Gastrointestinal Pathology. Группа авторов

2.13 Characteristic histology of eosinophilic esophagitis with basal cell hyperplasia, marked eosinophilic infiltrate with eosinophilic microabscesses.

      Immunohistochemical Studies and Molecular Features

      Currently, the examination of esophageal mucosal biopsies by hematoxylin and eosin (H&E) stained sections, with clinical correlation, remains the most reliable diagnostic test for EOE. The diagnostic value of ancillary studies in distinguishing eosinophilic esophagitis from gastroesophageal reflux disease and other conditions remains unproven.

      Immunohistochemical stains targeting eosinophil peroxidase, major basic protein, and eosinophil‐derived neurotoxin, have been reported to enhance detection of eosinophils compared to evaluation of H&E sections, but these stains are not widely used in routine clinical practice. A recent study suggested that the presence of intra‐squamous IgG4 deposits by immunohistochemistry may be a useful adjunctive marker for EOE.

      Molecular analyses of esophageal tissues, such as gene expression analysis of chemokines such as eotaxin‐3 (CCL26), and transcriptome analysis show promise to improve diagnosis and clinical monitoring, and to guide patient‐specific therapy.

      Differential Diagnosis

      Clinical

      Dysphagia and rings in the esophagus can occur from any inflammatory condition. Even eosinophils may be present in GERD alone. EOE typically requires a confirmatory biopsy from the upper and lower esophagus showing eosinophilic infiltrates. Desquamative conditions that should be excluded include bullous pemphigoid and lichen planus. These typically require deep biopsies and special immunofluorescence staining; thus, communication between endoscopist and pathologist is critical.

      Microscopic

The histologic appearance of EOE is not specific, and mucosal infiltration by eosinophils is a component of a variety of other esophageal inflammatory conditions (Table 2.4).

      GERD and PPI‐responsive esophageal eosinophilia exhibit considerable histologic overlap with EOE. In an untreated patient, fewer numbers of eosinophils with distal predominance may be suggestive of GERD. Correlation with response to PPI therapy is paramount.

      In eosinophilic gastroenteritis, obtaining biopsy specimens from the stomach and duodenum and other clinical symptoms such as nausea, vomiting, and diarrhea may be helpful in establishing a diagnosis.

      The presence of granulomas is helpful in diagnosing esophageal involvement by Crohn’s disease, but they are uncommon. Eosinophils may also be admixed with neutrophils and lymphocytes, and involvement of other parts of the GI tract is typically present.

      Infections are recognized by the identification of viral inclusions (such as HSV), and fungal or parasitic organisms. Mixed inflammation with neutrophils may also be present. Rare cases of HSV esophagitis occurring in a background of EOE have been described.

Table 2.4 Endoscopic and histologic features of the major causes of infectious esophagitis.

Organism	Endoscopic features	Morphological features	Ancillary studies
Candida	Focal or confluent white plaques	Parakeratosis with neutrophils Colonization of ulcers Budding yeast, pseudohyphae, occasional septate hyphae Superficial invasion typical	PAS‐diastase, GMS stains
Herpes simplex	Superficial ulcers, multiple	Edge of ulcer—inclusions in squamous cells and/or squamous debris of ulcer slough Multinucleation, ground glass nuclei, dense eosinophilic nuclear inclusions (Cowdry type A)	IHC
CMV	Single deep ulcer, linear ulcers	Base of ulcer—inclusions in endothelial and stromal cells Intranuclear (“owl's eye”) and granular cytoplasmic inclusions Atypical inclusions common	IHC

Table 2.5 Conditions associated with esophageal eosinophilia in the differential diagnosis of EOE.

GERD

PPI‐responsive esophageal eosinophilia

Eosinophilic gastrointestinal diseases

Crohn's disease

Infection (Candida, HSV, parasites)

Hypereosinophilic syndrome

Achalasia

Drug hypersensitivity injury

Vasculitis

Pemphigus

Connective tissue diseases

Graft versus host disease (GVHD)

In drug‐induced esophageal eosinophilia, there is a temporal relationship and resolution when the offending agent is withdrawn.

      Ancillary Studies (if Applicable)

      IHC for virus (HSV) and/or special stains for fungi (GMS, PAS‐diastase) are indicated if infection is suspected.

      Prognosis, Evolution, and Clinical Management

      EOE is initially treated with proton pump inhibitors. There is emerging evidence that PPIs affect specific inhibition of the chemokine, eotaxin, which blunts eosinophil infiltration. It may be difficult to distinguish GERD‐associated eosinophilia from EOE in this subgroup. For those that do not respond to PPI, options include identification and avoidance of food antigens (typically through a Six Food Elimination Diet; SFED) or suppression with topical corticosteroids, which can be from a swallowed metered dose inhaler, or from peroral viscous budesonide. For late‐stage, fibrotic disease, repeated, carefully monitored esophageal dilation is effective.

Lymphocytic Esophagitis

      Definition, General Features, Predisposing Factors

This uncommon and poorly characterized condition is histologically defined as the presence of dense lymphocytic infiltrates involving the esophageal mucosa without concomitant evidence of significant active inflammation. It is described in approximately 1/1000 esophageal biopsies, predominantly affecting older females (median age 63 years). This controversial entity lacks clearly defined clinical associations in adults, and likely represents a nonspecific reaction pattern to a wide variety of mucosal insults (Table 2.6), including GERD, medications, infection, motility disorders, and other immune‐mediated disorders. In the pediatric population, lymphocytic esophagitis has been described in association with Crohn’s disease and celiac disease.

      Clinical and Endoscopic Characteristics

      About 75% of patients present with esophageal symptoms, most commonly dysphagia or odynophagia, which may raise the suspicion of eosinophilic esophagitis. Similarly, the endoscopic impression