Pancreas • Volume 44, Number 4, May 2015
Letters to the Editor
Pierre Bedossa, MD, PhD Département de Pathologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France Sorbonne Paris Cité, Université Paris Diderot Paris, France
Philippe Ruszniewski, MD Sorbonne Paris Cité, Université Paris Diderot Paris, France Département de GastroentérologiePancréatologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Anne Couvelard, MD, PhD Sorbonne Paris Cité, Université Paris Diderot Paris, France Département de Pathologie, Hôpital Bichat DHU UNITY, AP-HP, Paris, France
Mucinous Cystic Neoplasm of the Pancreas With Increased IgG4+ Plasma Cells and Histopathologic Features of Autoimmune Pancreatitis/ IgG4—Related Disease To the Editor: rominent peritumoral and/or intratumoral lymphoplasmacytic infiltrates rich in immunoglobulin (Ig)G4+ plasma cells, storiform fibrosis, and obliterative phlebitis have been recognized as characteristic
P
histopathologic features of type 1 autoimmune pancreatitis (AIP), a manifestation of IgG4-related disease (IgG4-RD).1,2 Dense lymphoplasmacytic infiltrates with elevated IgG4+ plasma cells have also been described in several pancreatic neoplasms, including pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm (IPMN).3–8 We report the first case of a pancreatic mucinous cystic neoplasm (MCN) with histopathologic features of type 1 AIP/IgG4-RD localized to the cyst wall.
CASE REPORT A 33-year-old woman presented to the hospital with a large firm protuberant mass in the upper abdomen that increased in size
REFERENCES 1. Brugge WR, Lauwers GY, Sahani D, et al. Cystic neoplasms of the pancreas. N Engl J Med. 2004; 351:1218–1226. 2. Kishida Y, Matsubayashi H, Okamura Y, et al. A case of solid-type serous cystadenoma mimicking neuroendocrine tumor of the pancreas. J Dig Dis. 2014;15:211–215. 3. Falconi M, Bartsch DK, Eriksson B, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology. 2012;95: 120–134. 4. Lebtahi R, Cadiot G, Sarda L, et al. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J Nucl Med. 1997;38:853–858. 5. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–731. 6. Kulaksiz H, Eissele R, Rössler D, et al. Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies. Gut. 2002;50:52–60. 7. John M, Meyerhof W, Richter D, et al. Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2. Gut. 1996;38:33–39. 8. Reubi JC, Waser B, Schaer JC, et al. Somatostatin receptor SST1-SST5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001;28:836–846.
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FIGURE 1. A, The coronal contrast-enhanced computer tomography showing a large 15 cm low-attenuation mass in the region of the lesser sac, compressing the pancreatic tissue within the body and tail of the pancreas. B-F, Histologic features of pancreatic mucinous cystic neoplasm. B, Tall columnar mucin-containing epithelial lining and characteristic ovarian type stroma composed of bland spindle cells (H&E, original magnification, 100). C, Low power view of the cyst wall with dense inflammatory response and underlying fibrosis. (H&E, original magnification, 20) D, Dense inflammatory infiltrate consists predominantly of plasma cells, lymphocytes, and few eosinophils (H&E, original magnification, 400). E, Obliterative phlebitis (H&E, original magnification, 100). F, Numerous IgG4+ plasma cells by immunohistochemistry (original magnification, 400). H&E, hematoxylin and eosin. Editor's note: A color image accompanies the online version of this article. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pancreas • Volume 44, Number 4, May 2015
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Tabata et al4 Tabata et al4 Tabata et al4 Tabata et al4 Bateman et al5 Bateman et al5 Naitoh et al6 Urata et al7 Vaquero et al8 Vaquero et al8 Our case ++ + − − + + + − + + − 627 N/A N/A 29.4 N/A N/A 27.7 N/A 256 N/A 97.5 58% 43% 41% 46% 65% 26% N/A N/A 72% 41% 42% 53 28 13 40 173 63 >50 >10 >50 >50 75 + − − + + + + + + + + ++ − − + + + + + + N/A + Moderate Moderate Moderate High N/A N/A Low N/A Moderate N/A High N/A, not available.
IPMN IPMN IPMN IPMN IPMN IPMN IPMN IPMN IPMN IPMN MCN M M M M M M M M M M F 79 71 85 76 75 74 64 70 74 79 33 1 2 3 4 5 6 7 8 9 10 11
Reference Case No Age Sex Diagnosis Dysplasia Storiform Fibrosis Obliterative Phlebitis IgG4+ Plasma Cells/hpf IgG4:IgG Serum IgG4 (mg/dL) Distant Pancreas
DISCUSSION Dense lymphoplasmacytic infiltrates rich in IgG4+ plasma cells in combination with storiform fibrosis and obliterative phlebitis are 3 major histopathologic features
TABLE 1. Clinicopathologic Characteristics of Pancreatic Mucinous Neoplasms With Increased IgG4+ Plasma Cells
over the past few weeks and vague abdominal pain. She denied weight loss, fevers, chills, or diarrhea. On physical examination a palpable mass was identified in the left upper abdomen. The serum IgG and IgG4 levels were elevated at 1940 mg/dL (reference range 562–1585 mg/dL) and 97.5 mg/dL (reference range 4–86 mg/dL), respectively. Contrast-enhanced computer tomography revealed a large 15 cm in greatest dimension low-attenuation mass in the region of the lesser sac (Fig. 1A). The mass completely displaced and compressed the pancreatic tissue within the body and tail of the pancreas, while the pancreatic head appeared unremarkable. The patient underwent distal pancreatectomy with en block resection of the cystic pancreatic neoplasm, transverse mesocolon, spleen, distal pancreas, and segment of portal vein. The procedure was well tolerated and the patient was discharged a week after the surgery. The resection specimen contained a 15.5-cm pancreatic cyst filled with mucoid contents with a well-developed fibrous capsule varying in thickness from 0.3 to 1.5 cm. Histologic examination revealed an MCN lined by tall columnar mucincontaining epithelium and containing characteristic ovarian type stroma composed of bland spindle cells (Fig. 1B). A spectrum of dysplasia from low- to high-grade was present; however, no invasive adenocarcinoma was identified. The cyst wall contained a dense lymphoplasmacytic infiltrate with associated fibrosis, in areas demonstrating a storiform pattern, and frequent obliterative phlebitis (Fig. 1C–E). The inflammatory infiltrate was confined to the peritumoral area (within 1.5 cm of the cyst lining) and was not associated with pancreatic ducts or lobules. Pancreatic tissue away from the tumor did not have evidence of lymphoplasmacytic inflammation or fibrosis. The IgG and IgG4 immunohistochemistry revealed numerous positive plasma cells in the cyst wall (Fig. 1F). The mean number of IgG+ plasma cell was estimated to be 180/high power field (hpf), whereas the mean number of IgG4+ cells was 75/hpf. The IgG4+/IgG ratio was calculated as 41.7%. Review of consecutive cases from the Departments of Pathology at the Rhode Island and Miriam Hospitals identified 14 additional MCNs. None of these tumors was accompanied by lymphoplasmacytic infiltrates or fibrosis.
Letters to the Editor
www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
675
Pancreas • Volume 44, Number 4, May 2015
Letters to the Editor
characteristic of type 1 AIP and IgG4RD.1,2 In this case, we observed a MCN accompanied by all 3 of these features. Moreover, the number of IgG4+ plasma cells over 50/hpf and the IgG4+/IgG+ ratio greater than 40% fulfilled the Boston criteria for AIP/ IgG4-RD.2 The pancreatic tissue away from the cyst was completely normal, and further clinical and radiologic work-up did not reveal extrapancreatic manifestations of IgG4-RD. Furthermore, the clinical symptoms resolved after resection of the tumor. Therefore, we consider that the dense lymphoplasmacytic infiltrate with features of IgG4-RD surrounding the MCN in this case is not indicative of AIP/IgG4-RD, and likely represents an inflammatory antitumor response driven by Th2 cytokines. There is accumulating evidence that increased IgG4+ plasma cells may be associated not only with classic IgG4-RD but also with a variety of non-neoplastic and neoplastic conditions. The IgG4+ plasma cells may be significantly increased in inflammatory processes, including rheumatoid synovitis, oral cavity lesions including epulis plasmacellularis, radicular cysts, and oral lichen ruber.9 Elevated numbers of IgG4 have also been described as a component of antitumor inflammatory response in several malignancies from different sites, including pancreatic ductal adenocarcinoma3 and IPMN 4–8 (Table 1). It is not clear whether the morphologic features characteristic of AIP/IgG4-RD occur synchronously or precede IPMNs, or longstanding IPMNs induce IgG4+ plasma cell response. Although some authors proposed that IPMN may develop in a background of AIP based on the presence of lymphoplasmacytic infiltration with abundant plasma cells and storiform fibrosis at a location distant from IPMN,6 other hypothesized that the histologic changes consistent with type 1 AIP may be a secondary phenomenon that appeared several years after IPMN.7,8 The characteristic feature common to both pancreatic MCN and IPMN is mucin production. We have recently described that the sclerosing variant of mucoepidermoid carcinoma of salivary glands is associated with increased IgG4+ plasma cells.10 All 6 cases of sclerosing mucoepidermoid carcinoma demonstrated small areas of mucin extravasation composing 5% to 10% of the tumor mass. Although no definitive mucus extravasation was identified in this case, we hypothesize that mucin extravasation in these tumors may elicit an unusual immune response. In summary, we described the first case of pancreatic MCN associated with histologic features of AIP/IgG4-RD. This appears to be a relatively rare phenomenon, but one which should be considered when evaluating
676
www.pancreasjournal.com
mucinous neoplasms of the pancreas, including MCNs. A needle biopsy sampling the periphery of MCN may be misdiagnosed as AIP/IgG4-RD. Therefore, careful clinical and radiologic correlation with histologic findings is crucial in these cases. The authors declare no conflict of interest. Evgeny Yakirevich, MD, DSc Kammi J. Henriksen, MD Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Warren Alpert Medical School at Brown University Providence, RI [email protected]
with intraduct papillary mucinous neoplasm: report of two cases. Pancreatology. 2014;14: 316–318. 9. Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol. 2011;64: 237–243. 10. Tian W, Yakirevich E, Matoso A, et al. IgG4(+) plasma cells in sclerosing variant of mucoepidermoid carcinoma. Am J Surg Pathol. 2012;36:973–979.
Thomas Miner, MD
HNPCC-Associated Pheochromocytoma Expanding the Tumor Spectrum
Department of Surgery Rhode Island Hospital and Warren Alpert Medical School at Brown University Providence, RI
Murray B. Resnick, MD, PhD Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Warren Alpert Medical School at Brown University Providence, RI
REFERENCES 1. Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40:352–358. 2. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–1192. 3. Dhall D, Suriawinata AA, Tang LH, et al. Use of immunohistochemistry for IgG4 in the distinction of autoimmune pancreatitis from peritumoral pancreatitis. Hum Pathol. 2010;41: 643–652. 4. Tabata T, Kamisawa T, Hara S, et al. Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: a coincidental association. Pancreatology. 2013;13:379–383. 5. Bateman AC, Culver EL, Sommerlad M, et al. Intraduct papillary mucinous neoplasm of the pancreas: a tumour linked with IgG4-related disease? J Clin Pathol. 2013;66:671–675. 6. Naitoh I, Nakazawa T, Notohara K, et al. Intraductal papillary mucinous neoplasm associated with autoimmune pancreatitis. Pancreas. 2013;42:552–554. 7. Urata T, Naito Y, Izumi Y, et al. Localized type 1 autoimmune pancreatitis superimposed upon preexisting intraductal papillary mucinous neoplasms. World J Gastroenterol. 2013;19: 9127–9132. 8. Vaquero EC, Salcedo MT, Cuatrecasas M, et al. Autoimmune pancreatitis type-1 associated
To the Editor: ereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is the most common inherited colorectal cancer susceptibility syndrome. First described in 1966 by Dr Henry Lynch with the description of 2 large midwest kindred, HNPCC is due to germ line mutations in MLH1, MSH2, MSH6, or PMS2, which result in a deficiency in DNA mismatch repair. Hereditary nonpolyposis colorectal cancer is not only associated with an increased risk for colorectal cancer but also extracolonic cancers including the endometrium, ovary, pancreas, and brain. By instituting routine screening of all newly diagnosed colorectal adenocarcinomas for microsatellite instability, health systems have increased the yield of identifying patients with HNPCC, allowing for appropriate genetic counseling and screening.1 Although the common extracolonic malignancies associated with HNPCC have been identified, there are an increasing number of case reports of established HNPCC patients with neuroendocrine tumors (NETs), raising the possibility that this type of tumor could represent another extracolonic manifestation for which these patients are at increased risk. The increased incidence much like in the general population may be due to the increased use of crosssectional imaging for screening purposes.
H
CASE REPORT We report a case of a pheochromocytoma developing in a patient known to
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editor
Pierre Bedossa, MD, PhD Département de Pathologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France Sorbonne Paris Cité, Université Paris Diderot Paris, France
Philippe Ruszniewski, MD Sorbonne Paris Cité, Université Paris Diderot Paris, France Département de GastroentérologiePancréatologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Anne Couvelard, MD, PhD Sorbonne Paris Cité, Université Paris Diderot Paris, France Département de Pathologie, Hôpital Bichat DHU UNITY, AP-HP, Paris, France
Mucinous Cystic Neoplasm of the Pancreas With Increased IgG4+ Plasma Cells and Histopathologic Features of Autoimmune Pancreatitis/ IgG4—Related Disease To the Editor: rominent peritumoral and/or intratumoral lymphoplasmacytic infiltrates rich in immunoglobulin (Ig)G4+ plasma cells, storiform fibrosis, and obliterative phlebitis have been recognized as characteristic
P
histopathologic features of type 1 autoimmune pancreatitis (AIP), a manifestation of IgG4-related disease (IgG4-RD).1,2 Dense lymphoplasmacytic infiltrates with elevated IgG4+ plasma cells have also been described in several pancreatic neoplasms, including pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm (IPMN).3–8 We report the first case of a pancreatic mucinous cystic neoplasm (MCN) with histopathologic features of type 1 AIP/IgG4-RD localized to the cyst wall.
CASE REPORT A 33-year-old woman presented to the hospital with a large firm protuberant mass in the upper abdomen that increased in size
REFERENCES 1. Brugge WR, Lauwers GY, Sahani D, et al. Cystic neoplasms of the pancreas. N Engl J Med. 2004; 351:1218–1226. 2. Kishida Y, Matsubayashi H, Okamura Y, et al. A case of solid-type serous cystadenoma mimicking neuroendocrine tumor of the pancreas. J Dig Dis. 2014;15:211–215. 3. Falconi M, Bartsch DK, Eriksson B, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology. 2012;95: 120–134. 4. Lebtahi R, Cadiot G, Sarda L, et al. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J Nucl Med. 1997;38:853–858. 5. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–731. 6. Kulaksiz H, Eissele R, Rössler D, et al. Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies. Gut. 2002;50:52–60. 7. John M, Meyerhof W, Richter D, et al. Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2. Gut. 1996;38:33–39. 8. Reubi JC, Waser B, Schaer JC, et al. Somatostatin receptor SST1-SST5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001;28:836–846.
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FIGURE 1. A, The coronal contrast-enhanced computer tomography showing a large 15 cm low-attenuation mass in the region of the lesser sac, compressing the pancreatic tissue within the body and tail of the pancreas. B-F, Histologic features of pancreatic mucinous cystic neoplasm. B, Tall columnar mucin-containing epithelial lining and characteristic ovarian type stroma composed of bland spindle cells (H&E, original magnification, 100). C, Low power view of the cyst wall with dense inflammatory response and underlying fibrosis. (H&E, original magnification, 20) D, Dense inflammatory infiltrate consists predominantly of plasma cells, lymphocytes, and few eosinophils (H&E, original magnification, 400). E, Obliterative phlebitis (H&E, original magnification, 100). F, Numerous IgG4+ plasma cells by immunohistochemistry (original magnification, 400). H&E, hematoxylin and eosin. Editor's note: A color image accompanies the online version of this article. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pancreas • Volume 44, Number 4, May 2015
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Tabata et al4 Tabata et al4 Tabata et al4 Tabata et al4 Bateman et al5 Bateman et al5 Naitoh et al6 Urata et al7 Vaquero et al8 Vaquero et al8 Our case ++ + − − + + + − + + − 627 N/A N/A 29.4 N/A N/A 27.7 N/A 256 N/A 97.5 58% 43% 41% 46% 65% 26% N/A N/A 72% 41% 42% 53 28 13 40 173 63 >50 >10 >50 >50 75 + − − + + + + + + + + ++ − − + + + + + + N/A + Moderate Moderate Moderate High N/A N/A Low N/A Moderate N/A High N/A, not available.
IPMN IPMN IPMN IPMN IPMN IPMN IPMN IPMN IPMN IPMN MCN M M M M M M M M M M F 79 71 85 76 75 74 64 70 74 79 33 1 2 3 4 5 6 7 8 9 10 11
Reference Case No Age Sex Diagnosis Dysplasia Storiform Fibrosis Obliterative Phlebitis IgG4+ Plasma Cells/hpf IgG4:IgG Serum IgG4 (mg/dL) Distant Pancreas
DISCUSSION Dense lymphoplasmacytic infiltrates rich in IgG4+ plasma cells in combination with storiform fibrosis and obliterative phlebitis are 3 major histopathologic features
TABLE 1. Clinicopathologic Characteristics of Pancreatic Mucinous Neoplasms With Increased IgG4+ Plasma Cells
over the past few weeks and vague abdominal pain. She denied weight loss, fevers, chills, or diarrhea. On physical examination a palpable mass was identified in the left upper abdomen. The serum IgG and IgG4 levels were elevated at 1940 mg/dL (reference range 562–1585 mg/dL) and 97.5 mg/dL (reference range 4–86 mg/dL), respectively. Contrast-enhanced computer tomography revealed a large 15 cm in greatest dimension low-attenuation mass in the region of the lesser sac (Fig. 1A). The mass completely displaced and compressed the pancreatic tissue within the body and tail of the pancreas, while the pancreatic head appeared unremarkable. The patient underwent distal pancreatectomy with en block resection of the cystic pancreatic neoplasm, transverse mesocolon, spleen, distal pancreas, and segment of portal vein. The procedure was well tolerated and the patient was discharged a week after the surgery. The resection specimen contained a 15.5-cm pancreatic cyst filled with mucoid contents with a well-developed fibrous capsule varying in thickness from 0.3 to 1.5 cm. Histologic examination revealed an MCN lined by tall columnar mucincontaining epithelium and containing characteristic ovarian type stroma composed of bland spindle cells (Fig. 1B). A spectrum of dysplasia from low- to high-grade was present; however, no invasive adenocarcinoma was identified. The cyst wall contained a dense lymphoplasmacytic infiltrate with associated fibrosis, in areas demonstrating a storiform pattern, and frequent obliterative phlebitis (Fig. 1C–E). The inflammatory infiltrate was confined to the peritumoral area (within 1.5 cm of the cyst lining) and was not associated with pancreatic ducts or lobules. Pancreatic tissue away from the tumor did not have evidence of lymphoplasmacytic inflammation or fibrosis. The IgG and IgG4 immunohistochemistry revealed numerous positive plasma cells in the cyst wall (Fig. 1F). The mean number of IgG+ plasma cell was estimated to be 180/high power field (hpf), whereas the mean number of IgG4+ cells was 75/hpf. The IgG4+/IgG ratio was calculated as 41.7%. Review of consecutive cases from the Departments of Pathology at the Rhode Island and Miriam Hospitals identified 14 additional MCNs. None of these tumors was accompanied by lymphoplasmacytic infiltrates or fibrosis.
Letters to the Editor
www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
675
Pancreas • Volume 44, Number 4, May 2015
Letters to the Editor
characteristic of type 1 AIP and IgG4RD.1,2 In this case, we observed a MCN accompanied by all 3 of these features. Moreover, the number of IgG4+ plasma cells over 50/hpf and the IgG4+/IgG+ ratio greater than 40% fulfilled the Boston criteria for AIP/ IgG4-RD.2 The pancreatic tissue away from the cyst was completely normal, and further clinical and radiologic work-up did not reveal extrapancreatic manifestations of IgG4-RD. Furthermore, the clinical symptoms resolved after resection of the tumor. Therefore, we consider that the dense lymphoplasmacytic infiltrate with features of IgG4-RD surrounding the MCN in this case is not indicative of AIP/IgG4-RD, and likely represents an inflammatory antitumor response driven by Th2 cytokines. There is accumulating evidence that increased IgG4+ plasma cells may be associated not only with classic IgG4-RD but also with a variety of non-neoplastic and neoplastic conditions. The IgG4+ plasma cells may be significantly increased in inflammatory processes, including rheumatoid synovitis, oral cavity lesions including epulis plasmacellularis, radicular cysts, and oral lichen ruber.9 Elevated numbers of IgG4 have also been described as a component of antitumor inflammatory response in several malignancies from different sites, including pancreatic ductal adenocarcinoma3 and IPMN 4–8 (Table 1). It is not clear whether the morphologic features characteristic of AIP/IgG4-RD occur synchronously or precede IPMNs, or longstanding IPMNs induce IgG4+ plasma cell response. Although some authors proposed that IPMN may develop in a background of AIP based on the presence of lymphoplasmacytic infiltration with abundant plasma cells and storiform fibrosis at a location distant from IPMN,6 other hypothesized that the histologic changes consistent with type 1 AIP may be a secondary phenomenon that appeared several years after IPMN.7,8 The characteristic feature common to both pancreatic MCN and IPMN is mucin production. We have recently described that the sclerosing variant of mucoepidermoid carcinoma of salivary glands is associated with increased IgG4+ plasma cells.10 All 6 cases of sclerosing mucoepidermoid carcinoma demonstrated small areas of mucin extravasation composing 5% to 10% of the tumor mass. Although no definitive mucus extravasation was identified in this case, we hypothesize that mucin extravasation in these tumors may elicit an unusual immune response. In summary, we described the first case of pancreatic MCN associated with histologic features of AIP/IgG4-RD. This appears to be a relatively rare phenomenon, but one which should be considered when evaluating
676
www.pancreasjournal.com
mucinous neoplasms of the pancreas, including MCNs. A needle biopsy sampling the periphery of MCN may be misdiagnosed as AIP/IgG4-RD. Therefore, careful clinical and radiologic correlation with histologic findings is crucial in these cases. The authors declare no conflict of interest. Evgeny Yakirevich, MD, DSc Kammi J. Henriksen, MD Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Warren Alpert Medical School at Brown University Providence, RI [email protected]
with intraduct papillary mucinous neoplasm: report of two cases. Pancreatology. 2014;14: 316–318. 9. Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol. 2011;64: 237–243. 10. Tian W, Yakirevich E, Matoso A, et al. IgG4(+) plasma cells in sclerosing variant of mucoepidermoid carcinoma. Am J Surg Pathol. 2012;36:973–979.
Thomas Miner, MD
HNPCC-Associated Pheochromocytoma Expanding the Tumor Spectrum
Department of Surgery Rhode Island Hospital and Warren Alpert Medical School at Brown University Providence, RI
Murray B. Resnick, MD, PhD Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Warren Alpert Medical School at Brown University Providence, RI
REFERENCES 1. Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40:352–358. 2. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–1192. 3. Dhall D, Suriawinata AA, Tang LH, et al. Use of immunohistochemistry for IgG4 in the distinction of autoimmune pancreatitis from peritumoral pancreatitis. Hum Pathol. 2010;41: 643–652. 4. Tabata T, Kamisawa T, Hara S, et al. Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: a coincidental association. Pancreatology. 2013;13:379–383. 5. Bateman AC, Culver EL, Sommerlad M, et al. Intraduct papillary mucinous neoplasm of the pancreas: a tumour linked with IgG4-related disease? J Clin Pathol. 2013;66:671–675. 6. Naitoh I, Nakazawa T, Notohara K, et al. Intraductal papillary mucinous neoplasm associated with autoimmune pancreatitis. Pancreas. 2013;42:552–554. 7. Urata T, Naito Y, Izumi Y, et al. Localized type 1 autoimmune pancreatitis superimposed upon preexisting intraductal papillary mucinous neoplasms. World J Gastroenterol. 2013;19: 9127–9132. 8. Vaquero EC, Salcedo MT, Cuatrecasas M, et al. Autoimmune pancreatitis type-1 associated
To the Editor: ereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is the most common inherited colorectal cancer susceptibility syndrome. First described in 1966 by Dr Henry Lynch with the description of 2 large midwest kindred, HNPCC is due to germ line mutations in MLH1, MSH2, MSH6, or PMS2, which result in a deficiency in DNA mismatch repair. Hereditary nonpolyposis colorectal cancer is not only associated with an increased risk for colorectal cancer but also extracolonic cancers including the endometrium, ovary, pancreas, and brain. By instituting routine screening of all newly diagnosed colorectal adenocarcinomas for microsatellite instability, health systems have increased the yield of identifying patients with HNPCC, allowing for appropriate genetic counseling and screening.1 Although the common extracolonic malignancies associated with HNPCC have been identified, there are an increasing number of case reports of established HNPCC patients with neuroendocrine tumors (NETs), raising the possibility that this type of tumor could represent another extracolonic manifestation for which these patients are at increased risk. The increased incidence much like in the general population may be due to the increased use of crosssectional imaging for screening purposes.
H
CASE REPORT We report a case of a pheochromocytoma developing in a patient known to
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
