Adrenocortical tumors (ACT) can be suspected from clinical manifestations, blood testing and imaging studies (Ribeiro, Pinto et al. 2010). The definitive diagnosis is made on the basis of the gross and histologic appearance of tissue obtained surgically (Ribeiro, Pinto et al, 2010).
Routine blood testing for clinically suspected ACT includes measuring plasma cortisol, DHEA-S, testosterone, androstenedione, 17-hydroxyprogesterone, aldosterone, renin activity, deoxycorticosterone, and other 17-deoxysteroid precursors. Simultaneous elevation of glucocorticoid and androgen levels is a strong indication of an adrenal cortex tumor. Laboratory tests provide information useful not only for making a diagnosis but also for detection of tumor recurrence (Ribeiro, Pinto et al. 2010).
Hormone level indicators:
- Increased serum glucose and urine cortisol is indicative of Cushing syndrome.
- Excess serum androstenedione and dehydroepiandrosterone is indicative of virilization.
- Low serum potassium, low plasma renin, and high serum aldosterone are indicative of Conn syndrome.
- Excess serum estrogen is indicative of feminization.
Imaging modalities used to evaluate the possibility of ACT and disease extent include computed tomography (CT), sonography, magnetic resonance imaging (MRI), and positron emission tomography (PET)(Ribeiro, Pinto et al. 2010). MRI is preferred to CT scans due to the ability to image multiple planes, improved tissue contrast differentiation, and the absence of ionizing radiation. PET scans are useful to see metabolic activity in the tumor, detect distant metastases not easily seen on CT or MRI, tumor recurrence, and tumor invasion of the inferior vena cava. Sonography is useful for determining tumor invasion of the inferior vena cava (Ribeiro, Pinto et al. 2010). Currently our recommendation is that, in addition to sonography, all patients who have a suspected adrenal tumor should be examined by CT and MRI. Because the liver and lungs are the most common sites of metastasis at the time of diagnosis, CT scans of the chest and MRI of the abdomen are recommended for all patients with newly diagnosed ACT.
The definitive diagnosis of ACT is based on histology. A pathologist will examine the tissue to determine whether the ACT is a carcinoma or adenoma, although differentiating between the two can be challenging, especially in pediatric cases. The presence of local or regional invasion and high mitotic activity suggests the diagnosis of an aggressive phenotype (carcinoma). Tumor size or weight plays an important role in staging as well as serving as the best predictor for long-term surviva (Bugg, Ribeiro et al. 1994; Dehner and Hill 2009; Ribeiro, Pinto et al. 2010).
There are several staging criteria for pediatric ACT. The International Pediatric Adrenocortical Tumor Registry (IPACTR) has clear criteria for distinguishing children with excellent (disease stage I; >90% survival) from those with dismal prognosis (disease stage IV; < 25% survival) very well. However, the IPACTR criteria are not as clear for distinguishing children with disease stage II from those with disease stage III (Michalkiewicz, Sandrini et al. 2004. In an attempt to refine the IPACTR staging criteria, investigators from the Children’s Oncology Group’s (COG) proposed several changes (Ribeiro, Pinto et al. 2011) (See Table). However, defining classification schemes or disease staging systems that guide therapy for pediatric ACT is an evolving process. Note there are no definitions for histologic features in pediatric ACT due to the well-known difficulties of establishing histologic parameters with independent prognostic values.
IPACTR Staging of Adrenocortical Tumors in Children
|I||Tumor completely resected with negative margins, weight ≤200 grams, no metastasis|
|II||Tumor completely resected with negative margins, weight >200 grams, no metastasis|
|III||Tumor with regional lymph node metastasis, residual or inoperable tumor|
|IV||Tumor with hematogenous metastasis at presentation|
COG Staging of Adrenocortical Tumors in Children
|I||Completely resected, small tumors (<100 grams and <200 cubic centimeters) with normal postoperative hormone levels|
|II||Completely resected, large tumors (≥100 grams or ≥200 cubic centimeters) with normal postoperative hormone levels|
|III||Unsesectable, gross or microscopic residual disease.
Patients with Stage I or II tumors who fail to normalize hormone levels after surgery.
Patients with retroperitoneal lymph node involvement.
|IV||Presence of metastatic disease|