Kurt B. Schaberg

Immunohistochemical analysis of lichenoid reactions in patients treated with anti-PD-L1 and anti-PD-1 therapy.

Recent advances in the immunotherapeutic treatment of cancer have led to the development of multiple new directed therapies including monoclonal antibodies that block the immune checkpoint T‐cell receptor programmed death 1 (PD‐1) and the PD‐1 ligand, programmed death ligand 1 (PD‐L1). Various immune‐related toxicities have been associated with these drugs including, most commonly, skin rashes.

Intraductal Papillary Mucinous Neoplasms Often Contain Epithelium From Multiple Subtypes and/or Are Unclassifiable.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are subclassified into gastric, intestinal, pancreatobiliary, and oncocytic subtypes based on histologic features. The WHO classification scheme suggests use of immunohistochemical stains to help subtype IPMNs with ambiguous histology. Seventy-two pancreatic IPMN resections between 2008 and 2014 were retrospectively evaluated. Immunohistochemistry for CDX2, MUC2, and MUC5AC was performed on cases where the histologic subtype could not be determined on routine hematoxylin and eosin (H&E) sections. There were 41 gastric (57%), 8 intestinal (11%), 4 pancreatobiliary (6%), and 1 oncocytic (1%) IPMNs. Eighteen (25%) IPMNs were either unclassifiable due ambiguous morphology or contained distinct epithelium from >1 subtype (ie, “mixed”). Two IPMNs initially unclassifiable strictly by H&E morphology were definitively classified as intestinal after positive immunohistochemical staining with CDX2, MUC2, and MUC5AC. Immunohistochemistry for another 7 IPMNs unclassifiable by H&E did not indicate a clear subtype and often contained discordant results (eg, discordant CDX2 and MUC2 staining). In our experience, a considerable number of IPMNs are either unclassifiable or contain epithelium from >1 subtype. Furthermore, among those IPMNs initially unclassifiable by H&E morphology, application of immunohistochemical stains to aid in subtyping allow for definite classification in only a small subset of cases. These data, when taken in context with the significant ranges in the reported prevalence of specific histologic subtypes, suggest that accurate IPMN subtyping is poorly reproducible in up to 25% of cases, and in these problematic cases, immunohistochemistry adds little value.

Locally Advanced Intrahepatic Cholangiocarcinoma: Complete Pathologic Response to Neoadjuvant Chemotherapy Followed by Left Hepatic Trisectionectomy and Caudate Lobectomy

A 67-year-old man was initially evaluated for progressive right upper quadrant pain of several months duration. He denied jaundice, acholic stools, nausea, vomiting, or pruritus. Past medical history included prostate cancer, cholelithiasis, appendicitis, hyperlipidemia, chronic lower back pain, mild hypertension, mild asthma, and gastroesophageal reflux disease. Past surgical history included prostatectomy, cholecystectomy, and appendectomy. Family history was remarkable for a brother with prostate cancer and a sister with breast cancer. The patient had a remote history of smoking and alcohol abuse. Physical examination revealed right upper quadrant tenderness but no hepatosplenomegaly. He had mild central obesity, but no stigmata of cirrhosis. Initial laboratory findings (complete blood count and comprehensive metabolic panel) were unremarkable. Computed tomography (CT) revealed a dominant 8.5-cm left-sided liver lesionwith a satellite lesionmeasuring 3.7 cm. There was tumor thrombus into the left portal vein extending into the main portal vein (Fig. 1). Multiple enlarged regional lymph nodes were present in the porta hepatis and in the gastrohepatic ligament. Positron emission tomography (PET) displayed fluorodeoxyglucose (FDG) avidity in the liver tumor and in the lymph nodes, but no uptake at other sites. Core needle biopsy of the liver mass was consistent with adenocarcinoma (Fig. 1), with immunostaining suggestive of intrahepatic cholangiocarcinoma (ICC). Due to the presence of vascular invasion and extensive regional lymphadenopathy, the patient was referred for neoadjuvant chemotherapy. He initially received four cycles of gemcitabine and oxaliplatin q14 days. Subsequent CT scan revealed slight interval growth of the hepatic lesion. Regional lymph nodes remained unchanged. Consequently, the patient was switched to gemcitabine and cisplatin chemotherapy. After five cycles of gemcitabine and cisplatin q21 days, CT scan demonstrated a profound radiographic response: The dominant lesion decreased to 4.5 cm, and the satellite lesion decreased to 2.7 cm (Fig. 2). The tumor thrombus retracted off themain portal vein into the left portal vein. Regional lymph nodes also decreased in size. The patient subsequently underwent a left hepatic trisectionectomy, caudate lobectomy, and porta hepatis lymphadenectomy. He had an uncomplicated postoperative course. He was discharged on postoperative day 6. Formal pathologic analysis of the surgical specimen demonstrated fibrosis without any evidence of viable tumor cells in the primary tumor, satellite tumor, or the porta hepatis lymph nodes (Fig. 2). Surgical margins were negative for treated tumor. The patient remains alive with no evidence of disease 6 months after surgery, based on physical exam, tumor markers, and CT scan (Fig. 3).

Adenovirus Hepatitis: Clinicopathologic Analysis of 12 Consecutive Cases From a Single Institution

Adenoviruses are common pathogens that usually cause self-limited infections. However, in the immunocompromised host they can cause severe infections involving multiple organs including the liver. A search of the pathology database at Stanford University Medical Center (1995 to 2016) identified 12 cases of adenovirus hepatitis including biopsy and autopsy specimens. There were 8 pediatric patients, 7 of which had received orthotropic liver transplants and 1 of which was receiving chemotherapy for lymphoblastic leukemia. There were 4 adult patients, of which 1 was actively receiving chemotherapy for chronic lymphocytic leukemia and 2 had undergone hematopoietic stem cell transplantation for hematologic malignancies. One patient had lymphoplasmacytic lymphoma and had received chemotherapy over a year prior but was not receiving therapy at the time he contracted adenovirus hepatitis. In all cases, histologic sections showed nonzonal coagulative hepatocyte necrosis and characteristic intranuclear inclusions. Hepatocyte necrosis ranged from spotty to massive. The majority of cases (7/12; 58%) had no associated inflammation. If present, inflammation was focal and lymphohistiocytic. In 1 case, findings were focal within the liver, requiring an image-guided biopsy. This patient underwent a simultaneous nontargeted liver biopsy that lacked histologic evidence of adenovirus. Among the pediatric patients, 63% (5/8) died secondary to organ failure, while there was 100% (4/4) mortality in the adult population.

Factors contributing to suboptimal rates of childhood vaccinations in Vermont

Childhood immunizations are invaluable in preventing contagious diseases. Nonetheless, vaccines have become increasingly controversial with growing numbers of caregivers refusing to vaccinate their children. The percentage of fully vaccinated children in Vermont is one of the lowest nationally. This study set out to determine Vermont caregivers’ attitudes toward immunizations to better explain why the percentage of fully vaccinated children has fallen in Vermont. A survey regarding caregivers’ health care knowledge about children, their vaccination concerns, and their children’s vaccination status was sent to participants in the Vermont Women, Infants and Children’s Program from two districts. In total, 83% (n = 379) of respondents reported their children received all recommended vaccinations for their age. Respondents who considered themselves highly knowledgeable regarding their children’s health care and confident about the safety of vaccinations were significantly associated with reporting their children as being current on vaccinations and with their intent to continue vaccinations. Respondents indicated highest concern regarding the safety and number of vaccinations administered during one visit. Primary care providers were indicated as important resources for addressing concerns about vaccinations and health care knowledge of children. The results help to understand low vaccination rates in Vermont and can be used for targeting health campaigns to improve vaccination rates.

Feeling the Impact of Long-Term Total Parenteral Nutrition

A 21-year-old male, with known short bowel syndrome (42 cm jejunum with colon, no ileocecal valve) secondary to surgical therapy of mid-jejunal atresia and total parenteral nutrition (TPN) dependence, was evaluated in the Emergency Department with a one-day history of acute, severe, epigastric pain. He reported no nausea, vomiting, or diarrhea. His past medical history was significant for multiple abdominal surgeries (jejunal atresia repair, tapering jejunoplasty following stricture at the jejuno-colonic anastomosis), cholelithiasis (Fig. 1a), infections of central venous catheters, small bowel bacterial overgrowth, and acute pancreatitis. His medications included calcium carbonate, cholecalciferol, ciprofloxacin, fluticasone, loperamide, multivitamins, omega 3-6-9 fatty acids, potassium chloride, rifaximin, and ferrous sulfate. On examination, the patient was afebrile and had normal vital signs and abdominal examination. Laboratory values were notable for lipase 20 U/L, total bilirubin 1.6 mg/dL, AST 57 U/L, ALT 63 U/L, and alkaline phosphatase 244 U/L. Abdominal ultrasound revealed a 1.9-cm non-obstructing gallstone near the neck of the gallbladder, without common bile duct (CBD) dilation at 6 mm. After receiving hydromorphone and a ‘‘GI Cocktail’’ (antacid, viscous lidocaine, and anticholinergic), his pain improved, and he was discharged to home. The next day, he developed severe abdominal pain only minimally improved with medications. He was admitted and shortly thereafter became febrile. He was placed on piperacillin and tazobactam and vancomycin due to concern for ascending cholangitis. On hospital day 2, total bilirubin peaked at 4.2 mg/dL, he grew two forms of Escherichia coli from his central venous catheter, and he was switched to meropenem. On hospital day 3, he developed fluid-responsive hypotension, which was also treated with low-dose norepinephrine. A repeat abdominal ultrasound, with the patient changing positions, identified that the stone was immobile (Fig. 1b). Magnetic resonance cholangiopancreatography (MRCP) showed an impacted gallstone within the gallbladder neck with mass effect on the adjacent CBD, but no evidence of intrahepatic duct dilation (Fig. 2). Stent placement via endoscopic retrograde cholangiopancreatography (ERCP) with cholecystectomy versus immediate surgery was discussed. A joint decision was made by the pediatric surgical and gastroenterological services to proceed directly to laparoscopic surgery. At laparoscopy, it took 45 min to find the gallbladder, due to adhesions from previous operations. Eventually, the gallbladder was freed; after opening the fundus to identify the cystic duct, a cholangiogram identified that there were no stones in the CBD. A large stone was identified in the gallbladder that was externally compressing the CBD. Surgical findings and pathology results were consistent with the diagnosis of Mirizzi syndrome, Type I (Fig. 3). Postoperatively, the patient was intermittently febrile overnight while & Zachary M. Sellers zsellers@stanford.edu

Antisecretory medication is associated with decreased Helicobacter pylori detection in gastric marginal zone lymphoma.

Helicobacter pylori status influences the prognosis and management of gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), so accurate determination of H pylori status is of clinical importance. The low rate of histologic H pylori positivity among gastric MALT lymphoma cases at our institution prompted investigation for possible causes. A case series of 24 patients as having gastric MALT lymphoma (with no diffuse large B-cell component) in a tertiary care setting between 1997 and 2010 was identified, and clinical records were reviewed. Immunohistochemical staining for H pylori and BCL10 was performed. This study received institutional review board approval (protocol number M13-033). Thirty-nine percent of cases (9/23) were H pylori positive by histology, and 4 additional patients had positive serologic results; overall, 57% of cases (13/23) were positive for H pylori. Treatment with antisecretory medications was associated with a lower likelihood of histologic positivity (13% among treated patients vs 75% among untreated; P = .04). Nuclear localization of BCL10 was seen in 2 cases and was not associated with H pylori status. Antisecretory medications decrease the likelihood of histologic detection of H pylori in gastric MALT lymphoma cases. Incorporation of results of serologic or other testing is needed to ensure correct classification with respect to H pylori status.