A 65-year-old woman with a 40-pack-year smoking history presents with progressive neurological decline: memory loss, confusion, and personality changes. CSF analysis shows lymphocytic pleocytosis. Anti-Hu antibodies are positive. Which is the most common underlying malignancy?

Question

Accepted Answer

C. Small cell lung cancer. ## Paraneoplastic Encephalomyelitis (PEM) with Anti-Hu Antibodies

### Clinical Presentation
The patient exhibits:
- Cognitive dysfunction (memory loss, confusion)
- Personality changes
- Possible seizures, ataxia, or autonomic dysfunction
- CSF lymphocytic pleocytosis (indicating CNS inflammation)

### Antibody-Malignancy Association

| Antibody | Target Antigen | Most Common Malignancy | Frequency |
|---|---|---|---|
| Anti-Hu (ANNA-1) | HuD protein (neuronal) | SCLC | 80–90% |
| Anti-Yo (PCA-1) | Purkinje cell antigen | Breast/ovarian | 90% |
| Anti-Ri (ANNA-2) | RNA-binding protein | SCLC, breast | 50% |
| Anti-VGCC | P/Q-type calcium channel | SCLC | 50–60% |

**High-Yield:** Anti-Hu antibodies are present in 80–90% of SCLC cases with paraneoplastic neurological syndrome. The positive anti-Hu serology is virtually diagnostic of an underlying malignancy.

### Pathophysiology
Anti-Hu antibodies cross-react with HuD protein expressed in both tumor cells and neurons. This triggers T-cell-mediated cytotoxic destruction of neurons, causing encephalomyelitis.

### Clinical Pearl
**Key Point:** Anti-Hu seropositivity is a paraneoplastic marker with >95% specificity for malignancy. In a smoker with anti-Hu+ encephalomyelitis, SCLC is present in >80% of cases.

### Diagnostic Approach
1. **Serology:** Anti-Hu (ANNA-1), anti-Yo, anti-Ri, anti-VGCC
2. **Imaging:** Chest CT (SCLC screening), brain MRI (T2/FLAIR hyperintensities)
3. **CSF:** Lymphocytic pleocytosis, elevated protein, oligoclonal bands
4. **Oncology:** Urgent malignancy screening

### Management
1. Treat underlying malignancy (chemotherapy for SCLC)
2. Immunotherapy: IVIg, plasmapheresis, corticosteroids
3. Symptomatic seizure control

**Mnemonic:** **SCLC-Hu** = Small Cell Lung Cancer is the most common source of anti-Hu paraneoplastic neurological syndromes.

Answer

A. Colorectal cancer

Answer

B. Breast cancer

Answer

D. Ovarian cancer

A 65-year-old woman with a 40-pack-year smoking history presents with progressive neurological decline: memory loss, confusion, and personality changes. CSF analysis shows lymphocytic pleocytosis. Anti-Hu antibodies are positive. Which is the most common underlying malignancy?

Explanation

Paraneoplastic Encephalomyelitis (PEM) with Anti-Hu Antibodies

Clinical Presentation

Antibody-Malignancy Association

Pathophysiology

Clinical Pearl

Diagnostic Approach

Management

Practice similar questions

Join our NEET PG community

Antibody	Target Antigen	Most Common Malignancy	Frequency
Anti-Hu (ANNA-1)	HuD protein (neuronal)	SCLC	80–90%
Anti-Yo (PCA-1)	Purkinje cell antigen	Breast/ovarian	90%
Anti-Ri (ANNA-2)	RNA-binding protein	SCLC, breast	50%
Anti-VGCC	P/Q-type calcium channel	SCLC	50–60%