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 Wrong. Carcinoid tumors release serotonin, causing flushing, diarrhea, and damage to the right-sided heart valves. They are not strongly linked to smoking.
2. Squamous cell carcinoma correct Correct. A central lung mass in a heavy smoker, with high calcium (hypercalcemia) caused by PTH-related peptide (PTHrP), is the classic picture for squamous cell carcinoma. Under the microscope it shows keratin pearls and bridges between cells.
3. Adenocarcinoma Wrong. Adenocarcinoma is usually found in the outer (peripheral) part of the lung. It is the most common type in non-smokers and is linked to joint and bone changes called hypertrophic osteoarthropathy, not to PTHrP.
4. Large cell carcinoma Wrong. Large cell carcinoma is diagnosed only after other types are ruled out. Its cells look undifferentiated under the microscope, and it does not have this specific paraneoplastic pattern.
5. Small cell carcinoma Wrong. Small cell carcinoma is also central and linked to smoking, but the syndromes it causes from a distance (paraneoplastic syndromes) are too much ADH (causing low sodium, or hyponatremia), too much ACTH (causing Cushing syndrome), and Lambert–Eaton syndrome, not PTHrP-driven high calcium.

The point: Central lung tumors are squamous cell carcinoma and small cell carcinoma. Squamous cell carcinoma makes PTHrP. Small cell carcinoma makes ADH and ACTH. Adenocarcinoma and large cell carcinoma are usually found in the outer (peripheral) part of the lung.

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 Wrong. Hypertrophy means cells grow BIGGER without changing in number or type, as seen in heart muscle cells (cardiac myocytes) under extra pressure. Here the cell type itself has changed, rather than the size.
2. Anaplasia Wrong. Anaplasia means the cells have lost all their normal, specialized features, a sign of aggressive cancer. That is not what is described here.
3. Metaplasia correct Correct. This is Barrett esophagus, where one fully formed cell type, stratified squamous, is replaced by another type that copes better with the harsh, acidic environment, in this case intestine-type columnar cells with goblet cells. This process, called metaplasia, can in principle reverse, but it raises the risk of later dysplasia (abnormal growth) and adenocarcinoma (cancer).
4. Hyperplasia Wrong. Hyperplasia means more cells of the SAME type. Here, the cell type itself has changed, which is what makes this metaplasia instead.
5. Dysplasia Wrong. The question states there is no dysplasia. Dysplasia is disordered growth with abnormal-looking cells and structure, and it sits between metaplasia and cancer in the progression.

The point: The cell's adaptive responses: hypertrophy means bigger cells, hyperplasia means more cells, atrophy means fewer or smaller cells, and metaplasia means a different cell type altogether. The sequence from metaplasia to dysplasia to cancer (carcinoma) is important to know, and Barrett esophagus is its most tested example. Squamous cell carcinoma of the esophagus tends to occur higher up (proximally) and is linked to smoking and alcohol. Adenocarcinoma tends to occur lower down (distally) and is linked to Barrett esophagus.

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 Wrong. Contraction band necrosis is seen after blood flow is restored to heart tissue that was starved of oxygen (reperfusion of ischemic myocardium). It is a sign of reperfusion injury, not the tissue change that leads to rupture.
2. Dense collagenous scar with few cells Wrong. A dense collagen scar with few cells forms over weeks 2 to 8. A mature scar does not rupture, but it can stretch and bulge outward, which is how a true ventricular aneurysm forms.
3. Granulation tissue with capillaries and fibroblasts Wrong. Granulation tissue, made of small blood vessels (capillaries) and repair cells (fibroblasts), appears around days 7 to 10. By then collagen is starting to be laid down and the risk of rupture is going down.
4. Coagulative necrosis with preserved myofiber outlines and no inflammation Wrong. Coagulative necrosis with the outline of muscle fibers preserved and no inflammation describes the first 4 to 12 hours after the heart attack. At that point the wall is still structurally intact.
5. Dense neutrophil infiltrate with disintegrating myofibers correct Correct. Days 3 to 5 after a heart attack is when neutrophils (a type of white blood cell) flood in and break down the dead heart muscle cells with enzymes. The heart wall is at its weakest during this window, before scar-forming tissue (granulation tissue) arrives, which is exactly when free wall rupture, papillary muscle rupture, and septal (wall between chambers) rupture tend to happen.

The point: Use the timing after a heart attack to predict the complication. 0 to 24 hours: irregular heart rhythm (arrhythmia). 3 to 5 days: rupture of the free wall, septum, or papillary muscle, and inflammation around the heart (fibrinous pericarditis). 1 to 3 weeks: Dressler syndrome. Weeks to months: aneurysm and blood clot inside the heart chamber (mural thrombus).

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