Chronic Sclerosing Sialadenitis

Background

This is a rare inflammatory condition affecting the salivary glands that may clinically be mistaken for a malignancy. In fact, the older name for this disease is Kuttner's tumor. Patients usually present with a firm and painful swelling of one of the salivary glands. Biopsy or removal of the gland may occur because of the suspicion of a malignancy. Under the microscope, there are the characteristic changes of a chronic sclerosing process which gives the name to this disease. Although it is unclear what causes the disease, most investigators speculate that it is an abnormal immune reaction to some unidentified trigger. Salivary gland stones may be found in many of the lesions.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Kuttner's tumor

INCIDENCE/PREVALENCE Rare

DISEASE ASSOCIATIONS CHARACTERIZATION

LYMPHOMA

Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (Kuttner tumor).

Ochoa ER, Harris NL, Pilch BZ.

Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Am J Surg Pathol 2001 Dec;25(12):1546-50 Abstract quote
We report a case of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the salivary gland arising in a background of chronic sclerosing sialadenitis. Chronic sclerosing sialadenitis is a common fibrosing chronic inflammatory lesion of the submandibular gland, which is thought to be the result of sialolithiasis, and is not associated with a systemic autoimmune disease.

Salivary MALT lymphomas are typically associated with lymphoepithelial sialadenitis (LESA) in a patient with or without Sjogren's syndrome. Our case of salivary MALT lymphoma was neither preceded by Sjogren's syndrome nor accompanied by LESA.

This case suggests that chronic inflammatory processes other than Sjogren's syndrome may provide a substrate for the development of MALT lymphoma.

RETROPERITONEAL FIBROSIS

Chronic sclerosing sialadenitis of the submandibular gland associated with idiopathic retroperitoneal fibrosis.

Sekine S, Nagata M, Watanabe T.

Department of Pathology, Tsukuba University Hospital, University of Tsukuba, Ibaraki, Japan.
Pathol Int 1999 Jul;49(7):663-7 Abstract quote
We report a case of a 57-year-old man who developed a fibrosclerosing lesion in the submandibular gland and idiopathic retroperitoneal fibrosis (IRF) involving the unilateral periureteral region within a year.

Both lesions were resected surgically because of the suspicion of neoplasm. Pathologic examination revealed similar histologic and immunohistochemical features for both lesions, namely, fibrosclerosis with prominent hyalinizing collagen bundles and proliferation of myofibroblastic cells, and a non-neoplastic reactive nature. There was infiltration by lymphocytes with prominent lymph follicles, plasma cells and macrophages. The histologic and immunohistochemical findings suggest that the two lesions were of a similar pathogenesis, which was possibly mediated by macrophages.

We think that the present case may be an unusual form of multifocal fibrosclerosis. Although sialolithiasis is thought to be a major pathogenic factor for chronic sclerosing sialadenitis of the submandibular gland, the present case suggests that certain cases might have an etiology similar to IRF.

PATHOGENESIS CHARACTERIZATION

SIALOLITHS

Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases.

Harrison JD, Epivatianos A, Bhatia SN.

King's College School of Medicine and Dentistry, London, UK.

Histopathology 1997 Sep;31(3):237-51 Abstract quote
AIMS: Confusion about the aetiology and pathogenesis of chronic submandibular sialadenitis led to the present investigation of 154 cases in which many clinical and histological features were analysed.

METHODS AND RESULTS: By far the greatest number of histological factors, namely liths, atrophy, fibrosis, parenchymal inflammation, lymphoid germinal centres, mucous and ciliary metaplasia, salivary extravasation and glycosaminoglycan accumulation, was related to the degree of inflammation, which appears to be of the greatest importance in the aetiology and pathogenesis. Inflammation, atrophy and fibrosis were related to duration of symptoms, which supports the concept of a chronological progression through increasingly severe histological changes.

CONCLUSIONS: Inflammation possibly arises from ascending infection in a normal gland and exerts an obstructive and destructive effect on the parenchyma with the development of the related histological changes and a vicious circle involving further ascending infection. Normal glands contain microliths that possibly by localized obstruction cause atrophic foci that are reservoirs for ascending infection. Microliths and liths were unrelated: microliths were related to age as in normal glands whereas liths were related to duration of symptoms and appeared to be secondary to the sialadenitis. Many glands showed minimal changes, which raises the possibility of conservative treatment.

T LYMPHOCYTES

Chronic Sclerosing Sialadenitis of the Submandibular Gland is Mainly Due to a T Lymphocyte Immune Reaction.

Tiemann M, Teymoortash A, Schrader C, Werner JA, Parwaresch R, Seifert G, Kloppel G.

Departments of Hematopathology (MT, CS, RP) and Pathology (GK), University of Kiel.
Mod Pathol 2002 Aug;15(8):845-52 Abstract quote
The aim of our study was to investigate the role of immunopathological processes in the pathogenesis of chronic sclerosing sialadenitis of submandibular glands (Kuttner tumor). For this purpose, biopsy specimens from submandibular glands of 22 patients with the histological diagnosis of chronic sclerosing sialadenitis were analyzed.

Paraffin-embedded tissues were immunostained for T-lymphocyte subsets (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20, Ki-B3), and macrophages (Ki-M1P). Polymerase chain reaction and capillary electrophoresis were used to detect rearrangements of the T-cell receptor gamma chain and the CDRIII region of the immunoglobulin heavy chain. In all cases, abundant cytotoxic T cells were found, especially in close association with ducts and acini. T-cell receptor gamma chain rearrangements showed a monoclonal pattern in 6 cases (27.3%), an oligoclonal pattern in 8 (36.4%), and a polyclonal pattern in 8 (36.4%). The B-cell reaction was less pronounced and largely restricted to lymph follicles. Molecular analysis of immunoglobulin heavy chain revealed a polyclonal rearrangement in 17 cases (77.3%). In conclusion, there is an intimate relationship between the T-cell-dominated inflammatory infiltrate and acinar and duct cells.

This, together with the frequent demonstration of monoclonal and oligoclonal populations of cytotoxic T cells and their histopathological behavior, suggests that chronic sclerosing sialadenitis may be the result of an immune process triggered by intraductal agents.

Immunological similarities between primary sclerosing cholangitis and chronic sclerosing sialadenitis: report of the overlapping of these two autoimmune diseases.

Tsuneyama K, Saito K, Ruebner BH, Konishi I, Nakanuma Y, Gershwin ME.

Toyama City Hospital, Imaizumi, Toyama, Japan.

Dig Dis Sci 2000 Feb;45(2):366-72 Abstract quote
Primary sclerosing cholangitis (PSC) is characterized by destructive inflammation and fibrosis affecting the bile ducts. The etiology of PSC is still unknown, although lymphocytic infiltration in the portal areas suggests an immune-mediated destruction of the bile ducts. Patients with one autoimmune disease often suffer from one or more other autoimmune diseases. It is well known that there is a close relationship between PSC and inflammatory bowel disease, particularly ulcerative colitis(UC). However, the pathological findings in UC and other overlap diseases do not resemble those of PSC.

In the present study, we report a patient with chronic sclerosing sialadenitis (Kuttner's tumor) and PSC. It is compared the sclerosing changes in both salivary glands and bile ducts histologically. In addition, the expression pattern of mast cell tryptase, b-FGF, and HLA-DR were examined in both tissues immunohistochemically. Histological features of sclerosing change in both salivary and bile ducts were quite similar. Marked mast cell infiltration and b-FGF expression were seen in the sclerosing areas in both tissues. In active inflammatory areas of the salivary glands, HLA-DR expression was also seen.

We hypothesized that similar immune reactions occur in both the salivary gland and bile ducts and are responsible for the fibrosis that follows.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Chronic sclerosing sialadenitis of the submandibular and parotid glands: a report of a case and review of the literature.

Williams HK, Connor R, Edmondson H.

Department of Oral Pathology, Birmingham Dental Hospital and School, UK.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000 Jun;89(6):720-3 Abstract quote
Chronic sclerosing sialadenitis (also known as Kuttner tumor) is a chronic inflammatory condition of the salivary glands, first described by Kuttner in 1896.

Clinically, the disease cannot be distinguished from a true neoplasm. The submandibular gland is affected more commonly than any other salivary gland. This report is of a case of widespread swelling of the salivary glands in which histologic features of chronic sclerosing sialadenitis were seen in the submandibular and parotid glands.

The etiology, pathogenesis, and differential diagnosis of this disease and the clinical outcome of this case are discussed and presented.

VARIANTS

BILATERAL SALIVARY GLAND INVOLVEMENT

Chronic sclerosing sialadenitis (Kuttner's tumor): Unusual presentation with bilateral involvement of major and minor salivary glands.

Blanco M, Mesko T, Cura M, Cabello-Inchausti B.

Arkadi M. Rywlin MD Department of Pathology and Laboratory Medicine, and the Departments of Oncology, and Radiology, Mount Sinai Medical Center, Greater Miami, Miami Beach, FL.
Ann Diagn Pathol 2003 Feb;7(1):25-30 Abstract quote
In 1896 Kuttner reported four cases which he described as induration of the submandibular gland. Histologically, they showed chronic inflammation and fibrosis. Sporadic cases of this entity that have come to be known as Kuttner's tumor or chronic sclerosing sialadenitis of the submandibular gland and have been reported throughout the 20th century. This inflammatory tumor has been under-recognized, and awareness of its importance and probable immunologic background have recently become evident.

We report an unusual case of chronic sclerosing sialadenitis, affecting both parotid glands, both submandibular glands, and minor salivary glands of the oral cavity, and explore the immunohistochemical profile of this entity.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

CYTOLOGY

Kuttner tumor of the submandibular gland: fine-needle aspiration cytologic findings of seven cases.

Cheuk W, Chan JK.

Department of Pathology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China Special Administrative Region.

Am J Clin Pathol 2002 Jan;117(1):103-8 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 thefine-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.

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

Histochemical and biochemical determination of calcium in salivary glands with particular reference to chronic submandibular sialadenitis.

Harrison JD, Triantafyllou A, Baldwin D, Schafer H.

Department of Oral Pathology, Rayne Institute, King's College School of Medicine and Dentistry, London, England.
Virchows Arch A Pathol Anat Histopathol 1993;423(1):29-32 Abstract quote
Although salivary calcification is relatively common, little is known about the localization and content of the calcium of normal and diseased human salivary glands.

We investigated this in chronic submandibular sialadenitis with a variable mixture of relatively normal and extremely atrophic parenchyma and in normal submandibular, parotid and palatal glands. Calcium was localized histochemically in mucous acinar cells of submandibular and palatal glands at moderate to high levels, in serous acinar cells of submandibular and parotid glands at low to moderate or occasionally high levels, in mucous ductal cells at moderate to high levels, and in extremely atrophic parenchyma at low levels or not at all. Calcium was determined biochemically at relatively high levels in the different glands in the order palatal, submandibular, sialadenitis and parotid. However, the differences were small.

The results indicate that most salivary calcium is associated with secretory granules; this is the likely source of the calcium involved in salivary calcification.

IMMUNOPEROXIDASE

Abundant IgG4-Positive Plasma Cell Infiltration Characterizes Chronic Sclerosing Sialadenitis (Kuttner's Tumor).

Kitagawa S, Zen Y, Harada K, Sasaki M, Sato Y, Minato H, Watanabe K, Kurumaya H, Katayanagi K, Masuda S, Niwa H, Tsuneyama K, Saito K, Haratake J, Takagawa K, Nakanuma Y.

From the *Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa; daggerDepartment of Pathology, Fukui Saiseikai Hospital, Fukui; double daggerPathology Section, Kanazawa University Hospital, Kanazawa; section signThe Watanabe's Consultancy for Pathological Diagnosis, Kanazawa; parallelDepartment of Pathology, Ishikawa Prefectural Central Hospital, Kanazawa; paragraph signDepartment of Pathology, Kouseiren Takaoka Hospital, Takaoka; #First Department of Pathology, Toyama Medical and Pharmaceutical University School of Medicine, Toyama; **Department of Pathology, Toyama City Hospital, Toyama; and daggerdaggerDepartment of Pathology, Kurobe City Hospital, Kurobe, Japan.

Am J Surg Pathol. 2005 Jun;29(6):783-791. Abstract quote

Chronic sclerosing sialadenitis (CSS) is a cryptogenic tumor-like condition of the salivary gland(s). While immune-mediated processes are suspected in its pathogenesis, and CSS is occasionally reported to be associated with sclerosing pancreatitis, an IgG4-related disease, the exact immunopathologic processes of CSS remain speculative.

In this study, we examined the clinicopathologic findings of CSS (12 cases) in comparison with sialolithiasis (8 cases) and Sjogren's syndrome (13 cases), and tried to clarify whether CSS is an IgG4-related disease or not. Submandibular gland(s) were affected in all cases of CSS. CSS cases could be divided into two types: 5 cases were associated with sclerosing lesions in extrasalivary glandular tissue (systemic type), while only salivary gland(s) were affected in the remaining 7 cases (localized type). In the former type, which showed male predominance, bilateral salivary glands were frequently affected, and eosinophilia and elevations of gamma-globulin and IgG in serum were frequently found. Histologically, all cases of CSS showed marked lymphoplasmacytic infiltration admixed with fibrosis and the destruction of glandular lobules. Obliterative phlebitis was found in the affected salivary glands in all cases of CSS.

Immunohistochemically, the proportion of IgG4/IgG-positive plasma cells was more than 45% in CSS, while it was less than 5% in controls. The resemblance of the clinicopathologic features of CSS with those of sclerosing pancreatitis suggests the participation of a similar immunopathologic process with IgG4 disturbance in CSS.

The abundance of IgG4-positive plasma cells in the lesions would be useful for distinguishing CSS from other forms of sialadenitis.

Immunohistopathological investigation on unspecific chronic sclerosing sialadenitis of the submandibular gland (Kuttner tumor).

Ikeda M, Ikui A, Tanaka M, Omori H, Tomita H.

Department of Otolaryngology, Nihon University School of Medicine, Tokyo, Japan.
Auris Nasus Larynx 1994;21(2):103-10 Abstract quote
An immunohistochemical investigation was conducted on infiltrating lymphocytes in submandibular glands removed from three cases with unspecific chronic sclerosing sialadenitis of the submandibular gland (unspecific CSSS) which has been described for the first time by Kuttner. A high degree of lymphocyte infiltration was recognized and formation of lymphatic follicles was observed. In particular, activated B cells were predominantly observed in that part of the lymphatic follicles which was equivalent to germinal centers.

In the T cell subset, the helper/inducer T cells displayed significant dominance over suppressor/cytotoxic T cells, and were distributed in the dark peripheral zone of the follicles. The distribution pattern of these lymphocytes seemed to be similar to antigenically stimulated lymph nodes and it was recognized that the unspecific CSSS could be a site of exceedingly active local immune responses.

The authors believe that these findings support the view that unspecific CSSS (Kuttner tumor) is an immune disorder.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

GRANULOMATOUS SIALADENITIS

Granulomatous sialadenitis of the major salivary glands. A clinicopathological study of 57 cases.

van der Walt JD, Leake J.
Histopathology 1987 Feb;11(2):131-44 Abstract quote
Fifty-seven of 469 major salivary glands excised for various reasons were found to contain granulomas.

The aetiologies were tuberculosis (eight parotid, one sublingual), sarcoidosis (two parotid), calculous duct obstruction (34 submandibular), carcinomatous duct obstruction (four submandibular, one sublingual) and undetermined (four submandibular, three parotid). The tuberculous glands showed caseation in the majority of cases but two cases consisted predominantly of discrete granulomas with minimal necrosis. The sarcoid granulomas were typically non-caseating but a few were centrally necrotic. The cases of calculous and carcinomatous duct obstruction contained single to multiple small granulomas which contained mucin and were related to ruptured ducts.

It is suggested that the frequency of calculi and the mixture of serous and mucous acini in the submandibular gland account for the distribution of obstructive granulomas. This study establishes calculous sialadenopathy as a major cause of granulomatous sialadenitis.

NECROTIZING SIALOMETAPLASIA

Necrotizing sialometaplasia: literature review and presentation of five cases.

Grillon GL, Lally ET.
J Oral Surg 1981 Oct;39(10):747-53 Abstract quote
Necrotizing sialometaplasia is a benign, ulcerative, inflammatory process of the minor salivary glands, primarily found in the hard palate. It is often mistaken clinically and histologically for a malignant tumor (that is, mucoepidermoid or squamous cell carcinoma).

The lesion heals spontaneously in six to 12 weeks. It occurs primarily in persons between the ages of 40 and 60 and has been reported more frequently in men than women.

In necrotizing sialometaplasia the squamous metaplasia and tissue necrosis is confined to the existing ductal and lobular pattern of the salivary glands, a unique characteristic that aids in diagnosis. Five additional cases are presented.

NEONATAL SUPPURATIVE SUBMANDIBULAR SIALADENITIS

Neonatal suppurative submandibular sialadenitis: a rare clinical entity.

Ungkanont K, Kolatat T, Tantinikorn W.

Department of Otolaryngology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Int J Pediatr Otorhinolaryngol 1998 Mar 1;43(2):141-5 Abstract quote
Submandibular sialadenitis is very rare in the neonatal age group. Only four cases of isolated submandibular gland infection without the involvement of the parotid gland have been reported in the literature up to the present time.

We present a case of a premature newborn infant who developed fever and right submandibular swelling when he was 8 days old. Pus was found extruding from Wharton's duct. The pus culture yielded Pseudomonas aeruginosa.

The patient was treated conservatively with adequate hydration and intravenous ceftazidime for 14 days and the infection resolved. The possible predisposing factors were dehydration and prematurity. CT scan revealed no calculi and no anatomic derangement. Two months follow-up showed no evidence of recurrence. Previous literature is reviewed and discussed.

PROGNOSIS CHARACTERIZATION

GENERAL Benign but may be debilitating due to pain

TREATMENT CHARACTERIZATION

GENERAL Supportive

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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PATHOGENESIS	CHARACTERIZATION
SIALOLITHS
Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases. Harrison JD, Epivatianos A, Bhatia SN. King's College School of Medicine and Dentistry, London, UK.	Histopathology 1997 Sep;31(3):237-51 Abstract quote AIMS: Confusion about the aetiology and pathogenesis of chronic submandibular sialadenitis led to the present investigation of 154 cases in which many clinical and histological features were analysed. METHODS AND RESULTS: By far the greatest number of histological factors, namely liths, atrophy, fibrosis, parenchymal inflammation, lymphoid germinal centres, mucous and ciliary metaplasia, salivary extravasation and glycosaminoglycan accumulation, was related to the degree of inflammation, which appears to be of the greatest importance in the aetiology and pathogenesis. Inflammation, atrophy and fibrosis were related to duration of symptoms, which supports the concept of a chronological progression through increasingly severe histological changes. CONCLUSIONS: Inflammation possibly arises from ascending infection in a normal gland and exerts an obstructive and destructive effect on the parenchyma with the development of the related histological changes and a vicious circle involving further ascending infection. Normal glands contain microliths that possibly by localized obstruction cause atrophic foci that are reservoirs for ascending infection. Microliths and liths were unrelated: microliths were related to age as in normal glands whereas liths were related to duration of symptoms and appeared to be secondary to the sialadenitis. Many glands showed minimal changes, which raises the possibility of conservative treatment.
T LYMPHOCYTES
Chronic Sclerosing Sialadenitis of the Submandibular Gland is Mainly Due to a T Lymphocyte Immune Reaction. Tiemann M, Teymoortash A, Schrader C, Werner JA, Parwaresch R, Seifert G, Kloppel G. Departments of Hematopathology (MT, CS, RP) and Pathology (GK), University of Kiel.	Mod Pathol 2002 Aug;15(8):845-52 Abstract quote The aim of our study was to investigate the role of immunopathological processes in the pathogenesis of chronic sclerosing sialadenitis of submandibular glands (Kuttner tumor). For this purpose, biopsy specimens from submandibular glands of 22 patients with the histological diagnosis of chronic sclerosing sialadenitis were analyzed. Paraffin-embedded tissues were immunostained for T-lymphocyte subsets (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20, Ki-B3), and macrophages (Ki-M1P). Polymerase chain reaction and capillary electrophoresis were used to detect rearrangements of the T-cell receptor gamma chain and the CDRIII region of the immunoglobulin heavy chain. In all cases, abundant cytotoxic T cells were found, especially in close association with ducts and acini. T-cell receptor gamma chain rearrangements showed a monoclonal pattern in 6 cases (27.3%), an oligoclonal pattern in 8 (36.4%), and a polyclonal pattern in 8 (36.4%). The B-cell reaction was less pronounced and largely restricted to lymph follicles. Molecular analysis of immunoglobulin heavy chain revealed a polyclonal rearrangement in 17 cases (77.3%). In conclusion, there is an intimate relationship between the T-cell-dominated inflammatory infiltrate and acinar and duct cells. This, together with the frequent demonstration of monoclonal and oligoclonal populations of cytotoxic T cells and their histopathological behavior, suggests that chronic sclerosing sialadenitis may be the result of an immune process triggered by intraductal agents.
Immunological similarities between primary sclerosing cholangitis and chronic sclerosing sialadenitis: report of the overlapping of these two autoimmune diseases. Tsuneyama K, Saito K, Ruebner BH, Konishi I, Nakanuma Y, Gershwin ME. Toyama City Hospital, Imaizumi, Toyama, Japan.	Dig Dis Sci 2000 Feb;45(2):366-72 Abstract quote Primary sclerosing cholangitis (PSC) is characterized by destructive inflammation and fibrosis affecting the bile ducts. The etiology of PSC is still unknown, although lymphocytic infiltration in the portal areas suggests an immune-mediated destruction of the bile ducts. Patients with one autoimmune disease often suffer from one or more other autoimmune diseases. It is well known that there is a close relationship between PSC and inflammatory bowel disease, particularly ulcerative colitis(UC). However, the pathological findings in UC and other overlap diseases do not resemble those of PSC. In the present study, we report a patient with chronic sclerosing sialadenitis (Kuttner's tumor) and PSC. It is compared the sclerosing changes in both salivary glands and bile ducts histologically. In addition, the expression pattern of mast cell tryptase, b-FGF, and HLA-DR were examined in both tissues immunohistochemically. Histological features of sclerosing change in both salivary and bile ducts were quite similar. Marked mast cell infiltration and b-FGF expression were seen in the sclerosing areas in both tissues. In active inflammatory areas of the salivary glands, HLA-DR expression was also seen. We hypothesized that similar immune reactions occur in both the salivary gland and bile ducts and are responsible for the fibrosis that follows.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Chronic sclerosing sialadenitis of the submandibular and parotid glands: a report of a case and review of the literature. Williams HK, Connor R, Edmondson H. Department of Oral Pathology, Birmingham Dental Hospital and School, UK.	Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000 Jun;89(6):720-3 Abstract quote Chronic sclerosing sialadenitis (also known as Kuttner tumor) is a chronic inflammatory condition of the salivary glands, first described by Kuttner in 1896. Clinically, the disease cannot be distinguished from a true neoplasm. The submandibular gland is affected more commonly than any other salivary gland. This report is of a case of widespread swelling of the salivary glands in which histologic features of chronic sclerosing sialadenitis were seen in the submandibular and parotid glands. The etiology, pathogenesis, and differential diagnosis of this disease and the clinical outcome of this case are discussed and presented.
VARIANTS
BILATERAL SALIVARY GLAND INVOLVEMENT
Chronic sclerosing sialadenitis (Kuttner's tumor): Unusual presentation with bilateral involvement of major and minor salivary glands. Blanco M, Mesko T, Cura M, Cabello-Inchausti B. Arkadi M. Rywlin MD Department of Pathology and Laboratory Medicine, and the Departments of Oncology, and Radiology, Mount Sinai Medical Center, Greater Miami, Miami Beach, FL.	Ann Diagn Pathol 2003 Feb;7(1):25-30 Abstract quote In 1896 Kuttner reported four cases which he described as induration of the submandibular gland. Histologically, they showed chronic inflammation and fibrosis. Sporadic cases of this entity that have come to be known as Kuttner's tumor or chronic sclerosing sialadenitis of the submandibular gland and have been reported throughout the 20th century. This inflammatory tumor has been under-recognized, and awareness of its importance and probable immunologic background have recently become evident. We report an unusual case of chronic sclerosing sialadenitis, affecting both parotid glands, both submandibular glands, and minor salivary glands of the oral cavity, and explore the immunohistochemical profile of this entity.

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
GRANULOMATOUS SIALADENITIS
Granulomatous sialadenitis of the major salivary glands. A clinicopathological study of 57 cases. van der Walt JD, Leake J.	Histopathology 1987 Feb;11(2):131-44 Abstract quote Fifty-seven of 469 major salivary glands excised for various reasons were found to contain granulomas. The aetiologies were tuberculosis (eight parotid, one sublingual), sarcoidosis (two parotid), calculous duct obstruction (34 submandibular), carcinomatous duct obstruction (four submandibular, one sublingual) and undetermined (four submandibular, three parotid). The tuberculous glands showed caseation in the majority of cases but two cases consisted predominantly of discrete granulomas with minimal necrosis. The sarcoid granulomas were typically non-caseating but a few were centrally necrotic. The cases of calculous and carcinomatous duct obstruction contained single to multiple small granulomas which contained mucin and were related to ruptured ducts. It is suggested that the frequency of calculi and the mixture of serous and mucous acini in the submandibular gland account for the distribution of obstructive granulomas. This study establishes calculous sialadenopathy as a major cause of granulomatous sialadenitis.
NECROTIZING SIALOMETAPLASIA
Necrotizing sialometaplasia: literature review and presentation of five cases. Grillon GL, Lally ET.	J Oral Surg 1981 Oct;39(10):747-53 Abstract quote Necrotizing sialometaplasia is a benign, ulcerative, inflammatory process of the minor salivary glands, primarily found in the hard palate. It is often mistaken clinically and histologically for a malignant tumor (that is, mucoepidermoid or squamous cell carcinoma). The lesion heals spontaneously in six to 12 weeks. It occurs primarily in persons between the ages of 40 and 60 and has been reported more frequently in men than women. In necrotizing sialometaplasia the squamous metaplasia and tissue necrosis is confined to the existing ductal and lobular pattern of the salivary glands, a unique characteristic that aids in diagnosis. Five additional cases are presented.
NEONATAL SUPPURATIVE SUBMANDIBULAR SIALADENITIS
Neonatal suppurative submandibular sialadenitis: a rare clinical entity. Ungkanont K, Kolatat T, Tantinikorn W. Department of Otolaryngology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.	Int J Pediatr Otorhinolaryngol 1998 Mar 1;43(2):141-5 Abstract quote Submandibular sialadenitis is very rare in the neonatal age group. Only four cases of isolated submandibular gland infection without the involvement of the parotid gland have been reported in the literature up to the present time. We present a case of a premature newborn infant who developed fever and right submandibular swelling when he was 8 days old. Pus was found extruding from Wharton's duct. The pus culture yielded Pseudomonas aeruginosa. The patient was treated conservatively with adequate hydration and intravenous ceftazidime for 14 days and the infection resolved. The possible predisposing factors were dehydration and prematurity. CT scan revealed no calculi and no anatomic derangement. Two months follow-up showed no evidence of recurrence. Previous literature is reviewed and discussed.

Epidemiology
Disease Associations
Pathogenesis
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Kuttner's tumor
INCIDENCE/PREVALENCE	Rare

DISEASE ASSOCIATIONS	CHARACTERIZATION
LYMPHOMA
Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (Kuttner tumor). Ochoa ER, Harris NL, Pilch BZ. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.	Am J Surg Pathol 2001 Dec;25(12):1546-50 Abstract quote We report a case of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the salivary gland arising in a background of chronic sclerosing sialadenitis. Chronic sclerosing sialadenitis is a common fibrosing chronic inflammatory lesion of the submandibular gland, which is thought to be the result of sialolithiasis, and is not associated with a systemic autoimmune disease. Salivary MALT lymphomas are typically associated with lymphoepithelial sialadenitis (LESA) in a patient with or without Sjogren's syndrome. Our case of salivary MALT lymphoma was neither preceded by Sjogren's syndrome nor accompanied by LESA. This case suggests that chronic inflammatory processes other than Sjogren's syndrome may provide a substrate for the development of MALT lymphoma.
RETROPERITONEAL FIBROSIS
Chronic sclerosing sialadenitis of the submandibular gland associated with idiopathic retroperitoneal fibrosis. Sekine S, Nagata M, Watanabe T. Department of Pathology, Tsukuba University Hospital, University of Tsukuba, Ibaraki, Japan.	Pathol Int 1999 Jul;49(7):663-7 Abstract quote We report a case of a 57-year-old man who developed a fibrosclerosing lesion in the submandibular gland and idiopathic retroperitoneal fibrosis (IRF) involving the unilateral periureteral region within a year. Both lesions were resected surgically because of the suspicion of neoplasm. Pathologic examination revealed similar histologic and immunohistochemical features for both lesions, namely, fibrosclerosis with prominent hyalinizing collagen bundles and proliferation of myofibroblastic cells, and a non-neoplastic reactive nature. There was infiltration by lymphocytes with prominent lymph follicles, plasma cells and macrophages. The histologic and immunohistochemical findings suggest that the two lesions were of a similar pathogenesis, which was possibly mediated by macrophages. We think that the present case may be an unusual form of multifocal fibrosclerosis. Although sialolithiasis is thought to be a major pathogenic factor for chronic sclerosing sialadenitis of the submandibular gland, the present case suggests that certain cases might have an etiology similar to IRF.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
CYTOLOGY
Kuttner tumor of the submandibular gland: fine-needle aspiration cytologic findings of seven cases. Cheuk W, Chan JK. Department of Pathology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China Special Administrative Region.	Am J Clin Pathol 2002 Jan;117(1):103-8 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 thefine-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.