Histology · Year 1 · from Histology
Case 1: Sjogren Syndrome - Autoimmune Destruction of Exocrine Glands
Clinical Presentation
A 52-year-old woman presents with a 2-year history of progressively worsening dry mouth and dry eyes. She reports difficulty swallowing dry food without liquids, a gritty sensation in her eyes, and recurrent dental caries despite good oral hygiene. She also describes joint pain and fatigue.
Review of Systems
- Dry mouth (xerostomia): Needs water at bedside, difficulty speaking for prolonged periods
- Dry eyes (keratoconjunctivitis sicca): Uses artificial tears multiple times daily
- Parotid gland swelling: Intermittent bilateral parotid enlargement
- Vaginal dryness
- Joint pain without swelling
Physical Examination
- Dry, fissured tongue with reduced sublingual saliva pooling
- Dental caries at the cervical margins of multiple teeth
- Bilateral parotid gland enlargement, non-tender
- Corneal fluorescein staining showing punctate epithelial erosions
- Schirmer test: 3 mm wetting in 5 minutes (normal >10 mm)
Laboratory Findings
- ANA positive (1:640, speckled pattern)
- Anti-SSA (Ro) antibody: Positive
- Anti-SSB (La) antibody: Positive
- Rheumatoid factor: Positive
- ESR: 45 mm/hr (elevated)
The Histology Question
To confirm the diagnosis of Sjogren syndrome, a labial (lip) minor salivary gland biopsy is performed. The pathologist must assess for focal lymphocytic sialadenitis and calculate the focus score.
Histopathological Findings
Image: Minor salivary gland biopsy in Sjogren syndrome showing focal lymphocytic sialadenitis. Dense aggregates of lymphocytes (dark blue clusters) surround and infiltrate the glandular acini, leading to progressive destruction of secretory tissue.
Image source: Wikimedia Commons, Creative Commons License
Microscopic Description:
- Multiple minor salivary gland lobules are present
- Dense lymphocytic aggregates (foci) are present in periductal locations
- Each focus contains >50 mononuclear cells
- Focus score: 3 foci per 4 mm2 of glandular tissue (positive, >1 is diagnostic)
- Acinar atrophy is evident with loss of normal serous/mucous acini
- Ductal epithelium shows reactive changes
- Residual acini appear surrounded by lymphocytic infiltrate
- No evidence of lymphoma
Diagnosis
Sjogren Syndrome - confirmed by labial salivary gland biopsy showing focal lymphocytic sialadenitis with focus score of 3
Understanding the Histopathology
Normal Minor Salivary Gland Structure:
- Mixed glands (serous and mucous acini)
- Intercalated ducts leading to excretory ducts
- Myoepithelial cells surrounding acini
- Sparse lymphocytes in stroma
Sjogren Syndrome Changes:
| Structure | Normal | Sjogren Syndrome |
|---|---|---|
| Acini | Intact serous/mucous units | Atrophic, destroyed by inflammation |
| Ducts | Patent, normal epithelium | Hyperplastic, surrounded by lymphocytes |
| Stroma | Minimal lymphocytes | Dense lymphocytic foci (>50 cells) |
| Overall architecture | Preserved lobular pattern | Disrupted with fibrosis |
Focus Score Calculation:
- Count foci (aggregates of >50 lymphocytes) in periductal location
- Calculate foci per 4 mm2 of glandular tissue
- Focus score >1 supports diagnosis of Sjogren syndrome
Mechanism of Glandular Destruction
- Autoimmune Attack: T and B lymphocytes infiltrate the glands
- Target: Epithelial cells of ducts and acini express autoantigens
- Consequence: Progressive destruction of secretory acini
- Fibrosis: Acini replaced by fibrous tissue and fat
- Result: Reduced saliva and tear production (sicca syndrome)
Clinical Correlations
Why These Symptoms?:
- Xerostomia: Destruction of salivary gland acini reduces saliva production
- Dental caries: Saliva provides antimicrobial protection and pH buffering
- Keratoconjunctivitis sicca: Lacrimal gland destruction reduces tear production
- Other exocrine glands affected: Respiratory tract, vaginal, pancreatic (rarely)
Learning Points
- Glandular histology directly explains clinical symptoms: Loss of serous and mucous acini leads to reduced secretion
- Biopsy provides definitive diagnosis: Focal lymphocytic sialadenitis is the histologic hallmark
- Understanding normal structure aids interpretation:
- Recognize normal acinar architecture
- Identify abnormal lymphocytic infiltrates
- Assess degree of acinar loss
- Mixed gland composition matters: Minor salivary glands contain both serous and mucous elements, both targeted in Sjogren syndrome
- Lymphoma risk: Patients with Sjogren syndrome have 10-40x increased risk of B-cell lymphoma; persistent parotid enlargement warrants evaluation
Discussion Questions
- Why are minor salivary glands from the lip preferred for biopsy over parotid gland biopsy?
- How might the histologic appearance of remaining acini help distinguish Sjogren syndrome from other causes of dry mouth?
- What histologic features would suggest malignant transformation to lymphoma?