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LETTERS TO THE EDITOR
Diagnosis Please Case 196 From Thaworn Dendumrongsup, MD Abdominal Imaging Section, Department of Radiology, Prince of Songkla University, Hat Yai, Thailand 90110 University College London Hospital, Centre for Medical Imaging, London, England e-mail: [email protected] Editor: I read with great interest the Diagnosis Please article “Case 196: Immunoglobulin G4–related Disease” by Dr Gao and colleagues in the August 2013 issue of Radiology (1), in which they discuss the radiologic differential diagnosis of this amazing case extensively; however, I have concerns about some errors that appeared in the article. There were a number of inaccuracies in figure 8. The citation in the title of figure 8, “Diagnostic criteria for IgG4-related disease (2),” appears to be incorrect; the correct title may be “Diagnostic criteria for IgG4-related disease (8).” In addition, the immunoglobulin G4 (IgG4) level appears to be misstated. It was noted that “our patient had elevated IgG4 of 2673 mg/dL;” however, the correct statement should be “our patient had elevated IgG4 of 216 mg/dL.” An elevated serum IgG4 level of more than 135 mg/dL has been widely accepted as a cutoff value, with a sensitivity of 97% and specificity of 79.6% (2), but it should be interpreted with caution. There also appears to be an error with regard to criterion 3c: The letter “c” was misplaced. Moreover, the conclusion in the lower portion of figure 8 may not be simplified as shown. IgG4-related disease is a relatively new clinical entity. The proposed diagnostic criteria are still evolving without good validation, and I understand that the authors relied on the most up-to-date literature at the time they wrote the manuscript; however, the criteria appear to have changed since the time of manuscript submission. The diagnosis of IgG4-re-
lated disease requires a combination of clinical, histopathologic, radiologic, and serologic findings; terminology and several organ-specific diagnostic criteria (classified as definite, probable, and possible cases), including response to steroid criteria, have been proposed (3,4). However, the diagnostic criteria covering “all IgG4-related disease” are difficult to establish, and combination of comprehensive diagnostic criteria with organ-specific diagnostic criteria is suggested (3). Last, but not least, histology is a key component of diagnosis that deserves to be mentioned. According to the consensus statement on the pathology of IgG4-related disease (5), the pathologic diagnosis is based primarily on the morphologic appearance while the tissue IgG4-positive plasma cell count and the IgG4-positive–to–immunoglobulin G–positive plasma cell ratio are secondary in importance. The three major histopathologic features, namely dense lymphoplasmacytic infiltrate, obliterative phlebitis, and fibrosis arranged at least focally in a storiform pattern, are emphasized as specific features (2,5). A three-tiered diagnostic terminology, that is, histologically highly suggestive of IgG4-related disease, probable histologic features of IgG4-related disease, and insufficient histologic evidence of IgG4-related disease, has also been endorsed. In addition, because IgG4-positive plasma cells are ubiquitous in diverse localized nonspecific chronic inflammatory conditions, the appropriate cutoff for the numbers of IgG4-positive plasma cells per high-power field have been proposed and differ among the affected organs (4,5). For instance, more than 100 IgG4-positive plasma cells per high-power field are required in the lacrimal glands and salivary glands, more than 200 cells per high-power field are required in the skin, and more than 30 cells per high-power field are required in the retroperitoneal lesions. In contrast, more than 50 cells per high-power field and more than 10 cells per high-power field are needed to diagnose IgG4-related disease involving the pancreatico-hepa-
Radiology: Volume 270: Number 1—January 2014 n radiology.rsna.org
tobiliary system with surgical specimens and biopsy specimens, respectively. Therefore, close collaboration between the pathologists, radiologists, and referring physicians is crucial to diagnose IgG4-related disease and exclude its mimics. Radiologists should become more familiar with IgG4-related disease, as the authors stated, and future research would refine our diagnostic approaches for this perplexing clinical entity. Disclosures of Conflicts of Interest: No relevant conflicts of interest to disclose.
References 1. Gao Y, Seidman MA, Bankier AA. Case 196: immunoglobulin G4–related disease. Radiology 2013;268(2):604–609. 2. Masaki Y, Kurose N, Yamamoto M, et al. Cutoff values of serum IgG4 and histopathological IgG4+ plasma cells for diagnosis of patients with IgG4-related disease. Int J Rheumatol doi:10.1155/2012/580814. Published online May 10, 2012. Accessed September 17, 2013. 3. Okazaki K, Umehara H. Are classification criteria for IgG4-RD now possible? The concept of IgG4-related disease and proposal of comprehensive diagnostic criteria in Japan. Int J Rheumatol doi:10.1155/2012/357071. Published online May 29, 2012. Accessed September 17, 2013. 4. Okazaki K, Uchida K, Ikeura T, Takaoka M. Current concept and diagnosis of IgG4-related disease in the hepato-bilio-pancreatic system. J Gastroenterol 2013;48(3):303–314. 5. Deshpande V, Zen Y, Chan JKC, et al. Consensus statement on the pathology of IgG4related disease. Modern Pathology 2012; 25(9):1181–1192.
Response From Yiming Gao, MD, and Alexander A. Bankier, MD, PhD Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215 e-mail: [email protected] We thank Dr Dendumrongsup for his interest in our Diagnosis Please case and for his comments and suggestions. We
313
LETTERS TO THE EDITOR
certainly agree with his main comment about the rapidly evolving diagnostic criteria for IgG4-related disease. Therefore, we welcome that he brought to the readers’ attention some of the most recent literature published since we submitted our original case report. We also agree that radiologists should be familiar with up-to-date information about this complex disease, given the important role that imaging plays in its diagnosis. With regard to specific parts of our original text, please allow us to answer as follows: (a) The reference number next to the title of figure 8 should read “(8)” instead of “(2).” (b) The IgG4 level of our patient was 216 mg/dL, but her IgG level overall was 2673 mg/dL. We have re-visited the patient’s medical records and confirmed this. The point we wanted to communicate was that her overall IgG4 level was elevated. (c) The letter “c” was misplaced. The corrected version of figure 8 is shown in an erratum in this issue. We again thank Dr Dendumrongsup for his comments on our case. We hope that, over time, medicine will gain a better understanding of IgG4-related disease, with refined diagnostic approaches and further gains in knowledge. Disclosures of Conflicts of Interest: Y.G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. A.A.B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is a consultant for Spiration (Olympus Medical); receives author honoraria from Elsevier. Other relationships: none to disclose.
Errata “Case 196: Immunoglobulin G4–related Disease.” Radiology 2013;268(2): 604–609
314
Page 607, Figure 8 should appear as corrected here, with the accompanying corrected legend.
Figure 8
Figure 8: Diagnostic criteria for IgG4-related disease (IgG4-RD). To convert to SI units (grams per liter), multiply by 0.01. hpf = High-power field.
“Meaningful Use for Radiology: Current Status and Future Directions.” Radiology 2013;269(2):318–321 Page 321, the Disclosures of Conflicts of Interest, which should have appeared before the References, was inadvertently omitted and should read as follows: Disclosures of Conflicts of Interest: T.A.M. No relevant conflicts of interest to disclose. D.E.A. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: stock/stock options, Amirsys Corp/ STATdx; travel/accommodations/meeting expenses unrelated to activities listed,
LA Rad Soc invited talk on Meaningful Use; honorarium, LA Rad Soc. Other relationships: none to disclose. C.D.C. No relevant conflicts of interest to disclose. K.J.D. No relevant conflicts of interest to disclose. A.E.F. No relevant conflicts of interest to disclose. R.K. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: stock, royalties, and consultant, Medicalis Corp. Other relationships: author named on U.S. patent 6029138 (issued, licensed, and royalties) held by Brigham and Women’s Hospital and licensed to Medicalis Corp in 2000; the institution receives royalties from Medicalis. C.P.L. Financial activities related to the present article: grant to institution for demonstration project contract, Centers for Medicare and Medicaid Services. Financial activities not related to the present article: board membership to Radiology Advisory Board, GE Healthcare (paid travel reimbursements and honorarium); consultancy to Medical Advisory Board, Elsevier (paid travel reimbursement and honorarium); stock/stock options, Medical/Technical Advisory Board, Activate Networks (granted options for service, no money received); stock/ stock options, Board of Directors, Montage Healthcare (founders shares and investor; travel reimbursement received). Other relationships: none to disclose. R.L.A. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: board membership, RSNA (travel expenses); patent for steerable catheter to author and institution (no payments yet); royalties from Thomas Publishers for book. Other relationships: none to disclose.
radiology.rsna.org n Radiology: Volume 270: Number 1—January 2014
LETTERS TO THE EDITOR
Diagnosis Please Case 196 From Thaworn Dendumrongsup, MD Abdominal Imaging Section, Department of Radiology, Prince of Songkla University, Hat Yai, Thailand 90110 University College London Hospital, Centre for Medical Imaging, London, England e-mail: [email protected] Editor: I read with great interest the Diagnosis Please article “Case 196: Immunoglobulin G4–related Disease” by Dr Gao and colleagues in the August 2013 issue of Radiology (1), in which they discuss the radiologic differential diagnosis of this amazing case extensively; however, I have concerns about some errors that appeared in the article. There were a number of inaccuracies in figure 8. The citation in the title of figure 8, “Diagnostic criteria for IgG4-related disease (2),” appears to be incorrect; the correct title may be “Diagnostic criteria for IgG4-related disease (8).” In addition, the immunoglobulin G4 (IgG4) level appears to be misstated. It was noted that “our patient had elevated IgG4 of 2673 mg/dL;” however, the correct statement should be “our patient had elevated IgG4 of 216 mg/dL.” An elevated serum IgG4 level of more than 135 mg/dL has been widely accepted as a cutoff value, with a sensitivity of 97% and specificity of 79.6% (2), but it should be interpreted with caution. There also appears to be an error with regard to criterion 3c: The letter “c” was misplaced. Moreover, the conclusion in the lower portion of figure 8 may not be simplified as shown. IgG4-related disease is a relatively new clinical entity. The proposed diagnostic criteria are still evolving without good validation, and I understand that the authors relied on the most up-to-date literature at the time they wrote the manuscript; however, the criteria appear to have changed since the time of manuscript submission. The diagnosis of IgG4-re-
lated disease requires a combination of clinical, histopathologic, radiologic, and serologic findings; terminology and several organ-specific diagnostic criteria (classified as definite, probable, and possible cases), including response to steroid criteria, have been proposed (3,4). However, the diagnostic criteria covering “all IgG4-related disease” are difficult to establish, and combination of comprehensive diagnostic criteria with organ-specific diagnostic criteria is suggested (3). Last, but not least, histology is a key component of diagnosis that deserves to be mentioned. According to the consensus statement on the pathology of IgG4-related disease (5), the pathologic diagnosis is based primarily on the morphologic appearance while the tissue IgG4-positive plasma cell count and the IgG4-positive–to–immunoglobulin G–positive plasma cell ratio are secondary in importance. The three major histopathologic features, namely dense lymphoplasmacytic infiltrate, obliterative phlebitis, and fibrosis arranged at least focally in a storiform pattern, are emphasized as specific features (2,5). A three-tiered diagnostic terminology, that is, histologically highly suggestive of IgG4-related disease, probable histologic features of IgG4-related disease, and insufficient histologic evidence of IgG4-related disease, has also been endorsed. In addition, because IgG4-positive plasma cells are ubiquitous in diverse localized nonspecific chronic inflammatory conditions, the appropriate cutoff for the numbers of IgG4-positive plasma cells per high-power field have been proposed and differ among the affected organs (4,5). For instance, more than 100 IgG4-positive plasma cells per high-power field are required in the lacrimal glands and salivary glands, more than 200 cells per high-power field are required in the skin, and more than 30 cells per high-power field are required in the retroperitoneal lesions. In contrast, more than 50 cells per high-power field and more than 10 cells per high-power field are needed to diagnose IgG4-related disease involving the pancreatico-hepa-
Radiology: Volume 270: Number 1—January 2014 n radiology.rsna.org
tobiliary system with surgical specimens and biopsy specimens, respectively. Therefore, close collaboration between the pathologists, radiologists, and referring physicians is crucial to diagnose IgG4-related disease and exclude its mimics. Radiologists should become more familiar with IgG4-related disease, as the authors stated, and future research would refine our diagnostic approaches for this perplexing clinical entity. Disclosures of Conflicts of Interest: No relevant conflicts of interest to disclose.
References 1. Gao Y, Seidman MA, Bankier AA. Case 196: immunoglobulin G4–related disease. Radiology 2013;268(2):604–609. 2. Masaki Y, Kurose N, Yamamoto M, et al. Cutoff values of serum IgG4 and histopathological IgG4+ plasma cells for diagnosis of patients with IgG4-related disease. Int J Rheumatol doi:10.1155/2012/580814. Published online May 10, 2012. Accessed September 17, 2013. 3. Okazaki K, Umehara H. Are classification criteria for IgG4-RD now possible? The concept of IgG4-related disease and proposal of comprehensive diagnostic criteria in Japan. Int J Rheumatol doi:10.1155/2012/357071. Published online May 29, 2012. Accessed September 17, 2013. 4. Okazaki K, Uchida K, Ikeura T, Takaoka M. Current concept and diagnosis of IgG4-related disease in the hepato-bilio-pancreatic system. J Gastroenterol 2013;48(3):303–314. 5. Deshpande V, Zen Y, Chan JKC, et al. Consensus statement on the pathology of IgG4related disease. Modern Pathology 2012; 25(9):1181–1192.
Response From Yiming Gao, MD, and Alexander A. Bankier, MD, PhD Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215 e-mail: [email protected] We thank Dr Dendumrongsup for his interest in our Diagnosis Please case and for his comments and suggestions. We
313
LETTERS TO THE EDITOR
certainly agree with his main comment about the rapidly evolving diagnostic criteria for IgG4-related disease. Therefore, we welcome that he brought to the readers’ attention some of the most recent literature published since we submitted our original case report. We also agree that radiologists should be familiar with up-to-date information about this complex disease, given the important role that imaging plays in its diagnosis. With regard to specific parts of our original text, please allow us to answer as follows: (a) The reference number next to the title of figure 8 should read “(8)” instead of “(2).” (b) The IgG4 level of our patient was 216 mg/dL, but her IgG level overall was 2673 mg/dL. We have re-visited the patient’s medical records and confirmed this. The point we wanted to communicate was that her overall IgG4 level was elevated. (c) The letter “c” was misplaced. The corrected version of figure 8 is shown in an erratum in this issue. We again thank Dr Dendumrongsup for his comments on our case. We hope that, over time, medicine will gain a better understanding of IgG4-related disease, with refined diagnostic approaches and further gains in knowledge. Disclosures of Conflicts of Interest: Y.G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. A.A.B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is a consultant for Spiration (Olympus Medical); receives author honoraria from Elsevier. Other relationships: none to disclose.
Errata “Case 196: Immunoglobulin G4–related Disease.” Radiology 2013;268(2): 604–609
314
Page 607, Figure 8 should appear as corrected here, with the accompanying corrected legend.
Figure 8
Figure 8: Diagnostic criteria for IgG4-related disease (IgG4-RD). To convert to SI units (grams per liter), multiply by 0.01. hpf = High-power field.
“Meaningful Use for Radiology: Current Status and Future Directions.” Radiology 2013;269(2):318–321 Page 321, the Disclosures of Conflicts of Interest, which should have appeared before the References, was inadvertently omitted and should read as follows: Disclosures of Conflicts of Interest: T.A.M. No relevant conflicts of interest to disclose. D.E.A. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: stock/stock options, Amirsys Corp/ STATdx; travel/accommodations/meeting expenses unrelated to activities listed,
LA Rad Soc invited talk on Meaningful Use; honorarium, LA Rad Soc. Other relationships: none to disclose. C.D.C. No relevant conflicts of interest to disclose. K.J.D. No relevant conflicts of interest to disclose. A.E.F. No relevant conflicts of interest to disclose. R.K. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: stock, royalties, and consultant, Medicalis Corp. Other relationships: author named on U.S. patent 6029138 (issued, licensed, and royalties) held by Brigham and Women’s Hospital and licensed to Medicalis Corp in 2000; the institution receives royalties from Medicalis. C.P.L. Financial activities related to the present article: grant to institution for demonstration project contract, Centers for Medicare and Medicaid Services. Financial activities not related to the present article: board membership to Radiology Advisory Board, GE Healthcare (paid travel reimbursements and honorarium); consultancy to Medical Advisory Board, Elsevier (paid travel reimbursement and honorarium); stock/stock options, Medical/Technical Advisory Board, Activate Networks (granted options for service, no money received); stock/ stock options, Board of Directors, Montage Healthcare (founders shares and investor; travel reimbursement received). Other relationships: none to disclose. R.L.A. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: board membership, RSNA (travel expenses); patent for steerable catheter to author and institution (no payments yet); royalties from Thomas Publishers for book. Other relationships: none to disclose.
radiology.rsna.org n Radiology: Volume 270: Number 1—January 2014
