Anatomic Pathology / E-Cadherin/β-Catenin and CD10 in Pancreatic Neoplasms

Pancreatic endocrine neoplasm (PEN) and solid pseudopapillary neoplasm of the pancreas (SPN) frequently pose diagnostic challenges. We sought to determine which markers could provide the best immunophenotypic characterization of PEN and SPN, allowing separation on limited cytology samples. We retrieved 22 resected PEN (n = 12) and SPN (n = 10) tumors to serve as a training set for the performance of extensive immunohistochemical staining. Based on these results, we selected a subset of antibodies for application to 25 fine-needle aspiration (FNA) samples from PEN (n = 16) and SPN (n = 9). Chromogranin A, synaptophysin, CD56, and progesterone receptor (PR) highlighted PEN cases in the training set; E-cadherin was noted in a membranous pattern. SPN cases were most immunoreactive for α1-antitrypsin, vimentin, CD10, and PR, with nuclear staining for β-catenin; E-cadherin did not show a membranous pattern. Among all FNA samples tested, the immunohistochemical staining of E-cadherin (P = .0003), β-catenin (P = .00004), and CD10 (P = .00006) demonstrated the greatest difference between PEN and SPN. The pattern of E-cadherin/β-catenin expression was highly specific for distinguishing PEN from SPN. On limited FNA samples, the characteristic expression of E-cadherin/β-catenin and the expression of CD10 can be used to distinguish PEN from SPN. The origin of solid pseudopapillary neoplasm of the pancreas (SPN) remains largely unknown. This tumor has a predilection for young females and is usually located in the head or tail of the pancreas.1-4 Abdominal pain is the most common presenting clinical symptom,1 with other signs and symptoms including nausea, vomiting, fever, weight loss, and jaundice. This tumor is often found incidentally via imaging studies. Radiologically, this tumor exhibits solid and cystic areas, often with areas of hemorrhage.5 SPN can have a radiologic appearance and clinical features that overlap with pancreatic pseudocyst and radiologic/cytologic appearances that overlap with other pancreatic neoplasms, including acinar cell carcinoma, mucinous neoplasms, and pancreatic endocrine neoplasm (PEN).6-9 It is, therefore, important to establish a preoperative diagnosis of SPN because these tumors exhibit a different biologic behavior, and their management protocols may differ accordingly. Fine-needle aspiration (FNA) has been proven as a useful method for diagnosing pancreatic lesions.10,11 The cytomorphologic features of SPN and PEN have been described.8,12-16 However, their distinction in cytologic samples can be challenging owing to overlapping diagnostic features.12 In such circumstances, ancillary stains can provide much needed supportive evidence. Many studies have used a large number of stains to document an immunohistochemical profile associated with SPN and PEN.4,17-19 Review of these immunophenotypic patterns shows that SPN and PEN can have overlapping immunohistochemical staining patterns. Specifically, SPN Upon completion of this activity you will be able to: • describe the characteristic cytologic features of solid pseudopapillary neoplasm of the pancreas (SPN) and its differential diagnosis. • define the demographic profile in which SPN is most often identified. • list possible methods for obtaining tissue samples from a pancreatic mass. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit TM per article. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 972. Exam is located at www.ascp.org/ajcpcme. Downloaded from https://academic.oup.com/ajcp/article-abstract/132/6/831/1760451 by guest on 26 July 2018 832 Am J Clin Pathol 2009;132:831-839 832 DOI: 10.1309/AJCPVT8FCLFDTZWI © American Society for Clinical Pathology Burford et al / E-Cadherin/β-Catenin and CD10 in Pancreatic Neoplasms has been noted to demonstrate neuroendocrine differentiation on immunohistochemical stains and on electron microscopic studies.20-23 Thus, relying only on evidence of neuroendocrine differentiation on cytologic samples can lead to diagnostic errors. To add to this dilemma, often FNA samples do not have enough cellularity to perform a large battery of immunohistochemical stains. Therefore, antibodies need to be chosen judiciously to best use limited cytologic material to distinguish among these morphologic mimickers. This study was undertaken with an objective to identify the minimum number of immunohistochemical “stains” that can best distinguish SPN from PEN on FNA samples. Materials and Methods In an effort to determine the ideal number of antibodies best suited to distinguish SPN from PEN with a limited amount of clinical material, we used a 2-step approach. We used resected sections to perform immunohistochemical analyses based on the published literature and our own experience. Following that, we used a smaller panel of reagents on cytologic samples to determine those that could best distinguish SPN from PEN.

[1]  S. Serra,et al.  Membrane loss and aberrant nuclear localization of E‐cadherin are consistent features of solid pseudopapillary tumour of the pancreas. An immunohistochemical study using two antibodies recognizing different domains of the E‐cadherin molecule , 2008, Histopathology.

[2]  S. Jang,et al.  Loss of E-cadherin and cytoplasmic-nuclear expression of beta-catenin are the most useful immunoprofiles in the diagnosis of solid-pseudopapillary neoplasm of the pancreas. , 2008, Human pathology.

[3]  G. Stamp,et al.  E-cadherin/Catenin Complex Status in Solid Pseudopapillary Tumor of the Pancreas , 2008, The American journal of surgical pathology.

[4]  A. Sauvanet,et al.  Impaired E-Cadherin Expression and Glutamine Synthetase Overexpression in Solid Pseudopapillary Neoplasm of the Pancreas , 2008, Pancreas.

[5]  G. Siegal,et al.  Solid Pseudopapillary Tumor of the Pancreas: A Review of Salient Clinical and Pathologic Features , 2008, Advances in anatomic pathology.

[6]  M. Machado,et al.  Solid pseudopapillary neoplasm of the pancreas: distinct patterns of onset, diagnosis, and prognosis for male versus female patients. , 2008, Surgery.

[7]  V. Deshpande,et al.  Endoscopic ultrasound‐guided fine needle aspiration cytology of the pancreas: a morphological and multimodal approach to the diagnosis of solid and cystic mass lesions , 2007, Cytopathology : official journal of the British Society for Clinical Cytology.

[8]  G. Siegal,et al.  Fine-Needle Aspiration: A Powerful Modality in the Preoperative Diagnosis of Solid Pseudopapillary Neoplasm of the Pancreas , 2007 .

[9]  Jingwu Xie,et al.  Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of pancreas , 2007, Modern Pathology.

[10]  S. Serra,et al.  Nuclear expression of E-cadherin in solid pseudopapillary tumors of the pancreas. , 2007, JOP : Journal of the pancreas.

[11]  D. Klimstra Nonductal neoplasms of the pancreas , 2007, Modern Pathology.

[12]  G. Siegal,et al.  Solid-pseudopapillary neoplasm of the pancreas: Three cases with a literature review. , 2006, Applied immunohistochemistry & molecular morphology : AIMM.

[13]  B. Savaş,et al.  Solid pseudopapillary tumor of the pancreas: emphasis on differential diagnosis from aggressive tumors of the pancreas. , 2006, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology.

[14]  R. Bardales,et al.  Cytology of pancreatic acinar cell carcinoma , 2006, Diagnostic cytopathology.

[15]  Shi-zheng Zhang,et al.  Solid-pseudopapillary tumor of the pancreas: CT and MRI features of 3 cases. , 2006, Hepatobiliary & pancreatic diseases international : HBPD INT.

[16]  H. Lai,et al.  Malignant solid and pseudopapillary tumor of the pancreas--clinicohistological, immunohistochemical, and flow cytometric evaluation. , 2006, Hepato-gastroenterology.

[17]  I. Ramzy,et al.  Cytological diagnosis of endocrine tumors of the pancreas by endoscopic ultrasound‐guided fine‐needle aspiration biopsy , 2005, Diagnostic cytopathology.

[18]  R. Bardales,et al.  Pitfalls in Endoscopic Ultrasound-Guided Fine-Needle Aspiration and How to Avoid Them , 2005, Advances in anatomic pathology.

[19]  W. Nealon,et al.  Clinical, imaging, and cytopathological features of solid pseudopapillary tumor of the pancreas: A clinicopathologic study of three cases and review of the literature , 2005, Diagnostic cytopathology.

[20]  Marino E. Leon,et al.  Fine‐needle aspiration of adult small‐round‐cell tumors studied with flow cytometry , 2004, Diagnostic cytopathology.

[21]  R. Bardales,et al.  Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of solid-pseudopapillary tumor of the pancreas: a rare neoplasm of elusive origin but characteristic cytomorphologic features. , 2004, American journal of clinical pathology.

[22]  I. Eltoum,et al.  Endoscopic ultrasound-guided fine-needle aspiration. A cytopathologist's perspective. , 2003, American journal of clinical pathology.

[23]  V. Canzonieri,et al.  Solid pseudopapillary tumour of the pancreas. , 2003, The Lancet. Oncology.

[24]  S. Pambuccian,et al.  Solid‐pseudopapillary tumor of the pancreas: A neoplasm with distinct and highly characteristic cytological features , 2002, Diagnostic cytopathology.

[25]  I. Eltoum,et al.  Fine needle aspiration biopsy of the islet cell tumor of pancreas: a comparison between computerized axial tomography and endoscopic ultrasound-guided fine needle aspiration biopsy. , 2002, Annals of diagnostic pathology.

[26]  N. Nagahara,et al.  Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm. , 2001, Cancer research.

[27]  D. Klimstra,et al.  Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential. , 2000, Seminars in diagnostic pathology.

[28]  M. Zakowski,et al.  Comparative cytologic features of pancreatic acinar cell carcinoma and islet cell tumor , 1997, Diagnostic cytopathology.

[29]  G. Pelosi,et al.  Solid and cystic papillary neoplasm of the pancreas: A clinico‐cytopathologic and immunocytochemical study of five new cases diagnosed by fine‐needle aspiration cytology and a review of the literature , 1995, Diagnostic cytopathology.

[30]  F. Konishi,et al.  Papillary‐cystic neoplasm of the pancreas. A clinicopathologic study concerning the tumor aging and malignancy of nine cases , 1990, Cancer.