Aaron R. Huber

PD-1 Inhibitor Gastroenterocolitis Case Series and Appraisal of “Immunomodulatory Gastroenterocolitis”

PD‐1 inhibitors facilitate immune response against certain tumour types, including melanoma. These drugs have led to prolonged survival but can also result in autoimmune‐type side effects, including gastrointestinal inflammation. The histopathological effects of this medication class have not been well studied.

Benign fibroblastic polyps of the colon.

Benign fibroblastic polyps of the colon are a recently described entity among mucosal polyps found in the colorectum. These polyps are typically discovered on routine screening colonoscopy within the distal colon. Benign fibroblastic polyps occur most commonly in adult women in the sixth decade of life. Histologically, benign fibroblastic polyps are bland spindle cell lesions that fill the lamina propria and displace the surrounding crypts. The spindle cell proliferation lacks atypia and significant mitotic activity. Hyperplastic changes are frequently present both in the adjacent epithelium and within the lesions. Immunohistochemically, the cells of benign fibroblastic polyps are invariably positive for vimentin with rare focal positivity for CD34 and smooth muscle actin. They are negative for CD117 and S100 protein. Ultrastructurally, benign fibroblastic polyps have features of fibroblastic differentiation. These polyps are benign with no reports, to our knowledge, of recurrence or metastasis.

High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7

BackgroundCarbonic anhydrase IX (CA9) is a transmembrane glycoprotein related to hypoxia. Increased CA9 expression has been associated with decreased survival and cancer progression and has been targeted as a potential therapy for several cancers, including esophageal cancer. The reported percentages of expression of CA9 in esophageal adenocarcinoma vary, and CA9 expression in precancerous esophageal lesions has not been well studied.MethodsIn this study, we investigated CA9 expression in esophageal cancers and in precancerous lesions and explored the association of CA9 expression with prognostic factors and with stem cell and tumorigenesis-related markers including BMI1, cyclin E, ki67, MCM4 and MCM7 expression. Previously constructed tissue microarrays consisting of samples of 7 tissue types (columnar cell metaplasia, Barrett esophagus, low- and high-grade dysplasia, esophageal adenocarcinoma, squamous epithelium, and squamous cell carcinoma) were used for the immunostaining of CA9, BMI1, cyclin E, Ki67, MCM4 and MCM7.Results and discussionCA9 high expression occurred more frequently in glandular mucosa with or without dysplasia than in squamous epithelium or squamous cell carcinoma. Survival duration of esophageal adenocarcinoma did not significantly differ between patients with high CA9 expression and those with low expression. High CA9 expression is significantly associated with BMI1, cyclin E, Ki67, MCM4 and MCM7 expression.ConclusionsHigh CA9 expression may be related to the acidic environment caused by gastroesophageal reflux disease in the gastroesophageal junction and associated with tumorigenesis through BMI1, MCM4 and MCM7.

Focal Osseous Dysplasia

Focal osseous dysplasia (FOD) is one of the benign fibro-osseous lesions of the jaw bones and the most commonly occuring benign fibro-osseous lesion. This entity occurs more commonly in females and has a predilection for African Americans. Radiographically, the lesion has a variable appearance depending on the duration but may appear as a radiolucent to radiopaque lesion that can be well to poorly defined. Hisotologically, when biopsied, there are fragments of bony trabeculae intermixed with fibrous stroma with incomplete stromal vasculature. The main differential diagnosis is with ossifying fibroma, which is neoplastic while FOD is considered a reactive process. Most patients with FOD may be followed clinically without surgical intervention.

Cholestatic Liver Injury Associated With Dietary Supplements: A Report of Five Cases in Active Duty Service Members

The use of dietary supplements (DS) is common in the active duty population, often without physician knowledge or approval. DS have been associated with drug-induced liver injury, with rare cases resulting in liver failure or death. We report five cases of transient drug-induced liver injury temporally associated with the use of a total of six DS in active duty service members. All patients presented with elevated serum bilirubin and liver-associated enzymes: three patients had a cholestatic liver enzyme pattern, one had a hepatocellular pattern, and one had a mixed pattern. In all cases, percutaneous needle core biopsies of the liver were obtained and demonstrated a cholestatic pattern of injury with variable periportal fibrosis. Causality was considered highly probable for three cases, probable for one case, and possible for one case. Hepatotoxicity has been previously associated with four of the supplements in our cases. For the two remaining supplements, C4 Extreme and Animal Stak, we are unaware of any previous reports of hepatotoxicity. Health care professionals, in particular military physicians, should be aware of the potential risk of these supplements and be prepared to discuss these risks with their patients.

Elastotic Lesions of Intestinal Subserosal Fat: Report of Two Cases

We report 2 unusual elastotic lesions of intestinal subserosal fat. The first arose in the small bowel subserosa of a 64-year-old woman with volvulus. It was undetected macroscopically and consisted of a relatively circumscribed focus of elastosis, with essentially no evidence of fibrosis or blood vessel walls within. The second arose in the subserosa of the sigmoid colon in a 46-year-old woman with recurrent diverticulitis. It was also undetected macroscopically and consisted of a well-circumscribed nodule of elastic fibers surrounding prominent veins and arteries. Both patients had unremarkable postoperative courses. These lesions likely represent localized response to injury and are probably underrecognized.

Accuracy of vascular invasion reporting in hepatocellular carcinoma before and after implementation of subspecialty surgical pathology sign-out

Context: Liver cancers (including hepatocellular carcinoma [HCC] and cholangiocarcinoma) are the fifth most common cause of cancer death. The most powerful independent histologic predictor of overall survival after transplantation for HCC is the presence of microscopic vascular invasion (VI). Aims: Given that VI is known to have somewhat high interobserver variability in both HCC and other tumors, we hypothesized that pathologists with special interest and training in liver pathology would be more likely to identify and report VI in HCC than would general surgical pathologists. Settings and Design: We searched our departmental surgical pathology archives for transplant hepatectomies performed for HCC. Subjects and Methods: We identified 143 such cases with available sign-out reports and hematoxylin and eosin-stained slides. Statistical Analysis Used: Kappa results (level of agreement) were calculated. Results: Before surgical pathology subspecialty sign-out (SSSO) implementation, 49 of 88 HCC cases were reported as negative for VI; on rereview, 20 of these had VI. After SSSO implementation, 39 of 55 cases were reported as negative for VI; on our review, 8 of these had VI. Kappa (agreement) between general SO and subspecialty rereview was 0.562 (95% confidence interval [CI] = 0.411–0.714) “weak agreement.” Kappa (agreement) between SSSO and rereview by select liver pathologists was 0.693 (95% CI = 0.505–0.880) “moderate agreement.” Conclusions: Our study is one of only a few so far that have suggested improved accuracy of certain parameters under SSSO.

Clinicopathologic Findings of Intestinal Perineuromas of the Colon-an Institutional Experience of 78 Cases

Intestinal perineuromas (IPs) are a relatively recently described, under-recognized, mixed epithelial-mesenchymal lesion that can clinically present as a polypoid lesion on screening colonoscopy. Since they are frequently associated with epithelial polyps (hyperplastic polyps, sessile serrated adenomas/polyps), an overlooked diagnosis of an additional spindle component could possibly lead to IPs potentially being underreported. Distinguishing this entity from other spindle cell neoplasms of the gastrointestinal tract is also important. We present the largest case series of IPs to our knowledge, confirming that they are often left-sided and only rarely occur in the absence of an epithelial component. Increased awareness of IPs among gastroenterologists and pathologists and a heightened approach of examining the underlying stroma of epithelial serrated polyps will lead to better recognition of these benign polypoid lesions.

Heterotopic Respiratory Mucosa in the Rectum: An Unusual Type and Site of Heterotopia in the Gastrointestinal Tract

Although pancreatic and gastric heterotopias are common findings in the gastrointestinal tract, heterotopic respiratory mucosa (HRM) in the rectum is extremely rare and has only been reported twice previously. We are presenting, to our knowledge, the third case of HRM in the rectum. A 56-year-old man with a history of chronic diarrhea presented for diagnostic colonoscopy, where he was found to have a rectal subepithelial nodule. He was subsequently referred to a tertiary medical center for further evaluation with rectal endoscopic ultrasound. Endoscopically, the nodule was hypoechoic, 2 to 3 mm in size, located in the submucosa, and did not appear to invade the muscularis propria. An uncomplicated endoscopic submucosal resection was subsequently performed. Microscopically, the nodule showed a multicystic complex lesion located in the submucosa, lined by ciliated pseudostratified columnar epithelium and surrounded by thin to moderately thick smooth muscle bundles and multiple lobules of seromucinous glands. There was associated acute and chronic inflammation. The rectum overlying the subepithelial lesion was lined by congested and edematous colonic mucosa and demonstrated no connection with the underlying cystic lesion. Immunohistochemical stains showed positive p63 basal cell staining in the respiratory epithelium of the lesion, while CDX2, TTF-1, and estrogen receptors were all negative. HRM is a benign nonneoplastic lesion with unclear etiology. Pathologists and gastroenterologists should be aware of this entity and consider it in their differential diagnosis for a subepithelial nodule in the rectum, keeping in mind that neoplastic processes can also develop in this location.

The Great Imitator: Syphilis Presenting as an Inflammatory Pseudotumor of Liver

A married 64-year-old male presented with poor appetite, malaise, diarrhea, rectal bleeding, and 15-pound weight loss. He later developed a macular rash on the palms, soles, and chest, which was thought to represent a drug reaction. Imaging studies including computed tomography (CT) and positron emission tomography were performed, the latter showing hypermetabolic lesions including 2 left lower lobe pulmonary nodules, multiple hepatic lesions (up to 3 cm), and focal uptake in the rectum/anus. CT-guided liver biopsy was performed for evaluation of presumed lung cancer with liver metastases. The needle biopsy showed a dense lymphoplasmacytic infiltrate with admixed myofibroblasts and epithelioid histiocytes in a background of collagenized stroma (Figure 1A and B). There were focal areas of perineural plasma cell infiltration (Figure 1C) and abscesses. No well-formed granulomas were seen. The background liver showed dense plasmacellular and neutrophilic sinusoidal infiltrates as 745665 IJSXXX10.1177/1066896917745665International Journal of Surgical PathologyDeRoche and Huber research-article2017