Case 136 - Discussion

Uploaded: 2007-10-28, Updated: 2007-12-27

 
Adenocarcinoma of the Adrenal Cortex

The Key Features

  • Criteria for malignancy;

  • Positive: vimentin, inhibin, Melan-A (Mart-1, A103), Synaptophysin;

  • Negative: CD10, RCC, EMA, CEA, Chromogranin;

  • Cytokeratin: negative or focally positive

CLINICAL FEATURES

  • May or may not have functional activity;

  • Incidence in US: ~1/1,000,000;

  • M:F=1:1.5;

  • Age: 40-50 years;

  • Rarely bilateral;

  • 15-38% cases had metastases on initial presentation;

  • Most common clinical presentations: abdominal or flank pain, discomfort, or fullness, mass;

  • Imaging studies: often large with low intensity areas of necrosis, irregular contour, calcification.

GROSS FINDINGS

  • Average weight 510 - 1120 grams;

  • Coarsely lobulated appearance with soft, bulging pale-tan or yellow-white nodules;

  • Often necrosis, hemorrhage and cystic changes.

MICROSCOPIC FINDINGS

  • Architecture: variable, commonly a broad trabecular growth pattern with anastomosing columns and cords of cell, 10-20 or more cells wide, separated by delicate, gaping sinusoids lined by an attenuated endothelial layer; other patterns include nesting, alveolar, solid or diffuse arrangement, and rarely spindle or sarcomatous pattern; occasional myxoid foci;

  • Cytology: some tumor cells have lipid-depleted or acidophilic, compact cytoplasm; some contain abundant lipid-rich, pale-staining cytoplasm; cell borders are fairly well defined;

  • Nuclei: striking nuclear pleomorphism and hyperchromasia (alone is not sufficient for a diagnosis of malignancy!), occasional hyperlobated or multinucleate with prominent nucleoli or pseudoinclusions;

  • Intracytoplasmic hyaline globules: round to oval, refractile, deeply eosinophilic and PAS+;

  • Relative common mitoses and atypical mitoses;

  • Invasion: vascular invasion, capsular invasion;

  • Necrosis: broad and confluent;

  • Stromal alterations: broad fibrous bands intersect the tumor and subdivide the tumor into irregular nodules; dystrophic calcifications in 20 cases; myxoid changes, lipomatous or myelipomatous metaplasia.

CRITERIA FOR MALIGNANCY

  • A tumor is defined as adrenocortical carcinoma when three or more of the following criteria are met: (1) high nuclear grade, (2) mitotic rate 6 or more per 50 high power fields, (3) atypical mitosis, (4) clear cells less than 25%, (5) a diffuse architecture pattern in more than one-third of the tumor, (6) confluent necrosis, (7) venous invasion, (8) sinusoidal invasion, and (9) capsular invasion;

  • Usually large: >100 grams

VARIANTS

  • Oncocytic adrenal cortical carcinoma

  • Adrenal carcinosarcoma

  • Adrenal cortical blastoma

DIFFERENTIAL DIAGNOSES

 

CK

EMA

CEA

VIM

Inhibin

Melan A

RCC

AFP

CD10

NF

S100

CG

SYN

BGI

Cortical carcinoma

−/+

+

+

+

+/−

+/−

+/−

Pheochromocytoma

+/−

?

+

+

+

+

Renal cell carcinoma

+

+

+

+

+

+/-

+

Hepatocellular carcinoma

+

+/−

+

−/+

+

+/−

+/-

+/−

Metastatic carcinoma

+

+

+

+/−

+/-

+/−

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • Positive: vimentin, inhibin, Melan-A (Mart-1, A103), Synaptophysin, BCL2, Calretinin (focally);

  • Negative: cytokeratin, CD10, RCC, EMA, CEA, Chromogranin;

  • Cytokeratin: negative or focally positive.

ELECTRON MICROSCOPIC FINDINGS

  • Compact eosinophilic cells have sparse lipid droplets and occasional small, irregular microvillous extension of the cytoplasm;

  • Mitochondria are variable with most abundance in the oncocytic type carcinoma.

REFERENCES

  • AFIP, tumor of the adrenal glands and extra-adrenal paraganglia, series 3;

  • Rosai and Ackerman's Surgical Pathology, 9th edition;
  • Sasano H, Suzuki T, Moriya T. Recent advances in histopathology and immunohistochemistry of adrenocortical carcinoma. Endocr Pathol. 2006 Winter;17(4):345-54.

  • Differential Immunoprofiles of Hepatocellular Carcinoma, Renal Cell Carcinoma, and Adrenocortical Carcinoma: A Systemic Immunohistochemical Survey Using Tissue Array Technique. Appl Immunohistochem Molecul Morphol, Volume 13(4).December 2005.347-352.

  • Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas. Appl Immunohistochem Mol Morphol. 2003 Dec;11(4):330-3.