Pathology and pathophysiology for USMLE Step 1

A 63-year-old woman with a 40-pack-year smoking history is found to have a central lung mass. Serum calcium is 13.4 mg/dL, phosphate is low, and PTH is suppressed. PTH-related peptide is elevated. Which histologic subtype is most likely?

1. Carcinoid tumor Secretes serotonin, producing flushing, diarrhea and right-sided valvular disease, and is not strongly smoking-related.
2. Squamous cell carcinoma correct Correct. Central location in a heavy smoker with hypercalcemia driven by PTH-related peptide is the classic squamous picture. Histology shows keratin pearls and intercellular bridges.
3. Adenocarcinoma Typically peripheral, the commonest subtype in non-smokers, and linked to hypertrophic osteoarthropathy rather than PTHrP.
4. Large cell carcinoma A diagnosis of exclusion, undifferentiated on histology, without this specific paraneoplastic signature.
5. Small cell carcinoma Also central and smoking-related, but its paraneoplastic syndromes are ADH (hyponatremia), ACTH (Cushing) and Lambert–Eaton, not PTHrP hypercalcemia.

The point: Central lung tumors: squamous and small cell. Squamous makes PTHrP. Small cell makes ADH and ACTH. Peripheral: adenocarcinoma and large cell.

Source: USMLE Content Outline — pathology and pathophysiology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

A 62-year-old man with a 20-year history of gastroesophageal reflux undergoes endoscopy. Biopsy of the distal esophagus shows columnar epithelium with goblet cells replacing the normal squamous mucosa. There is no dysplasia. Which process does this represent?

1. Hypertrophy An increase in cell SIZE without a change in number or type, as in cardiac myocytes under pressure load.
2. Anaplasia Complete loss of differentiation, a feature of aggressive malignancy. Not present.
3. Metaplasia correct Correct. Barrett esophagus is the replacement of one differentiated cell type, stratified squamous, by another that is better adapted to the hostile environment, in this case intestinal-type columnar epithelium with goblet cells. Metaplasia is reversible in principle and is a risk factor for subsequent dysplasia and adenocarcinoma.
4. Hyperplasia An increase in the NUMBER of cells of the same type. The cell type has changed here, which is the defining feature.
5. Dysplasia Explicitly excluded by the stem. Dysplasia is disordered growth with architectural and cytological atypia, and it is the step between metaplasia and carcinoma.

The point: Adaptive responses: hypertrophy is bigger cells, hyperplasia is more cells, atrophy is fewer or smaller, metaplasia is a different cell type. Metaplasia to dysplasia to carcinoma is the sequence to know, and Barrett is its most examined example. Squamous cell carcinoma of the esophagus sits proximally and links to smoking and alcohol; adenocarcinoma sits distally and links to Barrett.

Source: USMLE Content Outline — general pathology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

A 68-year-old man dies suddenly 4 days after an anterior myocardial infarction. At autopsy there is 300 mL of blood in the pericardial sac and a rupture through the anterior left ventricular wall. Which histologic finding would you expect at the rupture site?

1. Contraction band necrosis only Seen after reperfusion of ischemic myocardium. It is a marker of reperfusion injury rather than the substrate for rupture.
2. Dense collagenous scar with few cells Weeks 2 to 8. A mature scar does not rupture; it dilates, which is how a true ventricular aneurysm forms.
3. Granulation tissue with capillaries and fibroblasts Days 7 to 10. By then collagen deposition is beginning and rupture risk is falling.
4. Coagulative necrosis with preserved myofiber outlines and no inflammation That is the first 4 to 12 hours. The wall is still mechanically intact at that point.
5. Dense neutrophil infiltrate with disintegrating myofibers correct Correct. Days 3 to 5 is the peak of neutrophilic infiltration and enzymatic digestion of dead myocytes. The wall is at its structurally weakest before granulation tissue arrives, which is exactly when free wall rupture, papillary muscle rupture and septal rupture cluster.

The point: Time the infarct from the complication. 0 to 24h: arrhythmia. 3 to 5 days: rupture (free wall, septum, papillary muscle) and fibrinous pericarditis. 1 to 3 weeks: Dressler. Weeks to months: aneurysm and mural thrombus.

Source: USMLE Content Outline — cardiovascular pathology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator