World J Gastroenterol. 2010 June 7; 16(21): 2692-2697.
Published online 2010 June 7. doi: 10.3748/wjg.v16.i21.2692.
©2010 Baishideng. All rights reserved
Solitary concomitant endocrine tumor and ductal adenocarcinoma of pancreas
Shu-Mei Chang, Chih-En Tseng, Department of Anatomic Pathology, Buddhist Dalin Tzu Chi General Hospital, Chiayi 622, Taiwan, China
Shih-Tang Yan, Department of Endocrinology and Metabolism, Buddhist Dalin Tzu Chi General Hospital, Chiayi 622, Taiwan, China
Chang-Kuo Wei, Department of General Surgery, Buddhist Dalin Tzu Chi General Hospital, Chiayi 622, Taiwan, China
Chih-Wen Lin, Department of Medical Imaging, Buddhist Dalin Tzu Chi General Hospital, Chiayi 622, Taiwan, China
Chih-En Tseng, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan, China
Received February 16, 2010; Revised March 25, 2010; Accepted April 1, 2010;
Pancreatic tumors with combined exocrine and endocrine features are rare. Most reported cases are classified as mixed exocrine and endocrine carcinoma of the pancreas. We report the first case of solitary concomitant endocrine tumor and ductal adenocarcinoma of the pancreas. A 58-year-old patient was admitted for uncontrolled diabetes mellitus and body weight loss. The tumor was fortuitously discovered in the pancreatic tail after a tumor survey panel. Grossly, the solitary tumor had a central fibrous band that clearly divided it into two parts. On microscopic examination, the tumor contained both endocrine and exocrine components distinctly separated by the central fibrous band. The exocrine part showed a poorly-differentiated adenocarcinoma. The endocrine part was strongly immunoreactive to chromogranin, synaptophysin and glucagon. We reviewed the literature on pancreatic tumors with combined exocrine and endocrine features. A simple classification for this group of neoplasms is suggested, including five types: amphicrine, mixed, collision, solitary concomitant and multiple concomitant.
Keywords: Pancreas, Concomitant tumor, Collision tumor, Mixed tumor, Glucagonoma
Pancreatic tumors, categorized according to exocrine and endocrine origin, are classified into ductal, acinar or endocrine types by morphological and immunohistochemical studies. Pancreatic endocrine tumor (PET) is uncommon and represents only 1%-2% of all pancreatic tumors[1
]. Pancreatic exocrine tumor is rarely associated with pancreatic endocrine tumor[2
]. Most reported cases are mixed ductal-endocrine carcinoma, mixed acinar-endocrine carcinoma and mixed ductal-acinar-endocrine carcinoma[2-7
]. These reported cases are classified according to World Health Organization (WHO) criteria[8
], in which mixed exocrine and endocrine carcinoma is defined as carcinoma containing intimately intermixed exocrine and endocrine components, and each component comprises at least one-third of the tumor tissue. By this definition, a solitary concomitant pancreatic tumor with distinctly separated exocrine and endocrine components cannot be classified as mixed exocrine and endocrine carcinoma. Here, we report a case of solitary concomitant endocrine tumor and ductal adenocarcinoma of the pancreas. This type of pancreatic tumor is especially rare and, to the best of our knowledge, has never been reported in the English literature.
A 58-year-old Chinese male was admitted to the endocrinology and metabolism ward in July 2009 for poorly controlled hyperglycemia, which was refractory to an oral hypoglycemic agent. He had a history of diabetes mellitus (DM), hypertension and chronic renal insufficiency for more than 4 years and had been receiving regular follow-up at the outpatient clinic of this hospital. On admission, laboratory test (Table ) revealed that his blood glucose was 561 mg/dL. Physical examination showed no skin rash or oral lesions. While he was hospitalized, daily high-dose insulin injection with Novomix 60 U/d was necessary to control his blood glucose level. The patient also complained of losing 10 kg of body weight in the prior two months. Therefore, he asked for a tumor marker examination. A tumor survey panel revealed an elevated carbohydrate antigen 19-9 (CA19-9) of 195 U/mL (normal, 0-37 U/mL) incidentally. Abdominal computed tomography (CT) demonstrated a 3.7 cm × 2.1 cm tumor in the pancreatic tail (Figure ) and unremarkable adrenal glands bilaterally. Whole body positron emission tomography showed moderately increased accumulation of fluorine-18 fluorodeoxyglucose (F-18 FDG) in the pancreatic tail with standard uptake values of 3.3 (initial) and 4.5 (delayed). No increased uptake in other organs or sites was identified. Thyroid ultrasound showed no focal lesion. The patient received distal pancreatectomy and splenectomy under the impression of pancreatic tail carcinoma. Neither liver metastasis nor peritoneal seeding was found during surgery. The postoperative course was uneventful. Initially, only an oral hypoglycemic agent was prescribed for controlling DM when the patient was discharged from the hospital. However, because hyperglycemia (268 mg/dL) and elevated glycosylated hemoglobulin HbA1c (8.1%) were found at follow-up in the outpatient clinic, insulin injection with Novomix 28 U/d was represcribed. The patient moved to another city for family support and admitted there one month after operation. Therefore we lost the follow-up of him.
Laboratory data on admission
Computed tomography (CT) scan demonstrating a 3.7 cm × 2.1 cm tumor (arrow) in pancreatic tail.
Grossly, the surgical specimen consisted of pancreatic tail tissue, 10 cm × 4 cm × 3.5 cm, and unremarkable spleen tissue (146 gm). A well-circumscribed gray-brown nodular mass, 3.8 cm × 3.2 cm × 2.2 cm, was found in the pancreatic parenchyma. On serial cuts, the nodular mass clearly showed a red-brown, hemorrhagic, centrally necrotic heterogenous part and a gray-white, focally hemorrhagic solid part (Figure ). A thin fibrous band was present between these two parts. No gross invasion to spleen, large vessels or resection margins was found.
Gross examination showing a well-circumscribed tumor with a central fibrous band (arrows) separating the right exocrine and the left endocrine parts.
The microscopic sections showed pancreatic tissue with a partially encapsulated tumor composed of two distinctly separated, exocrine and endocrine components (Figure ). The two components did not grow into each other and were completely separated by a small band of fibrous tissue and some residual, atrophic, benign exocrine glands. The endocrine part, up to 1.8 cm in diameter and occupying more than 40% of the pancreatic tumor, was well-circumscribed, completely enclosed by fibrous tissue and composed of uniform tumor cells containing small, round, monotonous nuclei and pale or mildly acidophilic cytoplasm (Figure ). These cells were arranged in gyriform or trabecullar patterns divided by slender fibrous connective tissue and rich vascular stroma. Neither mitotic figures nor cellular atypia was found. No evidence of necrosis, extrapancreatic spread or vascular invasion was present. Mucin and congo red stains were negative. On immunohistochemical (IHC) staining, the tumor cells were diffusely and strongly positive for chromogranin A (Figure ), synaptophysin (Figure ) and glucagon (Figure ). No expression of CA19-9 (Figure ), p53, Bcl-2, insulin, gastrin, vasointestinal peptide was demonstrated in the tumor. Ki-67 + cells were less than 0.5%. The exocrine component, a poorly-differentiated ductal adenocarcinoma, showed bizarre and hyperchromatic cells containing pleomorphic darkly staining nuclei, some mitoses and pale or acidophilic cytoplasm (Figure ). Scattered anaplastic nuclei were also found. These tumor cells were arranged in dilated ductal structures, small glands, cellular files or single cells, with large areas of necrosis and hemorrhage. The exocrine component showed focal invasion of peripancreatic soft tissue. The spleen and 9 peripancreatic lymph nodes were free of tumor. Mucin secretion was demonstrated by mucicarmine and periodic acid-Schiff with diastase stains. On immunohistochemical staining, this component was strongly positive for CA19-9 (Figure ), and negative for chromogranin A (Figure ), synaptophysin (Figure ), glucagon (Figure ), insulin, gastrin, vasointestinal peptide and Bcl-2. Ki-67 + cells were more than 25%. More than 55% of the ductal adenocarcinoma had strong intranuclear accumulation of p53 protein. In this case, the exocrine and endocrine components were clearly separated and different from each other in the single tumor. No collision or intermixing area could be found. With no other endocrine manifestations and focal lesion found in the thyroid and adrenal glands, MEN type 1 was not considered. Finally, a solitary concomitant endocrine tumor and ductal adenocarcinoma of the pancreas was diagnosed.