Neuroendocrine neoplasms
ACTH secreting tumors

Editor-in-Chief: Debra Zynger, M.D.
Raul S. Gonzalez, M.D.

Topic Completed: 21 January 2019

Minor changes: 10 March 2020

Copyright: 2002-2020,, Inc.

PubMed Search: Pancreas ACTH secreting tumors

Raul S. Gonzalez, M.D.
Page views in 2019: 458
Page views in 2020 to date: 238
Cite this page: Gonzalez RS. ACTH secreting tumors. website. Accessed July 2nd, 2020.
Definition / general
Essential features
  • Rare lesion mostly described in case reports
  • Patients develop Cushing syndrome clinically
  • Aggressive, with poor prognosis
ICD coding
  • ICD-10: E24.3 - Ectopic ACTH syndrome
  • Responsible for about 15% of cases of ectopic Cushing syndrome
  • May be more common in tail of pancreas
Clinical features
  • Mean age 42 years, with a female predominance (Am J Surg Pathol 2015;39:374)
  • Causes Cushing syndrome: central obesity, muscle weakness, glucose intolerance, hypertension
  • One-third of patients also have Zollinger-Ellison syndrome
  • Ten year survival is roughly 15% (Am J Surg Pathol 2015;39:374)
Diagnostic criteria
  • Determined clinically, not by immunohistochemical positivity for ACTH
Radiology images

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Pancreatic tail/body mass

Case reports
  • Surgical excision
Gross description
  • Firm, gray-white, well circumscribed lesions that may measure up to 5 cm
Gross images

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Pancreatic tail mass

Microscopic (histologic) description
  • Appears similar to other well differentiated neuroendocrine tumors of the pancreas
  • Lymphovascular and perineural invasion often present
  • Focal necrosis is rare
Microscopic (histologic) images
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ACTH producing tumor with Cushing syndrome

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Typical neuroendocrine tumor appearance

66 year old man with ultrasound guided biopsy: H&E and ACTH antibody

Cytology images

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Scattered neuroendocrine cells

Positive stains (IHC and special stains)
  • ACTH (though this does not establish the diagnosis), beta-endorphin, galectin3
  • Ki67 usually 3 - 20%, as these lesions are typically WHO grade 2
Electron microscopy description
Differential diagnosis
Board review style question #1
    A 45 year old woman presents with complaints of weight gain, increased facial hair, striae on her arms and easy bruising. An abdominal CT scan shows a 4 cm mass in the tail of her pancreas. What hormone is the tumor likely secreting?

  1. ACTH
  2. Cortisol
  3. Gastrin
  4. Glucagon
Board review answer #1
A. ACTH. The patient is presenting with Cushing syndrome, secondary to ACTH production by her pancreas lesion (likely a neuroendocrine tumor), which leads to increased cortisol production by the adrenal glands. Pancreatic tumors do not themselves secrete cortisol.

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Board review style question #2
    Which of the following is often seen microscopically in well differentiated pancreatic neuroendocrine tumors that secrete ACTH?

  1. Abundant necrosis
  2. Grade 3 mitotic rate
  3. Lymphocytic infiltration
  4. Perineural invasion
Board review answer #2
D. Perineural invasion. These tumors, which are commonly WHO grade 2, often show lymphovascular and perineural invasion. Focal necrosis may sometimes be seen.

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