A proposal for a new validated histological definition of the gastroesophageal junction

Present definitions of the gastroesophageal junction (GEJ) are the point of flaring of the tubular esophagus and the proximal limit of the gastric rugal folds. Neither of these has been validated as the true GEJ. This study aims to validate the location of the true GEJ using the criterion of esophageal submucosal glands. Ten esophagogastrectomy specimens, in which there was a well-defined point of flaring of the tubular esophagus that coincided with the proximal limit of gastric rugal folds, were examined by complete histological mapping to evaluate the distribution of esophageal submucosal glands and surface epithelial types. Oxyntocardiac and cardiac mucosa with or without intestinal metaplasia were present under rugal folds distal to the end of tubular esophagus in all patients to a length of 0.31 to 2.05 cm. Submucosal glands were present in the tubular esophagus and in the proximal pouch distal to the tubular esophagus in a distribution that closely coincided with squamous epithelium, oxyntocardiac, cardiac, and intestinal epithelia. Submucosal glands were never found under oxyntic mucosa. We conclude that a variable part of the saccular region distal to the tubular esophagus contains esophageal submucosal glands, therefore representing reflux-damaged distal esophagus. This results in an error, where up to 2.05 cm of distal reflux-damaged dilated esophagus can be mistaken as proximal stomach when presently accepted definitions for the GEJ are used. The true GEJ is the proximal limit of gastric oxyntic mucosa defined by histology.     

Pathology of the gastroesophageal junction

The gastroesophageal junction (GEJ) is a poorly defined anatomic area that represents the junction etween the distal esophagus and the proximal stomach (cardia). The true anatomic GEJ corresponds to the most proximal aspect of the gastric folds, which represents an endoscopically apparent transition oint in most individuals. Many, if not most, adults, particularly those with either physiologic or logic GERD, have a proximally displaced Z-line indicating that the histologic squamocolumnar nction (SCJ) is located above the anatomic GEJ. The histologic characteristics of short segments of columnar mucosa located above the anatomic GEJ in these individuals are similar to the gastric cardia, ng composed of either pure mucous glands or mixed mucous glands/oxyntic glands. Although controversial, some authors believe that the cardia is normally composed, at birth, of surface mucinous columnar epithelium and underlying oxyntic glands identical to the gastric corpus, whereas others maintain that the true anatomic cardia is normally composed of mucinous columnar epithelium with underlying mucous glands or mixed mucous and oxyntic glands. However, the preponderance of evidence supports the latter theory and that the length of mucosa composed of either mucous, or mixed mucous glands/oxyntic glands, increases with age and is presumed to be related to ongoing GERD. Inflammation of the true gastric cardia (carditis), which is most often due to H. pylori infection, is difficult to distinguish from columnar metaplasia of the distal esophagus secondary to GERD. From a pathologist's perspective, the differential diagnosis of true gastric carditis from esophageal columnar metaplasia of the distal esophagus in GEJ biopsies is difficult, but a variety of clinical, pathologic, and immunohistochemical methods can be used to help separate these two disorders. Nearly one-third of patients who present for upper GI endoscopy without endoscopic evidence of BE reveal foci of intestinal metaplasia in the GEJ. There are some studies to suggest that the risk of dysplasia and cancer is different in patients with intestinal metaplasia in the cardia related to H. pylori infection versus those with metaplastic columnar epithelium in the distal esophagus related to GERD. Chronic inflammation is generally considered the predominant underlying stimulus for the development of columnar metaplasia in the GEJ, regardless of the etiology. Columnar metaplasia and intestinal metaplasia in the distal esophagus represents a squamous to columnar cell transition and there is some evidence that this occurs through an intermediate, or transitional, phase of intestinalization termed multilayered epithelium. In contrast, intestinal metaplasia that develops in the true gastric cardia secondary to H. pylori infection represents a columnar to columnar metaplastic reaction. This review will focus on the clinical, pathologic, and pathogenetic aspects of GERD and H. pylori-induced inflammation of the GEJ region.     

The histopathologic spectrum of carcinomas involving the gastroesophageal junction in the Chinese

Carcinomas involving the gastroesophageal junction are common in China. The histopathologic characteristics of these cancers have not been systematically investigated. Reported are 41 such resected cancers from Chinese patients (30 men, 11 women). Their mean age was 62 years. The mean tumor size was 4.4 cm (range, 2 to 9 cm), and 58% were poorly differentiated. An unusual spectrum of tumor differentiation was observed, including adenocarcinomas (83%), adenosquamous (32%), colloid (2%), signet-ring (10%), squamous (5%), oncocytic (7%), pancreatic acinar (12%), and neuroendocrine (5%) carcinomas. Cancers with multiple types of differentiation in the same tumor were identified in 37 cases (90%). The adjacent gastric cardiac mucosa showed hyperplasia, oncocytic, and pancreatic acinar metaplasia, and mild chronic inflammation. Dysplasia was uncommon (n = 6). Barrett esophagus was not identified. Carcinomas involving the gastroesophageal junction in the Chinese are morphologically distinct, heterogeneous, and may be of esophageal origin.     

Neuroendocrine in Barrett's mucosa and adenocarcinomas of the gastroesophageal junction

We estimated the prevalence and prognostic significance of neuroendocrine (NE) cells in a series of 208 resection specimens containing gastroesophageal junction (GEJ) adenocarcinomas, with 56 specimens containing Barrett's mucosa. Immunohistochemically, chromogranin A (CGA) was positive in 49% (102/208) of GEJ adenocarcinomas and in 68% (38/56) of Barrett's mucosas. CGA in GEJ tumors correlated with pTNM stage. CGA in Barrett correlated with pTNM stage and tumor grade of the adjacent carcinoma. Patients with CGA in Barrett had better survival than patients without CGA in Barrett, with 5-year survival percentages of 56% and 9%, respectively. In multi-variate analysis, CGA in Barrett was an independent prognostic factor for survival after surgery. Therefore CGA in Barrett adjacent to GEJ adenocarcinoma might be helpful in the assessment of patient outcome.     

Anatomical and histological morphometry of the sural nerve in human fetuses

Introduction

In our study, the aim was to anatomically and histologically investigate the morphometric structures of the branches involved in the sural nerve and sural nerve formation.

食管胃交界腺癌——一个值得病理学家关注的问题

食管胃交界（esophagogastric junction or gastroesophageal junction）是指食管远端和胃近端——贲门的交界处,是一非常短的解剖学区域。食管胃交界腺癌是指横跨食管和胃交界的腺癌。在过去的几十年中,美国和西欧国家食管胃交界区域腺癌的发生率出现惊人的上升趋势。与此同时,胃癌的发生部位也发生了显著变化,远端胃癌的发病率明显下降而近端胃癌的发病率则呈明显增高的趋势,其原因尚不十分明确。     

Microvascularization of the mucocutaneous junction of the eyelid in fetuses and neonates

The aim of this study was to specify the microvascularization of the junctional region between the integuments of the superficial surface of the free margin of the eyelid and the palpebral conjunctival mucosa. The study was carried out using histological or transparified slices of upper and lower eyelids taken from fetuses and neonates, in which the vascular system was injected with agarized China ink. The mucocutaneous junction of the eyelid is located at the posterior border of the free margin and extends to its deep surface. It has vascular similarities to the oral cavity and the nasal pyramid. Under a thickened avascular epithelium, there is a papillary network composed of characteristic loops that are less raised than in the lips but more developed than in the nose. The superficial and deep vascular reticular networks are comparable in fundamental arrangement to those of other junctional zones. Thus, the palpebral mucocutaneous junction shows cutaneous-type microvascularization, just like the other junctional zones of the head.     

Barrett's metaplasia and adenocarcinoma of the esophagus and gastroesophageal junction

Most previous studies of Barrett's metaplasia have used biopsy material to document cell, gland, and architectural types, leading to inaccurate or incomplete conclusions. The present study presents data from eight esophagogastrectomy specimens of Barrett's metaplasia with associated neoplasia, which were evaluated topologically by use of dissecting microscopy, specimen radiography, scanning electron microscopy, and routine histologic examination. Barrett's metaplasia was found to be mosaic of cell, gland, and architectural types, showing variable degrees of atrophy and maturation toward intestinal and gastric epithelium. Zonation was not found. Surface mucous, goblet, absorptive, mucous neck, mucous gland, and neuroendocrine cells were found in all cases; Paneth, chief, and parietal cells were found in approximately half. The presence of villar architecture with lining goblet and absorptive cells is unique and can be used to make a biopsy diagnosis. In one case, only a minute residual focus of Barrett's metaplasia was found, suggesting that the pathogenesis of some cases of adenocarcinoma of the lower esophagus and gastric cardia unassociated with Barrett's metaplasia may be the same. Nine cases of adenocarcinoma of the gastroesophageal junction unassociated with Barrett's metaplasia, studied during the same time period, had similar epidemiologic characteristics including mean age, age range, and sex distribution. Multifocal dysplasia and carcinoma in situ were found in all but one case. In two of eight cases adenomatous change was present; one of these resembled a villous adenoma of the colon with malignant degeneration. Barrett's metaplasia thus appears to be important as a precursor of adenocarcinoma in the region of the lower esophagus and gastroesophageal junction. The significance of these findings in relation to previous reports is discussed.     

HER2 testing in gastric and gastroesophageal junction adenocarcinomas

HER2 evaluation has become standard practice in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinomas. In 2010, the international ToGA (Trastuzumab for Gastric Cancer) trial demonstrated improved survival in patients with HER2 overexpressing gastric and GEJ adenocarcinomas who were treated with trastuzumab (Herceptin^®) in combination with standard chemotherapy. The evaluation of HER2 in gastric and GEJ adenocarcinomas has several key differences compared to the HER2 evaluation that has been traditionally performed for breast carcinomas. In addition to differences in immunohistochemistry scoring, there are also differences in judging adequacy of biopsy specimens. Furthermore, the routine evaluation of HER2 expression in gastric and GEJ adenocarcinomas is still relatively new and widespread programs for quality assessment have not been well established. This review examines the critical issues to consider in the implementation of HER2 evaluation for gastric and GEJ adenocarcinomas.     

Vitamin D receptor expression in the mucosal tissue at the gastroesophageal junction

Barrett's esophagus is considered to be a precursor to adenocarcinoma and the information on VDR expression in normal and Barrett's esophagus is significantly lacking. In this study, we examined the expression of VDR in the lower esophagus and gastric cardia of normal and Barrett's esophagus by immunofluorescence. Columnar mucosa but not squamous mucosa at the gastroesophageal junction showed positive immunofluorescence to VDR. Submucosal glands and ducts deep to the normal squamous mucosa stained positive for VDR and localized in the cytoplasm and perinuclear regions with no nuclear staining. Interestingly, Barrett's mucosa stained strongly positive for VDR. Glandular structures in the mucosal layer were far less abundant in the Barrett's mucosa than in the normal gastric mucosa. As a result, fewer structures deep to the Barrett's epithelial layer stained positive for VDR when compared to normal gastric mucosa. These findings suggest that in normal esophagus VDR expression is restricted to columnar epithelium and glandular structures. Furthermore, strong VDR expression in Barrett's mucosa may indicate an increased sensitivity of this tissue to endogenous or therapeutic effects of Vitamin D.     

Relationship between histological findings and clinical findings in rheumatoid arthritis

The aim of the present study was to compare histological findings and clinical symptoms of patients with advanced stages of rheumatoid arthritis (RA). Synovial tissue specimens were obtained during reconstructive knee surgery from 93 RA patients (18 men; 75 women). The histological assessments of specimens were evaluated using two histological scoring systems reported by Rooney and Koizumi. Clinical symptoms (duration of morning stiffness, joint score, grip strength), laboratory data (erythrocyte sedimentation ratio, C-reactive protein (CRP), rheumatoid factor), X-ray findings (Larsen score) and drug usage were assessed before surgery. Significant statistical correlations between both histological scoring systems were observed; however, there was no significant correlation between the clinical findings and the histological scoring systems. A statistically significant correlation was found between the levels of CRP and Koizumi's scoring system. In addition, Koizumi score correlated significantly to X-ray findings. Rooney's scoring system had an inverse correlation to methotrexate history. Histological findings do not correlate to simultaneous clinical symptoms in advanced RA patients. However, our data indicate that observed histological changes reflect X-ray damage.     

Significance of acid-mucin-positive nongoblet columnar cells in the distal esophagus and gastroesophageal junction

Acidic mucin-positive nongoblet columnar cells (NGCC) have recently been observed in the surface epithelium of the gastroesophageal junction (GEJ) and distal esophagus in resections from patients with traditional long segment (>3 cm) Barrett's esophagus (BE). However, the significance of finding acidic mucin-positive NGCC in the surface epithelium of biopsy specimens from the distal esophagus/GEJ region in the absence of goblet cells (GC) remains unknown. Therefore, to determine the significance of mucin histochemical changes in the distal esophagus/GEJ region, we analyzed and compared the types, prevalence, and distribution of neutral and acidic mucins in biopsy specimens obtained from 2 groups of patients: those with (32 patients) and those without (107 patients) GC identified in this area. Various mucin histochemical stains (PAS-Ab pH 2.5, HID-Ab pH 2.5, PB/KOH/PAS) were used to identify neutral mucins, acidic mucins (sialomucins and sulphomucins), and o-acetylated sialomucins. The results were compared between the 2 patient groups and correlated with the clinical, endoscopic, and pathologic features. Compared with patients without GC, patients with GC had a significantly higher male/female ratio and a higher proportion of patients with greater than 3 cm of columnar epithelium within the esophagus. Acidic mucin (sialomucin and sulphomucin)-positive NGCC in the surface, foveolar, and glandular epithelium did not show any correlation with any of the clinical, endoscopic, or pathologic features, such as esophagitis, carditis, antritis, Helicobacter pylori infection, or length of columnar epithelium in the distal esophagus. However, acidic mucin-positive NGCC correlated strongly with the presence of GC (P < .001). For example, sialomucin-positive NGCC were present in 28 of 32 (88%) patients with GC compared with 31 of 107 (29%) patients without GC (P < .001). Similarly, sulphomucin-positive NGCC were present in 20 of 32 (62%) patients with GC, compared with 11 of 107 (10%) patients without GC (P < .001). Of the non-GC cases, all biopsy specimens that stained positively for sulphomucin in surface NGCC (11 specimens), except one, showed staining restricted to the surface of multilayered epithelium, a distinctive type of epithelium that shows morphological, ultrastructural, and cytochemical features of both squamous and columnar epithelium. Sialomucin positivity in surface NGCC from the distal esophagus/GEJ region is a sensitive (sensitivity 88%), but nonspecific (specificity 71%), indicator of GC metaplasia. In contrast, sulphomucin expression in NGCC from the same anatomic area is a less sensitive (sensitivity 62%), but more specific (specificity = 90%) marker for the presence of metaplastic epithelium, of either the GC or the multilayered epithelial cell type and thus may represent an early or incomplete form of intestinal metaplasia.     

Optical properties of adenocarcinoma and squamous cell carcinoma of the gastroesophageal junction

Photodynamic therapy (PDT) is an alternative to radical surgical resection for T1a or nonresectable carcinomas of the gastroesophageal junction. Besides the concentration of the photosensitizer, the light distribution in tissue is responsible for tumor destruction. For this reason, knowledge about the behavior of light in healthy and dysplastic tissue is of great interest for careful irradiation scheduling. The aim of this study is to determine the optical parameters (OP) of healthy and carcinomatous tissue of the gastroesophageal junction in vitro to provide reproducible parameters for optimal dosimetry when applying PDT. A total of 36 tissue samples [adenocarcinoma tissue (n=21), squamous cell tissue (n=15)] are obtained from patients with carcinomas of the gastroesophageal junction. The optical parameters are measured in 10-nm steps using new integrating sphere spectrometers in the PDT-relevant wavelength range of 300 to 1140 nm and evaluated by inverse Monte-Carlo simulation. Additional examinations are done in healthy tissue from the surgical safety margin. In the wavelength range of frequently applied photosensitizers at 330, 630, and 650 nm, the absorption coefficient in tumor tissue (adenocarcinoma 1.22, 0.16, and 0.15 mm(-1); squamous cell carcinoma 1.48, 0.13, and 0.11 mm(-1)) is significantly lower than in healthy tissue (stomach 3.34, 0.26, and 0.20 mm(-1); esophagus 2.47, 0.21, and 0.18 mm(-1)). The scattering coefficient of all tissues decreases continuously with increasing wavelength (adenocarcinoma 22.8, 12.99, and 12.52 mm(-1); squamous cell carcinoma 19.44, 9.35, and 8.98 mm(-1); stomach 20.55, 13.96, and 13.94 mm(-1); esophagus 20.34, 12.56, and 12.22 mm(-1). All tissues show an anisotropy factor between 0.80 and 0.94 over the entire spectrum. The maximum optical penetration depth for all tissues is achieved in the range of 800 to 1100 nm. At the wavelength range of 330, 630, and 650 nm, the optical penetration depth is significantly higher in carcinoma tissue (adenocarcinoma 0.27, 1.54, and 1.66 mm; squamous cell carcinoma 0.23, 1.71, and 1.84 mm) than in healthy tissue (stomach 0.16, 1.10, and 1.26 mm; esophagus 0.17, 1.47, and 1.65 mm; p<0.05). Above 1000 nm, a higher absorption coefficient of tumor tissue results in a lower optical penetration depth than in healthy tissue (p<0.05). The higher absorption and scattering of the tumor tissue in the wavelength range of available photosensitizer is associated with a low optical penetration depth. This necessitates higher energy doses and long application times or repeated applications to effectively treat large tumor volumes. Photosensitizers optimized for larger wavelength range need to be developed to increase the efficacy of PDT.     

Duodenal window revisited: A histological study using human fetuses

To assess the development of the duodenal window in fetuses, we examined semiserial histological sections of 59 human fetuses with a crown‐rump length of 27–156 mm (～4–18 weeks of gestation). In 44 of the 54 fetuses with horizontal sections, the duodenal window was formed by interdigitation of the anterior and posterior muscle slips from the proper duodenal circular muscle coat. The anterior slips approached the common bile duct from the anterior side and wound around the bile duct from the right aspect, whereas the posterior slips approached the main pancreatic duct from the posterior side, reaching the left or outer aspect of the duct without winding. These slips may become longitudinal muscles in the ampulla after birth. Six specimens showed variations in this typical pattern, in that the posterior muscle slips as well as the duodenal longitudinal muscle coat wound around the bile duct. In the remaining four specimens, we observed an abnormal union of the bile and pancreatic ducts, with the duodenal circular muscles suddenly ending along the window or slightly inserted into the right side of the common duct after joining. In all later‐stage fetuses, the common sphincter surrounded both the bile and pancreatic ducts in the ampulla. Consequently, at and along the duodenal window, the proper duodenal circular muscle seemed to contribute to fetal sphincter formation. The window was not a simple hiatus but a functional interface between the sphincter and the duodenal wall. Clin. Anat. 26:598–609, 2013. © 2012 Wiley Periodicals, Inc.     

Aggregate anaphylaxis in the monkey: haematological and histological findings

Haematological and histological studies were made following challenge in 8 monkeys (Macaca irus) sensitized with ovalbumin. Haemagglutinating, but no reaginic antibodies to ovalbumin were demonstrated before challenge. Both platelet and leucocyte counts decreased markedly (-80 and -89%, respectively) within 5 min after challenge. No evidence of haemoconcentration was found. Plasma fibrinogen decreased (-74%), indicating activation of the coagulation system. Histological examination revealed platelets, leucocytes, fibrin and a large number of hyaline globuli ('globular microemboli') in pulmonary capillaries and small arterioles. From their staining properties the globuli were considered to consist mainly of fibrin. Some globuli were also found in the liver and kidneys, but were rarely seen in other organs. It is concluded that the anaphylactic reaction in this experimental model can be classified as aggregate anaphylaxis, and it is suggested that platelet mediators play an important role in the early pulmonary vascular and respiratory response.