LETTERS TO THE EDITOR
Somatostatin Receptor Subtype 2 Expression and Somatostatin Receptor Scintigraphy Positivity in Pancreatic Serous Cystadenomas To the Editor: ancreatic serous cystadenomas (PSCs) are the most frequent pancreatic cystic tumors, accounting from 10% to 29% of all cystic neoplasms of the pancreas.1 They are considered as benign lesions, and thus observation is routinely considered for asymptomatic lesions. Diagnosis of PSC is most often established on computed tomography scan or magnetic resonance imaging but may be difficult in some cases, especially in some PSC histological variants. For instance, solid PSC, which is highly vascularized, can share radiological features with neuroendocrine tumors (NETs).2 Somatostatin receptor scintigraphy (SRS) is based on the
P
detection of somatostatin receptor subtype 2 (SST2R) with a radiolabeled synthetic somatostatin analog, 111In-DTPA0 octreotide being the most commonly used. Somatostatin receptor scintigraphy is the central modality for localization of pancreatic NETs and definition of the extent of the disease,3 with a sensitivity and specificity of 90 and 80%, respectively.4,5 Somatostatin receptor subtype 2 is expressed at high levels in most gastropancreatic NETs,6 and its expression correlates with SRS positivity.7 Besides gastropancreatic NETs, SST2R is also expressed in a variety of other endocrine and nonendocrine tumors, such as pituitary adenomas, meningiomas, and neuroblastomas,8 but to our knowledge, SST2R expression has never been explored in PSC. Here, we conducted a retrospective study to assess SST2R expression and SRS positivity in a series of PSC. Pancreatic serous cystadenomas either surgically resected or biopsied were retrospectively retrieved from the pathological files (department of pathology). Immunostaining was performed with an antiSST2R subtype A antibody (dilution 1:7000;
Biotrend, Destin, Fla). An immunohistochemical score (0/200) was calculated for each tumor by multiplying staining intensity (no staining, 0; weak, 1; strong, 2) by the percentage of stained cells. Somatostatin receptor scintigraphy was performed in patients for whom a preoperative diagnosis of NET was suspected, after intravenous injection of 222 MBq of indium 111 octreotide (Octreoscan). Images were acquired at 4 hours (whole-body scan and abdomen-centered image) and at 21 hours (head, thorax, and abdominal tomography) after intravenous injection. Fixation was evaluated as negative, moderate, or intense (R.L.). Results of Octreoscan were compared with those of definitive pathological examination. A total of 23 PSCs were included (Table 1). Patients were in majority women (83%), with a median age of 57 years (range, 31–79 years). Histologically, PSCs were in majority microcystic (65%), and the median size was 25 mm (range, 8–130 mm). Somatostatin receptor subtype 2 was expressed in 19 (82%) of the 23 cases (Table 1). The median SST2R score was 100 (range, 0–200), and 12 (52%)
TABLE 1. Patients Clinicopathological Characteristics, SST2R Score, and SRS Positivity Patient
Sex
Age, y
Preoperative Diagnosis
Pathological Diagnosis
Size, mm
SST2R Score (/200)
SRS Positivity, Yes/No
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
F M M F F F F F F F F F M F F F F F F F F M F
79 67 64 54 36 70 31 33 66 57 70 36 59 36 55 52 52 65 58 44 51 75 65
NET NET NET NET NET NET NET SC SC Adenocarcinoma IPMN IPMN SC SC NA NA MC SC IPMN IPMN SC IPMN Adenocarcinoma
Mi SC Mi SC Mi SC Mi SC Mi SC Mi SC Mi SC Ma SC Ma SC Ma SC and Mi SC IPMN and SC Mi SC Mi SC Mi SC Ma SC Ma SC Ma SC Mi SC Mi SC Mi SC Mi SC Ma SC Mi SC
50 50 25 21 8 40 15 130 65 12 10 18 20 55 50 11 35 90 10 10 40 45 15
200 20 50 100 60 100 0 0 0 10 100 200 100 0 60 100 200 100 100 100 120 80 60
Yes Yes No No No No No SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed
F, female; M, male; IPMN, intraductal papillary mucinous neoplasm; SC, serous cystadenoma; MC, mucinous cystadenoma; Mi SC, microcystic serous cystadenoma; Ma SC, macrocystic serous cystadenoma.
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www.pancreasjournal.com
Pancreas • Volume 44, Number 4, May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pancreas • Volume 44, Number 4, May 2015
Letters to the Editor
FIGURE 1. SST2R immunostaining and SRS in PSC. A, Patient 1, tissue section showing microcystic PSC made of numerous small cysts lined by cuboidal cells without atypias, scattered in a fibrous stroma (hematoxylin-eosin stain 20). B, Patient 1, immunostaining with anti-SST2A antibody showed intense membranous and/or cytoplasmic staining (intensity, 2), present in 100% of cells (score 200). C, Abdomen-centered image in patient 1, showing moderate fixation of the pancreatic tail (arrow). D, Computed tomography scan in patient 2 showing a voluminous hyperdense lesion of the pancreas's head (top panel). Tomography (middle panel) and reconstruction image (bottom panel) showed a moderate fixation of the lesion.
of the 23 tumors had a score greater than or equal to 100. Representative SST2R immunostaining is represented in Figure 1. Somatostatin receptor scintigraphy was performed in 7 patients for whom a preoperative diagnosis of NET was suspected and was positive in 2 cases (28%) (Table 1). The uptake was evaluated as moderate in both cases (Fig. 1). Somatostatin receptor scintigraphy positive tumors were larger than negative ones (mean size, 50 vs 22 mm), but the difference was not significant (P = 0.37). In summary, we demonstrate here the first evidence of SST2R expression and SRS positivity in PSC. The latter might be underestimated because the procedure was only performed in 7 patients with PSC mimicking NET on preoperative imaging. Facing an atypical pancreatic lesion, for
which both PSC and NET can be considered, SRS positivity might be misleading and wrongly suggest NET diagnosis.
Département de Médecine Nucléaire Hôpital Beaujon, DHU UNITY AP-HP, Clichy, France
ACKNOWLEDGMENT The authors gratefully acknowledge Sylvie Mosnier for performing SST2R immunostainings. The authors declare no conflict of interest.
Département de GastroentérologiePancréatologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Olivia Hentic, MD
Daniela Speisky, MD Département de Pathologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Nicolas Poté, MD
Alain Sauvanet, MD
Département de Pathologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France Sorbonne Paris Cité, Université Paris Diderot Paris, France [email protected]
Sorbonne Paris Cité, Université Paris Diderot Paris, France Département de Chirurgie Pancréaticobiliaire et Hépatique, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Rachida Lebtahi, MD, PhD
Marie-Pierre Vullierme, MD
Sorbonne Paris Cité, Université Paris Diderot Paris, France
Département de Radiologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
673
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.
674
www.pancreasjournal.com
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.
Somatostatin Receptor Subtype 2 Expression and Somatostatin Receptor Scintigraphy Positivity in Pancreatic Serous Cystadenomas To the Editor: ancreatic serous cystadenomas (PSCs) are the most frequent pancreatic cystic tumors, accounting from 10% to 29% of all cystic neoplasms of the pancreas.1 They are considered as benign lesions, and thus observation is routinely considered for asymptomatic lesions. Diagnosis of PSC is most often established on computed tomography scan or magnetic resonance imaging but may be difficult in some cases, especially in some PSC histological variants. For instance, solid PSC, which is highly vascularized, can share radiological features with neuroendocrine tumors (NETs).2 Somatostatin receptor scintigraphy (SRS) is based on the
P
detection of somatostatin receptor subtype 2 (SST2R) with a radiolabeled synthetic somatostatin analog, 111In-DTPA0 octreotide being the most commonly used. Somatostatin receptor scintigraphy is the central modality for localization of pancreatic NETs and definition of the extent of the disease,3 with a sensitivity and specificity of 90 and 80%, respectively.4,5 Somatostatin receptor subtype 2 is expressed at high levels in most gastropancreatic NETs,6 and its expression correlates with SRS positivity.7 Besides gastropancreatic NETs, SST2R is also expressed in a variety of other endocrine and nonendocrine tumors, such as pituitary adenomas, meningiomas, and neuroblastomas,8 but to our knowledge, SST2R expression has never been explored in PSC. Here, we conducted a retrospective study to assess SST2R expression and SRS positivity in a series of PSC. Pancreatic serous cystadenomas either surgically resected or biopsied were retrospectively retrieved from the pathological files (department of pathology). Immunostaining was performed with an antiSST2R subtype A antibody (dilution 1:7000;
Biotrend, Destin, Fla). An immunohistochemical score (0/200) was calculated for each tumor by multiplying staining intensity (no staining, 0; weak, 1; strong, 2) by the percentage of stained cells. Somatostatin receptor scintigraphy was performed in patients for whom a preoperative diagnosis of NET was suspected, after intravenous injection of 222 MBq of indium 111 octreotide (Octreoscan). Images were acquired at 4 hours (whole-body scan and abdomen-centered image) and at 21 hours (head, thorax, and abdominal tomography) after intravenous injection. Fixation was evaluated as negative, moderate, or intense (R.L.). Results of Octreoscan were compared with those of definitive pathological examination. A total of 23 PSCs were included (Table 1). Patients were in majority women (83%), with a median age of 57 years (range, 31–79 years). Histologically, PSCs were in majority microcystic (65%), and the median size was 25 mm (range, 8–130 mm). Somatostatin receptor subtype 2 was expressed in 19 (82%) of the 23 cases (Table 1). The median SST2R score was 100 (range, 0–200), and 12 (52%)
TABLE 1. Patients Clinicopathological Characteristics, SST2R Score, and SRS Positivity Patient
Sex
Age, y
Preoperative Diagnosis
Pathological Diagnosis
Size, mm
SST2R Score (/200)
SRS Positivity, Yes/No
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
F M M F F F F F F F F F M F F F F F F F F M F
79 67 64 54 36 70 31 33 66 57 70 36 59 36 55 52 52 65 58 44 51 75 65
NET NET NET NET NET NET NET SC SC Adenocarcinoma IPMN IPMN SC SC NA NA MC SC IPMN IPMN SC IPMN Adenocarcinoma
Mi SC Mi SC Mi SC Mi SC Mi SC Mi SC Mi SC Ma SC Ma SC Ma SC and Mi SC IPMN and SC Mi SC Mi SC Mi SC Ma SC Ma SC Ma SC Mi SC Mi SC Mi SC Mi SC Ma SC Mi SC
50 50 25 21 8 40 15 130 65 12 10 18 20 55 50 11 35 90 10 10 40 45 15
200 20 50 100 60 100 0 0 0 10 100 200 100 0 60 100 200 100 100 100 120 80 60
Yes Yes No No No No No SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed SRS not performed
F, female; M, male; IPMN, intraductal papillary mucinous neoplasm; SC, serous cystadenoma; MC, mucinous cystadenoma; Mi SC, microcystic serous cystadenoma; Ma SC, macrocystic serous cystadenoma.
672
www.pancreasjournal.com
Pancreas • Volume 44, Number 4, May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pancreas • Volume 44, Number 4, May 2015
Letters to the Editor
FIGURE 1. SST2R immunostaining and SRS in PSC. A, Patient 1, tissue section showing microcystic PSC made of numerous small cysts lined by cuboidal cells without atypias, scattered in a fibrous stroma (hematoxylin-eosin stain 20). B, Patient 1, immunostaining with anti-SST2A antibody showed intense membranous and/or cytoplasmic staining (intensity, 2), present in 100% of cells (score 200). C, Abdomen-centered image in patient 1, showing moderate fixation of the pancreatic tail (arrow). D, Computed tomography scan in patient 2 showing a voluminous hyperdense lesion of the pancreas's head (top panel). Tomography (middle panel) and reconstruction image (bottom panel) showed a moderate fixation of the lesion.
of the 23 tumors had a score greater than or equal to 100. Representative SST2R immunostaining is represented in Figure 1. Somatostatin receptor scintigraphy was performed in 7 patients for whom a preoperative diagnosis of NET was suspected and was positive in 2 cases (28%) (Table 1). The uptake was evaluated as moderate in both cases (Fig. 1). Somatostatin receptor scintigraphy positive tumors were larger than negative ones (mean size, 50 vs 22 mm), but the difference was not significant (P = 0.37). In summary, we demonstrate here the first evidence of SST2R expression and SRS positivity in PSC. The latter might be underestimated because the procedure was only performed in 7 patients with PSC mimicking NET on preoperative imaging. Facing an atypical pancreatic lesion, for
which both PSC and NET can be considered, SRS positivity might be misleading and wrongly suggest NET diagnosis.
Département de Médecine Nucléaire Hôpital Beaujon, DHU UNITY AP-HP, Clichy, France
ACKNOWLEDGMENT The authors gratefully acknowledge Sylvie Mosnier for performing SST2R immunostainings. The authors declare no conflict of interest.
Département de GastroentérologiePancréatologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Olivia Hentic, MD
Daniela Speisky, MD Département de Pathologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Nicolas Poté, MD
Alain Sauvanet, MD
Département de Pathologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France Sorbonne Paris Cité, Université Paris Diderot Paris, France [email protected]
Sorbonne Paris Cité, Université Paris Diderot Paris, France Département de Chirurgie Pancréaticobiliaire et Hépatique, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
Rachida Lebtahi, MD, PhD
Marie-Pierre Vullierme, MD
Sorbonne Paris Cité, Université Paris Diderot Paris, France
Département de Radiologie, Hôpital Beaujon DHU UNITY, AP-HP, Clichy, France
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
673
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.
674
www.pancreasjournal.com
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.
