FINAL DIAGNOSIS: ADRENAL CORTICAL CARCINOMA, 21 CM, WITH DIRECT EXTENSION INTO THE LIVER
Adrenal cortical carcinoma is an uncommon tumor which occurs at all ages and in both sexes, accounting for approximately 0.02% of all cancer (1). The average age at presentation ranges from approximately 40 to 50 years (2-5) with an overall male to female ratio of 1:1 (2-5). Most cases represent non-functioning tumors. However, when tumors are functional, they are most often found in women and children (2). Common presenting signs and symptoms include large abdominal mass, sometimes palpable, pain, weakness, lethargy and fever. Some authors have noted that tumors occur more often on the left side (2-4) and are seen more frequently in caucasians (2).
The tumors usually attain a large size prior to diagnosis and typically weigh over 100 grams, often exceeding 1,000 grams. The large size is thought to be due to the retroperitoneal location of the tumor producing symptoms only late in the course of disease, especially if the tumor is non-functioning. When the tumor is functioning, it is believed that the enzymatic activity of the cells is not sufficient to produce symptoms until late in the disease process. This also helps to explain the high incidence of distant metastasis at the time of initial presentation. Some authors report that up to 78% of patients have distant metastasis at presentation (4).
Gross findings include soft friable tumor with frequent areas of necrosis and hemorrhage. A capsule is seen but is often infiltrated by tumor. Venous invasion is also seen. Microscopically, the tumor is morphologically heterogeneous and exhibits a wide spectrum of differentiation/grade. Some tumor cells closely resemble normal adrenal cortical cells whereas others are totally undifferentiated. Giant cells with bizarre, sometimes multiple nuclei can be seen. Neutrophils may be abundant in the cytoplasm of these cells.
Most often the differential diagnosis includes adrenal cortical adenoma and renal cell carcinoma. Malignant melanoma and anaplastic carcinoma of the lung also can enter the differential. Many systems for distinguishing benign from malignant adrenal neoplasms have been proposed (6). Some systems use histologic criteria alone (7,8) while others combine histologic and non-histologic factors (9) including high nuclear grade, mitotic count > 5 per high power field, atypical mitoses, tumor cell necrosis, vascular invasion, capsular invasion, tumor size > 100 grams, urinary steroids, weight loss, and so forth, all features which are seen more often with adrenal cortical carcinoma.
It is often necessary to differentiate adrenal cortical carcinoma from renal cell carcinoma, especially in the absence of clinical manifestations of adrenal cortical hyperfunctioning. Adrenal carcinoma frequently invades the renal cortex and renal cell carcinoma often involves the adrenal gland, both by direct extension. Histologically the tumor cells and tumor architecture can look quite similar and distinction between the two cannot be made on routine hematoxylin and eosin staining. Immunohistochemical stains have aided in this distinction. Wick et al (10) reported vimentin positivity, EMA negativity, and blood group antigen negativity in adrenal cortical carcinoma. Renal cell carcinomas showed diffuse keratin positivity. A few of the adrenal cortical carcinomas were positive for keratin but all were negative by there was lack of trypsin digestion. More recently, Chivite et al (11) reported inhibin A as a potential good marker for adrenal cortical tumors showing diffuse positivity in 7 of 8 adrenal cortical carcinomas and negativity in 12 of 12 renal cell carcinomas, indicating thatinhibin may represent a good marker to aid in this distinction.
Prognosis in adrenal cortical carcinoma is poor. Didolkar et al (2) report an overall and median five-year survival rate of 14 months and 24%. Most studies conclude that early diagnosis and treatment by radical surgery offer the best odds for long term survival (2,4,5).
The case presented here represents a non-functioning 21cm adrenal cortical carcinoma in a 63 year-old woman with direct extension into the liver. No gross or histologic evidence of involvement of the kidney is noted. The tumor cells are histologically compatible with both renal cell carcinoma and adrenal cortical carcinoma. Immunohistochemical staining pattern is more compatible with adrenal cortical carcinoma. Given the gross findings and staining pattern, we believe this tumor represents an adrenal cortical carcinoma with direct extension into the liver. The patient was discharged following surgery in good condition but was unfortunately lost to follow-up.
Contributed by Patricia A. Aronica-Pollak, MD and Sheldon Bastacky, MD