|Year : 2012 | Volume
| Issue : 2 | Page : 289-291
Incidental cystic endocrine tumor of the pancreas: A case report with immunohistochemical study
Sanjay D Deshmukh1, Harveen K Gulati1, Vandana Gaopande1, Snehal Purandare2, Mani Anand1
1 Department of Pathology, Smt. Kashibai Medical College and General Hospital, Narhe, Pune - 410041, India
2 Department of Surgery, Smt. Kashibai Medical College and General Hospital, Narhe, Pune - 410041, India
|Date of Web Publication||26-Jul-2012|
Harveen K Gulati
Department of Pathology, Smt Kashibai Medical College and General Hospital, Narhe, Pune-410041
A large cystic lesion in the pancreatic tail was found incidentally in a 20-year-old female during laparoscopic cholecystectomy. Pre-operative work up had revealed calculi in gall bladder and in addition, a cystic lesion in pancreas suggesting the possibility of a pseudocyst. A laparoscopic enucleation of the cyst was performed along with the removal of gallbladder. Microscopic examination of the resected specimen revealed a pancreatic cystic endocrine tumor; however, this tumor had produced no symptoms. Immunohistochemical studies of the tumor cells showed positivity for neuron-specific enolase, chromogranin A, and synaptophysin indicating their neuroendocrine nature. Prognostic markers (CK19, CD10 and Ki67) indicated good prognosis. Although endocrine tumors of the pancreas are usually solid, cystic change occurs only rarely and such tumors should be considered in the differential diagnosis of patients who have a cystic lesion in the pancreas in view of their rare transformation into a malignant tumor.
Keywords: Cystic neuroendocrine tumors, pancreatic endocrine tumor, immunohistochemistry
|How to cite this article:|
Deshmukh SD, Gulati HK, Gaopande V, Purandare S, Anand M. Incidental cystic endocrine tumor of the pancreas: A case report with immunohistochemical study. J Can Res Ther 2012;8:289-91
|How to cite this URL:|
Deshmukh SD, Gulati HK, Gaopande V, Purandare S, Anand M. Incidental cystic endocrine tumor of the pancreas: A case report with immunohistochemical study. J Can Res Ther [serial online] 2012 [cited 2014 Sep 2];8:289-91. Available from: http://www.cancerjournal.net/text.asp?2012/8/2/289/98992
| > Introduction|| |
Neuroendocrine tumors of the pancreas are uncommon with an incidence of 1/1,000,000 population per year.  Cystic degeneration in pancreatic endocrine tumors (PETs) are even rarer and account for 2-10% of all pancreatic endocrine tumors.  These tumors are known to occur in two different settings: firstly, sporadic, presenting in sixth and seventh decade of life and secondly in association with MEN-1, presenting in younger patients with multiple tumors.  These are often non-functional tumors and pose a difficult problem in preoperative diagnosis as they are asymptomatic, secrete no tumor markers and have no specific radiological signs. Untill 2001, Ligneau et al found approximately 50 cases of cystic PETs (CPET).  On reviewing the literature, only a few series of cystic PET have been reported. , However, it must be mentioned that non functioning CPETs are documented mostly as single case reports and we believe that less than 80 cases of sporadic non functioning CPETs are documented so far. ,,
We present a case of a 20-year-old woman in whom the tumor was discovered incidentally, during the workup for calculus cholecystitis and was diagnosed radiologically as a pseudo-pancreatic cyst in the distal end of the pancreas. Histopathological and immunohistochemical studies from the cyst wall showed a benign tumor with small nests of endocrine cells. The extreme rarity of this lesion has prompted us to report this case.
| > Case Report|| |
A 20-year-old lady presented with pain in abdomen and dyspepsia. General and physical examination were unremarkable. She had past history of repeated bouts of upper abdominal pain off and on which was relieved by medication by local practitioners. On radiological, ultrasonography (USG) and computed tomography (CT) scan examination, gallbladder was distended with no wall thickening and two to three calculi. Apart from this, a 6.5 × 5.4 × 5.2 cm thin walled cystic lesion was noted in the tail region of pancreas in the stomach bed along with hyperdense calcified focus in the head and uncinate process of pancreas. Also seen was mild prominence of pancreatic duct (5 mm) in the head region. On the basis of the above findings, the radiologist reported it as suggestive of chronic pancreatitis with pseudo-pancreatic cyst and advised pathological correlation [Figure 1]. No abdominal lymphadenopathy was noted. The patient was taken up for laparoscopic removal of gallbladder and the pancreatic cyst. Intraoperatively, a large cyst was seen located posterior to the stomach in retroperitoneum and was intimately related to the tail of pancreas. The cyst could be enucleated and cyst fluid was aspirated which was dirty brownish in color. The collapsed cyst was then delivered via left hypochondrial port.
|Figure 1: CT scan of abdomen showing 6.5 × 5.4 × 5.2 cm thin walled cystic lesion in the tail of pancreas (arrow)|
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We received a cut open collapsed single cystic structure measuring 6.5 cm in largest diameter. Inner surface was rough and showed tiny protrusions. On histopathological examination, the sections from the cyst wall showed collagen rich fibrous tissue in which were embedded small clusters and nests of round cells. The cells were monotonous, small to medium in size with amphophilic cytoplasm with indistinct cell borders. The nucleus showed typical stippled nuclear chromatin and no mitoses were noted [Figure 2]. The cyst wall on luminal side revealed degenerative changes in the form of hemosiderin-laden macrophages, focal calcification and cholesterol clefts with giant cell reaction. However, no capsular invasion was observed. With the above findings, a diagnosis of benign unilocular macrocystic pancreatic endocrine tumor was offered. Neuroendocrine nature of these round cells was confirmed by performing immunohistochemistry (IHC) with neurone specific enolase (NSE), synaptophysin and chromogranin. Further IHC was performed to predict the prognosis with immune markers CD10, cytokeratin (CK) 19 which were negative and Ki67 which stained < 5% of the cells [Figure 3]. These findings corroborated the benign nature of the disease indicating a very good prognosis.
|Figure 2: Photomicrograph showing cyst wall with collagen rich fi brous tissue in which are embedded small nests of round cells (H and E 100×). Inset shows high power view (H and E 400×) of these cells with amphophilic cytoplasm and stippled nuclear chromatin|
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|Figure 3: Immunohistochemical staining of the tumor cells showing positivity for synaptophysin (a), chromogranin (b) and NSE (c) and negativity for CK 19 (e) and CD10 (f). Ki 67 immunostain (d) is showing|
staining in <5% of the cells
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In view of the pancreatic cyst being diagnosed as a neuroendocrine tumor, subsequently detailed medical history, physical examination, serum hormone levels and radiological investigations were done, which were non-contributory. MEN-1 syndrome was also excluded. Hyperparathyroidism was excluded by serum calcium levels, X-ray KUB region, radiological skeletal survey and USG of neck. Pituitary tumor was excluded by CT scan of head and serum prolactin levels. The patient was followed up for six months without any complications.
| > Discussion|| |
Owing to improved abdominal imaging, cystic lesions of pancreas are being diagnosed more frequently out of which majority (>90%) comprise inflammatory pseudocyst, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm and serous cystadenoma.  However rarely, pancreatic endocrine tumors (PETs), acinar cell carcinoma and pancreatic ductal adenocarcinoma can undergo cystic degeneration primarily.  The incidence of cyst formation in PETs is limited to <2% and is more commonly (3.5 times) associated with MEN-1 syndrome cases than in sporadic cases. [2,5]
Our case was a 20-year-old female who was much younger than the mean age in the sixth decade as reported in other studies. ,, It should be noted that, like our case, most non-syndromic cystic PETs are non functional and have normal serum hormone levels. ,,, These tumors are located in body and tail and show a hypervascular rim surrounding the tumor on radiologic imaging. , The tumor in our case was located in the tail region and on review of the CT scan after the histologic diagnosis, the cyst was found to have a hypervascular rim. The size of tumor in our case (65mm) was much larger than the median size documented by other workers (25-35mm). ,, As suggested by Charfi et al, the larger size in the present case may represent cystic degeneration secondary to hemorrhage and necrosis in large solid pancreatic endocrine tumors.  This hypothesis is further supported by the fact that the cyst contained hemorrhagic fluid and had hemosiderin-laden macrophages in the wall.
Two different subtypes of the tumor have been reported in literature based on gross and histologic appearances.  Most reported cases are of macrocystic subtype which are unilocular containing clear or hemorrhagic fluid with cyst wall showing small nests of tumor cells as was in the present case. , The microcystic subtype on the other hand have multiple fluid filled cysts lined by neuroendocrine cells with intervening solid areas containing similar cells in trabeculovescicular architecture.  No prognostic significance has been attributed to this morphologic classification till now. Our case was found to be positive for NSE, synaptophysin and chromogranin confirming the neuroendocrine nature of these cells. ,, Since, prediction of behavior of PETs based solely on clinicopathologic findings is difficult, a number of studies have attempted to predict the outcome of these tumors based on immunohistochemical markers. ,,, Negativity of markers like CK 19 and CD10 coupled with low Ki-67 index is an indicator of good behavior as was seen in our case. ,, However, other markers like epidermal growth factor receptor (EGFR) and transforming growth factor (TGF) showed no correlation with behavior of PETs. 
The treatment of these tumors mainly includes pancreatic resections (total, partial, proximal and distal) in most cases as the preoperative diagnosis was suggested on radiological examination; however, enucleation has been suggested as a treatment modality by Ligneau et al. especially in cases associated with MEN-1 syndrome. ,, To conclude, although cystic pancreatic endocrine tumor is a rare entity, it should be considered in the differential diagnosis of cystic pancreatic lesions and treated by partial pancreatic resection in view of a rare event of its transformation into a malignant tumor.  It must be noted that with the advances in imaging and immunohistochemical analysis, many centres will elucidate more on this rare neoplasm.
| > References|| |
|1.||Breysem L, Kersemans P, Vanbeckevoort D, Ectors N, Smet MH. Nonfunctioning neuroendocrine tumor of the pancreas in an 8-year-old girl. JBR-BTR 2007;90:528-31. |
|2.||Boninsegna L, Partelli S, D'Innocenzio MM, Capelli P, Scarpa A, Bassi C, et al. Pancreatic Cystic Endocrine Tumors: A different morphological entity associated with a less aggressive behaviour. Neuroendocrinology 2010;92:246-51. |
|3.||Charfi S, Marcy M, Bories E, Pesanti C, Caillol F, Giovannini M, et al. Cystic pancreatic endocrine tumors: An endoscopic Ultrasound-guided Fine-Needle Aspiration Biopsy with histologic correlation. Cancer 2009;117:203-10. |
|4.||Ligneau B, Lombard-Bohas C, Partensky C, Valette PJ, Calender A, Dumortier J, et al. Cystic endocrine tumors of the pancreas: Clinical, radiologic, and histopathologic features in 13 cases. Am J Surg Pathol 2001;25:752-60. |
|5.||Deshpande V, Lauwers GY. Cystic pancreatic endocrine tumors: A variant commonly confused with cystic adenocarcinoma. Cancer 2007;111:47-53. |
|6.||Brugge WR, Lewandrowski K, Lee-Lewandrowski EL, Centeno BA, Szydlo T, Regan S, et al. Diagnosis of Pancreatic Cystic Neoplasms: A report of the Cooperative Pancreatic Cyst Study. Gastroenterology 2004;126:1330-6. |
|7.||Ali A, Serra S, Asa SL, Chetty R. The predictive value of CK 19 and CD99 in pancreatic endocrine tumors. Am J Surg Pathol 2006;30:1588-94. |
|8.||Deschamps L, Handra-Luca A, O'Toole D, Sauanet A, Ruszniewski P, Belghiti J, et al. CD10 expression in pancreatic endocrine tumors: Correlation with prognostic factors and survival. Hum Pathol 2006;37:802-8. |
|9.||Jorda M, Ghorab Z, Fernandez G, Nassiri M, Hanly A, Nadji M. Low nuclear proliferative activity is associated with nonmetastasic islet cell tumors. Arch Pathol Lab Med 2003;127:196-9. |
|10.||Shrivastava A, Alexander J, Lomakin I, Dayal Y. Imunohistochemical expression of transforming growth factor and epidermal growth factor receptor in pancreatic endocrine tumors. Hum Pathol 2001;32:1184-9. |
[Figure 1], [Figure 2], [Figure 3]