Adrenal gland and paraganglia
Adrenocortical carcinoma
General

Author: Pallav Gupta, M.D. (see Authors page)

Revised: 18 January 2016, last major update September 2013

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Adrenocortical carcinoma[title]

Cite this page: Adrenocortical carcinoma, General. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/adrenocorticalcarcinoma.html. Accessed December 9th, 2016.
Epidemiology
  • Rare, 0.5 to 2 cases per million annually in US
  • No gender preference, bimodal age distribution with first peak in childhood, second peak in 4th-5th decade of life
  • Associated with Li Fraumeni syndrome, Beckwith-Wiedemann syndrome, congenital adrenal hyperplasia
Clinical Features
  • 50% are functional and associated with virilizing and other syndromes, but cannot determine function from morphology
  • Lack of function may be due to deletions in enzymes required for cortisol synthesis
  • Hormonally inactive ACCs usually present with gastrointestinal symptoms or back pain caused by mass effect
  • Highly necrotic tumors may cause fever and clinically simulate infectious process
  • Tend to invade adrenal vein, vena cava, adjacent kidney and retroperitoneum; may cause thromboemboli
  • Metastases to liver (60%), regional lymph nodes (40%), lungs (40%), peritoneal and pleural surfaces, bone, skin (anaplastic tumors) or retroperitoneum
  • 2 year survival is 50%, 5 year survival is 20-35%
Laboratory
  • High level of DHEA-S is suggestive of adrenocortical carcinoma; decreased serum DHEA-S is suggestive of adenoma
Radiology Description
  • CT / MRI or 18F-FDG PET may distinguish benign and malignant lesions
  • CT: central tumor necrosis, calcifications; larger and more heterogeneous tumor
Diagnosis
  • Only definitive criteria for malignancy are distant metastasis or local invasion
  • Often cannot differentiate between adenoma and carcinoma; sign out as adrenocortical neoplasm, and estimate risk of recurrent or metastatic tumor
  • In children, malignant appearing tumors often have good prognosis, particularly if < 5 years old at diagnosis, complete resection, tumor < 400g, < 15 mitotic figures/20 HPF and minimal tumor necrosis

Original Weiss criteria for malignancy (Am J Surg Pathol 1984;8:163), modified as indicated below, requires 3+ of these factors:
  • Nuclear grade III or IV based on Fuhrman criteria
  • > 5 mitotic figures/50 HPF (40x objective), counting 10 random fields in area of greatest number of mitotic figures on 5 slides with greatest number of mitoses
  • Presence of atypical mitotic figures (abnormal distribution of chromosomes or excessive number of mitotic spindles)
  • Clear or vacuolated cells comprising 25% or less of tumor
  • Diffuse architecture (more than 1/3 of tumor forms patternless sheets of cells; trabecular, cord, columnar, alveolar or nesting pattern is not considered to be diffuse)
  • Microscopic necrosis
  • Venous invasion (veins must have smooth muscle in wall; tumor cell clusters or sheets forming polypoid projections into vessel lumen or polypoid tumor thrombi covered by endothelial layer)
  • Sinusoidal invasion (sinusoid is endothelial lined vessel in adrenal gland with little supportive tissue; consider only sinusoids within tumor)
  • Capsular invasion (nests or cords of tumor extending into or through capsule with a stromal reaction); either incomplete or complete
  • Each criterion is scored 0 when absent and 1 when present in the tumor
  • Note: above criteria may not apply to childhood tumors

Modified Weiss criteria:
  • Mitotic rate >5 per 50 high-power fields
  • Cytoplasm (clear cells comprising 25% or less of the tumor)
  • Abnormal mitoses
  • Necrosis
  • Capsular invasion
  • Calculate: 2x mitotic rate criterion + 2x clear cytoplasm criterion + abnormal mitoses + necrosis + capsular invasion (score of 3 or more suggests malignancy, Am J Surg Pathol 2002;26:1612)
  • Each criterion is scored 0 when absent and 1 when present in the tumor
Prognostic Factors
Poor prognostic factors
  • Mitotic activity, venous invasion and weight of 50g+; diameter of 6.5 cm+, Ki-67/MIB1 labeling index of 4%+ and p53+ (Am J Surg Pathol 1997;21:556)
  • Stage plays important role; overall survival > 5 years for stage I and II (Best Pract Res Clin Endocrinol Metab 2009;23:273)
  • Overall cancer-specific mortality (CSM) rates have been reported between 16% and 38%
  • Five year survival for patients with disease confined to adrenal gland is size-dependent, varies from 61 to 82%; those with distant metastases at diagnosis have a five year survival of only 18%
Case Reports
Treatment
  • Surgical excision; excision of solitary lung metastases
  • Locoregional lymph node dissection for localized tumor (Ann Surg 2012;255:363)
  • Radiation therapy for metastatic tumor, particularly in bony disease and unresectable tumors
Gross Description
  • Unencapsulated; large (200 g, 20 cm)
  • Variegated cut surface due to hemorrhage, cysts, necrosis
  • Often soft, friable intratumoral nodules; often invasion of major veins
Gross Images
Images hosted on other servers:

Large tumor

250 g, 10 cm tumor

Large tumor compressing kidney

Large tumor dwarfing kidney

Micro Description
  • Various growth patterns of well differentiated to anaplastic cells (giant cells with bizarre hyperchromatic nuclei)
  • Capsular invasion, marked mitotic activity with atypical forms
  • May have neutrophils, tumor giant cells, sarcomatoid features, eosinophilic globular inclusions and necrosis
Micro Images
Images hosted on other servers:

Various images

Mitotic figure (arrow)

Various images


Images hosted on Nature.com:

Various images

Virtual Slides

Adrenocortical carcinoma

Cytology Description
  • Single cells, poorly cohesive cell clusters in necrotic background
  • Cytoplasm is vacuolated to densely eosinophilic
  • Often marked nuclear atypia and mitotic activity
Positive Stains
Negative Stains
  • CK7, CK20, EMA, CEA, B72.3 and chromogranin
Electron Microscopy Description
  • Tubular cristae in mitochondria and droplets of cytoplasmic fat
  • Occasionally dense core granules (associated with neuroendocrine immunostains)
Electron Microscopy Images
Image hosted on other servers:

Figure 3d

Molecular / Cytogenetics Description
  • Malignant cases compared to adenomas usually show loss of heterozygosity (61%) at some loci; retinoblastoma gene (80%), p53 (44%), 9p (26%), 1p (22%) and 3p (22%)
  • Loss of heterozygocity at 11p15 (insulin growth factor II)) associated with higher risk of tumor recurrence
Differential Diagnosis