Adrenal Nodule in Elderly Man

Specimen Type:

Adrenal Gland


A 83-year-old man with a previous diagnosis of clear cell renal cell carcinoma presented with an adrenal nodule. The patient underwent a biopsy of this nodule and representative cross-sections were submitted.

Pathologic Features:

Sections revealed minute fragments of tissue consisting of cords of cells with clear, granular cytoplasm (Fig.1). Definite but focal positivity for keratin (Fig.2), EMA (Fig.3), and CD10 (Fig.4) was present. No immunoreactivity for calretinin was observed.

Differential Diagnosis:

  • Normal adrenal cortex (Fig.5)
  • Metastatic clear cell renal cell carcinoma (Fig.6)

Normal adrenal cortex: (Fig.12.5) HE 400X The adrenal cortex consists of three histological zones which are zona glomerulosa, zona fasciculata, and zona reticularis. The zona glomerulosa lies beneath the capsule, is thin and focally incomplete and consists of cells with minimal eosinophilic cytoplasm and small, round, dark nuclei. The zona fasciculata consists of long columns of large cells with pale vacuolated cytoplasm, rich in smooth endoplasmic reticulum and lipid droplets and this may confer a foamy appearance to the cells. The zona reticularis consists of short anastomosing cords of eosinophilic cells.

Metastatic clear cell renal cell carcinoma: (Fig.12.6) HE 400X Adrenal metastases from renal cell carcinoma have been reported in 5.5% of patients undergoing nephrectomy, and in 19% of autopsy cases. Renal cell carcinoma can involve the ipsilateral adrenal gland by direct extension, and although metastasis is usually to the ipsilateral gland, controlateral metastasis can occur and potentially cause confusion with an adrenal neoplasm. Rarely, renal cell carcinoma presents with controlateral or bilateral adrenal metastases.


Atypical cords of clear and granular cells highly suspicious for but not diagnostic of metastatic clear cell renal cell carcinoma in the adrenal.

The adrenal gland is the fourth most common site of metastatic cancer, following lung, liver, and bone. Metastases to the adrenal most commonly originate in the lung and breast, but other site includes kidney, stomach, pancreas, and skin (malignant melanoma).

Renal cell carcinoma can have solitary adrenal metastasis years or even decades after resection of primary tumor. In our routinely practice, metastatic renal cell carcinoma is often difficult to differentiate from primary adrenal cortical neoplasm in an adrenal needle biopsy.

Cytomorphologically, several overlapping features were observed between primary adrenal cortical neoplasm and metastatic renal cell carcinoma, including: abundant clear cytoplasm, often with microvesicles, large nuclei with prominent nucleoli, bare nuclei, and prominent vascularity.

Immunohistochemical stainings may help render a diagnosis. Cytokeratin AE1/AE3, CD10 and EMA are expressed by renal cell carcinoma while MELAN-A, Calretinin, Synaptophysin and Inhibin are negative for renal cell carcinoma but positive for adrenal cortical carcinoma (see Table 1.).

In the current case, caution was warranted in rendering a definitive diagnosis of malignancy owing to the small size of the sample and the relatively low grade of the cancer, which can indeed mimick of adrenal cortex histologically in small samples such as this.

The report of this case indicates that: 1) an accurate diagnosis of metastatic clear cell renal cell carcinoma in needle biopsy can often be difficult due to overlapping cytomorphologic features with adrenal cortical neoplasm, and 2) immunohistochemistry studies are important techniques in the diagnostic workup in separating metastatic clear cell renal cell carcinoma from a primary adrenal cortical neoplasm.

Table1. Immunostains expressed by adrenal cortical and renal cell carcinomas.

Immunostain Class Adrenal cortical carcinoma Renal cell carcinoma
CD10 Negative Positive
EMA Negative Positive
AE1/AE3 Negative Positive
MELAN-A Positive Negative
Calretinin Positive Negative
Synaptophysin Positive Negative
Inhibin Positive Negative


  1. Flanigan RC, Campbell SC, Clark JI, et al. Metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003 ;4(5):385-90.
  2. Yang B, Ali SZ, Rosenthal DL. CD10 facilitates the diagnosis of metastatic renal cell carcinoma from primary adrenal cortical neoplasm in adrenal fine-needle aspiration. Diagn Cytopathol. 2002 ;27(3):149-52.
  3. Kumar D, Kumar S. Adrenal cortical adenoma and adrenal metastasis of renal cell carcinoma: immunohistochemical and DNA ploidy analysis. Mod Pathol. 1993; 6(1):36-41.