Criteria of Malignancy of Cortical Tumors

The criteria determining whether an adrenal neoplasm is benign or malignant are not precise. Currently, the only accepted criteria are metastasis, either synchronous or

TABLE 69-1. Adrenal Surgery in Lille, France, during the Period January 1985 to December 1999

Characteristic

Hyperplasia

Benign

'Malignant

Total

Pheochromocytoma

116

35

151

Cushing

12

27

13*

52

Conn

5

104

109

Virilizing

6

5*

11

Feminizing

2*

2

Nonsecretory

3

91

32*

126

Metastasis

13

18

Others

8

7

2*

17

Total

28

351

107

486

*54 malignant adrenal tumors: 46 adrenocortical carcinoma, 8 others.

*54 malignant adrenal tumors: 46 adrenocortical carcinoma, 8 others.

metachronous, and local invasion into surrounding structures. Adrenal tumors metastasize to the lung (72%), the liver (55%), the peritoneum (33%), the bone (24%), the contralateral adrenal (15%), and the brain (10%).

Local recurrence at reoperation is not an absolute criterion of malignancy because intraoperative disruption of the capsule of a benign tumor may result in local seeding, with growth and apparent invasion.

Large adrenal neoplasms are more likely to be malignant. Critical size and weight usually range from 6 to 10 cm in diameter and from 40 to 100 g, respectively. The size suggestive of malignant tumors may be greater for androgen-secreting tumors than for other tumors.

Not all patients with adrenocortical carcinomas have metastatic disease at presentation, nor do all of these cancers exceed 6 cm in diameter. Therefore, the clinical problem is to determine whether an adrenal mass is likely to be malignant at an early stage. In general, adrenal tumors larger than 4 cm in maximal diameter should be removed for fear of malignancy. Independent of the size, some other features in nonfunctioning tumors help determine whether a patient is best treated medically or surgically. Features other than size suggesting malignancy include:

1. Heterogeneous pattern on computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography

2. Irregular surface

3. Adjacent adenopathy

A method of defining malignancy histologically has been relatively simply defined by Weiss.8 This classification incorporates nine histologic features (Table 69-2). The presence of three or more of these features in a specimen correlates well with a clinically malignant outcome.

TABLE 69-2. Weiss Criteria for Malignancy: More than Three Features is Indicative of Malignancy

High nuclear grade

Mitotic rate > 5 per 50 high-power fields Atypical mitoses

Eosinophilic tumor cell cytoplasm (>75% of tumor cells) Diffuse architectural pattern (>33% of tumor) with broad fibrous and trabecular bands Foci of confluent necrosis (see Fig. 69-1) Venous invasion Sinusoidal invasion Capsular invasion

The Weiss histopathologic system is now the most commonly used method for assessing malignancy because of its simplicity, reliability, and excellent interobserver agreement.9 Some of the criteria are, however, less reliable than others, and a statistically modified system of weighting has been proposed9 (2 mitotic rate x 2 cytoplasm x abnormal mitosis x necrosis x capsular invasion) with a significant correlation with the Weiss system.

Cytologic criteria are not consistent enough to predict tumor behavior; cellular atypia and abundance of mitosis are only suggestive, as is aneuploidy flow cytometry.10 Needle biopsy is not recommended for diagnosis because it cannot differentiate between an adrenocortical adenoma and an adrenocortical carcinoma. There is also concern about rupture of the tumor capsule. A high mitotic index is perhaps more of prognostic than diagnostic significance in malignant adrenocortical cancers.11 Needle biopsy is, however, useful when metastatic disease to the adrenal is suspected.

Major diagnostic problems arise in the evaluation of patients with tumors between 3 and 6 cm in diameter, exhibiting weak mitotic activity, with few areas of necrosis without obvious capsular invasion. In such cases, immuno-histochemistry may prove helpful as benign tumors stain positively for vimentin (connective cell antigen) in 14% of cases versus 80% to 90% for malignant tumors. Synaptophysin (neuroendocrine cell antigen) is also more often expressed in malignant tumors.12 MIB-1, another immunohistochemical marker, has also shown promise in delineating benign from malignant adrenal tumors.913

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