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Figure 1.
Küttner submandibular tumor and dacryoadenitis. A, The patient suddenly developed a right proptosis of 3 mm with fullness of the outer aspect of the upper eyelid (arrow). Inset, The patient's right eye was mildly injected without chemosis. B, A coronal computed tomographic scan demonstrates an enlarged lacrimal gland (white arrow) along with superior rectus swelling (black arrow) on the right. C, Thickened fibrous septa separate chronically inflamed lobules of the left submandibular gland with some surviving ducts in the upper left of the field (hematoxylin-eosin, original magnification ×100). Inset, Germinal centers (arrows) are present in the midst of the infiltrating lymphoplasmacytic cells (hematoxylin-eosin, original magnification ×100). D, Uninvolved submandibular gland tissue composed of serous and seromucinous acini on the left is juxtaposed to inflamed lobules on the right (hematoxylin-eosin, original magnification ×100). Inset, Serous and seromucinous acini (arrows) (hematoxylin-eosin, original magnification ×200). E, Lacrimal gland tissue displays lymphoplasmacytic infiltrate with fibrosis. Glandular units are shown on the upper left (hematoxylin-eosin, original magnification ×100). F, Lacrimal gland acini with zymogen granules (arrow) are surrounded by lymphocytes and plasma cells (hematoxylin-eosin, original magnification ×400).

Küttner submandibular tumor and dacryoadenitis. A, The patient suddenly developed a right proptosis of 3 mm with fullness of the outer aspect of the upper eyelid (arrow). Inset, The patient's right eye was mildly injected without chemosis. B, A coronal computed tomographic scan demonstrates an enlarged lacrimal gland (white arrow) along with superior rectus swelling (black arrow) on the right. C, Thickened fibrous septa separate chronically inflamed lobules of the left submandibular gland with some surviving ducts in the upper left of the field (hematoxylin-eosin, original magnification ×100). Inset, Germinal centers (arrows) are present in the midst of the infiltrating lymphoplasmacytic cells (hematoxylin-eosin, original magnification ×100). D, Uninvolved submandibular gland tissue composed of serous and seromucinous acini on the left is juxtaposed to inflamed lobules on the right (hematoxylin-eosin, original magnification ×100). Inset, Serous and seromucinous acini (arrows) (hematoxylin-eosin, original magnification ×200). E, Lacrimal gland tissue displays lymphoplasmacytic infiltrate with fibrosis. Glandular units are shown on the upper left (hematoxylin-eosin, original magnification ×100). F, Lacrimal gland acini with zymogen granules (arrow) are surrounded by lymphocytes and plasma cells (hematoxylin-eosin, original magnification ×400).

Figure 2.
Immunohistochemical studies (immunoperoxidase method, diaminobenzidine chromogen). A, CD3+ T lymphocytes in the submandibular gland infiltrate. CD20+ B lymphocytes were slightly less represented (not shown) (original magnification ×200). B, CD20+ B lymphocytes in the lacrimal gland infiltrate, which mildly outnumbered T lymphocytes (not shown) (original magnification ×200). C, IgG4-positive plasma cells with cytoplasmic immunostaining are prominently represented in the submandibular gland infiltrate (original magnification ×200). D, IgG4-positive plasma cells in the lacrimal gland (original magnification ×400).

Immunohistochemical studies (immunoperoxidase method, diaminobenzidine chromogen). A, CD3+ T lymphocytes in the submandibular gland infiltrate. CD20+ B lymphocytes were slightly less represented (not shown) (original magnification ×200). B, CD20+ B lymphocytes in the lacrimal gland infiltrate, which mildly outnumbered T lymphocytes (not shown) (original magnification ×200). C, IgG4-positive plasma cells with cytoplasmic immunostaining are prominently represented in the submandibular gland infiltrate (original magnification ×200). D, IgG4-positive plasma cells in the lacrimal gland (original magnification ×400).

1.
Kitagawa  SZen  YHarada  K  et al.  Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Kuttner's tumor). Am J Surg Pathol 2005;29 (6) 783- 791
PubMed
2.
Stone  JHCaruso  PADeshpande  V Case records of the Massachusetts General Hospital: case 24-2009: a 26-year-old woman with painful swelling of the neck. N Engl J Med 2009;361 (5) 511- 518
PubMed
3.
Lee  LYChen  TCKuo  TT Simultaneous occurrence of IgG4-related chronic sclerosing dacryoadenitis and chronic sclerosing sialadenitis in a patient also with involvement of lymph node and Warthin's tumor [published online December 30, 2008]. Int J Surg Pathol
PubMed10.1177/1066896908329584
4.
Kamisawa  TOkamoto  A IgG4-related sclerosing disease. World J Gastroenterol 2008;14 (25) 3948- 3955
PubMed
5.
Kamisawa  TYoshiike  MEgawa  NNakajima  HTsuruta  KOkamoto  A Treating patients with autoimmune pancreatitis: results from a long-term follow-up study. Pancreatology 2005;5 (2-3) 234- 240
PubMed
6.
Neild  GHRodriguez-Justo  MWall  CConnolly  JO Hyper-IgG4 disease: report and characterisation of a new disease. BMC Med 2006;423
PubMed
7.
Mehta  MJakobiec  FFay  A Idiopathic fibroinflammatory disease of the face, eyelids, and periorbital membrane with immunoglobulin G4-positive plasma cells. Arch Pathol Lab Med 2009;133 (8) 1251- 1255
PubMed
8.
Cheuk  WYuen  HKChan  JK Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related sclerosing disease? Am J Surg Pathol 2007;31 (4) 643- 645
PubMed
9.
Takahira  MKawano  MZen  YMinato  HYamada  KSugiyama  K IgG4-related chronic sclerosing dacryoadenitis. Arch Ophthalmol 2007;125 (11) 1575- 1578
PubMed
10.
Sato  YOhshima  KIchimura  K  et al.  Ocular adnexal IgG4-related disease has uniform clinicopathology. Pathol Int 2008;58 (8) 465- 470
PubMed
11.
Cheuk  WYuen  HKChan  AC  et al.  Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol 2008;32 (8) 1159- 1167
PubMed
12.
Ochoa  ERHarris  NLPilch  BZ Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (Kuttner tumor). Am J Surg Pathol 2001;25 (12) 1546- 1550
PubMed
Research Letters
July 2010

IgG4-Positive Dacryoadenitis and Küttner Submandibular Sclerosing Inflammatory Tumor

Author Affiliations

Author Affiliations: Cogan Eye Pathology Laboratory (Drs Jakobiec, Stacy, and Mehta) and Division of Ophthalmic Plastic and Reconstructive Surgery (Dr Fay), Massachusetts Eye and Ear Infirmary, Boston.

Arch Ophthalmol. 2010;128(7):942-944. doi:10.1001/archophthalmol.2010.112

The coexistence of idiopathic inflammatory masses of the submandibular and lacrimal glands featuring lymphoid hyperplasia and fibrosclerosis is unknown to most ophthalmologists.13 The former is referred to as Küttner tumor. Systemic and autoimmune diseases, including Sjögren syndrome (SS) and lymphoma, are characteristically absent in this complex. In our case, IgG4-positive plasma cells were present in the lesions of both glands.

Report of a Case

A 69-year-old woman had left submandibular gland swelling that developed over 2 months in 2002. Biopsy revealed chronic sclerosing sialadenitis. Recurrence and rebiopsy in 2005 showed the same pathologic findings. In 2008, the patient had sudden bulging of her right eye with lateral eyelid fullness, pain, and double vision. Best-corrected visual acuities were 20/30 OD and 20/25 OS. The right eye exhibited mild epibulbar injection, painful limited abduction, and 3 mm of proptosis (Figure 1A). A computed tomographic scan demonstrated enlargement of the right lacrimal gland and lateral and superior rectus muscles (Figure 1B). Results from a general physical examination and standard serological studies were negative. Serum IgG4 levels were not obtained. The patient did not have diabetes or abdominal or urinary tract symptoms, and an abdominal computed tomographic scan was not performed. Biopsy of the lacrimal gland revealed sclerosing dacryoadenitis. The patient was treated with a prednisone taper over 2 months starting at 80 mg daily and decreasing by 10 mg every week. Seven months later, she manifested a nontender, palpable lacrimal gland with residual proptosis without recurrence of submandibular disease. The patient continued to feel well and no systemic disease has emerged over a clinical course of 7 years.

The submandibular and lacrimal gland biopsies displayed similar histopathologic features. The fibrous septa in the former were thickened and enclosed lobules of glandular tissue exhibiting a lymphoplasmacytic infiltrate with scattered follicles (Figure 1C). Interstitial fibrosis and acinar atrophy were juxtaposed with uninvolved lobules of well-preserved glandular tissue (Figure 1D). A smaller lacrimal gland biopsy specimen harbored a dense lymphoplasmacytic infiltrate (Figure 1E) with rare surviving acini (Figure 1F). The CD3+ T lymphocytes somewhat predominated over CD20+ B lymphocytes in the parotid gland (Figure 2A), whereas the converse was observed in the lacrimal gland (Figure 2B). In situ hybridization for immunoglobulin light chains confirmed polytypic infiltrates. Abundant IgG4-positive plasma cells were discovered, with an average of 99 per 4 high-power fields in the submandibular gland (Figure 2C) and 116 in the lacrimal gland (Figure 2D).

Comment

Unilateral, sclerosing, follicular, lymphoid hyperplasia of the submandibular gland (Küttner tumor) is an immunophenotypically polyclonal process with a favorable prognosis. It is typically unassociated with systemic disease and rarely encountered with dacryoadenitis.13 The submandibular and lacrimal diseases can be linked through the recently characterized spectrum of IgG4-positive sclerosing inflammatory diseases,3,4 which we documented in the biopsies of our patient's 2 lesions. Concomitant serological elevation of IgG4 levels may develop5,6; it was not evaluated in our patient but should probably be sought in orbital pseudotumors. Other IgG4-related diseases include autoimmune pancreatitis, sclerosing orbital inflammatory disease, Riedel struma, and retroperitoneal fibrosis.7 IgG4-positive disease is highly sensitive to corticosteroid therapy. The role of IgG4-positive plasma cells in fibrosclerosis is unknown.

In SS with dry eye and mouth symptoms, the lacrimal and parotid glands are usually bilaterally enlarged. Primary SS (formerly termed Mikulicz syndrome2) lacks a systemic cause, while secondary SS is associated with underlying autoimmune disease and sometimes lymphoma. Serum antibodies against SS type A (Ro) and SS type B (La) antigens and lymphoepithelial lesions (also called epimyoepithelial islands in the parotid gland but rarely seen in the lacrimal gland) are absent in idiopathic dacryoadenitis and Küttner tumor but diagnostic of SS. The lacrimal and salivary glands in SS are diffusely affected with a lymphoplasmacytic infiltrate, whereas the sialadenitis of Küttner tumor is often subtotal, which may sometimes be due to focal sialolithiasis. Isolated dacryoadenitis with IgG4-positive plasma cells without accompanying Küttner tumor has been previously reported810 and can evolve into lymphoma of the gland with generalized lymphadenopathy or a paraproteinemia as described in 3 of 6 cases.11 There is 1 documented case of a localized marginal zone lymphoma without systemic disease arising in a Küttner tumor.12

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Article Information

Correspondence: Dr Jakobiec, Cogan Eye Pathology Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles St, Ste 321, Boston, MA 02114 (fred_jakobiec@meei.harvard.edu).

Financial Disclosure: None reported.

Funding/Support: Dr Stacy is supported in part by the Heed Foundation.

References
1.
Kitagawa  SZen  YHarada  K  et al.  Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Kuttner's tumor). Am J Surg Pathol 2005;29 (6) 783- 791
PubMed
2.
Stone  JHCaruso  PADeshpande  V Case records of the Massachusetts General Hospital: case 24-2009: a 26-year-old woman with painful swelling of the neck. N Engl J Med 2009;361 (5) 511- 518
PubMed
3.
Lee  LYChen  TCKuo  TT Simultaneous occurrence of IgG4-related chronic sclerosing dacryoadenitis and chronic sclerosing sialadenitis in a patient also with involvement of lymph node and Warthin's tumor [published online December 30, 2008]. Int J Surg Pathol
PubMed10.1177/1066896908329584
4.
Kamisawa  TOkamoto  A IgG4-related sclerosing disease. World J Gastroenterol 2008;14 (25) 3948- 3955
PubMed
5.
Kamisawa  TYoshiike  MEgawa  NNakajima  HTsuruta  KOkamoto  A Treating patients with autoimmune pancreatitis: results from a long-term follow-up study. Pancreatology 2005;5 (2-3) 234- 240
PubMed
6.
Neild  GHRodriguez-Justo  MWall  CConnolly  JO Hyper-IgG4 disease: report and characterisation of a new disease. BMC Med 2006;423
PubMed
7.
Mehta  MJakobiec  FFay  A Idiopathic fibroinflammatory disease of the face, eyelids, and periorbital membrane with immunoglobulin G4-positive plasma cells. Arch Pathol Lab Med 2009;133 (8) 1251- 1255
PubMed
8.
Cheuk  WYuen  HKChan  JK Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related sclerosing disease? Am J Surg Pathol 2007;31 (4) 643- 645
PubMed
9.
Takahira  MKawano  MZen  YMinato  HYamada  KSugiyama  K IgG4-related chronic sclerosing dacryoadenitis. Arch Ophthalmol 2007;125 (11) 1575- 1578
PubMed
10.
Sato  YOhshima  KIchimura  K  et al.  Ocular adnexal IgG4-related disease has uniform clinicopathology. Pathol Int 2008;58 (8) 465- 470
PubMed
11.
Cheuk  WYuen  HKChan  AC  et al.  Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol 2008;32 (8) 1159- 1167
PubMed
12.
Ochoa  ERHarris  NLPilch  BZ Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (Kuttner tumor). Am J Surg Pathol 2001;25 (12) 1546- 1550
PubMed
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