LETTER TO THE EDITOR
Familial Adenomatous Polyposis and Pancreatic Cancer
To the Editor: n patients with familial adenomatous polyposis (FAP), the relative risk for pancreatic cancer was estimated to be 4.5 times of the general population.1 However, in the literature, the histological nature of the pancreatic neoplasms was atypical tumoral histology (with, probably, a reporting bias). Moreover, no specific pancreatic precancerous lesion has been described in patients with FAP, although 1 study reported the presence of pancreatic intra-epithelial neoplasia-3 ductal lesions in one 58-year-old patient with FAP after pancreaticoduodenectomy for severe duodenal polyposis.2 The rare reported histology concerns pancreatic cystic and pseudopapillarytumor,3 pancreatic glucagonoma,4 duodenal endocrine tumor,5 as well as acinar cell carcinoma (ACC).6,7 Among the patients observed in our unit from 1990 to 2009, we interestingly never identified a classical exocrine pancreatic carcinoma in a cohort of 127 patients
I
with FAP undergoing regular clinical evaluation as well as upper and lower endoscopic follow-up (data not shown). We report 4 cases of primary pancreatic tumors, all of unusual histology, observed in a tertiary reference center cohort of patients with FAP (Table 1). Histologically, all of these tumors were rare tumors, including 2 endocrine carcinomas, 1 ACC, and 1 pancreatoblastoma. Pancreatic endocrine tumors account for less than 1% of all pancreatic neoplasms. Acinar cell carcinoma constitutes a phenotypically and genotypically different entity from ductal adenocarcinoma and endocrine tumors. The morphological, immunohistochemical, and clinical features of ACC overlap with those of pancreatoblastoma, which is another rare pancreatic neoplasm (Fig. 1).8 We cannot be sure that these pancreatic tumors were related to the FAP disease. Indeed, we did not perform somatic adenomatous polyposis coli (APC) gene analysis in the 4 tumors described, as has been reportedin1patientwithapancreatoblastoma.9 Such analysis, by showing the invalidation of the second APC allele by a somatic event, would be an important argument on favor of the responsibility of the APC gene germ line mutation in pancreatic tumor occurrence in
patients with FAP. However, given the lack of exocrine adenocarcinoma identified in our experience and in the literature,1 the reported increased risk for pancreatic tumor in patients with FAP supposes that germ line APC mutation could favor the development of atypical pancreatic tumors more than in exocrine carcinoma. In view of the low prevalence of pancreatic cancer in patients with FAP, the scarcity of published data, and the high difficulty of pancreatic surveillance for neoplasia, no recommended pancreatic surveillance in patients with FAP could be elaborated and there will probably never be. Complex surveillance protocols including computed tomography scan, magnetic resonance imaging, and ultrasonography have been advocated in other genetic syndromes, such as hereditary pancreatitis, Peutz-Jeghers syndrome, familial pancreatic cancer, with much higher (up to 30%40%) cumulative risk for developing pancreatic exocrine cancer.10 The only recommendation could be careful clinical examination at least every year to detect any early symptom. Interestingly, all but 1 patient described in this series had long survival, with 2 patients being considered in complete remission for more than 5 years.
TABLE 1. Characteristics of Patients Age of Age, Age of FAP Pancreatic Case Sex y Diagnosis Cancer, y 1
M
63
23
63
2
M
22
22
22
3
M
63
35
53
4
M
35
25
35
Symptoms
Localization and Size Histology
Jaundice Pancreatic PDNEC, large 6 y after head/ cell type ampullectomy 40 mm Abdominal Pancreatic PDNEC, small pains head/ cell type 120 mm Abdominal Pancreatic ACC pains isthmus/ 25 mm Acute pancreatitis
Immunostain SP+, C-A+
SP+, C-A+
Treatment
Follow-up
PD and CT Alive 9 y after for liver 3 CT lines metastasis (liver metastasis) 4 CT lines Died 2 y after diagnosis
Cytokeratin+, Total PD and No evolution trypsin+, α1antrectomy 10 y after antitrypsin+, surgery SP-, C-APancreatic Pancreatoblastoma SP-, C-APD No evolution isthmus/ 5 y after 60 mm surgery
ACC, acinar cell carcinoma; C-A, chromogranin A; CT, chemotherapy; PD, pancreaticoduodenectomy; PDNEC, poorly differentiated neuroendocrine carcinoma; SP, synaptophysin.
512
www.pancreasjournal.com
Pancreas • Volume 44, Number 3, April 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pancreas • Volume 44, Number 3, April 2015
Letter to the Editor
Thomas Walter, MD, PhD Catherine Lombard-Bohas, MD Jean-Christophe Saurin, MD, PhD Department of Gastroenterology Edouard Herriot Hospital Lyon, France
REFERENCES
FIGURE 1. Histological and immunohistochemical features in cases 1, 2, and 3. In patient 1, the tumor is formed by masses of large, basophilic cells (A; hematoxylin and eosin staining, original magnification, 250), focally expressing chromogranin A (B; immunoperoxidase, original magnification, 210). In patient 2, the tumor has the typical appearance of neuroendocrine carcinoma, which is a small cell type (C; hematoxylin and eosin staining, original magnification, 190). In patient 3, the tumor is formed by acinar and glandular structures lined by cells expressing trypsin, mainly as extracellular deposits (D; immunoperoxidase, original magnification, 200).
The authors declare no conflict of interest. Driffa Moussata, MD, PhD
Francoise Berger, MD, PhD Department of Pathology Lyon Sud Hospital Pierre Bénite, France
Department of Gastroenterology Lyon Sud Hospital Pierre Bénite, France [email protected]
Jean-Yves Scoazec, MD, PhD
Leila Senouci, MD
Stephane Pinson, MD, PhD
Department of Gastroenterology Lyon Sud Hospital Pierre Bénite, France
Department of Genetic Edouard Herriot Hospital Lyon, France
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Department of Pathology Edouard Herriot Hospital Lyon, France
1. Giardiello FM, Offerhaus GJ, Lee DH, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993;34:1394–1396. 2. Gupta C, Mazzara PF. High-grade pancreatic intraepithelial neoplasia in a patient with familial adenomatous polyposis. Arch Pathol Lab Med. 2005;129:1398–1400. 3. Le Borgne J, Bouvier S, Fiche M, et al. Cystic and papillary tumor of the pancreas: diagnostic and developmental uncertainties. Apropos of a case. Chirurgie. 1997;122:31–34. 4. Stewart CJ, Imrie CW, Foulis AK. Pancreatic islet cell tumour in a patient with familial adenomatous polyposis. J Clin Pathol. 1994;47: 860–861. 5. July LV, Northcott KA, Yoshida EM, et al. Coexisting carcinoid tumors in familial adenomatous polyposis-associated upper intestinal adenomas. Am J Gastroenterol. 1999; 94:1091–1094. 6. Le Borgne J, Audoin AF, Dupas B, et al. Pancreatic cancer with acinar cells. Apropos of 1 case with immunocytochemical study. Chirurgie. 1989;115:322–327. 7. Seket B, Saurin JC, Scoazec JY, et al. Pancreatic acinar cell carcinoma in a patient with familial adenomatous polyposis. Gastroenterol Clin Biol. 2003;27:818–820. 8. Karagianopoulou G, Noussios G, Katsourakis A, et al. Acinar cell carcinoma of the pancreas: a case report and review of the literature. Acta Chir Belg. 2011;111:319–322. 9. Abraham SC, Wu TT, Klimstra DS, et al. Distincitve molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas: frequent alterations in the APC/beta-catenin pathway and chromosome 11p. Am J Pathol. 2001;159:1619–1627. 10. Canto MI, Goggins M, Yeo CJ, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004;2:606–621.
www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
513
Familial Adenomatous Polyposis and Pancreatic Cancer
To the Editor: n patients with familial adenomatous polyposis (FAP), the relative risk for pancreatic cancer was estimated to be 4.5 times of the general population.1 However, in the literature, the histological nature of the pancreatic neoplasms was atypical tumoral histology (with, probably, a reporting bias). Moreover, no specific pancreatic precancerous lesion has been described in patients with FAP, although 1 study reported the presence of pancreatic intra-epithelial neoplasia-3 ductal lesions in one 58-year-old patient with FAP after pancreaticoduodenectomy for severe duodenal polyposis.2 The rare reported histology concerns pancreatic cystic and pseudopapillarytumor,3 pancreatic glucagonoma,4 duodenal endocrine tumor,5 as well as acinar cell carcinoma (ACC).6,7 Among the patients observed in our unit from 1990 to 2009, we interestingly never identified a classical exocrine pancreatic carcinoma in a cohort of 127 patients
I
with FAP undergoing regular clinical evaluation as well as upper and lower endoscopic follow-up (data not shown). We report 4 cases of primary pancreatic tumors, all of unusual histology, observed in a tertiary reference center cohort of patients with FAP (Table 1). Histologically, all of these tumors were rare tumors, including 2 endocrine carcinomas, 1 ACC, and 1 pancreatoblastoma. Pancreatic endocrine tumors account for less than 1% of all pancreatic neoplasms. Acinar cell carcinoma constitutes a phenotypically and genotypically different entity from ductal adenocarcinoma and endocrine tumors. The morphological, immunohistochemical, and clinical features of ACC overlap with those of pancreatoblastoma, which is another rare pancreatic neoplasm (Fig. 1).8 We cannot be sure that these pancreatic tumors were related to the FAP disease. Indeed, we did not perform somatic adenomatous polyposis coli (APC) gene analysis in the 4 tumors described, as has been reportedin1patientwithapancreatoblastoma.9 Such analysis, by showing the invalidation of the second APC allele by a somatic event, would be an important argument on favor of the responsibility of the APC gene germ line mutation in pancreatic tumor occurrence in
patients with FAP. However, given the lack of exocrine adenocarcinoma identified in our experience and in the literature,1 the reported increased risk for pancreatic tumor in patients with FAP supposes that germ line APC mutation could favor the development of atypical pancreatic tumors more than in exocrine carcinoma. In view of the low prevalence of pancreatic cancer in patients with FAP, the scarcity of published data, and the high difficulty of pancreatic surveillance for neoplasia, no recommended pancreatic surveillance in patients with FAP could be elaborated and there will probably never be. Complex surveillance protocols including computed tomography scan, magnetic resonance imaging, and ultrasonography have been advocated in other genetic syndromes, such as hereditary pancreatitis, Peutz-Jeghers syndrome, familial pancreatic cancer, with much higher (up to 30%40%) cumulative risk for developing pancreatic exocrine cancer.10 The only recommendation could be careful clinical examination at least every year to detect any early symptom. Interestingly, all but 1 patient described in this series had long survival, with 2 patients being considered in complete remission for more than 5 years.
TABLE 1. Characteristics of Patients Age of Age, Age of FAP Pancreatic Case Sex y Diagnosis Cancer, y 1
M
63
23
63
2
M
22
22
22
3
M
63
35
53
4
M
35
25
35
Symptoms
Localization and Size Histology
Jaundice Pancreatic PDNEC, large 6 y after head/ cell type ampullectomy 40 mm Abdominal Pancreatic PDNEC, small pains head/ cell type 120 mm Abdominal Pancreatic ACC pains isthmus/ 25 mm Acute pancreatitis
Immunostain SP+, C-A+
SP+, C-A+
Treatment
Follow-up
PD and CT Alive 9 y after for liver 3 CT lines metastasis (liver metastasis) 4 CT lines Died 2 y after diagnosis
Cytokeratin+, Total PD and No evolution trypsin+, α1antrectomy 10 y after antitrypsin+, surgery SP-, C-APancreatic Pancreatoblastoma SP-, C-APD No evolution isthmus/ 5 y after 60 mm surgery
ACC, acinar cell carcinoma; C-A, chromogranin A; CT, chemotherapy; PD, pancreaticoduodenectomy; PDNEC, poorly differentiated neuroendocrine carcinoma; SP, synaptophysin.
512
www.pancreasjournal.com
Pancreas • Volume 44, Number 3, April 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pancreas • Volume 44, Number 3, April 2015
Letter to the Editor
Thomas Walter, MD, PhD Catherine Lombard-Bohas, MD Jean-Christophe Saurin, MD, PhD Department of Gastroenterology Edouard Herriot Hospital Lyon, France
REFERENCES
FIGURE 1. Histological and immunohistochemical features in cases 1, 2, and 3. In patient 1, the tumor is formed by masses of large, basophilic cells (A; hematoxylin and eosin staining, original magnification, 250), focally expressing chromogranin A (B; immunoperoxidase, original magnification, 210). In patient 2, the tumor has the typical appearance of neuroendocrine carcinoma, which is a small cell type (C; hematoxylin and eosin staining, original magnification, 190). In patient 3, the tumor is formed by acinar and glandular structures lined by cells expressing trypsin, mainly as extracellular deposits (D; immunoperoxidase, original magnification, 200).
The authors declare no conflict of interest. Driffa Moussata, MD, PhD
Francoise Berger, MD, PhD Department of Pathology Lyon Sud Hospital Pierre Bénite, France
Department of Gastroenterology Lyon Sud Hospital Pierre Bénite, France [email protected]
Jean-Yves Scoazec, MD, PhD
Leila Senouci, MD
Stephane Pinson, MD, PhD
Department of Gastroenterology Lyon Sud Hospital Pierre Bénite, France
Department of Genetic Edouard Herriot Hospital Lyon, France
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Department of Pathology Edouard Herriot Hospital Lyon, France
1. Giardiello FM, Offerhaus GJ, Lee DH, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993;34:1394–1396. 2. Gupta C, Mazzara PF. High-grade pancreatic intraepithelial neoplasia in a patient with familial adenomatous polyposis. Arch Pathol Lab Med. 2005;129:1398–1400. 3. Le Borgne J, Bouvier S, Fiche M, et al. Cystic and papillary tumor of the pancreas: diagnostic and developmental uncertainties. Apropos of a case. Chirurgie. 1997;122:31–34. 4. Stewart CJ, Imrie CW, Foulis AK. Pancreatic islet cell tumour in a patient with familial adenomatous polyposis. J Clin Pathol. 1994;47: 860–861. 5. July LV, Northcott KA, Yoshida EM, et al. Coexisting carcinoid tumors in familial adenomatous polyposis-associated upper intestinal adenomas. Am J Gastroenterol. 1999; 94:1091–1094. 6. Le Borgne J, Audoin AF, Dupas B, et al. Pancreatic cancer with acinar cells. Apropos of 1 case with immunocytochemical study. Chirurgie. 1989;115:322–327. 7. Seket B, Saurin JC, Scoazec JY, et al. Pancreatic acinar cell carcinoma in a patient with familial adenomatous polyposis. Gastroenterol Clin Biol. 2003;27:818–820. 8. Karagianopoulou G, Noussios G, Katsourakis A, et al. Acinar cell carcinoma of the pancreas: a case report and review of the literature. Acta Chir Belg. 2011;111:319–322. 9. Abraham SC, Wu TT, Klimstra DS, et al. Distincitve molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas: frequent alterations in the APC/beta-catenin pathway and chromosome 11p. Am J Pathol. 2001;159:1619–1627. 10. Canto MI, Goggins M, Yeo CJ, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004;2:606–621.
www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
513
