Neuroendocrine neoplasms

ACTH secreting tumors

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

Last author update: 29 January 2021
Last staff update: 26 August 2022

Copyright: 2002-2023,, Inc.

PubMed Search: ACTH secreting tumors pancreas pathology

Raul S. Gonzalez, M.D.
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Cite this page: Gonzalez RS. ACTH secreting tumors. website. Accessed February 6th, 2023.
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
  • 33% of patients also have Zollinger-Ellison syndrome
  • 10 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

AFIP 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
  • 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
Sample pathology report
  • Pancreas, tail, resection:
    • Pancreatic neuroendocrine tumor, WHO grade 1 (see synoptic report and comment)
    • Comment: The patient’s clinical history of Cushing syndrome is noted. This may be due to ACTH secretion by this tumor. Immunohistochemical stains for synaptophysin and chromogranin are positive and the Ki67 index is approximately 2.3%.
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 style 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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Reference: ACTH secreting tumors
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 style 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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Reference: ACTH secreting tumors
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