Extent Of High-grade Dysplasia Research Articles

Pancreatic juice cytology as sensitive test for detecting pancreatic malignancy in intraductal papillary mucinous neoplasm of the pancreas without mural nodule

ObjectiveRecent studies reported that mural nodule (MN) was the most associated with malignant intraductal papillary mucinous neoplasms (IPMNs). However, IPMNs without MN cannot be diagnosed as malignant if only MN is determined to be indicator of malignancy. This study aimed to investigate role of pancreatic juice cytology for IPMNs without MN. MethodsMedical records of 50 patients with histologically proven malignant IPMNs were reviewed. Exclusively for non-invasive cancer, extent of high-grade dysplasia along the main pancreatic duct (MPD) was determined microscopically. ResultsThirty-six percent IPMNs had no MN. Cyst and main MPD diameter were significantly smaller in IPMN without MN compared to those in IPMN with MN (23 ± 14.1 vs 35 ± 13.2 mm, p = 0.010; 6.6 ± 4.3 vs 10.9 ± 6.1 mm, p = 0.006). Sensitivity of pancreatic juice cytology was higher in IPMN without MN compared to that in IPMN with MN (94% vs 53%, p = 0.004) although it could be affected by selection bias of study patients. Absence of MN was determined to be an independent factor associated with true positive cytology (OR = 24.3, p = 0.005). Extent of high-grade dysplasia was significantly longer in IPMN with true positive cytology compared to that in IPMN with false negative cytology (46.8 ± 20.5 vs 26.4 ± 11.0 mm, p = 0.005), and tended to be longer in IPMN without MN compared to that in IPMN with MN (47.0 ± 19.0 vs 36.0 ± 20.1 mm, p = 0.16). ConclusionsSensitivity of pancreatic juice cytology was excellent in IPMN without MN. Pancreatic juice cytology may be a sensitive test for detection of pancreatic malignancy in IPMN without MN compared to high-risk imaging features.

Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the Gallbladder (Neoplastic Polyps, Adenomas, and Papillary Neoplasms That Are ≥1.0 cm)

The literature on the clinicopathologic characteristics of tumoral intraepithelial neoplasms (neoplastic polyps) of the gallbladder (GB) is fairly limited, due in part to the variability in definition and terminology. Most reported adenomas (pyloric gland type and others) were microscopic and thus regarded as clinically inconsequential, whereas papillary in situ carcinomas have been largely considered a type of invasive adenocarcinoma under the heading of "papillary adenocarcinomas." In this study, 123 GB cases that have a well-defined exophytic preinvasive neoplasm measuring ≥1 cm were analyzed. The patients were predominantly female (F/M=2:1) with a mean age of 61 y and a median tumor size of 2.2 cm. Half of the patients presented with pain, and in the other half the neoplasm was detected incidentally. Other neoplasms, most being gastrointestinal tract malignancies, were present in 22% of cases. Gallstones were identified in only 20% of cases. Radiologically, almost half were diagnosed as "cancer," roughly half with polypoid tumor, and in 10% the lesion was missed. Pathologic findings: (1) The predominant configuration was papillary in 43%, tubulopapillary in 31%, tubular in 26%. (2) Each case was assigned a final lineage type on the basis of the predominant pattern (>75% of the lesion) on morphology, and supported with specific immunohistochemical cell lineage markers. The predominant cell lineage could be identified as biliary in 50% (66% of which were MUC1), gastric foveolar in 16% (all were MUC5AC), gastric pyloric in 20% (92% MUC6), intestinal in 8% (100% CK20; 75% CDX2; 50%, MUC2), and oncocytic in 6% (17% HepPar and 17% MUC6); however, 90% of cases had some amount of secondary or unclassifiable pattern and hybrid immunophenotypes. (3) Of the cases that would have qualified as "pyloric gland adenoma," 21/24 (88%) had at least focal high-grade dysplasia and 18% had associated invasive carcinoma. Conversely, 8 of 47 "papillary adenocarcinoma"-type cases displayed some foci of low-grade dysplasia, and 15/47 (32%) had no identifiable invasion. (4) Overall, 55% of the cases had an associated invasive carcinoma (pancreatobiliary type, 58; others, 10). Factors associated significantly with invasion were the extent of high-grade dysplasia, cell type (biliary or foveolar), and papilla formation. Among systematically analyzed invasive carcinomas, tumoral intraepithelial neoplasia was detected in 6.4% (39/606). (5) The 3-year actuarial survival was 90% for cases without invasion and 60% for those associated with invasion. In contrast, those associated with invasion had a far better clinical outcome compared with pancreatobiliary-type GB carcinomas (3-yr survival, 27%), and this survival advantage persisted even with stage-matched comparison. Death occurred in long-term follow-up even in a few noninvasive cases (4/55; median 73.5 mo) emphasizing the importance of long-term follow-up. In conclusion, tumoral preinvasive neoplasms (≥1 cm) in the GB are analogous to their pancreatic and biliary counterparts (biliary intraductal papillary neoplasms, pancreatic intraductal papillary mucinous neoplasms, and intraductal tubulopapillary neoplasms). They show variable cellular lineages, a spectrum of dysplasia, and a mixture of papillary or tubular growth patterns, often with significant overlap, warranting their classification under 1 unified parallel category, intracholecystic papillary-tubular neoplasm. Intracholecystic papillary-tubular neoplasms are relatively indolent neoplasia with significantly better prognosis compared with pancreatobiliary-type GB carcinomas. In contrast, even seemingly innocuous examples such as those referred to as "pyloric gland adenomas" can progress to carcinoma and be associated with invasion and fatal outcome.

Barrett's esophagus: diagnostic challenges and recent developments

Inclusion of histologic classification into the risk assessment of adenocarcinoma arising from Barrett's esophagus (BE) has placed surgical pathologist in the center of clinical care and research endeavors. Recent advances in endoscopic diagnostic and therapeutic modalities demand additional proficiency in diagnosis and grading of dysplasia. The objectives of this study are as follows: (1) Discuss the definition of BE and features differentiating BE vs intestinal metaplasia involving cardia. (2) Describe the morphological approach of diagnosing and grading of dysplasia and differentiation of high-grade dysplasia from intramucosal carcinoma. (3) Role of special stains in diagnosis of BE and dysplasia. (4) Brief review the literature on histologic and endoscopic factors associated with progression of BE to adenocarcinoma. (5) Discuss the biomarkers in progression of BE to adenocarcinoma. The following conclusions from this review are important and should be applied in routine practice. Because of the controversy in defining BE, the histologic type of columnar mucosa and presence or absence of intestinal metaplasia should be specified in pathology report. The major limitations of appropriately diagnosing and grading dysplasia include technical problems related to biopsy processing and staining, presence of acute inflammation, and high interobserver variations among pathologists. The extent of high-grade dysplasia, high-grade dysplasia with certain endoscopic abnormalities, and low-grade dysplasia, when diagnosed with consensus by 2 or 3 gastrointestinal pathologists, has higher risk of progression to adenocarcinoma. All nonhistologic markers are still in the investigational phase and have not yet been validated in phase 3/4 prospective trials.

Extent of Low-Grade Dysplasia Is a Risk Factor for the Development of Esophageal Adenocarcinoma in Barrett's Esophagus

Previous studies that evaluated extent of high-grade dysplasia (HGD) as a risk factor for esophageal adenocarcinoma (EA) in Barrett's esophagus (BE) were conflicting, and no prior study has evaluated extent of low-grade dysplasia (LGD) as a risk factor. The aim of this discovery study was to evaluate the hypothesis that extent of LGD and HGD are risk factors for progression to EA. We evaluated baseline biopsies from 77 BE patients with dysplasia including 44 who progressed to EA and 33 who did not progress during follow-up. The total numbers of LGD and HGD crypts were determined separately by counting all crypts and the extent of LGD, HGD, and total dysplasia were correlated with EA outcome. Thirty-one and 46 patients had a maximum diagnosis of LGD and HGD, respectively. When the crypts were stratified by dysplasia grade, the mean number of LGD crypts per patient was borderline higher in progressors (93.9) compared with nonprogressors (41.2, P= 0.07), and the mean proportion of LGD crypts per patient was significantly higher in progressors (46.4%vs 26.0%, P= 0.037). Neither the mean number of HGD crypts per patient (P= 0.14) nor the mean proportion of HGD crypts per patient (P= 0.20) was significantly associated with EA outcome. The extent of LGD is a significant risk factor for the development of EA in BE in this study. Although the presence of HGD is significantly associated with a greater relative risk for development of EA, the extent of HGD was not an independent risk factor for progression.

Barrett metaplasia: reassessment of treatment and follow-up.

The incidence of esophageal adenocarcinoma continues to rise in the Western world, with a mean 5-year survival of less than 20%. There has therefore been increasing interest in the precursor lesion, Barrett's esophagus. However, adenocarcinoma will not develop in most patients with Barrett's esophagus. This review summarizes the data on the management of Barrett's esophagus that have been published since January 2003. The control of reflux symptoms significantly improves quality of life, and surgical antireflux therapy may gradually cause regression of the Barrett segment compared with proton pump inhibitor therapy. The data substantiate the claim that the cancer risk in Barrett esophagus is lower than had hitherto been suggested. The risk factors for progression include increasing age and length of segment, macroscopic inflammatory changes, loss of heterozygosity over several genetic loci, and increased proliferation status. The extent of high-grade dysplasia may not accurately predict cancer development, and continued surveillance, rather than intervention, for such patients may decrease the chances of curative treatment. Long-term follow-up data are beginning to accumulate for nonsurgical treatment strategies. Chemoprevention trials are under way to evaluate the role of acid suppression and nonsteroidal anti-inflammatory drugs and their derivatives. At this time, endoscopic surveillance and surgical management remain the mainstay, but continued research efforts should enable risk stratification and cancer prevention in the future.

Endoscopic appearance and extent of high-grade dysplasia in Barrett’s esophagus can predict the presence of cancer at esophagectomy

Endoscopic appearance and extent of high-grade dysplasia in Barrett's esophagus can predict the presence of cancer at esophagectomy

The approach to high grade dysplasia in Barrett’s esophagus

Buttar et al. at the Mayo Clinic performed a study whose aim was to determine whether patients who have Barrett’s esophagus with focal high-grade dysplasia (HGD) have the same risk of developing adenocarcinoma as those with diffuse high grade dysplasia. Barrett’s esophagus is a change in the normal esophageal squamous epithelial lining to specialized columnar epithelium, which is typically seen in patients with gastroesophageal reflux disease (1). Of the patients who develop Barrett’s esophagus, approximately 5–10% will be at risk of developing adenocarcinoma (2). Currently, the best predictor for the development of cancer is histological classification of dysplasia on biopsy. Patients who have biopsy-proven HGD have an increased risk of progressing to adenocarcinoma (3). Surgical resection is typically the therapeutic recommendation for operative candidates who are diagnosed with HGD (4). However, it is not known whether the extent of HGD has any correlation with the risk of developing adenocarcinoma. This study involved a retrospective cohort of 100 consecutive patients who had histology-proven HGD on esophageal biopsy with no obvious adenocarcinoma. Slides were reviewed and results confirmed by two expert pathologists. Thirty-three patients were categorized as having focal HGD, in which histological features were limited to a single focus of five or fewer crypts, and 67 were categorized as having diffuse HGD, in which histological features involved more than five crypts in a single biopsy specimen or more than one biopsy fragment. The endpoint of the study was the histological diagnosis of esophageal adenocarcinoma, with the index point being the first endoscopic biopsy diagnosis of HGD at the Mayo Clinic. Cancer-free survival was determined by the interval between the index date and the diagnosis of cancer/esophagectomy or the date of the last cancer-free endoscopic surveillance. Nine of the patients with focal HGD and 25 of the patients with diffuse HGD were managed surgically. The remaining patients were carefully observed undergoing endoscopic surveillance every 3 months by the same endoscopist utilizing an intensive biopsy protocol involving four quadrant biopsy specimens taken at 1 cm intervals. The results showed that cancer-free survival rates at 1 and 3 yr were 93% and 86%, respectively, for focal HGD versus 62% and 44% for diffuse HGD ( p < 0.001). Within the 8-yr follow-up, 32 of the 100 patients developed adenocarcinoma (four patients categorized as focal HGD and 28 patients categorized with diffuse HGD). Nineteen of these 32 patients were diagnosed with adenocarcinoma within 6 months of their diagnosis with HGD (two patients with focal HGD and 17 with diffuse HGD). Fifteen of the 34 patients who underwent esophagectomy as therapy were found to have adenocarcinoma not previously recognized by biopsy samples (one in a patient with focal and 14 in patients with diffuse). The remaining 66 patients not undergoing esophagectomy underwent endoscopic surveillance alone or combined with photodynamic therapy. Of these 66 patients, three of the focal and 17 of the diffuse were diagnosed with adenocarcinoma. Their conclusion was that the patients with diffuse HGD were more likely to develop cancer during the 1st yr after diagnosis and on continuing follow-up than were patients with focal HGD.

The approach to high grade dysplasia in Barrett's esophagus.

The approach to high grade dysplasia in Barrett's esophagus.

Extent of high-grade dysplasia in barrett's esophagus correlates with risk of adenocarcinoma

Extent of high-grade dysplasia in barrett's esophagus correlates with risk of adenocarcinoma

Extent of high-grade dysplasia in Barrett's esophagus correlates with risk of adenocarcinoma

The identification of any high-grade dysplasia (HGD) in Barrett's esophagus has been considered to be an indication for esophagectomy because of the increased risk of cancer. The aim of this study was to determine if a limited extent of HGD has the same potential for cancer as diffuse HGD. A retrospective cohort study was performed to assess the risk of developing adenocarcinoma in relationship to the extent of HGD found on endoscopic surveillance. The extent of HGD was defined as focal if cytologic and/or architectural changes of HGD were limited to a single focus of 5 or fewer crypts and diffuse if more than 5 crypts were involved in a single biopsy specimen or if HGD involved more than one biopsy fragment. The relative risk of cancer was assessed using a Cox proportional hazard model, and cancer-free survival was determined using survival curves. Sixty-seven patients with diffuse HGD and 33 with focal HGD satisfied selection criteria. Cancer-free survival rates at 1 and 3 years were 93% and 86% for focal HGD compared with 62% and 44% for diffuse HGD (P < 0.001). On univariate analysis, extent of HGD (relative risk, 5.36; 95% confidence interval, 1.84-15.56), nodularity on endoscopy (relative risk, 3.98; 95% confidence interval, 1.97-8.04), and lack of acid suppression (relative risk, 2.48; 95% confidence interval, 1.16-5.28) were associated with an increased risk of esophageal adenocarcinoma. Diffuse HGD had a 3.7-fold increase in the risk of esophageal cancer compared with focal HGD (P = 0.02) on multivariate analysis. Patients with focal HGD are less likely to have cancer during the first year after diagnosis or on subsequent follow-up compared with diffuse HGD.

Does the extent of high grade dysplasia in Barrett's esophagus matter?

Does the extent of high grade dysplasia in Barrett's esophagus matter?