Gastrointestinal Pathology. Группа авторов

such as alkali (lye) or acid ingestion, typically shows extensive edema, erythema, and hemorrhage in addition to necrotic exudates. Clinical history is key and the mucosa is seldom biopsied. Esophageal involvement by cutaneous bullous disorders may need to be excluded by immunofluorescence studies for IgG and C3. Severe eosinophilic esophagitis may also exhibit sloughing membranes, but is recognized by the marked intraepithelial eosinophilic infiltration. Black esophagus (i.e. acute esophageal necrosis) is a rare condition that arises in debilitated patients with multiple comorbidities such as hypoperfusion, sepsis, diabetic ketoacidosis, and malignancy. It results from the combining effect of ischemia and corrosive injury of gastric contents. The clinical presentation is distinctive with bleeding and a characteristic diffuse circumferential black mucosal discoloration of the distal esophagus with an abrupt transition at the gastroesophageal junction.

      Prognosis, Evolution and Management

      The clinical course and outcome in patients with sloughing esophagitis is primarily related to the presence of significant underlying diseases. In the few patients with follow‐up biopsies documented, most have shown endoscopic and histologic resolution.

Graft Versus Host Disease of the Esophagus

      Definition, General Features, Predisposing Factors

Graft versus host disease (GVHD) is an important complication of allogeneic stem cell transplantation, leading to considerable morbidity and mortality. Gastrointestinal tract involvement is frequent, and endoscopy with biopsy plays a central role in the diagnosis and management of patients with suspected GVHD. Although the pathologic features of GVHD are well described in glandular mucosa, they are less so for the esophagus. Manifestations of esophageal injury may occur in the acute or chronic phases of GVHD. Diagnosis requires correlation of the clinical and pathologic features.

      Clinical and Endoscopic Characteristics

Symptoms of esophageal GVHD include dysphagia and odynophagia. Endoscopically, acute presentations of GVHD have been described as showing bullous disease or a desquamative process with mucosal cast formation (Figure 2.19). In the chronic phase, the presence of webs, strictures, or concentric rings involving the mid‐upper esophagus on EGD or barium contrast imaging are considered diagnostic features (Figure 2.20).

      Microscopic Features

The histologic features of esophageal GVHD are similar to those of other sites in the GI tract. The squamous epithelium exhibits apoptosis, intraepithelial lymphocytosis, basal vacuolization, and necrosis in severe cases (Figure 2.21). Apoptotic keratinocytes are prominent in the basal and suprabasal region and the associated lymphocytosis can have a lichenoid interface appearance. The extent of the findings can be graded as mild, moderate, or severe. Severe GVHD is characterized by erosion and/or ulceration. Involvement of deeper layers with submucosal fibrosis has been described in chronic GVHD, but this layer is seldom represented in biopsy samples. Due to potential discordance among the observed clinical severity, endoscopic abnormalities, and histologic findings, it is recommended that a minimum of 8–10 serial H&E stained sections be cut to detect minimal histologic changes of GVHD. Finally, comparison to prior biopsies should be noted in order to assess treatment effects.

Figure 2.19 Endoscopic appearance of acute GVHD of esophagus with diffuse mucosal desquamation.

Figure 2.20 Endoscopic appearance of inflammatory stricture with persistent desquamation in chronic esophageal GVHD.

Figure 2.21 Microscopic appearance of acute GVHD of esophagus with basal apoptosis, lymphocytic infiltration, and dyskeratotic epithelial elements.

      Differential Diagnosis

The major differential diagnostic considerations include other types of esophageal mucosal injury that may lead to increased apoptosis, such as drug or infection. Knowledge of the clinical context is important, as epithelial apoptosis in the setting of stem cell transplantation likely represents GVHD, whereas mycophenolate‐associated injury occurs in solid organ transplant recipients. Cytomegalovirus infection also causes apoptosis, and may coexist with GVHD, necessitating immunohistochemical staining for exclusion. In cases where bullae or desquamation is observed endoscopically, the differential diagnosis may also include other vesiculobullous dermatologic disorders involving the esophagus.

      Prognosis, Evolution, and Clinical Management

      Systemic immunomodulatory therapy is indicated for patients with moderate to severe GHVD. Corticosteroids are used as first‐line therapy, and other agents considered as options in an algorithmic approach.

Radiation Esophagitis

      Definition, General Features, Predisposing Factors

      Radiation injury to the esophagus is a dose‐limiting toxicity occurring as either an acute or late complication of radiation therapy of thoracic neoplasms. The risk of radiation esophagitis is increased by concurrent chemotherapy and radiation dose–volumetric parameters, which may be related to underlying vascular changes and ischemic injury. Overall, symptomatic radiation esophagitis is rare, affecting <1% of treated patients.

      Clinical and Endoscopic Characteristics

      Patients with acute esophageal radiation toxicity (which develops within two to three weeks of exposure) complain of dysphagia, odynophagia, and/or substernal chest pain. Late manifestations (≥3 months) include stricture formation, chronic ulcerations, and fistula formation. Endoscopic abnormalities, depending on the time course, include mucositis, ulceration, strictures, or fistulas.

      Microscopic Features

      Macrocytic changes and cytologic atypia of squamous epithelial cells and stromal cells are common, often associated with multinucleation and bizarre hyperchromatic nuclei. Notably, the cells maintain an abundant cytoplasm and mitosis is rare. Submucosal fibrosis and obliterative vasculitis may also be evident in deeper biopsy specimens.

      Immunohistochemical Studies and Molecular Features

      Immunohistochemical stains may be useful in the differential diagnosis of viral esophagitis.

      Differential Diagnosis

      The squamous epithelial cytologic atypia may mimic carcinoma, which can be of particular concern for recurrent or persistent tumor in patients being treated for primary esophageal carcinomas, as radiation changes and neoplasia can coexist. Review of the prior tumor histology, if available, and assessment for evidence of invasion can be helpful.

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