggests malignancy, tuberculosis, pancreatitis, or nephrotic syndrome. Here, we present a case of low SAAG ascites caused by epithelioid peritoneal mesothelioma in a woman with no known liver disease. The diagnosis proved elusive until diagnostic laparoscopy with biopsy was performed.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.¹.

A common problem in the assessment of Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors is distinguishing tumor from non-tumor. This is because background stromal lymphocytes, entrapped non-neoplastic glands, and the delicate vascular network characteristic of neuroendocrine tumors frequently contain a subset of proliferating cells. Furthermore, in small biopsies, crush and cautery artifact can alter the morphologic appearance of tumor cells, making the Ki67 proliferative index more difficult to assess. To address these issues, we developed a synaptophysin-Ki67 double stain using a commercially available immunohistochemistry kit, allowing simultaneous visualization of tumor and proliferating nuclei. To test this method, three gastrointestinal pathologists individually graded 50 gastrointestinal neuroendocrine tumors first using synaptophysin-Ki67 double-stained slides and then, after a washout period, using Ki67-only stained slides (along with routine hematoxylin- and eosin-stained slides). Interobserver agreement on Ki67 proliferative index was moderate using the Ki67-only stained slides (intraclass correlation 0.51, 95% confidence interval: 0.35-0.66) and improved using the synaptophysin-Ki67 double stain (intraclass correlation 0.79, 95% confidence interval: 0.69-0.86). Similarly, interobserver agreement on tumor grade was fair with Ki67-only stained slides (κ=0.39, P<0.001) and improved with the double stain (κ=0.58, P<0.001). Analysis of individual pathologists' scores revealed that fewer total number of tumor cells counted correlated with higher grade designation and appeared to contribute to grade discordance. In tumors cited as particularly challenging to assess by the pathologists, three of four tumors were grade discordant with the Ki67-only stain, whereas all four tumors were grade concordant with the synaptophysin-Ki67 stain. The synaptophysin-Ki67 double stain is the first technique to address specifically the histomorphologic challenges of evaluating Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors. Although further validation is needed, this study provides evidence that the synaptophysin-Ki67 double stain can improve interobserver agreement.

We have identified 8 cases of gastritis characterized by the presence of purple to black granular deposits in the superficial mucosa associated with marked reactive epithelial changes. In each case, the patient had taken OsmoPrep, a tablet form of sodium phosphate used for bowel preparation just before upper endoscopy and had undergone concurrent colonoscopy. Endoscopic findings ranged from normal gastric mucosa to severe inflammation, congestion, and friability. No other gastrointestinal sites were noted to contain the deposits or show similar mucosal injury. On initial histologic review, the deposits raised the differential diagnosis of elemental iron and mucosal calcinosis. However, none of the patients was noted to be taking iron supplements, and none had a history of renal disease or other cause of calcium dysmetabolism. Histochemical stains revealed the deposits were negative on Perls' iron stain (8/8 cases), positive on von Kossa stain (7/8 cases), and negative on Alizarin Red stain (8/8 cases)-a histochemical profile compatible with sodium phosphate but inconsistent with mucosal calcium. A crushed OsmoPrep tablet was subjected to processing and demonstrated similar histologic features and histochemical profile. In addition, biopsies of 20 consecutive patients who did not take OsmoPrep and who underwent concurrent endoscopy and colonoscopy were reviewed, and no deposits with similar histochemical profile were identified. In summary, we have characterized a unique form of gastritis associated with OsmoPrep use. Attention to clinical history and use of a select panel of histochemical stains allow for accurate diagnosis.

The hallmark of nonalcoholic steatohepatitis is hepatocellular inflammation and injury in the setting of hepatic steatosis. Recent work has indicated that dynamic ¹⁸F-FDG PET with kinetic modeling has the potential to assess hepatic inflammation noninvasively, while static FDG-PET is less promising. Because the liver has dual blood supplies, kinetic modeling of dynamic liver PET data is challenging in human studies. This paper aims to identify the optimal dual-input kinetic modeling approach for dynamic FDG-PET of human liver inflammation. Fourteen patients with nonalcoholic fatty liver disease were included. Each patient underwent 1 h dynamic FDG-PET/CT scan and had liver biopsy within six weeks. Three models were tested for kinetic analysis: the traditional two-tissue compartmental model with an image-derived single-blood input function (SBIF), a model with population-based dual-blood input function (DBIF), and a new model with optimization-derived DBIF through a joint estimation framework. The three models were compared using Akaike information criterion (AIC), F test and histopathologic inflammation score. Results showed that the optimization-derived DBIF model improved liver time activity curve fitting and achieved lower AIC values and higher F values than the SBIF and population-based DBIF models in all patients. The optimization-derived model significantly increased FDG K₁ estimates by 101% and 27% as compared with traditional SBIF and population-based DBIF. K₁ by the optimization-derived model was significantly associated with histopathologic grades of liver inflammation while the other two models did not provide a statistical significance. In conclusion, modeling of DBIF is critical for dynamic liver FDG-PET kinetic analysis in human studies. The optimization-derived DBIF model is more appropriate than SBIF and population-based DBIF for dynamic FDG-PET of liver inflammation.

Dynamic ¹⁸F-FDG PET with tracer kinetic modeling has the potential to noninvasively evaluate human liver inflammation using the FDG blood-to-tissue transport rate K ₁. Accurate kinetic modeling of dynamic liver PET data and K ₁ quantification requires the knowledge of dual-blood input function from the hepatic artery and portal vein. While the arterial input function can be derived from the aortic region on dynamic PET images, it is difficult to extract the portal vein input function accurately from PET images. The optimization-derived dual-input kinetic modeling approach has been proposed to overcome this problem by jointly estimating the portal vein input function and FDG tracer kinetics from time activity curve fitting. In this paper, we further characterize the model properties by analyzing the structural identifiability of the model parameters using the Laplace transform and practical identifiability using computer simulation based on fourteen patient datasets. The theoretical analysis has indicated that all the kinetic parameters of the dual-input kinetic model are structurally identifiable, though subject to local solutions. The computer simulation results have shown that FDG K ₁ can be estimated reliably in the whole-liver region of interest with reasonable bias, standard deviation, and high correlation between estimated and original values, indicating of practical identifiability of K ₁. The result has also demonstrated the correlation between K ₁ and histological liver inflammation scores is reliable. FDG K ₁ quantification by the optimization-derived dual-input kinetic model is promising for assessing liver inflammation.