A 62-year-old man is referred to a gastroenterologist because of difficulty swallowing for the past 5 months. He has difficulty swallowing both solid and liquid foods, but there is no associated pain. He denies any shortness of breath or swelling in his legs. He immigrated from South America 10 years ago. He is a non-smoker and does not drink alcohol. His physical examination is unremarkable. A barium swallow study was ordered and the result is given below. Esophageal manometry confirms the diagnosis. What is the most likely underlying cause of this patient’s condition?

Pharyngoesophageal diverticulum

Gastroesophageal reflux disease

Squamous cell carcinoma of the esophagus

A 45-year-old man comes to the physician for the evaluation of painful swallowing and retrosternal pain over the past 2 days. He was recently diagnosed with HIV infection, for which he now takes tenofovir, emtricitabine, and raltegravir. There is no family history of serious illness. He has smoked one pack of cigarettes daily for the past 20 years. He drinks 2–3 beers per day. He does not use illicit drugs. Vital signs are within normal limits. Physical examination of the oral cavity shows no abnormalities. The patient's CD4+ T-lymphocyte count is 80/mm3 (normal ≥ 500). Empiric treatment is started. Two weeks later, he reports no improvement in his symptoms. Esophagogastroduodenoscopy is performed and shows multiple well-circumscribed, round, superficial ulcers in the upper esophagus. Which of the following is the most likely underlying cause of this patient's symptoms?

Infection with herpes simplex virus

Degeneration of inhibitory neurons within the myenteric plexuses

Transient lower esophageal sphincter relaxation

Allergic inflammation of the esophagus

An 85-year-old man who recently immigrated to the US from Spain presents to your office complaining of hoarseness and dysphagia for the past 2 months. He says his symptoms have been getting progressively worse, and he expresses concerns about the difficulty swallowing as he cannot eat well and has even lost 9 kg (20 lb) since his last visit 3 months ago. He denies any shortness of breath, coughing of blood, and chest pain. His bowel and bladder habit are normal. Past medical history is unremarkable. He has a 60-pack-year history of smoking tobacco and drinks alcohol occasionally. Which of the following is the most likely cause of his symptoms?

Malignant proliferation of squamous cells

Transformation leading to metaplasia in the lower esophagus

Malignant proliferation of glandular tissue in the esophagus

Reduced lower esophageal pressure

A 56-year-old man comes to the physician because of intermittent retrosternal chest pain. Physical examination shows no abnormalities. Endoscopy shows salmon pink mucosa extending 5 cm proximal to the gastroesophageal junction. Biopsy specimens from the distal esophagus show nonciliated columnar epithelium with numerous goblet cells. Which of the following is the most likely cause of this patient's condition?

Esophageal exposure to gastric acid

Hypermotile esophageal contractions

Atopic inflammation of the esophagus

Fungal infection of the lower esophagus

Neoplastic proliferation of esophageal epithelium

A 28-year-old male presents to his primary care physician with complaints of intermittent abdominal pain and alternating bouts of constipation and diarrhea. His medical chart is not significant for any past medical problems or prior surgeries. He is not prescribed any current medications. Which of the following questions would be the most useful next question in eliciting further history from this patient?

"Can you tell me more about the symptoms you have been experiencing?"

"Does the diarrhea typically precede the constipation, or vice-versa?"

"Is the diarrhea foul-smelling?"

"Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"

"Are the symptoms worse in the morning or at night?"

A 47-year-old woman presents for a routine wellness checkup. She complains of general fatigue and lethargy for the past 6 months. She does not have a significant past medical history and is currently not taking any medications. The patient reports that she drinks “socially” approx. 6 nights a week. She says she also enjoys a “nightcap,” which is 1–2 glasses of wine before bed every night. She denies any history of drug use or smoking. The patient is afebrile, and her vital signs are within normal limits. A physical examination reveals pallor of the mucous membranes. Her laboratory findings are significant for a mean corpuscular volume of 72 fL, leukocyte count of 5,300/mL, hemoglobin of 11.0 g/dL, and platelet count of 420,000/mL. Which of the following is the most likely cause of this patient’s thrombocytosis?

Chronic myelogenous leukemia (CML)

A 61-year-old man with a history of stage IIIa lung adenocarcinoma that has been treated with wedge resection and chemotherapy presents to the primary care clinic. He is largely asymptomatic, but he demonstrates a persistent microcytic anemia despite iron supplementation. Colonoscopy performed 3 years earlier was unremarkable. His past medical history is significant for diabetes mellitus type II, hypertension, acute lymphoblastic leukemia as a child, and hypercholesterolemia. He currently smokes 1 pack of cigarettes per day, drinks a glass of pinot grigio per day, and currently denies any illicit drug use. His vital signs include: temperature, 36.7°C (98.0°F); blood pressure, 126/74 mm Hg; heart rate, 87/min; and respiratory rate, 17/min. On physical examination, his pulses are bounding, complexion is pale, but breath sounds remain clear. Oxygen saturation was initially 91% on room air, with a new oxygen requirement of 2 L by nasal cannula. Which of the following lab values would suggest anemia of chronic disease as the underlying etiology?

Decreased serum iron and transferrin, increased ferritin, normal serum transferrin receptor

Decreased serum iron and transferrin, decreased ferritin, normal serum transferrin receptor

Increased serum iron and transferrin, increased ferritin, normal serum transferrin receptor

Decreased serum iron, increased transferrin, decreased ferritin, increased serum transferrin receptor

Decreased serum iron, decreased transferrin, increased ferritin, increased serum transferrin receptor

Esophageal pathology for USMLE Step 2 CK: High-Yield Pathology Lessons

Structural & Motor Issues - Gut Feeling Gone Wrong

Achalasia: Dysphagia to solids and liquids. Failure of LES relaxation + loss of peristalsis. Caused by loss of Auerbach (myenteric) plexus.
- Barium swallow shows "bird-beak" sign.
- Associated with Chagas disease & eosinophilic esophagitis.
Mallory-Weiss Syndrome: Partial-thickness mucosal tear at GE junction from forceful retching. Painful hematemesis.
Boerhaave Syndrome: Transmural, distal esophageal rupture. Surgical emergency.
- Presents with severe chest pain, crepitus (Hamman's sign).
Esophageal Webs/Rings: Dysphagia to solids.
- Plummer-Vinson Syndrome: 📌 Triad: Esophageal webs, iron-deficiency anemia, dysphagia.

Achalasia: Bird-beak sign on barium swallow

⭐ Patients with long-standing achalasia have an increased risk for developing esophageal squamous cell carcinoma.

Esophagitis - The Burning Question

Reflux (GERD): Most common. Histo: Basal zone hyperplasia, elongated lamina propria papillae, scattered eosinophils & neutrophils.
Eosinophilic (EoE): Allergic history (asthma, food allergies). Endoscopy: Stacked circular rings ("feline esophagus"), linear furrows. Histo: >15 eosinophils per high-power field (hpf).
Infectious: Occurs in immunocompromised hosts.
- Candida: White pseudomembranes; pseudohyphae on biopsy.
- HSV-1: Punched-out ulcers; Cowdry type A inclusions.
- CMV: Linear ulcers; "owl's eye" inclusions.
Pill-Induced: Bisphosphonates, tetracyclines, NSAIDs. Causes sudden-onset odynophagia.

⭐ Eosinophilic esophagitis is distinguished from GERD by dense eosinophilic infiltration (>15/hpf) and frequent non-response to proton pump inhibitor (PPI) trials.

Endoscopic findings of various esophagitis types

GERD Complications - Barrett's & Bleeds

Barrett's Esophagus: Intestinal metaplasia (squamous → columnar epithelium) in the distal esophagus.
- Key risk factor for esophageal adenocarcinoma.
- Dx: Endoscopy shows salmon-colored mucosa extending >1 cm above the gastroesophageal junction; biopsy confirms goblet cells.
- Management: High-dose PPIs and regular endoscopic surveillance.
Bleeding: Can manifest as hematemesis or melena.
- Erosive Esophagitis: Chronic acid damages mucosa, causing superficial bleeding.
- Esophageal Ulcers: Deeper erosions leading to more significant bleeding.
- Mallory-Weiss Tears: Longitudinal tears at the GE junction from forceful retching.

⭐ High-Yield: The definitive diagnosis of Barrett's esophagus requires biopsy confirmation of intestinal metaplasia with goblet cells, not just endoscopic findings.

Barrett's Esophagus: Endoscopic and Anatomical Views

Esophageal Neoplasms - Malignant Highway

Two main types: Squamous Cell Carcinoma (SCC) & Adenocarcinoma.
Presents with progressive dysphagia (solids → liquids), weight loss, odynophagia.

SCC: More common worldwide. 📌 Squamous ~ Superior.
Adenocarcinoma: More common in the US. 📌 Adeno ~ Above stomach.

⭐ Adenocarcinoma has overtaken SCC as the most common type in the US, paralleling the rise in obesity and GERD.

High‑Yield Points - ⚡ Biggest Takeaways

GERD is the top cause of esophagitis, leading to Barrett esophagus (intestinal metaplasia), a precursor for adenocarcinoma in the distal third.

Squamous cell carcinoma, linked to alcohol and tobacco, typically arises in the proximal two-thirds.

Achalasia involves loss of the myenteric plexus, causing failed LES relaxation and a "bird-beak" sign.

Mallory-Weiss tears are mucosal lacerations from vomiting; Boerhaave syndrome is a transmural rupture.

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