A 24-year-old man comes to the physician because of 2 episodes of bleeding from the rectum over the past month. The patient’s father died of colon cancer at the age of 42. The patient has no history of any serious illness and takes no medications. He does not smoke. His vital signs are within normal limits. Physical examination shows a small hard mass over the right mandible that is nontender and fixed to the underlying bone. A similarly hard and painless 5 × 5 mass is palpated over the rectus abdominis muscle. On examination of the rectum, a polypoid mass is palpated at fingertip. Proctosigmoidoscopy shows numerous polyps. Which of the following best explains these findings?

Familial polyposis of the colon

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

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)

Colon polyps and neoplasms for USMLE Step 2 CK: High-Yield Pathology Lessons

Polyp Primer - Benign Bumps & Bad Seeds

Non-Neoplastic (Benign)
- Hyperplastic: Most common; no malignant potential. Sawtooth/serrated appearance.
- Hamartomatous: Disorganized tissue. Includes Juvenile polyps & Peutz-Jeghers syndrome polyps.
Neoplastic (Adenomatous): Premalignant; potential based on histology & size (↑ risk > 1 cm).
- Adenoma-Carcinoma Sequence: Progression from normal mucosa to cancer.

Endoscopic and Histologic Views of Colonic Polyps

⭐ Villous histology carries the highest malignant potential of all adenomas. The more villous the features, the more vicious the polyp.

Adenomas - The Villains in Waiting

Benign but premalignant precursors to colorectal carcinoma, characterized by epithelial dysplasia.
Histologic Types:
- Tubular: Most common (~75%); pedunculated, smaller, lower cancer risk.
- Villous: Sessile, larger, high malignant potential. 📌 Villous is villainous.
- Tubulovillous: Mixture of features.
Malignant potential correlates with ↑ size (>2 cm), ↑ villous histology, and high-grade dysplasia.

⭐ The adenoma-carcinoma sequence (mutations in APC, KRAS, p53) is the key pathway for most colorectal cancers.

Histology of colon polyps: tubular, tubulovillous, villous

Colorectal Carcinoma - The Final Boss

Two major molecular pathways lead to CRC:

Presentation by Location:
- Right-sided (Ascending): Exophytic mass, iron deficiency anemia, weight loss.
- Left-sided (Descending): Infiltrating mass, obstruction, change in stool caliber, hematochezia.
Diagnosis: Colonoscopy with biopsy is the gold standard.
Staging: TNM staging is critical for prognosis and treatment.
Tumor Marker: CEA (Carcinoembryonic Antigen) used for monitoring recurrence, not screening.

⭐ Right-sided (ascending) CRC often presents with insidious iron-deficiency anemia from occult bleeding, while left-sided (descending) CRC is more likely to cause obstruction and changes in bowel habits ("pencil-thin stools").

Family Matters - Inherited Risks

Familial Adenomatous Polyposis (FAP)
- Autosomal dominant mutation of APC gene on chromosome 5q.
- Develops 100s to 1000s of adenomatous polyps.
- Prophylactic colectomy required; 100% risk of CRC by age 40 if untreated.
- Variants: Gardner Syndrome (osteomas, skin cysts), Turcot Syndrome (brain tumors).
Lynch Syndrome (HNPCC)
- Autosomal dominant mutation in DNA mismatch repair genes (e.g., MSH1, MSH2).
- Associated with endometrial, ovarian, and skin cancers.

⭐ Amsterdam II Criteria for Lynch Syndrome (HNPCC): 3-2-1 Rule

3 or more relatives with Lynch-associated cancer (CRC, endometrial, etc.).

2 or more successive generations affected.

1 or more relatives diagnosed before age 50.

Colon polyps: Endoscopic view and gross specimen

High‑Yield Points - ⚡ Biggest Takeaways

Adenomatous polyps are the primary precursors to colorectal cancer (CRC), following the adenoma-carcinoma sequence (mutations in APC, KRAS, p53).

Villous adenomas carry a significantly higher malignant risk than tubular adenomas.

Familial Adenomatous Polyposis (FAP), an autosomal dominant condition from APC mutation, requires prophylactic colectomy.

Lynch Syndrome (HNPCC) is the most common inherited CRC, caused by mismatch repair gene defects.

Iron deficiency anemia in an older male is CRC until proven otherwise.

Left-sided cancers often present with an "apple-core" lesion on imaging.

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