The classification of appendiceal mucinous neoplasms has been controversial, largely focused on a particular subset of low-grade mucinous tumors that, despite their innocuous appearance, can ...disseminate to the peritoneal cavity as pseudomyxoma peritonei (PMP). Recent WHO classification of these tumors as low-grade appendiceal mucinous neoplasms acknowledges their unique morphologic appearance and biologic behavior. Still, debate about the use of this term and its parameters continues to impede the adoption of consensus classification for appendiceal mucinous neoplasms. The classification of PMP has also been the subject of debate, with international authorities advocating for the use of malignant terminology to describe all grades of PMP, even though some authorities consider low-grade PMP to be dissemination of adenomatous epithelium in the peritoneum. Recent data also emphasize the importance of histologic grade of the peritoneal tumors in defining prognosis of these patients.
Low grade appendiceal mucinous neoplasms can spread to the peritoneum as pseudomyxoma peritonei even though they are not obviously invasive in the appendix. During the past several decades, several ...problematic issues surrounding this enigmatic tumor have been debated in the literature, including appropriate nomenclature for the appendiceal tumors and their peritoneal metastases. In this article, the most contentious issues in the area of appendiceal mucinous tumors are examined. First, the classification systems that have been proposed for these tumors are compared in the context of whether the appendiceal mucinous tumors are ruptured adenomas or invasive carcinomas. The controversy about the nature of pseudomyxoma peritonei and its classification systems is discussed in the following section. A brief discussion follows that examines the issue of localized pseudomyxoma peritonei and its clinical significance. Next reviewed is the largely resolved controversy about whether ovarian mucinous tumors in this setting are separate primaries or are metastases from the appendiceal tumor. Finally, the controversy about the most effective treatment of patients with pseudomyxoma peritonei is discussed.
Fibrin ring granulomas are an uncommon finding in liver biopsies although they have been described in liver injury secondary to several infectious and noninfectious entities, most notably Q fever. ...Immune checkpoint inhibitors are recent advances in cancer therapy, and stimulate the immune system to cause antitumoral effects but may also lead to adverse immune events such as hepatitis and colitis. We report 2 patients on combination ipilimumab/nivolumab who developed hepatitis and had fibrin ring granulomas in their liver biopsies.
The vermiform appendix is the primary site of several distinctive benign and malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma peritonei (PMP). A consensus on their ...terminology was reached by an international panel of pathologists and clinicians working under the auspices of the Peritoneal Surface Oncology Group International (PSOGI), and this review discusses the application of the PSOGI classification to routine reporting. We discuss diagnosis and differential diagnosis together with implications for patient management, covering low‐grade appendiceal mucinous neoplasms, high‐grade appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.
Appendiceal adenomas and low-grade appendiceal mucinous neoplasms (LAMNs) confined to the appendix are cured by appendectomy. However, involvement of the proximal margin raises concern for residual ...disease. Some patients with a positive margin at appendectomy undergo cecal resection to eliminate a perceived risk for tumor recurrence or dissemination, although that likelihood is assumed rather than demonstrated.
To determine whether involvement of the proximal appendiceal resection margin by adenoma or LAMN is a risk factor for local development of recurrence or pseudomyxoma peritonei.
Appendiceal adenomas and LAMNs confined to the appendix were considered for the study if they showed neoplasia or dissecting mucin at the proximal margin. The presence or absence of residual tumor in cecal resections was determined. Follow-up data were obtained from clinical records.
Sixteen patients (14 female, 2 male) with LAMN (n = 15) or adenoma (n = 1) and an involved proximal resection margin were identified, including 9 with neoplastic epithelium within the lumen and 7 with acellular mucin in the appendiceal wall at the margin. Six patients underwent cecal resection and the others were nonsurgically followed. No cecal resection had residual neoplasia. No patient developed recurrence or pseudomyxoma peritonei (mean follow-up, 4.7 years).
In patients with LAMNs confined to the appendix, involvement of the appendectomy margin by neoplastic epithelium or acellular mucin does not predict recurrence of disease, even without further surgery. A conservative approach to managing these patients can be justified.
Goblet cell carcinoid tumors are amphicrine tumors whose biological behavior ranges from indolent to highly aggressive, depending on tumor grade. Current grading systems for these tumors are based on ...identifying an adenocarcinoma arising in the setting of a goblet cell carcinoid tumor, which distinguishes this tumor from other gastrointestinal tract adenocarcinomas. Because goblet cell tumors are predominantly tumors of mucin secreting cells, we propose that they be classified as goblet cell adenocarcinomas, and graded using a methodology that has parallels in colorectal adenocarcinoma grading. We graded a large series of goblet cell adenocarcinomas by assessing the proportion of the tumor that demonstrates tubular or clustered growth. Histologic grade correlated with overall survival independent of stage, with median overall survival of 204, 86, and 29 months for low-grade, intermediate-grade, and high-grade goblet cell adenocarcinomas, respectively. Tumor stage also correlated with overall survival. We also graded the tumors according to previously proposed grading systems, and found that these systems are valid, in that they segregate patients according to prognosis.
Secondary causes of nonalcoholic fatty liver disease Kneeman, Jacob M.; Misdraji, Joseph; Corey, Kathleen E.
Therapeutic Advances in Gastroenterology,
05/2012, Letnik:
5, Številka:
3
Book Review, Journal Article
Recenzirano
Odprti dostop
Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. ...Defined as the accumulation of fatty acid content greater than 5% of liver weight, NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis. The pathophysiology of NAFLD involves increased de novo synthesis of fatty acids in hepatocytes, the retention of lipids due to impaired hepatocyte apolipoprotein secretion or beta-oxidation. The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. In this review, we discuss uncommon but important causes of NAFLD, including inborn errors of metabolism, iatrogenic causes, viral hepatitis, and nutritional disorders to provide practicing clinicians with an understanding of the less well recognized causes of NAFLD.
There is limited data on the spectrum of molecular alterations in goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix. We used next generation sequencing to determine ...mutations of potential pathogenetic and therapeutic significance in this rare group of tumors. Adequate DNA was successfully extracted in 34/46 cases and the final group included 18 goblet cell carcinoids and 16 adenocarcinoma ex goblet cell carcinoids. Illumina TruSeq™ was used for sequencing exons of a custom 282 gene panel using an Illumina HiSeq 2000. All cases had a minimum coverage depth of at least 50 reads. After filtering through the Exome Sequencing Project, the number of mutations per case ranged from 0–9 (mean:3). The mutational burden in adenocarcinoma ex goblet cell carcinoids was significantly higher than goblet cell carcinoids (mean 5 vs. 3; p < 0.05) but the spectrum of alterations overlapped between the two groups. The most frequent mutations included ARID1A (4/34), ARID2 (4/34), CDH1 (4/34), RHPN2 (4/34), and MLL2 (3/34). Some mutations typically seen in conventional colorectal adenocarcinomas were also identified but with much lower frequency (APC :4/34; KRAS :2/34). MLL2 and KRAS mutations were only seen in adenocarcinoma ex goblet cell carcinoids and TP53 mutations were limited to poorly differentiated adenocarcinoma ex goblet cell carcinoids (2/34). Copy number changes could be evaluated in 15/34 cases and showed low copy number gains in CDKN1B (6/15) and NFKBIA (6/15), among others. The overlapping molecular alterations suggest that goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids are best considered two grades of differentiation of the same tumor rather than two distinct histological types. Mutations in TP53, CDH1 and MLL2 mutations were predominantly present in the adenocarcinoma ex goblet cell carcinoid group consistent with transformation to a higher grade lesion. The unique mutational profile also offers an explanation for the poor chemosensitivity in these tumors and highlights the need for developing new targeted therapies.
Inflammatory hepatocellular adenoma (HCA) is a recently categorized entity of hepatocellular neoplasms. We investigated whether gadoxetic acid-enhanced MRI can distinguish inflammatory HCA from focal ...nodular hyperplasia (FNH).
From January 1, 2009, through January 1, 2013, gadoxetic acid-enhanced MRI examinations from two institutions were reviewed for HCA, with specific histologic features of inflammatory HCA. Biopsy and resection slides were reviewed, and immunohistochemistry for glutamine synthetase was performed in a subset to confirm the initial diagnosis.
A total of 10 possible cases of inflammatory HCA were identified in the pathology database. On the basis of glutamine synthetase staining performed for this study, three cases were rediagnosed as FNH and thus were excluded from the study. Therefore, a total of seven patients with inflammatory HCA were identified. On gadoxetic acid-enhanced MRI, four of these patients had classic features of FNH (group A, FNH mimics), and three had imaging features suggestive of HCA (group B, typical inflammatory HCA). Imaging features that were considered diagnostic of FNH included isointense or minimal T2 hyperintensity, arterial enhancement, and diffuse hyperintensity on hepatobiliary phase. Three of the four patients with FNH mimics had slides available for pathologic rereview, and the diagnosis of inflammatory HCA was supported by glutamine synthetase immunohistochemistry findings. The pathology reports of the remaining four cases were rereviewed and were also found to have features consistent with inflammatory HCA.
Inflammatory HCA can mimic FNH on MRI, including hepatobiliary phase hyperintensity. Moreover, conventional pathology using histopathology alone may lead to misclassification of inflammatory HCA.
Aims
There is limited information regarding the clinicopathological and immunohistochemical characteristics of gastric pyloric gland adenomas (PGAs).
Methods and results
Sixty‐seven cases of gastric ...PGA from 57 patients were analysed. PGAs occurred with similar frequency in men and women (47.4 and 52.6%, respectively), with a mean age of 66 years. Most presented in the gastric body/fundus (67.2%). Fifteen cases (22.4%) developed against a background of autoimmune gastritis (AIG), whereas normal mucosa was seen in 35.8%. Only 16.4% (11 cases) developed in patients with a genetic predisposition, most commonly familial adenomatous polyposis. Low‐grade lesions had a mean size of 1.5 cm, while PGAs with high‐grade dysplasia (HGD) or adenocarcinoma had a mean size of 3.5 cm (P < 0.001) and more commonly showed tubulovillous architecture (50.0 versus 25.6% in low‐grade dysplasia; P = 0.040). Most PGAs (61.2%) co‐expressed mucin (MUC)5AC and MUC6 (mixed type), which was associated significantly with HGD or adenocarcinoma (P = 0.013). AIG was also associated with HGD (P = 0.027), but genetic predisposition did not correlate with the grade of dysplasia (P = 0.793). The recurrence rate of PGA was similar for high‐ (11.8%) and low‐grade lesions (7.4%) (P = 0.624).
Conclusions
The risk of HGD increases with the size of PGA, tubulovillous architecture and the presence of AIG as well as mixed immunophenotype. As the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be excised completely if possible, particularly if they are large or show high‐grade features.
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