Spindle Cell PET with Cushing’s Syndrome 145 Case Report 145 Department of Pathology, University Health Network/ Toronto Medical Laboratories, University of Toronto, Toronto, Canada. Address correspondence to Dr. Runjan Chetty, Department of Pathology, Princess Margaret Hospital, Fourth Floor, Suite 302, Room 312, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. E-mail: runjan.chetty@uhn.on.ca Endocrine Pathology, vol. 16, no. 2, 145–152, Summer 2005 © Copyright 2005 by Humana Press Inc. All rights of any nature whatsoever reserved. 1046–3976/05/16:145–152/ $30.00 Spindle Cell Pancreatic Endocrine Tumor Associated with Cushing’s Syndrome Runjan Chetty, MB BCH, FRCPATH, FRCPC, DPHIL and Stefano Serra, MD Abstract A 59-yr old female presented with Cushing’s syndrome due to ectopic ACTH production. At the time of initial diagnosis an obvious source for the Cushing’s syndrome was not found and the patient was treated with bilateral adrenalectomy. Three years later she presented with hyperpigmentation and evidence of ACTH overproduction. This time a CT scan localized a mass to the tail of the pancreas and a distal pancreatectomy was per- formed. The mass was composed of compact plump spindle cells arranged in interlacing fascicles, was well circumscribed, and did not display angioinvasion. Although isolated punctate foci of necrosis were noted, the overall mitotic count was 1 per 10 high power fields. Immunohistochemistry showed the tumor to be positive for chromogranin, synaptophysin, and ACTH. This case highlights an unusual histological variant of pancreatic endocrine tumor (PET), namely, one composed almost exclusively of interlacing spindle-shaped cells. This raises a wide differential diagnosis and the use of immunohistochemistry is required to arrive at the correct diagnosis. ACTH-producing PET are usually aggressive lesions with metastases at the time of presentation and aggressive biological behavior. However, this case was characterized by an indolent clinical course. Key Words: Pancreas; spindle cells; endocrine tumor; Cushing’s syndrome; ectopic ACTH. paper is, therefore, to highlight an unusual histological variant of PET, discuss the dif- ferential diagnosis, and review the perti- nent literature on ACTH-producing PET. Case Report 59-yr-old female presented in 1996 with symptoms of Cushing’s syndrome due to ectopic ACTH secretion, with fever, muscle weakness, edema, weight gain, glucose intolerance, hypertension, and hypokalemia. At the time, she underwent extensive investigation including CT of the chest, abdomen, and head, and an octreotide scan. These investigations were negative and the patient underwent bilateral Introduction Several morphological variants of pan- creatic endocrine tumors (PET) have been described [1]. Among the more unusual cytomorphological variants are PET com- posed of oncocytes, so-called rhabdoid cells, and clear cells. A dominant spindle cell morphology (constituting 90% of the PET) is rare and raises a wide range of his- tological entities in the differential diag- nosis. Functional PET are well recognized, but ACTH production resulting in Cushing’s syndrome is uncommon. The case that we wish to describe is a combination of two unusual features of PET: a spindle cell PET that produced ACTH resulting in Cushing’s syndrome. The purpose of this