A 70-year-old male visits his primary care physician because of progressive weight loss. He has a 20-year history of smoking 2 packs of cigarettes a day and was diagnosed with diabetes mellitus 6 years ago. After physical examination, the physician tells the patient he suspects adenocarcinoma at the head of the pancreas. Which of the following physical examination findings would support the diagnosis?

Lymphadenopathy of the umbilicus

A 53-year-old man comes to the physician because of fatigue, recurrent diarrhea, and an 8-kg (17.6-lb) weight loss over the past 6 months. He has a 4-month history of recurrent blistering rashes on different parts of his body that grow and develop into pruritic, crusty lesions before resolving spontaneously. Physical examination shows scaly lesions in different phases of healing with central, bronze-colored induration around the mouth, perineum, and lower extremities. Laboratory studies show: Hemoglobin 10.1 mg/dL Mean corpuscular volume 85 μm3 Mean corpuscular hemoglobin 30.0 pg/cell Serum Glucose 236 mg/dL Abdominal ultrasonography shows a 3-cm, solid mass located in the upper abdomen. This patient's mass is most likely derived from which of the following types of cells?

Gastrointestinal enterochromaffin cells

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 previously healthy 59-year-old man comes to the physician with a 6-month history of worsening headaches, difficulty chewing, and progressive hearing loss. Examination shows a mildly tender, 1-cm, hard swelling over the left maxilla. The remainder of the examination shows no abnormalities. Serum studies show a calcium concentration of 8.5 mg/dL, alkaline phosphatase activity of 112 U/L, and parathyroid hormone concentration of 310 pg/mL. Audiometry shows bilateral mixed conductive and sensorineural hearing loss. Which of the following processes is the most likely cause of this patient's condition?

Increased activity of nuclear factor-κB

Decreased activity of carbonic anhydrase II

Decreased expression of menin protein

Defective synthesis of type I collagen

A 15-year-old Caucasian male is brought to his pediatrician by his parents, who note the development of a tremor in their child. Urine and serum analysis reveal elevated levels of copper. Which of the following clinical manifestations would the physician most expect to see in this patient?

Hepatocytes that stain with Prussian blue

Pancreatic diseases for USMLE Step 1: High-Yield Pathology Lessons

Acute Pancreatitis - Fiery Digestive Fury

Etiology: 📌 I GET SMASHED (Idiopathic, Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion sting, Hypercalcemia/Hypertriglyceridemia, ERCP, Drugs).
Pathophysiology: Premature activation of trypsinogen to trypsin within the pancreas, leading to autodigestion.

Diagnosis: Requires 2 of 3 criteria:
- Acute epigastric pain radiating to the back.
- ↑ Serum amylase or lipase (>3x ULN).
- Characteristic findings on imaging.

CT: Acute Pancreatitis with Peripancreatic Fat Stranding

⭐ Hypocalcemia is a poor prognostic sign, resulting from saponification of peripancreatic fat by activated lipases.

Complications: Pseudocyst, abscess, necrosis, ARDS, renal failure.

Chronic Pancreatitis - Scars & Stones

Pathophysiology: Irreversible inflammation leads to fibrosis and calcified stones, causing progressive loss of exocrine (digestion) and endocrine (insulin) function.
Etiology: Alcohol abuse (most common, adults); Cystic fibrosis (children). Also autoimmune, hereditary, or idiopathic.
Clinical Features: Persistent epigastric pain radiating to the back, malabsorption (steatorrhea, weight loss), and late-onset diabetes mellitus.
Diagnosis: CT scan is best for detecting calcifications & ductal dilation ("chain of lakes" appearance). ↓ fecal elastase confirms exocrine insufficiency.

CT: Chronic Pancreatitis with Calcifications & Duct Dilation

⭐ Amylase and lipase are often normal due to burnout of acinar cells, unlike in acute pancreatitis.

Pancreatic Neoplasms - Silent Tumors

Pancreatic Ductal Adenocarcinoma (PDAC): Most common, aggressive malignancy.
- Presentation: Late; often unresectable.
  - Head (~75%): Painless obstructive jaundice, weight loss, steatorrhea.
  - Body/Tail: Abdominal pain radiating to the back, weight loss.
- Risk Factors: Smoking (strongest), chronic pancreatitis, diabetes, age > 50, family history (BRCA2).
- Tumor Marker: ↑ CA 19-9.
- Genetics: KRAS (most common), p53, SMAD4.
Pancreatic Neuroendocrine Tumors (PanNETs): Functional or non-functional.
- Insulinoma: Hypoglycemia (Whipple's triad).
- Gastrinoma: Zollinger-Ellison syndrome (refractory peptic ulcers).
- Glucagonoma: Necrolytic migratory erythema, diabetes, DVT.
- VIPoma: Watery diarrhea, hypokalemia, achlorhydria (WDHA syndrome).

CT: Pancreatic head mass, biliary dilation (arrow)

⭐ Courvoisier's Sign: A palpable, non-tender gallbladder in a jaundiced patient suggests malignant obstruction (e.g., pancreatic cancer), not gallstones.

High‑Yield Points - ⚡ Biggest Takeaways

Acute pancreatitis is most commonly caused by gallstones and alcohol; diagnosis relies on elevated serum lipase.

Chronic pancreatitis, mainly from alcoholism, leads to pancreatic calcifications, steatorrhea, and diabetes mellitus.

Pancreatic adenocarcinoma typically presents as painless jaundice if in the pancreatic head; CA 19-9 is the tumor marker.

Courvoisier sign-a palpable, non-tender gallbladder-suggests malignant obstruction.

Pancreatic pseudocysts are a hallmark complication of acute pancreatitis, lacking a true epithelial lining.

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