Successful Treatment of Recurrent Colonic Adenocarcinoma with Metastatic Tumor Thrombus in the Superior Mesenteric Vein with Surgical Excision and Venous Reconstruction.

BACKGROUND Patients cured of Hodgkin lymphoma (HL) are at increased risk of second malignancies, such as lung, breast, and colon cancer. Isolated metastasis of these malignancies to the vasculature is rare. We present a unique case of a patient cured of HL who developed colon cancer and later presented with an isolated metastases of colon cancer to the superior mesenteric vein. The patient is now in complete remission 5 years after surgical excision of the superior mesenteric vein metastases followed by chemotherapy. CASE REPORT A 56-year-old woman presented with a past medical history notable for stage III HL diagnosed at age 13 years that was treated by splenectomy, chemotherapy, and mantle with inverted Y radiation. She underwent a right nephrectomy at age 51 years for renal cell carcinoma. At age 56, an 8-cm mass in the transverse colon was found during surveillance imaging. She underwent right hemicolectomy for pathological stage IIA (T3N0M0) adenocarcinoma. A liver adenoma was identified a year later. Two years after hemicolectomy, an abdominal recurrence was identified, and she underwent a resection of a superior mesenteric vein mass with porto-mesenteric reconstruction. Pathology revealed metastatic colonic adenocarcinoma, 1 of 7 lymph nodes positive for cancer, and clear margins. She received 6 months of fluorouracil chemotherapy and remained free of recurrences for 5 years. CONCLUSIONS Isolated vascular recurrences of colon cancer can be cured with resection and systemic chemotherapy. Diagnosis and treatment of venous recurrences remains challenging owing to the lack or percutaneous access for biopsy and the difficulty of venous reconstruction.

Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity.

Human genome-wide association studies found single-nucleotide polymorphisms (SNPs) near LYPLAL1 (Lysophospholipase-like protein 1) that have sex-specific effects on fat distribution and metabolic traits. To determine whether altering LYPLAL1 affects obesity and metabolic disease, we created and characterized a mouse knockout (KO) of Lyplal1. We fed the experimental group of mice a high-fat, high-sucrose (HFHS) diet for 23 weeks, and the controls were fed regular chow diet. Here, we show that CRISPR-Cas9 whole-body Lyplal1 KO mice fed an HFHS diet showed sex-specific differences in weight gain and fat accumulation as compared to chow diet. Female, not male, KO mice weighed less than WT mice, had reduced body fat percentage, had white fat mass, and had adipocyte diameter not accounted for by changes in the metabolic rate. Female, but not male, KO mice had increased serum triglycerides, decreased aspartate, and decreased alanine aminotransferase. Lyplal1 KO mice of both sexes have reduced liver triglycerides and steatosis. These diet-specific effects resemble the effects of SNPs near LYPLAL1 in humans, suggesting that LYPLAL1 has an evolutionary conserved sex-specific effect on adiposity. This murine model can be used to study this novel gene-by-sex-by-diet interaction to elucidate the metabolic effects of LYPLAL1 on human obesity.

Measuring the Submucosal Depth of Invasion in Endoscopic Mucosal Resections for Barrett-associated Adenocarcinoma: Practical Issues and Relevance for the Decision for Esophagectomy.

CONTEXT.­: Endoscopic mucosal resection (EMR) has made it possible for Barrett esophagus patients with superficial cancers to be treated without esophagectomy. Recent guidelines recommend measuring depth of invasion (DOI) in submucosal cancers based on reports that in low-risk cancers, submucosal invasion 500 µm or less is associated with low nodal metastasis rates. However, pathologists face challenges in reproducibly measuring DOI. OBJECTIVE.­: To determine how often DOI measurements could impact treatment and to evaluate reproducibility in measuring submucosal DOI in EMR specimens. DESIGN.­: Consecutive adenocarcinoma EMR cases were identified, including cases of "low histologic risk" submucosal cancer, as follows: those with negative deep margins, no high-grade histology (G3), and no lymphovascular invasion. Submucosal DOI was measured by 7 pathologists according to guidelines. RESULTS.­: Of 213 cancer EMR cases, 46 were submucosa invasive and 6 cases were low histologic risk submucosal cancers for which measurement could impact decision-making. Of these low histologic risk cases, 3 were categorized as superficial, indicating that measurement would be a clinically actionable decision point in only 1.4% of adenocarcinoma EMRs. Interobserver agreement for in-depth categorization between 7 pathologists was moderate (κ = 0.42), and the range of measurements spanned the 500-µm relevant threshold in 40 of 55 measured samples (72.7%). CONCLUSIONS.­: While therapeutic decisions would rarely have depended on DOI measurements alone in our cohort, interobserver variability raises concerns about their use as a sole factor on which to offer patients conservative therapy. Responsibly reporting and clinically using submucosal DOI measurements will require practical experience troubleshooting common histologic artifacts, as well as multidisciplinary awareness of the impact of variable specimen-handling practices.

Granulomas in the Liver, with a Focus on Infectious Causes.

Hepatic granulomas are encountered in approximately 2% to 10% of liver biopsies. There are many potential infectious and noninfectious causes; granulomas can be generally classified by their morphology, which may be helpful in refining the differential diagnosis. This article provides a review of hepatic granulomas with an emphasis on infectious causes.

Chronic Colitis in Biopsy Samples: Is It Inflammatory Bowel Disease or Something Else?

Chronic colitis, regardless of type, is defined histologically by chronic inflammation, mainly plasmacytosis, in the lamina propria. Specific diagnosis of chronic colitides in biopsies can be challenging for practicing pathologists. This article focuses on discussing specific histologic features in biopsies of the inflammatory bowel diseases (IBDs), including ulcerative colitis, Crohn colitis, and colitis of indeterminate type. It also offers suggestions as to how to separate the IBDs from other chronic colitides, such as lymphocytic colitis, collagenous colitis, diverticular disease-associated colitis, diversion colitis, and chronic colitides that are due to drugs. Normal histology in colon biopsies is also briefly discussed.

A Historical Perspective and Exposé on Serrated Polyps of the Colorectum.

This article offers a historical perspective on the discovery of 3 types of serrated colorectal polyps recognized in the past 60 years. The first to be discovered was the hyperplastic polyp, which is still the most commonly encountered serrated polyp. In the past 20 years, the carcinoma-associated sessile serrated adenoma/polyp has been recognized, but its diagnosis can be difficult owing to overlapping histologic features with hyperplastic polyps. Less is known about the third type, the traditional serrated adenoma, because it is far less common than the other 2 types, and its association with cancer is currently under investigation.

Olmesartan-Associated Enteropathy: A Review of Clinical and Histologic Findings.

Olmesartan is an antihypertensive medication belonging to the angiotensin II receptor blocker class of drugs that has recently been associated with severe enteropathy. Olmesartan-associated enteropathy is uncommon and may be difficult to recognize because of its clinical and histologic similarities to other clinical entities, including celiac sprue and autoimmune enteropathy. The purpose of this article is to review the clinical and histologic findings of olmesartan-associated enteropathy that have been reported in the literature and to discuss clinical entities to consider in the differential diagnosis of olmesartan-associated enteropathy.

CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression.

Recent molecular advances have identified a novel, clinically aggressive subgroup of undifferentiated round cell sarcomas defined molecularly by oncogenic fusion of the gene, CIC, and either DUX4 or its paralog, DUX4L, herein termed CIC-DUX sarcomas. Morphologically, CIC-DUX sarcomas are round cell sarcomas with high-grade nuclear features, including vesicular chromatin and nucleoli, patchy clear cell foci, myxoid change, and necrosis. Here, we studied a cohort of 10 cases, including 6 newly identified cases, 2 with paired metastases. Given our prior observation of trisomy 8 in these tumors, we assayed for amplification and expression of MYC (c-Myc) and representative downstream targets. Trisomy 8 was detected in 5/7 testable cases, with further amplification of MYC locus in 6/7 testable cases and immunohistochemical expression of MYC in 10/10. The canonical MYC transcriptional target, p21, but not MTDH, was differentially expressed compared with Ewing sarcomas. Given prior observation of induction of ETS-family transcription factors by the fusion oncoprotein, we assayed and identified highly prevalent positivity for ERG (9/10) and FLI1 (8/8). These findings are cautionary regarding use of these immunostains in prospective case workup, whereas the prevalent MYC amplification may represent a therapeutically targetable oncogenic pathway in CIC-DUX sarcomas.

Undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion: a novel highly aggressive soft tissue tumor with distinctive histopathology.

A subset of small round cell sarcomas remains difficult to classify. Among these, a rare tumor harboring a t(4;19)(q35;q13.1) with CIC-DUX4 fusion has been described. The aim of this study is to better understand its clinicopathologic features. Four cases of CIC-DUX4 sarcoma, all arising in adults (3 women, 1 man, aged 20 to 43 y), were identified using conventional cytogenetic, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) methods. All 4 tumors demonstrated CIC-DUX4 fusion transcript by both RT-PCR and FISH and CIC rearrangement by FISH. Cytogenetic results from 2 tumors showed t(4;19)(q35;q13.1) occurring as part of a simple karyotype in 1 tumor and as part of a complex karyotype in the other, the latter from a postchemotherapy specimen. Both tumors harbored trisomy 8 and lacked any other known sarcoma-associated translocation. No EWS or SYT rearrangements were detected by RT-PCR or FISH. The tumors had small round cell morphology with a distinctive constellation of histologic features including extensive geographic necrosis, mild nuclear pleomorphism with coarse chromatin and prominent nucleoli, clear cell areas, and focal myxoid matrix. Only focal staining for CD99 was present in each tumor. Two had very focal cytokeratin staining. All tumors were negative for desmin, myogenin, TLE-1, and S100 protein, whereas nuclear INI-1 staining was retained. The tumors were highly aggressive, and all patients died of disseminated disease within 16.8 months. CIC-DUX4 sarcoma represents a novel translocation-associated sarcoma with distinctive histopathologic features and rapid disease progression.