Publications by authors named "Dora Lam-Himlin"

67 Publications

Exogenous copper exposure causing clinical wilson disease in a patient with copper deficiency.

BMC Gastroenterol 2021 Jul 8;21(1):278. Epub 2021 Jul 8.

Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA.

Background: Human Swayback is a disease characterized by acquired copper deficiency which primarily manifests as myeloneuropathy. Common causes include malabsorptive disorders, gastric surgery, total parenteral nutrition and excessive zinc intake. In contrast, copper supplementation should be closely monitored as excessive doses can lead to acute intoxication and in chronic cases, cirrhosis. Copper derangements are rare, however it is important to consider them due to potential severe complications.

Case Presentation: We present a middle-aged man who had been previously diagnosed with Human Swayback after presenting with various neurological symptoms. The patient was subsequently placed on copper supplementation. A decade later, he was referred to our hospital for liver transplant evaluation due to new diagnosis of decompensated end-stage liver disease after an abdominal surgery. His initial workup was suggestive of Wilson disease-subsequent ATP7B gene was negative. Ultimately, the patient underwent liver transplantation; liver explant was significant for a copper dry weight concentration of 5436 mcg/g.

Conclusions: Human Swayback is a very rare copper-related disease which deserves awareness due to its potential irreversible health effects in the human body. Additionally, in patients who require copper supplementation, serial levels should be monitored to ensure adequate copper levels.
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http://dx.doi.org/10.1186/s12876-021-01859-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265109PMC
July 2021

RNA-Seq Reveals Differences in Expressed Tumor Mutation Burden in Colorectal and Endometrial Cancers with and without Defective DNA-Mismatch Repair.

J Mol Diagn 2021 05 4;23(5):555-564. Epub 2021 Feb 4.

Division of Laboratory Genetics and Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Tumor mutation burden (TMB) is an emerging biomarker of immunotherapy response. RNA sequencing in FFPE tissue samples was used for determining TMB in microsatellite-stable (MSS) and microsatellite instability-high (MSI-H) tumors in patients with colorectal or endometrial cancer. Tissue from tumors and paired normal tissue from 46 MSI-H and 12 MSS cases were included. Of the MSI-H tumors, 29 had defective DNA mismatch-repair mutations, and 17 had MLH1 promoter hypermethylation. TMB was measured using the expressed somatic nucleotide variants (eTMB). A method of accurate measurement of eTMB was developed that removes FFPE-derived artifacts by leveraging mutation signatures. There was a significant difference in the median eTMB values observed between MSI-H and MSS cases: 27.3 versus 6.7 mutations/megabase (mut/Mb) (P = 3.5 × 10). Among tumors with defective DNA-mismatch repair, those with mismatch-repair mutations had a significantly higher median eTMB than those with hypermethylation: 28.1 versus 17.5 mut/Mb (P = 0.037). Multivariate analysis showed that MSI status, tumor type (endometrial or colorectal), and age were significantly associated with eTMB. Additionally, using whole-exome sequencing in a subset of these patients, it was determined that DNA TMB correlated well with eTMB (Spearman correlation coefficient, 0.83). These results demonstrate that RNA sequencing can be used for measuring eTMB in FFPE tumor specimens.
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http://dx.doi.org/10.1016/j.jmoldx.2021.01.008DOI Listing
May 2021

Some Morphology Frontiers of Dysplasia in the Tubular Gastrointestinal Tract: The Rodger C. Haggitt Memorial Lecture.

Am J Surg Pathol 2022 Jan;46(1):e1-e14

Department of Pathology, The University of Pittsburgh, Pittsburgh, PA.

This review, based on the content of the 2020 US Gastrointestinal Pathology Society's Rodger Haggitt Lecture, concerns an array of tubular gastrointestinal tract dysplastic or possible "predysplastic lesions" with an almost purely morphologic focus based on our collaborative efforts over the past few years. These processes include esophageal epidermoid metaplasia, Barrett esophagus-associated dysplasia, polypoid gastric dysplastic lesions, small intestinal dysplasia, and the ability of metastases to mimic it, the controversial "serrated epithelial change" encountered in the setting of long-standing ulcerative and Crohn colitis, and recently described anal columnar human papilloma virus-associated neoplasms.
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http://dx.doi.org/10.1097/PAS.0000000000001637DOI Listing
January 2022

Gastrointestinal Malakoplakia: Clinicopathologic Analysis of 26 Cases.

Am J Surg Pathol 2020 09;44(9):1251-1258

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD.

Malakoplakia is an inflammatory process related to defective macrophage response to bacterial infection. To further characterize the clinicopathologic manifestations of gastrointestinal malakoplakia, 26 cases were identified from 6 institutions. Hematoxylin and eosin-stained slides and available stains were reviewed, and pertinent clinicopathologic features analyzed. Sixteen patients were women (62%). Mean patient age was 64 (range: 24 to 83). Sites included the colorectum (n=23), appendix (n=1), and stomach (n=2). Clinical indications for tissue procurement included screening (n=14), tumor resection (n=5), diarrhea (n=1), adenoma surveillance (n=1), ulcerative colitis flare (n=1), abdominal pain (n=1), and appendicitis (1). All cases featured histiocytes with abundant, pale, eosinophilic cytoplasm focally containing Michaelis-Gutmann bodies. The process frequently involved the mucosa (n=19), with architectural distortion in 13 cases. Lymphoid aggregates were present in 18 cases, which were prominent or obscuring in 11 (all colon biopsies) and provoked concern for lymphoma in 2. Associated findings included adenocarcinoma (n=5), adenoma (n=2), gastric hyperplastic polyps (n=1), chemical gastritis (n=1), collagenous colitis (n=1), and active chronic colitis (n=2). In cases with available stains, Michaelis-Gutman bodies were highlighted by Periodic Acid-Schiff with diastase, Von Kossa, and iron stains. Although 2 cases were positive for Tropheryma whipplei antibody, no T. whipplei transcripts were detected on real-time polymerase chain reaction. All patients with available follow-up are alive and well with no additional instances of malakoplakia. Malakoplakia of the gastrointestinal tract is a benign, incidental finding. Although histologic features in the stomach and colon resections are similar to those at other sites, exuberant lymphocytic response in colon biopsies and immunoreactivity with T. whippleii antibody may provoke initial confusion and lead to unnecessary time and resource investment.
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http://dx.doi.org/10.1097/PAS.0000000000001491DOI Listing
September 2020

Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation.

J Clin Invest 2020 04;130(4):1931-1947

Department of Medicine, and.

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence of acute pancreatitis. Pancreatic triglyceride lipase (PNLIP) increased in adipose tissue during pancreatitis and entered adipocytes by multiple mechanisms, hydrolyzing adipose triglyceride and generating excess NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike obese adipocyte-specific ATGL knockouts, had lower visceral adipose tissue lipolysis, milder inflammation, less severe organ failure, and improved survival. PNLIP-knockout mice, unlike ATGL knockouts, were protected from adipocyte-induced pancreatic acinar injury without affecting NEFA signaling or acute pancreatitis induction. Therefore, during pancreatitis, unlike diverticulitis, PNLIP leaking into visceral adipose tissue can cause excessive visceral adipose tissue lipolysis independently of adipocyte-autonomous ATGL, and thereby worsen organ failure.
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http://dx.doi.org/10.1172/JCI132767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108918PMC
April 2020

Eosinophilic esophagitis: imaging features with endoscopic and pathologic correlation.

Abdom Radiol (NY) 2020 03;45(3):591-600

Department of Gastroenterology and Hepatology, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA.

Objective: We aim to review the imaging features of eosinophilic esophagitis on fluoroscopy and present how they can correlate with endoscopic and pathologic findings.

Results: Eosinophilic esophagitis is a chronic immune-mediated disease that results in esophageal dysfunction. Upper esophagogastroduodenoscopy is high yield and required for biopsies to demonstrate the hallmark histologic findings of eosinophil-predominant inflammation. While esophagogastroduodenoscopy is currently mandatory for diagnosis, imaging findings can provide valuable information regarding the structural and functional properties of the esophagus. In addition, fluoroscopic studies may be very helpful in the setting of subtle findings and to evaluate fibrotic remodeling changes.

Conclusion: Radiologic examinations are a valuable tool in the assessment of eosinophilic esophagitis and can highlight changes of fibrostenotic disease, as overall narrowing can be more conspicuous fluoroscopically than endoscopically. As the disease increases in prevalence, it is critical that physicians recognize this condition and facilitate diagnosis and treatment.
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http://dx.doi.org/10.1007/s00261-019-02374-9DOI Listing
March 2020

Anastomosing hemangioma of the liver: a case series.

Abdom Radiol (NY) 2019 08;44(8):2781-2787

Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Purpose: To report imaging and pathologic features of five pathologically proven anastomosing hemangiomas of the liver (AHL).

Methods: A retrospective review for AHL was conducted using our institutional database from 6/2004 to 3/2018. Histology proven AHL with radiologic imaging available for review were included. A total of five patients who met our criteria were identified from our institutional database. Computed tomography, ultrasound, and magnetic resonance imaging findings, including location, size, attenuation/signal intensity, enhancement characteristics, and additional imaging data were reviewed. The clinical and pathological data were also reviewed.

Results: The imaging characteristics of AHL are variable, but features such as peripheral or diffuse hyperintensity on diffusion weighted imaging, arterial hyperenhancement without globular interrupted enhancement, and persistent enhancement without complete filling in the delayed phases were more characteristic of AHL. Imaging also demonstrated a lack of aggressive features.

Conclusions: AHL present a diagnostic dilemma as they can mimic more malignant lesions, such as angiosarcoma, both on imaging and at pathology. While the imaging characteristics of AHL are variable, there are some features which can help distinguish AHL from other liver lesions. When the diagnosis of anastomosing hemangioma is known, the management of choice is primarily surveillance, as intervention can cause unnecessary morbidity, and no degeneration to malignancy has been identified to date.
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http://dx.doi.org/10.1007/s00261-019-02043-xDOI Listing
August 2019

Local excision for patients with stage I anal canal squamous cell carcinoma can be curative.

J Gastrointest Oncol 2019 Apr;10(2):171-178

Department of Medical Oncologyy, Mayo Clinic, Rochester, MN, USA.

Background: Definitive concurrent chemoradiation is the current standard of care for all stage I anal canal squamous cell carcinoma. Local excision as primary treatment for selected stage I lesions has been reported in the literature but is not currently recommended by major guidelines. We herein compared the oncologic outcomes of patients with stage I anal canal squamous cell carcinoma treated with local excision alone versus chemoradiation to determine if there are any significant differences in outcomes including disease free survival, overall survival (OS) and local failure rate.

Methods: A retrospective review of all patients treated for stage I anal canal squamous cell carcinoma between 1990 and 2016 was conducted. Data collected included baseline demographics, staging studies, pathology, treatment received, relapse pattern and survival.

Results: A total of 57 patients were treated for stage I anal canal squamous cell carcinoma between 1990 and 2016; 13 were treated with local excision alone and 44 were treated with chemoradiation therapy. Baseline characteristics in both cohorts of patients were comparable. Median follow-up duration of the local excision and the chemoradiation cohorts were 106 and 70 months, respectively. Of the 13 patients in local excision cohort, two patients had disease recurrence, at 21 and 97 months from the diagnosis. Both patients were long term survivors with salvage treatment. In chemoradiation cohort, 1 out of 44 patients had a local recurrence at 1 year who underwent curative resection. Five-year progression free survival (PFS) of subjects in local excision cohort and chemoradiation cohort were 91% and 83%, respectively (P=0.57).

Conclusions: Local excision as primary treatment may be safe and effective for a selected group of stage I anal canal squamous cell carcinoma patients.
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http://dx.doi.org/10.21037/jgo.2018.12.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465491PMC
April 2019

Identification of key challenges in liver pathology: data from a multicenter study of extramural consults.

Hum Pathol 2019 05 8;87:75-82. Epub 2019 Mar 8.

Department of Pathology, University of Washington Medical Center, Seattle, WA, USA.

Extramural consultation for challenging pathology cases is an important part of patient care. The specific reasons why liver cases are submitted in consultation are poorly understood. To study patterns in extramural consultation, data were gathered from 1360 liver/GI/pancreatobiliary consults submitted to 7 academic centers. Liver cases comprised 40% of consults and are the focus of this paper. They were submitted for questions on medical (61%) and tumor pathology (39%). A preliminary diagnosis was provided by the referring pathologist in 65% of cases. The most common questions in medical liver pathology were on general classification of a hepatitic pattern of injury (37%), primary biliary cirrhosis (14%), fatty liver disease (13%), autoimmune hepatitis (12%), and etiology of cirrhosis (10%). Most tumor consults were submitted for classification (83%). The most common final tumor consultant diagnoses for benign tumors were hepatic adenoma or focal nodular hyperplasia (52%) and for malignant tumors were metastatic malignancies (47%), hepatocellular carcinoma (32%), or cholangiocarcinoma (8%). For cases submitted with a diagnosis of malignancy, the diagnosis was concordant (43% of cases), concordant but with a generic diagnosis for which a more specific diagnosis could be rendered (37%), or discordant with a major change in diagnosis from malignant to benign or change in tumor type (17%). In conclusion, analysis of consult patterns identifies challenging areas in medical and tumor liver pathology, areas that benefit from consult services and can be focused on by continuing medical educational activities.
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http://dx.doi.org/10.1016/j.humpath.2019.03.001DOI Listing
May 2019

Knowledge gaps in the appendix: a multi-institutional study from seven academic centers.

Mod Pathol 2019 07 14;32(7):988-996. Epub 2019 Feb 14.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Appendix pathology represents uncommonly encountered specimens with unique diagnostic challenges. To delineate common knowledge gaps, extramural consults submitted to seven institutions between 2016-2017 were reviewed. All appendix consults were resections (100%, n = 43), and the majority were directed for consultation by the originating pathologist (95%, n = 41) with no additional studies performed by the consultant (65%, n = 28). This study was dominated by inquiries related to low grade appendiceal mucinous neoplasms (44%, n = 19) and goblet cell carcinoid related neoplasms (19%, n = 8). Of the 43 appendiceal consults, 19 were submitted by the contributing pathologist as low grade appendiceal mucinous neoplasm, but only half of these were diagnosed by the consultant as such (n = 9). Low grade appendiceal mucinous neoplasm-related consultation themes included diverticular disease, criteria for invasion, high grade atypia, extra-appendiceal mucin, and staging. Examples of major disagreements that were downgraded included consults submitted as low grade appendiceal mucinous neoplasm and diagnosed by the consultant as serrated polyp (n = 3), appendicitis (n = 1), and benign appendix (n = 1). Examples of major disagreements-upgraded included cases submitted as low grade appendiceal mucinous neoplasm and diagnosed by the consultant as low grade appendiceal mucinous neoplasm with high-risk features (n = 2) and mucinous adenocarcinoma (n = 2). One case contained both a major disagreement-upgrade (low grade appendiceal mucinous neoplasm changed to high grade appendiceal mucinous neoplasm) and a major disagreement-downgrade (pT3 changed to Tis). Of the 15 cases diagnosed by the consultants as low grade appendiceal mucinous neoplasm, submitted diagnoses included low grade appendiceal mucinous neoplasm (n = 9), adenocarcinoma (n = 5), and one case was submitted without a diagnosis. For goblet cell carcinoid-related consults, the usual inquiry related to distinguishing goblet cell carcinoid from goblet cell carcinoid with adenocarcinoma (adenocarcinoma ex-goblet cell carcinoid). Of the 38 overall consults with a submitted diagnosis, 53% (n = 20) were disagreements, and most of these were major disagreements-downgraded (n = 13).
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http://dx.doi.org/10.1038/s41379-019-0216-xDOI Listing
July 2019

90Y-TheraSpheres: The New Look of Yttrium-90.

Am J Surg Pathol 2019 05;43(5):688-694

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD.

Selective internal radiation therapy with Y-TheraSphere or Y-SIRSphere is used in the treatment of unresectable hepatic malignancies. To the best of our knowledge, this is the first Y-TheraSpheres series. BTG International Canada Inc. provided nonradiated microspheres from the Nordion manufacturer. The histologic processed microspheres were colorless, refractile, polarizable, 20 to 30 μm in diameter, and an occasional internal bulls'-eye seen with the condenser out and an internal cross seen with polarized light. Identical microspheres were identified in 15 hepatectomy specimens from four centers between February 2016 and March 2018. The patients were usually male (male=10, female=5) with a mean age of 59 years. All patients had a prior diagnosis of hepatocellular carcinoma (HCC) and documented Y-TheraSphere (mean duration from last deployment=32 wk). All surgical pathology specimens in these 15 patients were reviewed, but the microspheres were only identified in the hepatectomy specimens. During manuscript preparation, one case of Y-TheraSpheres gastritis was prospectively identified from a separate patient with a history of HCC and Y-TheraSpheres. In conclusion, recognition of Y-TheraSpheres is important so that one may consider the possibility of a nearby malignancy and or establish the cause of the background inflammatory or radiation-related injury. These structures can be easy to miss because the subtle morphology is distinct from previously reported Y-SIRSphere. Clues to the diagnosis include a history of HCC and background radiation change. We report the characteristic morphology as microspheres that overlap in size with Y-SIRSphere, but can be differentiated based on Y-TheraSpheres' colorless appearance with occasional internal bulls'-eyes with the condenser out and an internal cross with polarized light.
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http://dx.doi.org/10.1097/PAS.0000000000001223DOI Listing
May 2019

The inverted appendix - a potentially problematic diagnosis: clinicopathologic analysis of 21 cases.

Histopathology 2019 May 20;74(6):853-860. Epub 2019 Mar 20.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Aims: Inverted appendices are rare, but have the potential to cause diagnostic confusion among endoscopists and pathologists. The aim of this study was to describe the clinicopathological features of inverted appendices seen at our institution over the last 30 years.

Methods And Results: Twenty-one inverted appendices were identified and the clinical and pathological features reviewed. Patients were predominantly middle-aged women. Most cases were detected incidentally on colonoscopy. Endoscopically, inverted appendices appeared polypoid in the proximal caecum. All resections featured associated pathological processes, including endometriosis (n = 3), inflammatory mucocoele (n = 1), low-grade appendiceal mucinous neoplasm (n = 2), traditional serrated adenoma (n = 1) and inflammatory fibroid polyp (n = 1). Five cases were endoscopically mischaracterised as caecal polyps and removed via polypectomy; initial pathological impressions were erroneous in most cases. All polypectomies featured a dome-like configuration covered by mucosa on the convex surface; the majority had aggregates of ganglion cells and neural plexi embedded in muscularis propria. The vast majority of cases, regardless of the procedure, showed lymphoid aggregates. Among post-polypectomy patients with follow-up, none experienced perforation-associated morbidity despite the histological presence of muscularis propria.

Conclusions: The diagnosis of an inverted appendix should be considered in polypectomy specimens from the caecum or appendiceal orifice with (i) dome-like tissue configuration covered by mucosa on the convex surface, (ii) a deep, robust smooth muscle component with ganglion cells (muscularis propria) and (iii) associated lymphoid aggregates. Prompt recognition on H&E will avoid unnecessary time and resource investment.
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http://dx.doi.org/10.1111/his.13824DOI Listing
May 2019

Intestinal metaplasia of the gastric cardia: findings in patients with versus without Barrett's esophagus.

Gastrointest Endosc 2019 04 14;89(4):759-768. Epub 2018 Nov 14.

Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.

Background And Aims: There is controversy about finding intestinal metaplasia (IM) of the gastric cardia on biopsy. The most recent American College of Gastroenterology guideline comments that IM cardia is not more common in patients with Barrett's esophagus (BE). It provides limited guidance on whether the cardia should be treated when patients with BE undergo endoscopic eradication therapy (EET) and whether the cardia should undergo biopsy after ablation. The aims of our study were to determine the frequency in the proximal stomach of (1) histologic gastric cardia mucosa and (2) IM cardia. A third aim was to explore the frequency of advanced pathology (dysplasia and adenocarcinoma) in the cardia after patients with BE have undergone EET.

Methods: Consecutive patients undergoing esophagogastroduodenoscopy between January 2008 and December 2014 who had proximal stomach biopsies were included. Patients who had histologically confirmed BE were compared with those without BE.

Results: Four hundred sixty-two patients, 289 with BE and 173 without BE, were included. Histologically confirmed cardiac mucosa was found in 81.6% of all patients. This was more frequent in those with versus without BE (86% vs 75%; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.28-3.32; P = .003). IM cardia was more common in the BE group (17% vs 7%; OR, 2.67; 95% CI, 1.38-5.19; P = .004). Advanced pathology was more likely in the patients with BE who had undergone EET.

Conclusions: Cardiac mucosa is present in most patients who undergo endoscopy for upper GI symptoms. IM cardia is more common in patients with BE than those without. Advanced histologic changes in the cardia were seen only in the subgroup of patients with BE who had undergone EET.
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http://dx.doi.org/10.1016/j.gie.2018.10.048DOI Listing
April 2019

Some observations on Barrett esophagus and associated dysplasia.

Ann Diagn Pathol 2018 Dec 28;37:75-82. Epub 2018 Sep 28.

Department of Pathology, Cedars Sinai Health System, United States of America.

Biopsy samples from esophageal columnar metaplasia and dysplasia are commonly encountered in Western pathology practice and knowing a few pitfalls can save both pathologists and patients a great deal of anxiety. Herein we discuss criteria for Barrett esophagus, evaluation of dysplasia, and some pitfalls in reviewing endoscopic mucosal resections. Also included is a summary of suggested follow-up for patients with Barrett esophagus.
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http://dx.doi.org/10.1016/j.anndiagpath.2018.09.013DOI Listing
December 2018

Metastatic renal cell carcinoma presenting with melena.

Clin Case Rep 2018 May 24;6(5):961-962. Epub 2018 Mar 24.

Department of Pathology Mayo Clinic Scottsdale Arizona.

Renal cell carcinoma is a highly malignant neoplasm. Metastasis to the pancreas and gastrointestinal tract is rare. In this case report, we show images of metastatic renal cell carcinoma to the upper gastrointestinal tract in a patient who presented with melena.
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http://dx.doi.org/10.1002/ccr3.1492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930209PMC
May 2018

The outlet patch: gastric heterotopia of the colorectum and anus.

Histopathology 2018 Aug 30;73(2):220-229. Epub 2018 May 30.

Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.

Aims: Gastric heterotopia (GH) has been described throughout the gastrointestinal tract. However, the colorectal region is an extremely rare location for it. We describe the clinicopathological features of GH of the colon, rectum and anus.

Methods And Results: We identified 33 cases in 20 males and 13 females (median age = 54 years; range = 4 months-73 years). Sites included the rectum (n = 26), anus (n = 4), ileocaecal junction (n = 1), ascending colon (n = 1) and descending colon (n = 1). Presenting symptoms (n = 27) included haematochezia (41%) and altered bowel habits (4%); 15 patients (55%) were asymptomatic. On colonoscopy (n = 31), all appeared as solitary lesions (median size = 6.5 mm, range = 2-55 mm), either as polyps (61%), raised erythematous patches (23%), an ulcer (10%), within a rectal diverticulum (3%) or a haemorrhoid (3%). Patients were managed by polypectomy. One with an associated carcinoma in the area of GH underwent resection. No morbidity related to GH itself was reported following excision. Histologically, heterotopic gastric mucosa was oxyntic (85%), mixed oxyntic and non-oxyntic (12%) and not specified (3%) types. In five patients a pyloric gland adenoma (PGA) arose from heterotopic gastric mucosa, two of which contained a focus of invasive adenocarcinoma. One case had associated surface foveolar-type low-grade dysplasia. Another had associated adenocarcinoma arising from the heterotopic mucosa. One example harboured Helicobacter pylori organisms.

Conclusions: We highlight the features of GH in the distal GIT - the 'outlet patch'. Association with PGA, surface dysplasia and adenocarcinoma suggests that lower tract GH can undergo neoplastic transformation.
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http://dx.doi.org/10.1111/his.13632DOI Listing
August 2018

Treponema pallidum Immunohistochemistry is positive in human intestinal Spirochetosis.

Diagn Pathol 2018 Jan 22;13(1). Epub 2018 Jan 22.

Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Scottsdale, AZ, 85259, USA.

Background: Human intestinal spirochetosis (IS) has been recognized for decades, but whether it represents commensalism or a pathogenic process remains controversial. IS is diagnosed on routine stains with confirmation by silver stains but these stains are labor intensive and slow to read. We evaluated the Treponema pallidum immunostain as a diagnostic adjunct for IS.

Methods: We retrieved biopsies from 33 patients with IS for this study. Each case was tested by Warthin-Starry (WS) and T. pallidum immunohistochemistry (IHC). Species specific genotyping was performed in 3 cases.

Results: Patients with IS ranged from 22 to 82 years without gender predilection. IS involved normal (n = 15), and inflamed (n = 5) mucosa and colonic polyps (n = 13). Warthin-Starry and T. pallidum IHC were positive in all cases including both species of Brachyspira. Six (18%) symptomatic patients were treated for IS, and experienced resolution. In patients diagnosed with incidental IS on cancer screening (n = 5), follow up biopsies, without therapy, were negative for IS. T. pallidum IHC required 75 min less hands-on time than WS for performance and was faster to interpret.

Conclusions: T. pallidum IHC can be used to confirm the diagnosis of IS and is easier to perform and faster to interpret than WS.
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http://dx.doi.org/10.1186/s13000-017-0676-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389163PMC
January 2018

A Mysterious DRESS Case: Autoimmune Enteropathy Associated with DRESS Syndrome.

Case Rep Gastrointest Med 2017 26;2017:7861857. Epub 2017 Nov 26.

Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare but potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities, and extensive organ involvement. Here, we present a case of a young woman with DRESS syndrome following exposure to vancomycin with renal, cutaneous, and gastrointestinal involvement. To the best of our knowledge, this is the first case description in the literature of DRESS of the gastrointestinal tract with autoimmune enteropathy.
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http://dx.doi.org/10.1155/2017/7861857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733168PMC
November 2017

Substantial Interobserver Agreement in the Diagnosis of Dysplasia in Barrett Esophagus Upon Review of a Patient's Entire Set of Biopsies.

Am J Surg Pathol 2018 03;42(3):376-381

Department of Pathology and Laboratory Medicine, Mayo Clinic Arizona, Scottsdale, AZ.

The pathologic diagnosis of dysplasia in Barrett esophagus (BE) suffers from interobserver disagreement. Many of the studies demonstrating disagreement in the diagnosis of dysplasia have pathologists review individual biopsy slides in isolation. To more closely mimic daily practice, 3 pathologists reviewed hematoxylin and eosin slides made from 549 individual biopsy jars obtained from 129 unique patients with a diagnosis of BE. Each pathologist reviewed the entirety of a given patient's biopsy material. The grade of dysplasia present in each biopsy jar was given as well as an overall highest grade of dysplasia from the patient's entire set of biopsies. The interobserver agreement in the diagnosis of dysplasia per biopsy jar and per patient's set of biopsies was measured by Fleiss κ statistic for multiple raters. The κ values for each diagnosis was higher in the per patient analysis compared with the per biopsy jar analysis indicating that pathologists are more likely to agree on the overall grade of dysplasia compared with the grade in an individual biopsy jar. In the per patient analysis, the interobserver agreement in the diagnosis of nondysplastic BE and high-grade dysplasia were substantial (κ=0.66; 95% confidence interval [CI], 0.56-0.76 and κ=0.76; 95% CI, 0.66-0.86, respectively). The interobserver agreement in the diagnosis of low-grade dysplasia (LGD) was fair (κ=0.31; 95% CI, 0.21-0.42). When LGD and high-grade dysplasia were collapsed into 1 category of positive for dysplasia, the interobserver agreement in the per patient analysis remained substantial (κ=0.70; 95% CI, 0.60-0.80), suggesting that much of the disagreement in LGD is not due to lack of recognition of dysplastic Barrett's mucosa, but rather the degree of dysplasia. These results indicate that pathologists can reliably distinguish between nondysplastic BE and dysplastic BE when a patient's entire set of biopsies is reviewed as a group. When second opinions are obtained, all available slides from that endoscopic procedure should be sent for review.
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http://dx.doi.org/10.1097/PAS.0000000000000988DOI Listing
March 2018

Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and Extent of PD-L1 Expression by Tumor Cells.

Am J Clin Pathol 2017 Nov;148(5):441-449

Department of Laboratory Medicine and Pathology.

Objectives: Programmed death ligand 1 (PD-L1) expression in pancreatic ductal adenocarcinoma (PDA) has been described, but unselected PDAs have shown limited clinical responsiveness to anti-programmed death 1 (PD-1)/PD-L1 therapy.

Methods: We studied 24 cases of undifferentiated pancreatic carcinoma (UPC) using immunohistochemistry for PD-L1 (E1L3N clone), CD3, CD20, CD68, and DNA mismatch repair proteins in this study. Slides were scored for extent of PD-L1 expression on tumor cells and tumor-infiltrating immune cells.

Results: PD-L1 expression was more frequent in UPCs than in PDAs (63% vs 15%, P < .01). The extent of PD-L1 expression was greater in UPCs, with 13 (87%) of 15 cases containing 10% or more positive tumor cells compared with three of seven PDAs (P = .05). Both tumor groups showed similar numbers of tumor-infiltrating T cells, B cells, and macrophages.

Conclusions: UPC is enriched for PD-L1 expression in frequency and extent, relative to conventional PDA. Anti-PD-1/PD-L1 agents may represent a valuable therapeutic approach for this subset of highly aggressive pancreatic carcinoma.
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http://dx.doi.org/10.1093/ajcp/aqx092DOI Listing
November 2017

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Mod Pathol 2018 01 1;31(1):141-149. Epub 2017 Sep 1.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone.
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http://dx.doi.org/10.1038/modpathol.2017.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758901PMC
January 2018

Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia.

Mod Pathol 2017 11 21;30(11):1613-1621. Epub 2017 Jul 21.

Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA.

Esophageal epidermoid metaplasia is a rare condition that involves the proximal-to-middle third of the esophagus. It is sharply demarcated and defined histologically by epithelial hyperplasia, a prominent granular cell layer, and superficial hyperorthokeratosis. In addition, preliminary studies have suggested an association between esophageal epidermoid metaplasia and esophageal squamous neoplasia (squamous dysplasia and esophageal squamous cell carcinoma). To further characterize esophageal epidermoid metaplasia and better define its relationship to squamous neoplasia of the esophagus, we performed targeted next-generation sequencing on uninvolved esophageal squamous mucosa and matching esophageal epidermoid metaplasia specimens from 18 patients. Further, we evaluated both synchronous and metachronous high-grade squamous dysplasia/esophageal squamous cell carcinoma by next-generation sequencing from 5 of the 18 (28%) patients, and compared these findings to corresponding esophageal epidermoid metaplasia specimens. Targeted next-generation sequencing revealed 12 of 18 (67%) esophageal epidermoid metaplasia specimens' harbored alterations in genes often associated with esophageal squamous cell carcinoma. The most frequently mutated genes consisted of TP53 (n=10), PIK3CA (n=2), EGFR (n=2), MYCN (n=1), HRAS (n=1), and the TERT promoter (n=1). Sequencing of synchronous and metachronous high-grade squamous dysplasia/esophageal squamous cell carcinoma identified shared genetic alterations with corresponding esophageal epidermoid metaplasia specimens that suggests a clonal relationship between these entities. In addition, the presence of a TP53 mutation in esophageal epidermoid metaplasia specimens correlated with concurrent or progression to high-grade squamous dysplasia/esophageal squamous cell carcinoma. No genetic alterations were detected in uninvolved esophageal squamous mucosa. On the basis of these findings, we conclude esophageal epidermoid metaplasia is a precursor to in situ and invasive esophageal squamous neoplasia. Further, the detection of TP53 mutations in esophageal epidermoid metaplasia specimens may serve as an early detection biomarker for high-grade squamous dysplasia/esophageal squamous cell carcinoma.
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http://dx.doi.org/10.1038/modpathol.2017.73DOI Listing
November 2017

Ibrutinib-induced acute liver failure.

Leuk Lymphoma 2018 02 11;59(2):512-514. Epub 2017 Jul 11.

a Division of Gastroenterology and Hepatology , Mayo Clinic , Phoenix , AZ , USA.

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http://dx.doi.org/10.1080/10428194.2017.1346251DOI Listing
February 2018

Sevelamer resin bezoar presenting as a cecal mass.

Gastrointest Endosc 2017 12 1;86(6):1186-1187. Epub 2017 Jul 1.

Department of Laboratory Medicine and Pathology, Mayo Clinic in Arizona, Scottsdale, Arizona, USA.

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http://dx.doi.org/10.1016/j.gie.2017.06.021DOI Listing
December 2017

Black Cohosh Hepatotoxicity with Autoimmune Hepatitis Presentation.

Case Rep Gastroenterol 2017 Jan-Apr;11(1):23-28. Epub 2017 Jan 27.

Gastroenterology Fellow, Mayo Clinic, Scottsdale, AZ, USA.

Herbal medicines have been used for the treatment of various ailments since time immemorial. Black cohosh (BC) is well known for the treatment of postmenopausal symptoms, with conflicting evidence supporting its safety and benefits. We present a rare case of BC-induced autoimmune hepatitis (AIH) with hepatotoxicity in a 69-year-old female. To our knowledge, this represents the third case of BC-induced AIH.
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http://dx.doi.org/10.1159/000452735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301124PMC
January 2017

Challenges to "Classic" Esophageal Candidiasis: Looks Are Usually Deceiving.

Am J Clin Pathol 2017 01;147(1):33-42

Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Objectives: We undertook the first case control study of histologically confirmed esophageal candidiasis (EC).

Methods: A computer search from July 2012 through February 2015 identified 1,011 esophageal specimens, including 40 cases of EC and 20 controls.

Results: The EC incidence was 5.2%; it was associated with immunosuppression and endoscopic white plaques and breaks. Smoking was a predisposing factor, and alcohol was protective. EC had no unique symptoms, and 54% of endoscopic reports did not suspect EC. Important histologic clues included superficial and detached fragments of desquamated and hyper-pink parakeratosis, acute inflammation, intraepithelial lymphocytosis, dead keratinocytes, and bacterial overgrowth. Thirty percent had no neutrophilic infiltrate. Pseudohyphae were seen on H&E in 92.5% (n = 37/40). "Upfront" periodic acid-Schiff with diastase (PAS/D) on all esophageal specimens would have generated $68,333.49 in patient charges. Our targeted PAS/D strategy resulted in $13,044.87 in patient charges (cost saving = 80.9%, $55,288.62).

Conclusions: We describe the typical morphology of EC and recommend limiting PAS/D to cases where the organisms are not readily identifiable on H&E and with at least one of the following: (1) ulcer, (2) suspicious morphology, and/or (3) clinical impression of EC.
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http://dx.doi.org/10.1093/ajcp/aqw210DOI Listing
January 2017

Mucosubmucosal elongated colonic polyp.

VideoGIE 2017 Apr 23;2(4):85-87. Epub 2017 Jan 23.

Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA.

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http://dx.doi.org/10.1016/j.vgie.2017.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990669PMC
April 2017

Positron emission tomography/computed tomography imaging of adrenocorticotropic hormone-producing small-cell neuroendocrine carcinoma of the cervix.

Int J Gynaecol Obstet 2017 May 3;137(2):197-198. Epub 2017 Feb 3.

Department of Laboratory Medicine, Mayo Clinic, Scottsdale, Arizona, USA.

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http://dx.doi.org/10.1002/ijgo.12104DOI Listing
May 2017

Hepatoid Carcinoma of the Pancreas: Case Report, Next-Generation Tumor Profiling, and Literature Review.

Case Rep Gastroenterol 2016 Sep-Dec;10(3):605-612. Epub 2016 Oct 18.

Division of Transplant and Hepatopancreatobiliary Surgery, Mayo Clinic Arizona, Phoenix, Ariz., USA.

Fewer than 25 cases of hepatoid carcinoma of the pancreas have been reported in the literature. We present a case in a 61-year-old male with a remote history of Hodgkin's lymphoma and gastric neuroendocrine cell hyperplasia. On surveillance endoscopic ultrasound, an 8 × 5 mm cystic lesion was seen in the tail of the pancreas. MRI showed a focal pancreatic duct cut-off with mild ductal dilation. Fine needle aspiration was performed, which was concerning for acinar cell carcinoma. The patient underwent distal pancreatectomy and recovered uneventfully. Final pathology demonstrated a 1.3-cm hepatoid carcinoma of the pancreas, with a final clinicopathological stage of T1N0M0. Next-generation nucleic acid sequencing of the tumor did not suggest a viable adjuvant chemotherapeutic agent, and no adjuvant therapy was administered. The patient has no evidence of disease 6 months following resection. A further characterization and description of the outcomes of these rare tumors is warranted to help guide providers and counsel patients.
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http://dx.doi.org/10.1159/000448064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121547PMC
October 2016

An Unusual Suspect: Lymphoepithelial Cyst of the Pancreas.

Case Rep Gastrointest Med 2016 26;2016:5492824. Epub 2016 Oct 26.

Mayo Clinic Arizona, Division of Gastroenterology and Hepatology, Scottsdale, AZ, USA.

Lymphoepithelial cysts (LECs) of the pancreas are benign, rare pancreatic cysts that are found predominantly in men. These cysts can present as a diagnostic conundrum given their rarity and difficulty of distinguishing these cysts from those with malignant potential. We present an incidental case of a LEC in a middle-aged man.
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http://dx.doi.org/10.1155/2016/5492824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101372PMC
October 2016
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