Biochemistry



Pathology

Lecture 40 Pathology of Salivary Glands

1) To be familiar with inflammatory lesions of salivary gland. Inflammation of the salivary gland (sialadenitis) may be of traumatic, viral, bacterial, or autoimmune origin. Mucoceles are the most common inflammatory salivary gland lesion. The most common form of viral sialadenitis is mumps affecting mainly the parotids. Sjögren syndrome is an autoimmune disease affecting the salivary glands.

2) To know the clinical features, autoimmune characteristics and pathologic features of Sjögren’s syndrome.

Clinical features: a chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands. Occurring typically in older women between ages of 50 and 60. Keratoconjunctivitis produces blurred vision, burning and itching, and thick secretions accumulate in the conjunctival sac. Xerostomia results in difficulty swallowing, decreased taste, cracks in the mouth, and dry mucosa.

Autoimmune characteristics: lymphocytic infiltration and fibrosis is mediated by CD4+ helper T cells and B cells, including plasma cells that secrete antibody locally. Antibodies include rheumatoid factor, ANAs, and most importantly ribonucleoprotein antigens SS-A and SS-B. 60% of patients have an accompanying autoimmune disorder such as rheumatoid arthritis, SLE, polymyositis, scleroderma, etc.

Pathologic features: periductal and perivascular lymphocytic infiltration. The ductal lining epithelial cells may show hyperplasia, thus obstructing the ducts. Later, there is atrophy of the acini, fibrosis, hyalinization.

3) To be aware of the features of necrotizing sialometaplaisa and its potential for confusion with carcinoma. Necrotizing sialometaplasia generally affects a minor salivary gland, frequently in the palate. There is necrosis and inflammation of the salivary gland with marked squamous metaplasia. However, it is important to recognize that this lesion is an inflammatory process and not to be confused with squamous cell carcinoma.

4) To know the general attributes of neoplasia in the salivary gland. Salivary gland tumors are relatively uncommon and represent less than 2% of tumors in humans. About 65-80% arise within the parotid and 10% in the submandibular gland. 15-30% of tumors of the parotid are malignant, in contrast to 40% in the submandibular gland, 50% in the minor salivary glands, and 70-90% of sublingual tumors. This indicates that the likelihood of a salivary gland tumor being malignant is inversely proportional to the size of the gland. Surgical removal is limited due to the adjacent facial nerve.

5) To know the clinical course and pathologic features of pleomorphic adenoma, Warthin’s tumor and mucoepidermoid tumor of salivary gland.

|Disease |Clinical course |Pathologic features |

|Pleomorphic adenoma |Generally slow; recurrences common (excision |Gross: encapsulated, lobulated |

| |problems due to facial nerve) may give rise to |Micro: epithelial cells as ducts or cords amid |

| |carcinoma. |myxoid/cartilaginous tissue. |

|Warthin's tumor |Slow-growing, benign |Papillary enlargement of duck-type epithelial cells |

| | |over lymphoid tissue, often protruding into cystic |

| | |spaces. |

|Mucoepidermoid tumor |Unpredictable for most, based on histology (overtly |Epithelial cells demonstrating a mixture of squamous |

| |malignant tumors tend to behave aggressively) |and mucus secreting cells; spectrum of differentiation|

| | |is broad (from very mature to poorly differentiated) |

6) To be responsible for all material in the handout for Pathology of Salivary Glands. Review Handout.

7) To be able to answer all questions posed in the Directed Reading on Pathology of Salivary Glands.

1. What are the two principal antigenic targets in Sjögren syndrome?

Rheumatoid factor (75%) and ANAs (50-80%).

2. What are the two ribonuclease proteins (RNP) antigens to which autoantibodies are directed in Sjögren syndrome?

Ribonucleoproteins SS-A (Ro) and SS-B (La).

3. What type of lymphocytes are probably initiator's of Sjögren syndrome?

CD4+ T helper cells.

4. What is the main cell type infiltrating the salivary gland in Sjögren syndrome?

Activated CD4+ helper T cells and some B cells, including plasma cells secrete antibody locally.

5. What is the age and gender predilection for Sjögren disease?

Women between the ages of 50 and 60.

6. What is the relative risk of developing a lymphoid malignancy for patients with Sjögren syndrome versus a normal patient population?

Patients have about a 40-fold increase risk of developing lymphoid malignancies.

7. What lymphocyte cell type is most likely to produce a lymphoma in Sjögren syndrome?

Activated B lymphocytes can produce a neoplastic, monoclonal B cell tumor.

8. What are the main effects of Sjögren syndrome on the mouth and eyes?

Dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia).

9. What do dehydration, phenothiazine therapy and recent major thoracic or abdominal surgery have in common with respect to salivary glands?

They all predispose a patient to suppurative bacterial perotitis, sialadenitis.

10. Proximally what percent of salivary gland neoplasms arise in the parotid? The submandibular gland?

65-80% arise in the parotid, 10% in the submandibular gland, and the remainder in the minor salivary glands, including the sublingual glands.

11. The likelihood of the salivary gland tumor being malignant is more or less ___inversely proportional___ to the size of the gland.

12. What is a pleomorphic adenoma?

There are benign tumors that are derived from a mixture of ductal (epithelial) and myoepithelial cells, and therefore they show both epithelial and mesenchymal differentiation.

13. What do the gray-white, translucent areas in a pleomorphic adenoma correspond to histologically?

A matrix with varying degrees of myxoid, hyaline, chondroid (cartilagenous), and even osseous tissue.

14. What are the relative percentages of malignant transformation to duration of tumor in pleomorphic adenoma?

The incidence of malignant transformation increases with tumor duration, being about 2% for tumors present 15 years.

15. What is a Warthin tumor? What gender is more likely affected?

A Warthin tumor is a benign neoplasm arising almost exclusively in the parotid gland. It occurs more commonly in males and females.

16. What are the two major types of cells present in Warthin tumor?

Epithelial and lymphoid.

17. What are the two cell populations present in a mucoepidermoid carcinoma?

Variable mixtures squamous cells, mucus-secreting cells, and intermediate cells.

18. What is the most common form of malignant tumor primary in the salivary glands?

Mucoepidermoid carcinoma.

19. Low-grade mucoepidermoid carcinomas are often composed of what type of cells? How does this contrast with a high-grade tumors?

Cords, sheets, or cystic configurations of squamous, mucus, or intermediate cells, with small to large mucus filled vacuoles. The low-grade tumor cells may be regular and benign appearing while a high-grade cells are highly anaplastic and unmistakably malignant.

20. What are the relative survival rates for low-grade versus high-grade mucoepidermoid carcinomas?

Low-grade: recurrence 15%, metastasize rarely, the five-year survival rate 90%.

High-grade: recurrence 25-30%, metastasize 30%, five-year survival rate 50%.

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