3. A 52-year-old man is evaluated for a 4-month history of slowly
progressive unilateral proptosis. He reports enlargement of the glands
under his jaw on both sides. He generally feels well and has no other
medical problems. He takes no medications.
On physical examination, vital signs are normal. Marked proptosis of the
left eye is noted; there is no inflammation of the sclerae or conjunctivae.
There is bilateral enlargement of the lacrimal, parotid, and submandibular
glands. There is an enlarged lymph node at the angle of the jaw on the
right. The remainder of the examination is normal.
Laboratory studies include a normal complete blood count with
differential, chemistry panel, liver chemistries, antinuclear antibody panel,
and urinalysis.
MRI of the head and orbits demonstrates a homogeneous enhancing
mass behind the left eye and enlargement of the parotid and submandibular
glands. Biopsy of the ocular mass demonstrates a lymphoplasmacytic
infiltrate with storiform fibrosis and obliterative phlebitis, rare neutrophils,
and no granulomas; a monoclonal population of cells is not identified.
Which of the following is the most likely diagnosis?
A. Hodgkin lymphoma
B. IgG4-related disease
C. Sarcoidosis
4. A 52-year-old man is evaluated for a 4-month history of slowly
progressive unilateral proptosis. He reports enlargement of the glands
under his jaw on both sides. He generally feels well and has no other
medical problems. He takes no medications.
On physical examination, vital signs are normal. Marked proptosis of the
left eye is noted; there is no inflammation of the sclerae or conjunctivae.
There is bilateral enlargement of the lacrimal, parotid, and
submandibular glands. There is an enlarged lymph node at the angle of
the jaw on the right. The remainder of the examination is normal.
Laboratory studies include a normal complete blood count with
differential, chemistry panel, liver chemistries, antinuclear antibody panel,
and urinalysis.
MRI of the head and orbits demonstrates a homogeneous enhancing
mass behind the left eye and enlargement of the parotid and
submandibular glands. Biopsy of the ocular mass demonstrates a
lymphoplasmacytic infiltrate with storiform fibrosis and obliterative
phlebitis, rare neutrophils, and no granulomas; a monoclonal population of
cells is not identified. Which of the following is the most likely diagnosis?
A. Hodgkin lymphoma
B. IgG4-related disease
C. Sarcoidosis
29. A 52-year-old man is evaluated for a 4-month history of slowly
progressive unilateral proptosis. He reports enlargement of the glands
under his jaw on both sides. He generally feels well and has no other
medical problems. He takes no medications.
On physical examination, vital signs are normal. Marked proptosis of the
left eye is noted; there is no inflammation of the sclerae or conjunctivae.
There is bilateral enlargement of the lacrimal, parotid, and submandibular
glands. There is an enlarged lymph node at the angle of the jaw on the
right. The remainder of the examination is normal.
Laboratory studies include a normal complete blood count with
differential, chemistry panel, liver chemistries, antinuclear antibody panel,
and urinalysis.
MRI of the head and orbits demonstrates a homogeneous enhancing
mass behind the left eye and enlargement of the parotid and submandibular
glands. Biopsy of the ocular mass demonstrates a lymphoplasmacytic
infiltrate with storiform fibrosis and obliterative phlebitis, rare neutrophils,
and no granulomas; a monoclonal population of cells is not identified.
Which of the following is the most likely diagnosis?
A. Hodgkin lymphoma - No Reed-Sternberg cells
B. IgG4-related disease
C. Sarcoidosis
30. A 52-year-old man is evaluated for a 4-month history of slowly
progressive unilateral proptosis. He reports enlargement of the glands
under his jaw on both sides. He generally feels well and has no other
medical problems. He takes no medications.
On physical examination, vital signs are normal. Marked proptosis of the
left eye is noted; there is no inflammation of the sclerae or conjunctivae.
There is bilateral enlargement of the lacrimal, parotid, and submandibular
glands. There is an enlarged lymph node at the angle of the jaw on the
right. The remainder of the examination is normal.
Laboratory studies include a normal complete blood count with
differential, chemistry panel, liver chemistries, antinuclear antibody panel,
and urinalysis.
MRI of the head and orbits demonstrates a homogeneous enhancing
mass behind the left eye and enlargement of the parotid and submandibular
glands. Biopsy of the ocular mass demonstrates a lymphoplasmacytic
infiltrate with storiform fibrosis and obliterative phlebitis, rare neutrophils,
and no granulomas; a monoclonal population of cells is not identified.
Which of the following is the most likely diagnosis?
A. Hodgkin lymphoma
B. IgG4-related disease
C. Sarcoidosis
34. A 52-year-old man is evaluated for a 4-month history of slowly
progressive unilateral proptosis. He reports enlargement of the glands
under his jaw on both sides. He generally feels well and has no other
medical problems. He takes no medications.
On physical examination, vital signs are normal. Marked proptosis of the
left eye is noted; there is no inflammation of the sclerae or conjunctivae.
There is bilateral enlargement of the lacrimal, parotid, and
submandibular glands. There is an enlarged lymph node at the angle of
the jaw on the right. The remainder of the examination is normal.
Laboratory studies include a normal complete blood count with
differential, chemistry panel, liver chemistries, antinuclear antibody panel,
and urinalysis.
MRI of the head and orbits demonstrates a homogeneous enhancing
mass behind the left eye and enlargement of the parotid and submandibular
glands. Biopsy of the ocular mass demonstrates a lymphoplasmacytic
infiltrate with storiform fibrosis and obliterative phlebitis, rare neutrophils,
and no granulomas; a monoclonal population of cells is not identified.
Which of the following is the most likely diagnosis?
A. Hodgkin lymphoma
B. IgG4-related disease
C. Sarcoidosis
36. A 52-year-old man is evaluated for a 4-month history of slowly
progressive unilateral proptosis. He reports enlargement of the glands
under his jaw on both sides. He generally feels well and has no other
medical problems. He takes no medications.
On physical examination, vital signs are normal. Marked proptosis of the
left eye is noted; there is no inflammation of the sclerae or conjunctivae.
There is bilateral enlargement of the lacrimal, parotid, and
submandibular glands. There is an enlarged lymph node at the angle of
the jaw on the right. The remainder of the examination is normal.
Laboratory studies include a normal complete blood count with
differential, chemistry panel, liver chemistries, antinuclear antibody panel,
and urinalysis.
MRI of the head and orbits demonstrates a homogeneous enhancing
mass behind the left eye and enlargement of the parotid and
submandibular glands. Biopsy of the ocular mass demonstrates a
lymphoplasmacytic infiltrate with storiform fibrosis and obliterative
phlebitis, rare neutrophils, and no granulomas; a monoclonal population of
cells is not identified. Which of the following is the most likely diagnosis?
A. Hodgkin lymphoma
B. IgG4-related disease
C. Sarcoidosis
40. References Include
1. Hoy, D., Brooks, P., Blyth, F. & Buchbinder, R. The Epidemiology of low back pain. Best Practice & Research Clinical
Rheumatology 24, 769–781 (2010).
2. Finley, C. R. et al. What are the most common conditions in primary care? Systematic review. Can Fam Physician 64,
832–840 (2018).
3. Niska, R., Bhuiya, F. & Xu, J. National Hospital Ambulatory Medical Care Survey: 2007 emergency department
summary. Natl Health Stat Report 1–31 (2010).
4. De Virgilio, A. et al. Idiopathic hypertrophic pachymeningitis: an autoimmune IgG4-related disease. Immunologic
Research 65, 386–394 (2016).
5. Maher, M., Zanazzi, G., Faust, P., Nickerson, K. & Wong, T. T. IgG4-related hypertrophic pachymeningitis of the spine
with MPO-ANCA seropositivity. Clinical Imaging 46, 108–112 (2017).
6. Lu, L. X., Della-Torre, E., Stone, J. H. & Clark, S. W. IgG4-Related Hypertrophic Pachymeningitis. JAMA Neurol 71, 785–
9 (2014).
7. Sato, M. et al. Multifocal Fibrosclerosis with Hypertrophic Pachymeningitis and a Soft Tissue Mass around the Thoracic
Vertebral Bodies: A Case Report with Review of the Literature. Intern. Med. 54, 2267–2272 (2015).
8. Deshpande, V. et al. Consensus statement on the pathology of IgG4-related disease. 25, 1181–1192 (2012).
9. Wallace, Z. S. et al. IgG4-related disease and hypertrophic pachymeningitis. Medicine 92, 206–216 (2013).
10. Stone, J. H. et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system
manifestations. Arthritis Rheum 64, 3061–3067 (2012).
11. Hamano, H. et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344, 732–
738 (2001).
12. Kamisawa, T. et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut 52, 683–
687 (2003).
13. Umehara, H. et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Modern
Rheumatology 22, 1–14 (2012).
14. Lu, Z. et al. IgG4-related spinal pachymeningitis. Clin Rheumatol 35, 1549–1553 (2015).
15. Takeuchi, S., Osada, H., Seno, S. & Nawashiro, H. IgG4-Related Intracranial Hypertrophic Pachymeningitis : A Case
Report and Review of the Literature. J Korean Neurosurg Soc 55, 300–3 (2014).
16. Regev, K., Nussbaum, T., Cagnano, E., Giladi, N. & Karni, A. Central Nervous System Manifestation of IgG4-Related
Disease. JAMA Neurol 71, 767–4 (2014).
17. Radotra, B. D., Aggarwal, A., Kapoor, A., Singla, N. & Chatterjee, D. An orphan disease: IgG4-related spinal
pachymeningitis: report of 2 cases. J Neurosurg Spine 25, 790–794 (2016).
18. Chan, S.-K., Cheuk, W., Chan, K.-T. & Chan, J. K. C. IgG4-related sclerosing pachymeningitis: a previously
unrecognized form of central nervous system involvement in IgG4-related sclerosing disease. Am. J. Surg. Pathol. 33,
1249–1252 (2009).
41. References Include
19. Khosroshahi, A. et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-
Related Disease. Arthritis & Rheumatology 67, 1688–1699 (2015).
20. Sakai, T., Kondo, M., Yoshii, S. & Tomimoto, H. [IgG4-related disease that presented cranial, cervical, lumbar and
sacral hypertrophic pachymeningitis associated with infundibulo-hypophysitis]. Rinsho Shinkeigaku 54, 664–667 (2014).
21. Choi, S.-H., Lee, S. H., Khang, S. K. & Jeon, S. R. IgG4-related sclerosing pachymeningitis causing spinal cord
compression. Neurology 75, 1388–1390 (2010).
22. Lindstrom, K. M., Cousar, J. B. & Lopes, M. B. S. IgG4-related meningeal disease: clinico-pathological features and
proposal for diagnostic criteria. Acta Neuropathol 120, 765–776 (2010).
23. Della-Torre, E., Bozzolo, E. P., Passerini, G., Doglioni, C. & Sabbadini, M. G. IgG4-related pachymeningitis: evidence
of intrathecal IgG4 on cerebrospinal fluid analysis. Ann Intern Med 156, 401–403 (2012).
24. Tajima, Y. & Mito, Y. Cranial neuropathy because of IgG4-related pachymeningitis; intracranial and spinal mass
lesions. Case Reports 2012, (2012).
25. Della-Torre, E. et al. Cerebrospinal fluid analysis in immunoglobulin G4-related hypertrophic pachymeningitis. The
Journal of Rheumatology 40, 1927–1929 (2013).
26. Gu, R., Hao, P.-Y., Liu, J.-B., Wang, Z.-H. & Zhu, Q.-S. Cervicothoracic spinal cord compression caused by IgG4-
related sclerosing pachymeningitis: a case report and literature review. Eur Spine J 25 Suppl 1, 147–151 (2016).
27. Stone, J. H., Zen, Y. & Deshpande, V. IgG4-related disease. N Engl J Med 366, 539–551 (2012).
28. Della-Torre, E. et al. Diagnostic value of IgG4 Indices in IgG4-Related Hypertrophic Pachymeningitis. Journal of
Neuroimmunology 266, 82–86 (2014).
29. Okazaki, K. & Umehara, H. Current Concept of IgG4-Related Disease. Curr. Top. Microbiol. Immunol. 401, 1–17
(2017).
30. Popkirov, S., Kowalski, T., Schlegel, U. & Skodda, S. Immunoglobulin-G4-related hypertrophic pachymeningitis with
antineutrophil cytoplasmatic antibodies effectively treated with rituximab. Journal of Clinical Neuroscience 22, 1038–
1040 (2015).
31. Umehara, H. et al. Current approach to the diagnosis of IgG4-related disease – Combination of comprehensive
diagnostic and organ-specific criteria. Modern Rheumatology 27, 381–391 (2017).
32. Hart, P. A. et al. Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo
Clinic experience. Gut 62, 1607–1615 (2013).
33. Carruthers, M. N., Stone, J. H., Deshpande, V. & Khosroshahi, A. Development of an IgG4-RD Responder Index. Int J
Rheumatol 2012, 1–7 (2012).
The most likely diagnosis is IgG4-related disease, a recently described condition characterized by lymphoplasmacytic infiltration and enlargement of various structures, including the pancreas, lymph nodes, salivary glands, periaortic region leading to retroperitoneal fibrosis, kidneys, and skin. Most patients are men (60%-80%) over the age of 50 years. Typical presentation is the subacute development of a mass in the affected organ (for example, an orbital pseudotumor) or diffuse organ enlargement. Up to 90% of patients have multiple organ involvement. Lymphadenopathy is common, as is lacrimal and salivary gland involvement. Most patients lack constitutional symptoms at the time of diagnosis and generally feel well. Staining for IgG4-producing plasma cells reveals large numbers in the tissue.
Hodgkin lymphoma usually presents with palpable lymphadenopathy or a mediastinal mass that requires tissue biopsy for diagnosis. Biopsy is likely to show mainly clonal malignant Hodgkin/Reed-Sternberg cells in a background of granulocytes, plasma cells, and lymphocytes. Reed-Sternberg cells appear as large cells with large, pale nuclei containing large purple nucleoli, and their appearance is indicative of Hodgkin disease. The patient's biopsy findings are not consistent with Hodgkin lymphoma.
Sarcoidosis is a multisystem disease characterized by noncaseating granulomas that form in tissues and most commonly affects the lungs. The absence of granulomas on biopsy is helpful to distinguish IgG4-related disease from sarcoidosis.
Sjögren syndrome can present with enlargement of the salivary glands. However, it is associated with focal, centrilobular collections of lymphocytes on biopsy without the histology characteristic for IgG4-related disease present in this patient. Patients with Sjögren syndrome also usually have positive anti-Ro/SSA and anti-La/SSB antibodies, which are not present in this patient.
The most likely diagnosis is IgG4-related disease, a recently described condition characterized by lymphoplasmacytic infiltration and enlargement of various structures, including the pancreas, lymph nodes, salivary glands, periaortic region leading to retroperitoneal fibrosis, kidneys, and skin. Most patients are men (60%-80%) over the age of 50 years. Typical presentation is the subacute development of a mass in the affected organ (for example, an orbital pseudotumor) or diffuse organ enlargement. Up to 90% of patients have multiple organ involvement. Lymphadenopathy is common, as is lacrimal and salivary gland involvement. Most patients lack constitutional symptoms at the time of diagnosis and generally feel well. Staining for IgG4-producing plasma cells reveals large numbers in the tissue.
Hodgkin lymphoma usually presents with palpable lymphadenopathy or a mediastinal mass that requires tissue biopsy for diagnosis. Biopsy is likely to show mainly clonal malignant Hodgkin/Reed-Sternberg cells in a background of granulocytes, plasma cells, and lymphocytes. Reed-Sternberg cells appear as large cells with large, pale nuclei containing large purple nucleoli, and their appearance is indicative of Hodgkin disease. The patient's biopsy findings are not consistent with Hodgkin lymphoma.
Sarcoidosis is a multisystem disease characterized by noncaseating granulomas that form in tissues and most commonly affects the lungs. The absence of granulomas on biopsy is helpful to distinguish IgG4-related disease from sarcoidosis.
Sjögren syndrome can present with enlargement of the salivary glands. However, it is associated with focal, centrilobular collections of lymphocytes on biopsy without the histology characteristic for IgG4-related disease present in this patient. Patients with Sjögren syndrome also usually have positive anti-Ro/SSA and anti-La/SSB antibodies, which are not present in this patient.
The most likely diagnosis is IgG4-related disease, a recently described condition characterized by lymphoplasmacytic infiltration and enlargement of various structures, including the pancreas, lymph nodes, salivary glands, periaortic region leading to retroperitoneal fibrosis, kidneys, and skin. Most patients are men (60%-80%) over the age of 50 years. Typical presentation is the subacute development of a mass in the affected organ (for example, an orbital pseudotumor) or diffuse organ enlargement. Up to 90% of patients have multiple organ involvement. Lymphadenopathy is common, as is lacrimal and salivary gland involvement. Most patients lack constitutional symptoms at the time of diagnosis and generally feel well. Staining for IgG4-producing plasma cells reveals large numbers in the tissue.
Hodgkin lymphoma usually presents with palpable lymphadenopathy or a mediastinal mass that requires tissue biopsy for diagnosis. Biopsy is likely to show mainly clonal malignant Hodgkin/Reed-Sternberg cells in a background of granulocytes, plasma cells, and lymphocytes. Reed-Sternberg cells appear as large cells with large, pale nuclei containing large purple nucleoli, and their appearance is indicative of Hodgkin disease. The patient's biopsy findings are not consistent with Hodgkin lymphoma.
Sarcoidosis is a multisystem disease characterized by noncaseating granulomas that form in tissues and most commonly affects the lungs. The absence of granulomas on biopsy is helpful to distinguish IgG4-related disease from sarcoidosis.
Sjögren syndrome can present with enlargement of the salivary glands. However, it is associated with focal, centrilobular collections of lymphocytes on biopsy without the histology characteristic for IgG4-related disease present in this patient. Patients with Sjögren syndrome also usually have positive anti-Ro/SSA and anti-La/SSB antibodies, which are not present in this patient.
The most likely diagnosis is IgG4-related disease, a recently described condition characterized by lymphoplasmacytic infiltration and enlargement of various structures, including the pancreas, lymph nodes, salivary glands, periaortic region leading to retroperitoneal fibrosis, kidneys, and skin. Most patients are men (60%-80%) over the age of 50 years. Typical presentation is the subacute development of a mass in the affected organ (for example, an orbital pseudotumor) or diffuse organ enlargement. Up to 90% of patients have multiple organ involvement. Lymphadenopathy is common, as is lacrimal and salivary gland involvement. Most patients lack constitutional symptoms at the time of diagnosis and generally feel well. Staining for IgG4-producing plasma cells reveals large numbers in the tissue.
Hodgkin lymphoma usually presents with palpable lymphadenopathy or a mediastinal mass that requires tissue biopsy for diagnosis. Biopsy is likely to show mainly clonal malignant Hodgkin/Reed-Sternberg cells in a background of granulocytes, plasma cells, and lymphocytes. Reed-Sternberg cells appear as large cells with large, pale nuclei containing large purple nucleoli, and their appearance is indicative of Hodgkin disease. The patient's biopsy findings are not consistent with Hodgkin lymphoma.
Sarcoidosis is a multisystem disease characterized by noncaseating granulomas that form in tissues and most commonly affects the lungs. The absence of granulomas on biopsy is helpful to distinguish IgG4-related disease from sarcoidosis.
Sjögren syndrome can present with enlargement of the salivary glands. However, it is associated with focal, centrilobular collections of lymphocytes on biopsy without the histology characteristic for IgG4-related disease present in this patient. Patients with Sjögren syndrome also usually have positive anti-Ro/SSA and anti-La/SSB antibodies, which are not present in this patient.
Typically self-limited
Can be associated with sarcoidosis, IBD
treatment: NSAIDs, colchicine, low-dose prednisone
Also known as uveoparotid fever
The most likely diagnosis is IgG4-related disease, a recently described condition characterized by lymphoplasmacytic infiltration and enlargement of various structures, including the pancreas, lymph nodes, salivary glands, periaortic region leading to retroperitoneal fibrosis, kidneys, and skin. Most patients are men (60%-80%) over the age of 50 years. Typical presentation is the subacute development of a mass in the affected organ (for example, an orbital pseudotumor) or diffuse organ enlargement. Up to 90% of patients have multiple organ involvement. Lymphadenopathy is common, as is lacrimal and salivary gland involvement. Most patients lack constitutional symptoms at the time of diagnosis and generally feel well. Staining for IgG4-producing plasma cells reveals large numbers in the tissue.
Hodgkin lymphoma usually presents with palpable lymphadenopathy or a mediastinal mass that requires tissue biopsy for diagnosis. Biopsy is likely to show mainly clonal malignant Hodgkin/Reed-Sternberg cells in a background of granulocytes, plasma cells, and lymphocytes. Reed-Sternberg cells appear as large cells with large, pale nuclei containing large purple nucleoli, and their appearance is indicative of Hodgkin disease. The patient's biopsy findings are not consistent with Hodgkin lymphoma.
Sarcoidosis is a multisystem disease characterized by noncaseating granulomas that form in tissues and most commonly affects the lungs. The absence of granulomas on biopsy is helpful to distinguish IgG4-related disease from sarcoidosis.
Sjögren syndrome can present with enlargement of the salivary glands. However, it is associated with focal, centrilobular collections of lymphocytes on biopsy without the histology characteristic for IgG4-related disease present in this patient. Patients with Sjögren syndrome also usually have positive anti-Ro/SSA and anti-La/SSB antibodies, which are not present in this patient.
The most likely diagnosis is IgG4-related disease, a recently described condition characterized by lymphoplasmacytic infiltration and enlargement of various structures, including the pancreas, lymph nodes, salivary glands, periaortic region leading to retroperitoneal fibrosis, kidneys, and skin. Most patients are men (60%-80%) over the age of 50 years. Typical presentation is the subacute development of a mass in the affected organ (for example, an orbital pseudotumor) or diffuse organ enlargement. Up to 90% of patients have multiple organ involvement. Lymphadenopathy is common, as is lacrimal and salivary gland involvement. Most patients lack constitutional symptoms at the time of diagnosis and generally feel well. Staining for IgG4-producing plasma cells reveals large numbers in the tissue.
Hodgkin lymphoma usually presents with palpable lymphadenopathy or a mediastinal mass that requires tissue biopsy for diagnosis. Biopsy is likely to show mainly clonal malignant Hodgkin/Reed-Sternberg cells in a background of granulocytes, plasma cells, and lymphocytes. Reed-Sternberg cells appear as large cells with large, pale nuclei containing large purple nucleoli, and their appearance is indicative of Hodgkin disease. The patient's biopsy findings are not consistent with Hodgkin lymphoma.
Sarcoidosis is a multisystem disease characterized by noncaseating granulomas that form in tissues and most commonly affects the lungs. The absence of granulomas on biopsy is helpful to distinguish IgG4-related disease from sarcoidosis.
Sjögren syndrome can present with enlargement of the salivary glands. However, it is associated with focal, centrilobular collections of lymphocytes on biopsy without the histology characteristic for IgG4-related disease present in this patient. Patients with Sjögren syndrome also usually have positive anti-Ro/SSA and anti-La/SSB antibodies, which are not present in this patient.
Typically self-limited
Can be associated with sarcoidosis, IBD
treatment: NSAIDs, colchicine, low-dose prednisone
