Table of Contents
Epidemiology | Clinical features | Laboratory | Radiology description | Diagnosis | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Gupta P. Adrenal cortical carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/adrenocorticalcarcinoma.html. Accessed February 27th, 2021.
Epidemiology
- Rare, 0.5 to 2 cases per million annually in U.S.
- 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+, Ki67 / 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
- 18 month old boy with coexistent choroid plexus carcinoma, both tumors p53+ (Arch Pathol Lab Med 2002;126:70)
- 40 year old man with giant adrenocortical carcinoma (Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014;158:474)
- 63 year old man with adenosquamous carcinoma (Arch Pathol Lab Med 1995;119:260)
- 3 women (44 - 55 years old) with primary rhabdoid adrenocortical carcinoma (Histopathology 2013;62:771)
- MSH2 carrier without MSH2 mutation in adrenal tumor (Hum Pathol 2000;31:1522)
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
Microscopic (histologic) 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
Microscopic (histologic) images
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
- Vimentin, MelanA / MART1 (Arch Pathol Lab Med 2002;126:170, Am J Surg Pathol 1998;22:57), synaptophysin and inhibin (usually, Mod Pathol 1998;11:1160)
- Also bcl2 (Mod Pathol 1998;11:716), adrenal 4 binding protein (regulates expression of steroid enzymes, Hum Pathol 1995;26:1154) and p53
- Variable synaptophysin, neurofilament, neuron specific enolase, calretinin, HepPar1, S100 and CAM 5.2
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)
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
- Adrenal cortical adenoma: see Modified Weiss criteria above
- Adrenal medullary tumors: inhibin-, MelanA-, calretinin- and chromogranin+
- Hepatocellular carcinoma
- Renal cell carcinoma: usually contains glands which may contain red blood cells, glycogen+, keratin+, EMA+, CD10+, MelanA-, synaptophysin- and inhibin-
Additional references