# Clinical Cases: Thyroid Nodules and Cancer

## Case 1: Papillary Thyroid Carcinoma

### Patient Demographics
- **Age:** 35 years
- **Sex:** Female
- **Occupation:** Pediatric nurse

### Chief Complaint
"I found a lump in my neck while putting on a necklace."

### History of Present Illness
A 35-year-old woman noticed a painless lump in the right side of her neck 2 weeks ago while adjusting her necklace. She has no symptoms of hyperthyroidism or hypothyroidism. She denies dysphagia, hoarseness, or neck pain. She has no history of head or neck radiation. She reports that her aunt had thyroid cancer in her 40s. The lump has not changed in size since she first noticed it.

### Physical Examination
- **Vital Signs:** BP 118/74 mmHg, HR 72 bpm
- **General:** Healthy-appearing woman in no distress
- **Neck:**
  - 1.5 cm firm, non-tender nodule in right thyroid lobe
  - Nodule moves with swallowing
  - Fixed to underlying tissue
  - Left thyroid lobe normal
  - Single 1 cm firm, non-tender lymph node in right level VI (central) compartment
- **Voice:** Normal

### Workup
- **Laboratory Studies:**
  - TSH: 1.8 mIU/L (normal)
  - Calcitonin: Normal (rules out medullary thyroid cancer)
- **Ultrasound Thyroid:**
  - Right lobe: 1.6 cm hypoechoic nodule with irregular margins, microcalcifications, and taller-than-wide shape (highly suspicious features)
  - Left lobe: Normal
  - Right central neck: 1.2 cm lymph node with loss of fatty hilum, microcalcifications
  - TI-RADS 5 (highly suspicious)
- **Fine Needle Aspiration (FNA):**
  - Thyroid nodule: Bethesda VI - Malignant (papillary thyroid carcinoma)
  - Lymph node: Positive for metastatic papillary thyroid carcinoma

### Diagnosis
**Papillary thyroid carcinoma** with central compartment lymph node metastasis

### Treatment
1. **Surgical resection:**
   - Total thyroidectomy (nodule >1 cm with confirmed malignancy)
   - Central neck lymph node dissection (confirmed metastasis)
   - Consider lateral neck dissection if suspicious lateral nodes
2. **Post-operative:**
   - Levothyroxine replacement with TSH suppression (goal TSH 0.1-0.5 mIU/L for intermediate risk)
   - Radioactive iodine (I-131) ablation for intermediate/high-risk patients
3. **Monitoring:**
   - Serum thyroglobulin (tumor marker) - should be undetectable after total thyroidectomy/RAI
   - Anti-thyroglobulin antibodies
   - Neck ultrasound every 6-12 months initially
4. **Prognosis:** Excellent - >95% 10-year survival for papillary thyroid cancer

### Clinical Pearl
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy (80-85% of cases). Ultrasound features that increase suspicion for malignancy include hypoechogenicity, microcalcifications (psammoma bodies), irregular margins, taller-than-wide shape, and extrathyroidal extension. The TI-RADS (Thyroid Imaging Reporting and Data System) standardizes nodule evaluation and FNA recommendations. While PTC frequently metastasizes to lymph nodes, this does not significantly worsen prognosis in most patients. Thyroglobulin serves as an excellent tumor marker after total thyroidectomy, as it should only be produced by thyroid tissue.

### Clinical Image
![Papillary Thyroid Carcinoma Ultrasound](case_01_image.jpg)

*Ultrasound image showing a hypoechoic thyroid nodule with irregular margins and microcalcifications, features suspicious for papillary thyroid carcinoma.*

**Image Source:** Radiopaedia - "Papillary thyroid carcinoma"
**License:** CC BY-NC-SA 3.0
**URL:** https://radiopaedia.org/cases/papillary-thyroid-carcinoma-2

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## Case 2: Medullary Thyroid Carcinoma with MEN2A

### Patient Demographics
- **Age:** 28 years
- **Sex:** Male
- **Occupation:** Electrician

### Chief Complaint
"I had genetic testing because my mother was diagnosed with thyroid cancer, and they found I have a mutation."

### History of Present Illness
A 28-year-old man presents after genetic testing revealed he carries a RET proto-oncogene mutation (codon 634). His mother was recently diagnosed with medullary thyroid carcinoma at age 52 and subsequently found to have this mutation. Cascade genetic testing was recommended for all first-degree relatives. The patient is asymptomatic with no palpable thyroid nodules and no symptoms of hyperthyroidism, hypercalcemia, or pheochromocytoma. He has had episodes of headache with sweating over the past year that he attributed to work stress.

### Physical Examination
- **Vital Signs:** BP 148/92 mmHg (elevated), HR 88 bpm
- **General:** Well-appearing young man
- **Neck:** Thyroid gland normal size, no palpable nodules, no lymphadenopathy
- **Cardiovascular:** Regular rhythm, no murmurs
- **Abdomen:** No masses palpable
- **Skin:** No café-au-lait spots, no neuromas

### Workup
- **Laboratory Studies:**
  - TSH: 2.2 mIU/L (normal)
  - Calcitonin: 86 pg/mL (elevated, normal <10)
  - CEA: 4.2 ng/mL (mildly elevated)
  - Plasma metanephrines: Elevated (normetanephrine 2.4 nmol/L)
  - Calcium: 10.8 mg/dL (high-normal)
  - PTH: 78 pg/mL (elevated)
  - 24-hour urine catecholamines: Elevated
- **Genetic testing:** RET mutation codon 634 (MEN2A - high risk)
- **Ultrasound Thyroid:** Two small hypoechoic nodules in right lobe (4mm and 6mm)
- **CT/MRI Abdomen:** 2.5 cm right adrenal mass, hyperintense on T2
- **MIBG Scan:** Uptake in right adrenal mass consistent with pheochromocytoma

### Diagnosis
**Multiple Endocrine Neoplasia Type 2A (MEN2A)** with:
1. Medullary thyroid carcinoma (early/microscopic)
2. Pheochromocytoma (right adrenal)
3. Primary hyperparathyroidism (developing)

### Treatment
**ORDER OF SURGERY IS CRITICAL:**
1. **First: Adrenalectomy for pheochromocytoma**
   - Alpha-blockade (phenoxybenzamine) for 10-14 days pre-operatively
   - Then add beta-blockade (never beta before alpha)
   - Adequate volume expansion
   - Laparoscopic right adrenalectomy
2. **Second: Total thyroidectomy with central lymph node dissection**
   - After recovery from adrenalectomy
   - Prophylactic surgery indicated even without palpable tumor given RET mutation
3. **Parathyroid management:**
   - Inspect parathyroids at surgery
   - Remove only grossly enlarged glands
   - Consider autotransplantation if all glands enlarged
4. **Post-operative:**
   - Levothyroxine replacement
   - Monitor calcitonin and CEA
   - Screen for contralateral pheochromocytoma
   - Genetic counseling for family members

### Clinical Pearl
MEN2A is an autosomal dominant syndrome caused by RET proto-oncogene mutations, characterized by medullary thyroid carcinoma (>95% penetrance), pheochromocytoma (50%), and primary hyperparathyroidism (20-30%). Medullary thyroid carcinoma arises from parafollicular C cells that produce calcitonin. In MEN2 patients, pheochromocytoma MUST be diagnosed and treated before thyroidectomy, as anesthetic induction in an undiagnosed pheochromocytoma can trigger life-threatening hypertensive crisis. Prophylactic thyroidectomy is recommended for RET mutation carriers, with timing based on the specific mutation's risk level.

### Clinical Image
![Medullary Thyroid Carcinoma Histology](case_02_image.jpg)

*Histopathology of medullary thyroid carcinoma showing nests of tumor cells with amyloid stroma (Congo red positive) and immunohistochemistry positive for calcitonin.*

**Image Source:** Wikimedia Commons - "Medullary thyroid carcinoma"
**License:** CC BY-SA 3.0
**URL:** https://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg

---

## Case 3: Follicular Thyroid Carcinoma

### Patient Demographics
- **Age:** 55 years
- **Sex:** Female
- **Occupation:** Retired teacher

### Chief Complaint
"My doctor found a thyroid nodule on a CT scan done for something else."

### History of Present Illness
A 55-year-old woman had a CT scan of her chest performed for evaluation of chronic cough, which incidentally revealed a thyroid nodule. She is asymptomatic with no neck mass, dysphagia, hoarseness, or symptoms of thyroid dysfunction. She has no history of head/neck radiation and no family history of thyroid cancer. She has had the cough for 3 months, attributed to post-nasal drip.

### Physical Examination
- **Vital Signs:** Normal
- **General:** Well-appearing woman in no distress
- **Neck:**
  - 2.5 cm smooth, firm nodule in left thyroid lobe
  - Mobile with swallowing
  - No cervical lymphadenopathy
- **Pulmonary:** Clear to auscultation

### Workup
- **Laboratory Studies:**
  - TSH: 3.4 mIU/L (normal)
- **Ultrasound Thyroid:**
  - Left lobe: 2.8 cm isoechoic to slightly hypoechoic nodule
  - Smooth margins, no calcifications
  - Increased peripheral vascularity ("halo" sign)
  - TI-RADS 4 (moderately suspicious)
- **FNA Cytology:**
  - Bethesda IV - Follicular neoplasm/suspicious for follicular neoplasm
  - "Microfollicular pattern, scant colloid"
- **Molecular Testing (Afirma, ThyroSeq):** Suspicious - cannot rule out malignancy

### Diagnosis
**Follicular neoplasm** - cannot distinguish benign follicular adenoma from follicular thyroid carcinoma on cytology; requires surgical pathology

### Treatment
1. **Diagnostic surgery:**
   - Thyroid lobectomy (hemithyroidectomy) initially
   - Final pathology determines if benign adenoma vs. carcinoma
2. **If follicular carcinoma confirmed on final pathology:**
   - Completion thyroidectomy (removal of remaining lobe)
   - Radioactive iodine ablation for intermediate/high-risk features
   - TSH suppression with levothyroxine
3. **If benign follicular adenoma:**
   - No further surgery needed
   - Levothyroxine only if hypothyroid post-lobectomy

**Post-operative pathology result:** Follicular thyroid carcinoma with capsular and vascular invasion (minimally invasive)

### Final Treatment
- Completion thyroidectomy performed
- Low-dose radioactive iodine ablation
- Levothyroxine with TSH suppression to 0.5-2.0 mIU/L (low-risk after complete resection)
- Surveillance with thyroglobulin, neck ultrasound

### Clinical Pearl
Follicular thyroid carcinoma is the second most common thyroid malignancy (10-15% of cases). Unlike papillary carcinoma, it spreads hematogenously rather than via lymphatics, with common metastases to bone and lung. The critical diagnostic challenge is that FNA cannot distinguish follicular adenoma from carcinoma - this distinction requires demonstrating capsular or vascular invasion on surgical pathology. The Bethesda System category IV ("Follicular neoplasm") has a 15-30% malignancy rate, making diagnostic surgery necessary. Molecular testing can help stratify risk but cannot definitively rule out malignancy in most cases.

### Clinical Image
![Follicular Thyroid Carcinoma Histology](case_03_image.jpg)

*Histopathology of follicular thyroid carcinoma demonstrating capsular invasion, the key feature distinguishing it from benign follicular adenoma.*

**Image Source:** Wikimedia Commons - "Follicular thyroid carcinoma"
**License:** CC BY-SA 3.0
**URL:** https://commons.wikimedia.org/wiki/File:Follicular_thyroid_carcinoma_-_capsular_invasion.jpg