Sjogren's Syndrome

Background

This is an autoimmune disorder characterized by multisystem changes. Like other autoimmune disorders, there is an association with primary biliary cirrhosis, sclerosing cholangitis, pancreatitis, interstitial nephritis, interstitial lymphocytic pneumonitis, and peripheral vasculitis. The characteristic symptoms of dry eyes and dry mouth result from the body's attack upon these salivary glands leading to dysfunction and later fibrosis. One little known symptom is dyspareunia, caused by vaginal dryness. Local moisturising cream and lubricating jelly provide some benefit. Eestrogen deficiency may worsen the preexisting condition in postmenopausal women, so local or systemic oestrogen replacement may also be helpful.

Diagnostic Criteria for Sjogren's Syndrome (SS)
Keratoconjunctitis sicca
Xerostomia
Extensive lymphocytic infiltrate on minor salivary gland biospy
Laboratory evidence of a systemic autoimmune disorder

The diagnostic criteria given above cannot be made in the presence of lymphoma, graft-vs-host disease, AIDS, and sarcoidosis.

The pathologist must carefully document the degree of involvement of the salivary gland by lymphocytes to establish the diagnosis. These salivary gland biopsies are usually performed upon the lower lip and reveal a lymphocytic infiltrate called a benign lymphoepithelial lesion. It is the degree of lymphocytic infiltrate combined with the above diagnostic criteria which establishes the diagnosis of SS.

Occasionally, SS may progress to a B-cell lymphoma. In these cases, the salivary tissue is obliterated by the lymphocytic infiltrate with scattered lymphoepithelial islands. About 1/3 of the patients developing lymphoma will die of the disease and distant metastases may occur in 25% of patients.

HISTOLOGICAL TYPES CHARACTERIZATION

General

At least 4 lobules with at least 2 foci of lymphocytes per 4 mm2 A focus is defined as a cluster of 50 or more lymphocytes
Lymphoid population may be monoclonal

Epimyoepithelial islands may form a continuous hypertrophic structure derived from proliferating duct cells These islands may be seen in 25% of salivary gland lymphomas

VARIANTS

Extranodal marginal-zone B-cell lymphoma of the salivary gland

Susan L. Abbondanzo, MD

From the Department of Hematopathology, Armed Forces Institute of Pathology, Washington, DC.

Ann Diagn Pathol 5: 246-254, 2001 Abstract quote

Primary non-Hodgkin's lymphoma of the salivary gland is an uncommon tumor that most often occurs in the parotid gland. The most common subtype is marginal-zone B-cell lymphoma, extranodal, mucosa-associated lymphoid tissue type. This subtype has recently been included in the Revised European-American Classification of Lymphoid Neoplasms, as well as in the upcoming World Health Organization classification of hematopoietic and lymphoid neoplasms.

This low-grade lymphoma usually arises in a background of benign lymphoepithelial lesion or myoepithelial sialadenitis that is associated with the autoimmune disease Sj�gren's syndrome. It occasionally develops in patients who do not have a history of autoimmune disease. When mucosa-associated lymphoid tissue lymphoma occurs in the salivary gland, as in other extranodal sites such as the stomach, it is usually an indolent neoplasm that tends to remain localized for long periods of time, even without treatment. Eventually, however, the tumor may disseminate or transform to a higher grade. The histologic distinction of myoepithelial sialadenitis from low-grade B-cell mucosa-associated lymphoid tissue lymphoma can be a difficult diagnostic challenge and many of these lesions continue to be ambiguously diagnosed as �pseudolymphoma.� Immunophenotypic or flow cytometric analysis may be useful in showing an aberrant phenotype or immunoglobulin light-chain restriction, which helps to support a diagnosis of malignant lymphoma in most cases. Molecular genetic analysis for immunoglobulin gene rearrangements also may be useful in showing monoclonality, although the exact significance of this finding in some cases remains controversial.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

KUTTNER TUMOR (CHRONIC SCLEROSING SIALADENITIS)

Kuttner Tumor of the Submandibular Gland Fine-Needle Aspiration Cytologic Findings of Seven Cases

Wah Cheuk, MBBS
John K.C. Chan, MBBS

Am J Clin Pathol 2002;117:103-108 Abstract quote

Kuttner tumor or chronic sclerosing sialadenitis is a benign inflammatory condition of the submandibular gland that mimics a malignant neoplasm clinically because of presentation as a hard mass. This is an underrecognized entity in the surgical pathology and cytology literature.

We describe the fine-needle aspiration cytologic findings of 7 cases with histologic correlation. The 6 men and 1 woman (age, 47-72 years) had unilateral (4 cases) or bilateral (3 cases) submandibular masses known to be present for 1 month to 6 years (mean, 15 months). The aspirates were paucicellular to moderately cellular. They were characterized by scattered tubular ductal structures often enveloped by collagen bundles or lymphoplasmacytic infiltrate, isolated fragments of fibrous stroma, a background rich in lymphoid cells, and paucity or absence of acini. Histologic examination of the excised submandibular glands revealed preserved lobular architecture, thickening of interlobular septa by sclerotic tissue, dense lymphoplasmacytic infiltrate, preservation of ducts with periductal fibrosis, and variable loss of acini.

In combination with the clinical findings, the fine-needle aspiration cytologic findings can strongly suggest the diagnosis of Kuttner tumor and may obviate the need of surgical intervention.

Oral Surg 1974;37:217-230.
Arthritis Rheum 1986;29:577-585.

Commonly Used Terms

Autoimmune Disorders
Lymphoma
Salivary Glands

Internet Links

Last Updated 1/14/2002

HISTOLOGICAL TYPES	CHARACTERIZATION
General
At least 4 lobules with at least 2 foci of lymphocytes per 4 mm2	A focus is defined as a cluster of 50 or more lymphocytes Lymphoid population may be monoclonal
Epimyoepithelial islands may form a continuous hypertrophic structure derived from proliferating duct cells	These islands may be seen in 25% of salivary gland lymphomas
VARIANTS
Extranodal marginal-zone B-cell lymphoma of the salivary gland Susan L. Abbondanzo, MD From the Department of Hematopathology, Armed Forces Institute of Pathology, Washington, DC.	Ann Diagn Pathol 5: 246-254, 2001 Abstract quote Primary non-Hodgkin's lymphoma of the salivary gland is an uncommon tumor that most often occurs in the parotid gland. The most common subtype is marginal-zone B-cell lymphoma, extranodal, mucosa-associated lymphoid tissue type. This subtype has recently been included in the Revised European-American Classification of Lymphoid Neoplasms, as well as in the upcoming World Health Organization classification of hematopoietic and lymphoid neoplasms. This low-grade lymphoma usually arises in a background of benign lymphoepithelial lesion or myoepithelial sialadenitis that is associated with the autoimmune disease Sj�gren's syndrome. It occasionally develops in patients who do not have a history of autoimmune disease. When mucosa-associated lymphoid tissue lymphoma occurs in the salivary gland, as in other extranodal sites such as the stomach, it is usually an indolent neoplasm that tends to remain localized for long periods of time, even without treatment. Eventually, however, the tumor may disseminate or transform to a higher grade. The histologic distinction of myoepithelial sialadenitis from low-grade B-cell mucosa-associated lymphoid tissue lymphoma can be a difficult diagnostic challenge and many of these lesions continue to be ambiguously diagnosed as �pseudolymphoma.� Immunophenotypic or flow cytometric analysis may be useful in showing an aberrant phenotype or immunoglobulin light-chain restriction, which helps to support a diagnosis of malignant lymphoma in most cases. Molecular genetic analysis for immunoglobulin gene rearrangements also may be useful in showing monoclonality, although the exact significance of this finding in some cases remains controversial.