A 36-year-old woman comes to the physician for a follow-up visit after she had a PET scan that showed a nodule on the thyroid gland. She has no difficulty or pain while swallowing. She was treated for non-Hodgkin lymphoma at the age of 28 years, which included external beam radiation to the head and neck and 4 cycles of chemotherapy. She appears healthy. Vital signs are within normal limits. Physical examination shows no abnormalities. Serum studies show: Glucose 82 mg/dL Creatinine 0.7 mg/dL Thyroid-stimulating hormone 3 μU/mL Ultrasound of the neck shows a 1.2-cm (0.5-in) nodule on the left lobe of the thyroid with irregular margins and microcalcifications. A fine-needle aspiration biopsy shows Psammoma bodies and cells with clear, ground-glass, empty nuclei. Which of the following is the most appropriate next step in management?

Observation and follow-up in 3 months

A 65-year-old man with a 40-pack-year smoking history presents with hemoptysis and a persistent cough. Chest CT shows a 3.5 cm centrally located mass in the right main bronchus. Positron emission tomography confirms a malignant nodule. Bronchoscopy with transbronchial biopsy is performed and a specimen sample of the nodule is sent for frozen section analysis. The tissue sample is most likely to show which of the following tumor types?

Metastasis of colorectal cancer

A 75-year-old woman comes to the physician because of a 3-month history of involuntary weight loss and a painless lump on her neck. Physical examination shows a firm, irregular swelling on the right side of the neck. Ultrasonography of the thyroid gland shows a 2-cm nodule with irregular margins and microcalcifications in the right thyroid lobe. A biopsy of the thyroid nodule is performed. Which of the following changes would be most consistent with anaplasia?

Negative staining of tumor cells for thyroglobulin

Disorganized proliferation of mature thyroid cells

Increased expression of thyroid transcription factor-1

Replacement of thyroid cells by normal squamous epithelium

Reduced number of functional thyroid cells

A 45-year-old man comes to the physician for the evaluation of difficulty swallowing that has worsened over the past year. He also reports some hoarseness and generalized bone, muscle, and joint pain. During the past six months, he has had progressive constipation and two episodes of kidney stones. He also reports recurrent episodes of throbbing headaches, diaphoresis, and palpitations. He does not smoke or drink alcohol. He takes no medications. His vital signs are within normal limits. Physical examination and an ECG show no abnormalities. Laboratory studies show calcium concentration of 12 mg/dL, phosphorus concentration of 2 mg/dL, alkaline phosphatase concentration of 100 U/L, and calcitonin concentration of 11 pg/mL (N < 8.8). Ultrasonography of the neck shows hypoechoic thyroid lesions with irregular margins and microcalcifications. Which of the following is the most likely underlying cause of this patient's condition?

Altered RET proto-oncogene expression

Disrupted menin protein function

A 27-year-old woman comes to the physician for a routine health maintenance examination. She feels well. She had a chlamydia infection at the age of 22 years that was treated. Her only medication is an oral contraceptive. She has smoked one pack of cigarettes daily for 6 years. She has recently been sexually active with 3 male partners and uses condoms inconsistently. Her last Pap test was 4 years ago and results were normal. Physical examination shows no abnormalities. A Pap test shows atypical squamous cells of undetermined significance. Which of the following is the most appropriate next step in management?

Perform loop electrosurgical excision procedure

A 62-year-old man comes to the physician for a follow-up examination after having been diagnosed with stage II adenocarcinoma of the left lower lung lobe without evidence of distant metastases 1 week ago following an evaluation for a chronic cough. He has hypertension and type 2 diabetes mellitus. He has smoked one pack of cigarettes daily for the past 40 years. His current medications include metformin, sitagliptin, and enalapril. He is 177 cm (5 ft 10 in) tall and weighs 65 kg (143 lb); BMI is 20.7 kg/m2. He appears lethargic. Vital signs are within normal limits. Pulse oximetry shows an oxygen saturation of 98%. Examination shows inspiratory wheezing at the left lung base. The remainder of the examination shows no abnormalities. A complete blood count and serum concentrations of electrolytes, creatinine, glucose, and liver enzymes are within the reference range. Spirometry shows an FEV1 of 1.6 L. The diffusing lung capacity for carbon monoxide (DLCO) is 66% of predicted. Which of the following is the most appropriate next step in the management of this patient?

Administer cisplatin and vinorelbine

Administer cisplatin and etoposide

A 68-year-old man is brought to the emergency department because of fever, progressive weakness, and cough for the past five days. He experienced a similar episode 2 months ago, for which he was hospitalized for 10 days while visiting his son in Russia. He states that he has never fully recovered from that episode. He felt much better after being treated with antibiotics, but he still coughs often during meals. He sometimes also coughs up undigested food after eating. For the last 5 days, his coughing has become more frequent and productive of yellowish-green sputum. He takes hydrochlorothiazide for hypertension and pantoprazole for the retrosternal discomfort that he often experiences while eating. He has smoked half a pack of cigarettes daily for the last 30 years and drinks one shot of vodka every day. The patient appears thin. His temperature is 40.1°C (104.2°F), pulse is 118/min, respirations are 22/min, and blood pressure is 125/90 mm Hg. Auscultation of the lungs shows right basal crackles. There is dullness on percussion at the right lung base. The remainder of the physical examination shows no abnormalities. Laboratory studies show: Hemoglobin 15.4 g/dL Leukocyte count 17,000/mm3 Platelet count 350,000/mm3 Na+ 139 mEq/L K+ 4.6 mEq/L Cl- 102 mEq/L HCO3- 25 mEq/L Urea Nitrogen 16 mg/dL Creatinine 1.3 mg/dL An x-ray of the chest shows a right lower lobe infiltrate. Which of the following is the most likely explanation for this patient's symptoms?

Weak tone of the lower esophageal sphincter

Unrestricted growth of pneumocytes with invasion of the surrounding tissue

Uncoordinated contractions of the esophagus

Formation of a tissue cavity containing necrotic debris

A 68-year-old man comes to the physician because of a 6-month history of difficulty swallowing pieces of meat and choking frequently during meal times. He also sometimes regurgitates foul-smelling, undigested food particles. Examination shows a 3 x 3 cm soft cystic, immobile mass in the upper third of the left side of his neck anterior to the left sternocleidomastoid muscle that becomes prominent when he coughs. A barium swallow shows an accumulation of contrast on the lateral aspect of the neck at the C5 level. Which of the following is the most likely underlying cause for this patient's condition?

Increased intrapharyngeal pressure

Remnant of the embryological omphalomesenteric duct

Inadequate relaxation of lower esophageal sphincter

Remnant of the thyroglossal duct

Remnant of the second branchial cleft

Thyroid nodule evaluation — USMLE Lesson

🩺 Diagnosis - First Steps & Suspicions

Initial Presentation: Most nodules are asymptomatic, discovered incidentally.
⚠️ Red Flags for Malignancy:
- Rapid growth, hoarseness, dysphagia.
- History of head/neck radiation.
- Family history (e.g., MEN2, RET proto-oncogene).
- Firm, fixed nodule; cervical lymphadenopathy.

⭐ The first step in evaluating a thyroid nodule is always measuring the serum TSH level. This determines if the nodule is hyperfunctioning ("hot") or non-functioning ("cold"), guiding the subsequent workup.

Thyroid Nodule Evaluation Algorithm

👁️ Radiology - Ultrasound's Sharp Eyes

Ultrasound is the primary imaging modality to risk-stratify nodules and determine the need for FNA. The ACR TI-RADS system standardizes reporting by assigning points to suspicious features.

High-Risk Features (↑ Malignancy):
- Solid & Markedly Hypoechoic: Darker than adjacent strap muscle.
- Microcalcifications: Punctate echogenic foci <1 mm.
- Irregular Margins: Infiltrative, spiculated, or microlobulated.
- Taller-than-Wide Shape: Suggests aggressive, infiltrative growth.
- Extrathyroidal Extension: Obvious invasion into surrounding tissues.
Low-Risk Features: Purely cystic (anechoic), spongiform/honeycomb appearance (aggregate of microcysts), isoechoic/hyperechoic.

Thyroid Nodule Ultrasound: High-Risk Features

⭐ Microcalcifications are the most specific ultrasound finding for papillary thyroid carcinoma (PTC), often representing psammoma bodies.

Pathology - Cells Tell The Tale

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🔪 Management - The Decisive Cut

Management is guided by Fine Needle Aspiration (FNA) cytology (Bethesda system).

Indeterminate (III/IV): Repeat FNA, molecular testing, or diagnostic lobectomy.
Suspicious/Malignant (V/VI): Surgical resection.
- Lobectomy: For small (<4 cm), unifocal, low-risk tumors.
- Total Thyroidectomy: For large tumors (>4 cm), bilateral disease, or metastasis.

⭐ For indeterminate nodules (Bethesda III/IV), molecular testing (e.g., Afirma, ThyroSeq) on the FNA sample can help rule out malignancy, potentially avoiding diagnostic surgery.

⚡ Biggest Takeaways

Initial evaluation is always TSH and thyroid ultrasound.

If TSH is low, perform a radionuclide scan; "hot" nodules are rarely malignant and don't need FNA.

If TSH is normal/high, use ultrasound findings to guide Fine-Needle Aspiration (FNA).

FNA is the single most accurate test to diagnose thyroid cancer.

High-risk US features prompting FNA: microcalcifications, irregular margins, hypoechogenicity, taller-than-wide shape.

Malignant FNA requires surgery (thyroidectomy).

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