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CORRESPONDENCE
Year : 2015  |  Volume : 11  |  Issue : 8  |  Page : 280-282

Pancreatic neuroendocrine carcinoma diagnosed using endoscopic ultrasound-guided fine needle aspiration: A case report and literature review


Department of Gastroenterology, Wuhan Central Hospital, Wuhan 430014, China

Date of Web Publication26-Nov-2015

Correspondence Address:
Jie Wu
Department of Gastroenterology, Wuhan Central Hospital, No. 26 Shengli Road, Wuhan 430014
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.170535

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 > Abstract 

Pancreatic neuroendocrine carcinoma (NEC) is a rare pancreatic neoplasm. In this study, we report the case of a 67-year-old male who was admitted with epigastric pain, which began during the previous week. The planar imaging of the magnetic resonance imaging sequence detected oval shapes in the neck and tail of the pancreas. Endoscopic ultrasonography showed low-echo lumps at these sites. Endoscopic ultrasound-guided fine needle aspiration was performed on the pancreatic masses. Pathology results indicated that the tissue taken from the pancreas was consistent with small cell NEC. We also review the current published literature on pancreatic NEC.

Keywords: Endoscopic ultrasonography, endoscopic ultrasound-guided fine needle aspiration, pancreatic neuroendocrine carcinoma


How to cite this article:
Shi G, Sun C, Sun L, Ren H, Song Q, Wu J. Pancreatic neuroendocrine carcinoma diagnosed using endoscopic ultrasound-guided fine needle aspiration: A case report and literature review. J Can Res Ther 2015;11, Suppl S4:280-2

How to cite this URL:
Shi G, Sun C, Sun L, Ren H, Song Q, Wu J. Pancreatic neuroendocrine carcinoma diagnosed using endoscopic ultrasound-guided fine needle aspiration: A case report and literature review. J Can Res Ther [serial online] 2015 [cited 2019 Sep 17];11:280-2. Available from: http://www.cancerjournal.net/text.asp?2015/11/8/280/170535


 > Introduction Top


Pancreatic neuroendocrine carcinoma (NEC) is a rare neoplasm. It accounts for only 1–2% of all pancreatic neoplasms. This neoplasm often grows slowly but shows a high degree of malignancy. The lack of any specific clinical manifestation makes a preoperative diagnosis of pancreatic NEC difficult. We report a case of pancreatic NEC diagnosed by endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA).


 > Case Report Top


A 67-year-old male patient was admitted with intermittent dull epigastric pain, radiating to his back, which began 1 week earlier; there was no obvious cause of pain. Physical examination found that the abdomen was flat and soft. Abdominal palpation was slightly painful in the epigastric area. Neither rebound pain nor any abdominal mass was found by palpation. The patient had been hypertensive for 1 year but had not received any medical treatment. His blood pressure fluctuated between 160/90 mmHg and 205/120 mmHg. In 2006, the patient underwent a colectomy on the left half of his colon and lymph node dissection for colon cancer. There was no retroperitoneal lymph node enlargement on computerized tomography (CT) reexamination 6 months postsurgery. Upon admission, the planar imaging of the magnetic resonance imaging (MRI) sequence showed oval-shaped images in the neck and tail of the pancreas. The diameter of the round shadow measured up to 3.0 cm. Some of the signal shades showed unclear boundaries. Enhanced CT scanning showed annular enhancement in the lesions on the neck and tail of the pancreas and enlarged retroperitoneal lymph nodes behind the pancreas [Figure 1]a. Laboratory examination results were as follows: CA125, 38.2 u/mL; serum amylase, 550 u/L; serum lipase, 960 u/L; and levels of CA19-9, CA15-3, alpha-fetoprotein, and carcinoembryonic antigen were within the normal range. EUS showed a 32 mm × 29 mm low-echo lump in the neck of the pancreas [Video #1], and a 33 mm × 16 mm lump in the body of the pancreas [Video #2]. Echo in the lumps was heterogeneous, and the lump boundaries were ragged. The main pancreatic duct was slightly enlarged (diameter, 4 mm); [Figure 1]b. EUS-FNA was performed on the lesion on the neck of the pancreas using a Cook Echo-3-22 needle [Video #1], and a sample of the mass was biopsied [Figure 1]c. Following the aspiration, the patient did not report any significant discomfort. Pathology results indicated that the features of the tissue taken from the neck of pancreas were consistent with small cell NEC. Immunohistochemistry staining for CD99, protein kinase C, cytokeratin (CK) 8/18, and CD56 was positive. Staining for CgA and SyN was weakly positive. Staining for other markers including vimentin, CD10, CA199, and CK19 was negative. The Ki-67 labeling index was approximately 60% [Figure 1]d. Thus, the diagnosis was confirmed clinically as pancreatic cancer. The patient was transferred to the Department of Oncology to undergo conservative chemotherapy instead of surgery.
Figure 1: (a) Enhanced computerized tomography scan showing annular enhancement in the lesions on the neck and tail of the pancreas and enlarged retroperitoneal lymph nodes behind the pancreas. (b) Endoscopic ultrasonography showing a low-echo lump in the pancreas neck. Echo in the lumps is inhomogeneous, and the lump boundaries are ragged. (c) Endoscopic ultrasound-guided fine needle aspiration in the neck of the pancreas. (d) Pathological examination showing pancreatic cells overlapping with each other. Combined with immunohistochemistry, this is consistent with small cell neuroendocrine carcinoma

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 > Discussion Top


A neuroendocrine neoplasm (NEN) is a heterogeneous neoplasm that originates in the neuroendocrine system. In 2010, WHO published a new nomenclature and classification system for NENs of the digestive system. In the new system, a well-differentiated NEN (Ki-67 <20%) is defined as a neuroendocrine tumor; it is classified as either a Grade 1 (G1) or Grade 2 (G2) NEN and as carcinoid. On the other hand, a poorly differentiated NEN is termed an NEC; it is defined as a Grade 3 (G3) NEN and includes small cell NEC, large cell NEC, and poorly differentiated NEC.[1] Pancreatic NEC is a rare occurrence; it is an NEC that originates in gastrointestinal cells that are involved in amine precursor uptake and decarboxylation.[2] It accounts for only 1–2% of pancreatic neoplasms.[3] This type of neoplasm often grows slowly but shows a high degree of malignancy. In addition, the lack of a specific clinical manifestation makes preoperative diagnosis even more difficult. According to a study by Halfdanarson et al., the morbidity of pancreatic NEC in the USA is as low as 22/1,000,000.[4] The percentage accounts for in all pancreatic carcinomas is rising.

Due to its slow growth, the clinical manifestations of pancreatic NEC are highly diverse. In some cases, the carcinoma may secret gastrin, 5-hydroxytryptamine, substance P, and endorphins. Carcinoid syndrome can be induced by excessive hormone secretion.[5] In our reported case, the patient had no previous history of hypertension, but he had been hypertensive for more than 1 year. His blood pressure was between 160/90 and 205/120 mmHg, although there were no obvious predisposing causes. It is possible that hormone secretion by the pancreatic NEC may have induced this hypertension.

Homogeneous, annular, or heterogeneous enhancement can be observed on enhanced CT scans of pancreatic NEC. Blood vessels often show high-intensity signals on CT and MRI scans, but low-intensity signals are more homogeneous and nonspecific.[6] Therefore, it is difficult to distinguish pancreatic NEC from other pancreatic neoplasms using only iconographic methods such as CT and MRI. On EUS imaging, pancreatic NEC usually exhibits low-echo heterogeneous lumps of irregular shape inside the pancreas. Since pancreatic NEC is a hypervascular neoplasm, many low-velocity and low resistance blood flow signals are observed with color Doppler flow imaging. However, based on our experience, pancreatic NEC and pancreatic NEN are not easily distinguishable using only EUS imaging. An additional EUS-FNA is an effective way to distinguish between them. Since it was first described by Chatzipantelis et al. in 2008,[7] EUS-FNA combined with immunohistochemical and cytological examinations has provided accurate preoperative diagnoses for most pancreatic NEC patients. EUS-FNA is often the preferred technique for tissue acquisition in the diagnosis of suspected intrathoracic and intra-abdominal pathologies.[8],[9],[10] EUS-FNA achieves similar accuracy to US-FNA in the diagnosis of pancreatic masses, but with a lower complication rate.[11] The patient in this report has also benefited from this method. Over the past 2 years, EUS-FNA has been successfully performed in our department on patients with lesions of the mediastinum, pancreas, and other organs neighboring the digestive ducts. The cancer detection rate can be up to 90% with this technique. It is important to note that the needle size can affect the diagnostic accuracy of EUS-FNA.[12] We usually use a fine 22 G needle to perform EUS-FNA. Compared with thoracoscope- or laparoscope-guided surgical biopsies and surface ultrasound-guided biopsy, EUS-FNA can show otherwise undetectable lesions on surface ultrasound. This is because the ultrasound probe can get closer to the lesion location in EUS. In addition, it results in fewer complications since the needle penetrates fewer tissues and organs, inflicting far less collateral damage.[13] Recent guidelines on EUS-FNA published by the European Society of Gastrointestinal Endoscopy address the technique and its complications. Regarding pancreatic lesions, they focus on the incidence of acute pancreatitis after EUS-FNA, which ranges from 0.26% to 2%.[14] Moreover, high ultrasound frequency (5–10 MHz) in EUS has made the vertical and horizontal resolutions significantly higher than those of surface ultrasound. An experienced operator can perform an accurate centesis on a small lesion, the diameter of which may be <5 mm. The accuracy of EUS-FNA in percutaneous centesis exceeds that guided by any other current imaging techniques.[15] Sample processing and sample interpretation can also influence the diagnostic accuracy of FNA.[9] Diagnosis can be confirmed by pathological examination after EUS-FNA on the pancreas, along with immunohistochemical tests on neuroendocrine cell markers such as CgA, neuron-specific enolase and synaptophysin, and other common endocrine hormones in the pancreas. The patient in this report was diagnosed with small cell NEC. The diagnosis was confirmed by high-grade pancreatic cancer with positive CgA and SyN staining, and a Ki-67 index of 60%.

Pancreatic NEC is characterized as a high-grade malignancy in which the tumor size is often >2 cm 3. The carcinoma can invade into the duodenum, common bile duct, and retroperitoneal vascular structures. It is usually accompanied by lymph node metastasis. Distant metastasis can be seen in the liver, stomach, and spleen. Most patients present with middle- or late-stage disease at diagnosis and the prognosis is generally not optimistic.[16] The 5-, 10-, and 20-year survival rates are 33%, 17%, and 10%, respectively.[17] Surgery is the main treatment option for pancreatic NEC. The extent of the resection depends on the location of the neoplasms and metastasis. Radical excision of the tumor is the preferred outcome of the resection.[18] Metastatic carcinoma is not a surgical contraindication. Surgical removal of the primary tumor and metastasis as completely as possible, combined with comprehensive postsurgery therapy can usually improve the prognosis.[19]

Financial support and sponsorship

The Clinical Research Funded Projects of the Health and Family Planning Committee of Wuhan, Hubei Province, China. (No. WX 15D63).

The Youth Research Funded Projects of the Central Hospital of Wuhan, Hubei Province, China. (No. YQ14B04).

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification of Tumours of the Digestive System. Lyon: IARC Press; 2010.  Back to cited text no. 1
    
2.
Oberstein PE, Remotti H, Saif MW, Libutti SK. Pancreatic neuroendocrine tumors: entering a new era. JOP 2012;13:169-73.  Back to cited text no. 2
    
3.
Rampurwala MM, Kumar A, Kannan S, Kowalczyk P, Khera S. Non-functioning pancreatic neuroendocrine tumors – A case report and review of literature. J Gastrointest Cancer 2011;42:257-62.  Back to cited text no. 3
    
4.
Halfdanarson TR, Rabe KG, Rubin J, Petersen GM. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol 2008;19:1727-33.  Back to cited text no. 4
    
5.
Liakakos T, Roukos DH. Everolimus and sunitinib: from mouse models to treatment of pancreatic neuroendocrine tumors. Future Oncol 2011;7:1025-9.  Back to cited text no. 5
    
6.
Lewis RB, Lattin GE Jr, Paal E. Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics 2010;30:1445-64.  Back to cited text no. 6
    
7.
Chatzipantelis P, Salla C, Konstantinou P, Karoumpalis I, Sakellariou S, Doumani I. Endoscopic ultrasound-guided fine-needle aspiration cytology of pancreatic neuroendocrine tumors: a study of 48 cases. Cancer 2008;114:255-62.  Back to cited text no. 7
    
8.
Sahai AV. Endoscopic ultrasound-guided fine-needle aspiration: Getting to the point. Endosc Ultrasound 2014;3:1-2.  Back to cited text no. 8
[PUBMED]  Medknow Journal  
9.
Eisendrath P, Ibrahim M. How good is fine needle aspiration? What results should you expect? Endosc Ultrasound 2014;3:3-11.  Back to cited text no. 9
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10.
Fujii LL, Levy MJ. Basic techniques in endoscopic ultrasound-guided fine needle aspiration for solid lesions: Adverse events and avoiding them. Endosc Ultrasound 2014;3:35-45.  Back to cited text no. 10
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11.
Okasha HH, Naga MI, Esmat S, Naguib M, Hassanein M, Hassani M, et al. Endoscopic ultrasound-guided fine needle aspiration versus percutaneous ultrasound-guided fine needle aspiration in diagnosis of focal pancreatic masses. Endosc Ultrasound 2013;2:190-3.  Back to cited text no. 11
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12.
Costache MI, Iordache S, Karstensen JG, Saftoiu A, Vilmann P. Endoscopic ultrasound-guided fine needle aspiration: from the past to the future. Endosc Ultrasound 2013;2:77-85.  Back to cited text no. 12
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13.
Chaya C, Nealon WH, Bhutani MS. EUS or percutaneous CT/US-guided FNA for suspected pancreatic cancer: when tissue is the issue. Gastrointest Endosc 2006;63:976-8.  Back to cited text no. 13
    
14.
Iglesias-Garcia J, Lariño-Noia J, Domínguez-Muñoz JE. When to puncture, when not to puncture: Pancreatic masses. Endosc Ultrasound 2014;3:91-7.  Back to cited text no. 14
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15.
Sun SY. The diagnosis and intervention techniques of endoscopic ultrasound. Beijing, China: The People's Medical Publishing House; 2011. p. 309.  Back to cited text no. 15
    
16.
Waisberg DR, Fava AS, Martins LC, Matos LL, Franco MI, Waisberg J. Colonic carcinoid tumors: a clinicopathologic study of 23 patients from a single institution. Arq Gastroenterol 2009;46:288-93.  Back to cited text no. 16
    
17.
Franko J, Feng W, Yip L, Genovese E, Moser AJ. Non-functional neuroendocrine carcinoma of the pancreas: incidence, tumor biology, and outcomes in 2,158 patients. J Gastrointest Surg 2010;14:541-8.  Back to cited text no. 17
    
18.
Bonney GK, Gomez D, Rahman SH, Verbeke CS, Prasad KR, Toogood GJ, et al. Results following surgical resection for malignant pancreatic neuroendocrine tumours. A single institutional experience. JOP 2008;9:19-25.  Back to cited text no. 18
    
19.
White M, Edwards L, Cawich S. Metastatic pancreatic neuroendocrine carcinoma: Does aggressive surgical intervention improve outcome? Neuroendocrinology 2012;96:67.  Back to cited text no. 19
    


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