Gastrointestinal Pathology. Группа авторов
cell carcinoma and dysplasia. The regenerating epithelial cells have round nuclei with minimally thickened nuclear membranes; fine chromatin; and large, irregular nucleoli, and generally have abundant cytoplasm. Further, maturation toward the epithelial surface can usually be found. In difficult cases, additional biopsies should be requested after medical treatment of the esophagitis. However, in some cases, inflammatory pseudotumors with marked atypia of the reactive stromal cells will need to be differentiated from poorly differentiated carcinoma or sarcoma. Cytokeratin immunohistochemistry (IHC) may be helpful when trying to distinguish between reparative reactions and malignancy.
Less commonly, activated lymphocytes in areas of ulceration may appear atypical and raise the suspicion for lymphoma. In some cases, immunohistochemistry and/or flow cytometry may be necessary to assess for clonality.
Prognosis, Evolution, and Clinical Management
GERD management is based on the severity and potential for complications and largely consists of lifestyle modification, anti‐acid medications or surgery. Most nonerosive or minimally erosive (Los Angeles Grade A) responds to a combination of lifestyle modifications and low‐dose (single daily proton pump inhibitor [PPI] such as omeprazole) anti‐acid therapy. Lifestyle modifications include weight loss, avoiding large meals with two to three hours of bedtime (where gravity no long prevents “upward” reflux), and minimizing specific refluxogenic foods (alcohol, mint, fatty food, chocolate, caffeine). PPI therapy is highly effective, even for severe erosive GERD but may require twice‐daily therapy. More than 95% of patients will heal erosive disease on PPI therapy.
Surgical therapy is aimed at restoring the lower esophageal sphinter pressure zone and angle of His, and reducing hiatal hernias. Surgery is also highly effective with more than 80% of individuals having sustained elimination or reduction in GERD symptoms and use of PPI. The major side effect of surgery is retention of gas in the stomach (“gas‐bloat syndrome”) due to the inability to naturally belch swallowed air.
Eosinophilic Esophagitis
Definition, General Features, Predisposing Factors
Eosinophilic esophagitis (EOE) is a chronic, immune‐mediated or antigen‐mediated inflammatory condition characterized by symptomatic esophageal dysfunction and eosinophil predominant mucosal inflammation. EOE represents a type 2 (Th2) helper T cell and cytokine‐mediated disorder involving genetic predisposition, environmental exposures, and allergic background. Food‐based antigens appear to be the dominant mediators of EOE, although aeroallergens may also act as triggers in susceptible patients.
Since it was first established as a distinct clinicopathologic entity in 1993, EOE has become an increasingly recognized cause of dysphagia and esophageal dysfunction, particularly among patients refractory to medical treatment of gastroesophageal reflux disease.
EOE is reported worldwide, with highest prevalence in the United States and Western Europe. It occurs more frequently in children and young adults, although it is increasingly recognized in older adults, and is more common in males (male‐to‐female ratio of 3–4 : 1). A history of other allergic conditions may be present, such as asthma and atopic dermatitis, as well as peripheral eosinophilia, which are more common in children.
Current diagnostic criteria for EOE include a combination of clinical and pathologic features (Table 2.3).
Table 2.3 Definition of eosinophilic esophagitis and diagnostic criteria.
| Symptoms related to esophageal dysfunction |
| Eosinophil‐predominant inflammation on esophageal biopsy, characteristically consisting of a peak value of ≥15 eosinophils per high‐power field (EOS/HPF) |
| Mucosal eosinophilia is isolated to the esophagus and persists after a PPI trial |
| Secondary causes of esophageal eosinophilia excluded (Table 2.5) |
| A response to treatment (dietary elimination; topical corticosteroids) supports the diagnosis of EOE, but is not required. |
Figure 2.12 Endoscopic appearance of eosinophilic esophagitis (a) with so‐called feline esophagus appearance and (b) with extensive white microabcesses. Subtle circular rings and longitudinal furrows also present.
Clinical Features and Endoscopic Characteristics
Eosinophilic esophagitis (EOE) is increasing in prevalence and often seasonal with spikes during typically airborne allergy season. It presents with dysphagia to solids, classically with pills sticking. Other atopic symptoms are common. At endoscopy, the esophagus has white punctate spots (eosinophilic microabscess), rings, longitudinal furrows (Figure 2.12), and desquamates easily with insufflation or dilation. In late stages, the esophagus may be very narrowed and poorly distensible.
Microscopic Features
Esophageal biopsies are required to diagnose EOE. Eosinophils are generally absent from the esophageal squamous epithelium in normal individuals. The histologic hallmark is the presence of an increased number of eosinophils within the squamous epithelium (Figure 2.13). Although there is no exact threshold number that establishes a diagnosis, 15 eos/HPF (peak count) in at least one biopsy is considered a “minimum” threshold.
Eosinophilia may be patchy, and it is recommended that two to four biopsies from at least two locations in the esophagus should be taken to maximize diagnostic yield. The distribution of eosinophilia is important, as they may be identified in both proximal and distal biopsies or be more prominent in proximal biopsies. Practically, only intact eosinophils with visible nuclei should be counted and eosinophilic granules should not be included, although degranulated eosinophils may be a useful clue.
Other histologic findings may be present although none of these should be considered pathognomonic. These features include moderate‐marked reactive basal hyperplasia, eosinophilic microabscesses (superficial aggregates of ≥4 eosinophils), superficial layering of eosinophils, and subepithelial fibrosis. The presence of subepithelial fibrosis is also associated with eosinophils in the lamina propria and correlates with fibro‐stenotic complications of EOE, but may not be identifiable depending on biopsy depth. Other inflammatory cells, such as lymphocytes and mast cells, can also be increased. When reporting the cases, a note is useful to summarize additional relevant histologic features and to provide an overall assessment of the case based on all available biopsies (including prior biopsies, if applicable). For example, active esophagitis with intraepithelial eosinophils (peak count of # per HPF) followed by a note. When large numbers of eosinophils are present (e.g. >40 per HPF), an exact count may be difficult and it is appropriate to report the peak count as such (e.g. “peak count of >40 per HPF”).