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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 2  |  Page : 222-226
Weiss criteria in large adrenocortical tumors: A validation study

1 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
2 Sahara Hospital, Lucknow, India
3 Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
4 Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Date of Web Publication12-Jun-2010


Background: Several systems including pathologic criteria alone or in combination with clinical features have been proposed to differentiate between benign and malignant adrenocortical tumors and assess their prognosis. The Weiss system appears to be the most commonly used method for assessing malignancy but there are only a few studies which have evaluated its diagnostic power. Since we see large adrenocortical carcinoma (ACC), we attempt to evaluate the diagnostic power of Weiss system in large ACC. Materials and Methods: In this study clinicopathological characteristics of 42 adrenocortical neoplasms are studied and classified into adrenocortical adenoma (ACA) and ACC based on Weiss score of less than or equal to three or greater than three. Results: The histological criteria of Weiss appeared to predict tumor prognosis accurately. Five year survival of patients with Weiss scores of less than or equal to three was 100% compared to 0% of those with Weiss scores greater than three. The average weights of ACA and ACC were 13.0 plus/minus 8.4 grams and 621.1 plus/minus 335.2 grams respectively; average sizes of ACA and ACC were 2.8 plus/minus 1.0 cmsand 13.6 plus/minus 3.7 cms respectively. Conclusion: Weiss score was found to be a good prognostic factor for tumors of the adrenal cortex.

Keywords: Adrenocortical tumor, pathology, weiss criteria

How to cite this article:
Jain M, Kapoor S, Mishra A, Gupta S, Agarwal A. Weiss criteria in large adrenocortical tumors: A validation study. Indian J Pathol Microbiol 2010;53:222-6

How to cite this URL:
Jain M, Kapoor S, Mishra A, Gupta S, Agarwal A. Weiss criteria in large adrenocortical tumors: A validation study. Indian J Pathol Microbiol [serial online] 2010 [cited 2023 Feb 3];53:222-6. Available from:

   Introduction Top

Adrenocortical carcinoma (ACC) is a rare malignant tumor with an annual incidence estimated at 0.5-2.0 cases per million per year. [1] Reported series are a few as the infrequent occurrence of this cancer precludes extensive studies. The differential diagnosis of adrenal cortical adenoma (ACA) and carcinoma has been considered problematic, and rather complex schemes have been elaborated to assist in the separation. [2],[3],[4],[5] Invasion of surrounding tissues and distant metastases define these neoplasms as carcinomas. However, in the absence of these characteristics, differentiating between adenomas and carcinomas is critical as well as controversial.

Among the various criteria proposed, the one proposed by Weiss [2] which requires only histopathological findings has been most widely employed. The nine histological criteria are: (i) high nuclear grade, (ii) mitotic rate greater than five per 50 high power fields (HPF), (iii) atypical mitotic figures, (iv)eosinophilic tumor cell cytoplasm (greater than 75% tumor cells), (v) diffuse architecture (greater than 33% of tumor), (vi) necrosis, (vii) venous invasion, (viii). sinusoidal invasion, and (ix) capsular invasion. A tumor is labeled malignant when it meets four or more of these histological criteria.

We undertook this study to assess 42 adrenocortical neoplasms based on the Weiss system to evaluate the diagnostic value of this system to assess malignancy in adrenocortical tumors, particularly large tumors.

   Materials and Methods Top

This study comprises a consecutive series of 42 cases of adrenal cortical tumors admitted over last 18 years, from January 1989 to June 2006, at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, and a tertiary referral hospital of North India. Pertinent clinical, operative, gross pathologic findings and follow-up data were obtained from patient records. The histopathologic diagnosis of primary adrenocortical tumors and assessment of the Weiss system were reviewed.

The nine Weiss histopathologic criteria of malignancy were precisely defined and carefully assessed for each tumor: [2]

  1. Nuclear grade: nuclear grade III and IV based on criteria of Fόhrman et al.[6]
  2. Mitotic rate: greater than 5/50 HPF (x40 objective). According to Weiss, "mitosis was evaluated by counting 10 random high-power-fields in the area of the greatest numbers of mitotic figures on the five slides with greatest number of mitoses. If less than five slides were available for a case, a correspondingly greater number of fields per slide were used to make fifty high power-fields."
  3. Atypical mitotic figures: "mitosis was regarded as atypical when it definitely showed an abnormal distribution of chromosomes or an excessive number of mitotic spindles."
  4. Cytoplasm: presence of less than or equal to 25% "clear or vacuolated cells resembling the normal zona fasciculata."
  5. Diffuse architecture: diffuse architecture was present "if greater than one-third of the tumor formed patternless sheets of cells." Trabecular, columnar, alveolar or nesting organizations were regarded as nondiffuse patterns.
  6. Necrosis: necrosis was "regarded as present when occurring in at least confluent nests of cells."
  7. Venous invasion: Weiss defined a vein as an "endothelial-lined vessel with smooth muscle as a component of the wall."
  8. Sinusoid invasion: a sinusoid was defined as "endothelial-lined vessel in the adrenal gland with little supportive tissues." Only sinusoids located within the tumor were considered
  9. Invasion of tumor capsule: "invasion of the capsule was accepted as present when nests or cords of tumor extended into or through the capsule, with a corresponding stroma reaction."

Each Weiss criterion was scored 0 when absent and 1 when present. Thus, each tumor was graded from 0 to 9, determining a total Weiss score. The tumors with three or less of these histological criteria were classified as ACA, those with four or more of these histological criteria were classified as ACC. All the slides were reviewed by a pathologist (MJ) who was blinded to clinical features and gross findings.

Tumors were classified as functioning when they were associated with endocrine manifestations or elevated hormone levels. Nonfunctioning tumors were defined as tumors that did not secrete excess hormones.

Statistical analysis

Categorical data was expressed with percentage. Continuous variables were expressed as the mean plus/minus the standard deviation (SD). Percentages were compared using chi-square tests. Means were compared using Student's t test. The survival rates were calculated using Kaplan-Meier methods. P values of less than 0.05 were taken to indicate statistically significant differences.

   Results Top

The present series includes 42 adrenocortical tumors of which 19 were ACA and 23 were ACC. The age range of patient's was 1-68 years. The mean age at presentation of adrenocortical carcinomas (24.1 plus/minus 19.5 years) was lower than that of adenomas (31.7 plus/minus 14.2 years). However, the age range of carcinomas (1-68 years) was greater than that of adenomas (3-53 years). The sex distribution in patients with carcinomas and adenomas was similar with a female predominance and a male;female ratio of 0.7. Clinically, 12 patients presented with Cushing's syndrome (six carcinomas, six adenomas), 10 with virilization (eight carcinomas, two adenomas), 12 with Conn's syndrome (two carcinomas, 10 adenomas), and eight (seven carcinomas, one adenoma) were nonfunctioning tumors. There was no statistically significant difference in age, sex and tumor location between benign and malignant tumors [Table 1].

The weight of ACA ranged from 0.7 to 40 grams with an average of 13.0 plus/minus 8.4 grams, whereas the weight of the ACC ranged from 57 to 1500 g with an average of 621.1 plus/minus 335.2 grams. The size of the adrenocortical adenomas was one to five centimeter with an average of 2.8 plus/minus 1.0 cm [Figure 1]a. Size of the ACC ranged from six to 22 cm with an average of 13.6 plus/minus 3.7 cms [Figure 1]b. The mean size and weight of the malignant tumors were found to be statistically significantly higher than that of the benign tumors [Table 2].

Using Weiss system it was found that all ACC possessed four or more of these criteria of malignancy, and 19 (82.6%) had seven or more. None of our malignant cases had a Weiss score of three. Eosinophilic tumor cell cytoplasm and mitotic rate greater than 5/50 HPF were the most frequent criteria seen in all the carcinomas. The adenomas showed 0-2 criteria of malignancy with high nuclear grade as the most frequent feature [Table 3], [Figure 2], [Figure 3] and [Figure 4].

The patients were followed up over a period of eight to 210 months with mean follow-up duration of 64.9 months. All patients of ACA were alive on a follow-up period of 8-210 months. Of the ACC, follow-up was available in 15 out of 23 patients with maximum follow-up duration of 53 months. Of these 15, 11 died: two of them died peroperatively due to intraoperative complications, nine of these died over a follow-up period of eight to 36 months. Among these 11 patients who died, three had liver metastasis. There was one patient each of pulmonary metastasis, inferior vena cava invasion, splenic invasion and Gerota's fascia invasion. Four patients were alive after a period of 17 - 53 months. None of these patients had local invasion or distant metastasis by the tumor. After five years, 100% of the patients with Weiss's scores of less than or equal to three were alive compared to 0% of those with Weiss's score of four to eight.

   Discussion Top

Adrenal carcinoma develops at all ages from early infancy to the seventh and eighth decades of life. However, there appears to be a bimodal age distribution with the first peak occurring before five years of age and the second peak in the fourth to fifth decade of life. In most series there is a predominance of women with no significant correlation of survival with sex. Presentation on the left side was more common with few tumors presenting bilaterally. [7] The present series saw a unimodal peak with eight (35%) patients presenting at an age of less than 10 years. There was slight female preponderance and more cases were seen on the left side. Also, in our series, the proportion of malignant ACC was higher than ACA.

Adrenal tumors can be classified as functional (FT) when their hormonal secretions result in clinical consequences: Cushing syndrome, virilization syndrome, feminization syndrome, or a mixed Cushing- virilizing syndrome. Tumors are considered nonfunctional (NF) when the tumors do not secrete excessive hormones or produce hormonal precursors and/or active hormones in quantities insufficient to have clinical consequences. [8] In a series of 47 patients with adrenal carcinoma, 44 had FT tumors, and only three were NF. [8] Wooten and King reported 59% FT tumors and 41% NF tumors in their survey. [8] In the present study six (26%) of the ACC cases were nonfunctional. The presentation was most frequently that of virilization (eight patients) followed by Cushing syndrome (six patients) and Conn's syndrome (two patients).

In another study of 107 adrenocortical tumors, the weight of 39 tumors with Weiss scores of 0 to 3 varied from 2.5 g to 190 g, with an average of 23.38 plus/minus 41.36 g and a median weight of 12 g, whereas the weight of 31 tumors with Weiss scores of four to eight varied from four to 2600 g with an average of 376.13 plus/minus 538.76 g and a median weight of 160 g, with a statistically significant difference between the groups. [9] The size of 39 tumors with Weiss scores from zero to three were between one to 13 cm, with an average of 3.67 plus/minus 2.2 cm and a median size of three cm while the size of 47 tumors with Weiss's scores of four to eight varied from 1.5 cm to 30 cm with an average of 9.64 plus/minus 5.8 cm and a median size of nine cm, with a statistically significant difference between the two groups.

The most critical point in adrenocortical pathology is the differential diagnosis between ACA and ACC; there is no single histological criterion which can reliably differentiate between the two. Several multiparametric systems have been published for delineating malignancy. In 1979, Hough et al. proposed a system based on a combination of a nonhistopathologic with a histopathologic index of malignancy to separate malignant from benign cortical tumors. [4] In 1984, Weiss [2] proposed a system for evaluating adrenocortical malignancy based on nine histopathologic criteria found to be associated with adrenal cortical tumors that had metastasized or locally recurred. Malignant tumors met four or more of these histological criteria. The threshold for malignancy was lowered in 1989: presence of three or more of these nine histopathologic criteria was significant for a malignant clinical behavior. [3] In 1985, Van Slooten et al [5] developed a system based on seven histopathologic parameters, the presence of which was combined with a numeric value yielding a histopathologic index to differentiate benign from malignant tumors. The Weiss system appears to be the most utilized among these three distinct systems because of its simplicity and reliability.

In our study the Weiss system was found to be extremely useful in distinguishing benign adrenocortical tumors from malignant ones. This was validated by the fact that no adenoma was larger than five cms and no carcinoma was smaller than six cms. The five-year survival of all patients with tumors classified as adenomas based on a Weiss score of three or less was 100% while none of the patients with tumors classified as carcinomas based on a Weiss score of four or more with available follow-up survived for more than five years (the maximum survival being 53 months). Mitotic rate greater than 5/50 per HPF and eosinophilic tumor cell cytoplasm were the most frequently observed criteria. In the study by Aubert et al [1] eosinophilic tumor cell cytoplasm and high nuclear grade were the most frequently observed criteria among the carcinomas.

In summary, this retrospective study confirms the diagnostic value of the Weiss system for differentiating between benign and malignant adrenocortical tumors. The higher incidence of overtly functioning and advanced malignancy in our series may be due to lesser utilization of the cross sectional imaging studies as compared to the Western world. Ours is one of the few studies which address the validation of Weiss criteria in advanced and large ACCs, thus further emphasizing the excellent correlation between size and weight of the tumor on one hand and Weiss criteria on the other.

   References Top

1.Aubert S, Wacrenier A, Leroy X, Devos P, Carnaille B, Proye C, Wemeau JL, Lecomte-Houcke M, Leteurtre E. Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol 2002;26:1612-9.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984;8:163-9.  Back to cited text no. 2  [PUBMED]    
3.Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma.Am J Surg Pathol 1989;13:202-6.  Back to cited text no. 3  [PUBMED]    
4.Hough AJ, Hollifield JW, Page DL, Hartmann WH. Prognostic factors in adrenal cortical tumors: A mathematical analysis of clinical and morphologic data. Am J Clin Pathol 1979;72:390-9.  Back to cited text no. 4  [PUBMED]    
5.van Slooten H, Schaberg A, Smeenk D, Moolenaar AJ. Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer 1985;55:766-73.  Back to cited text no. 5  [PUBMED]    
6.Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6:655-63.  Back to cited text no. 6  [PUBMED]    
7.Wajchenberg BL, Albergaria Pereira MA, Medonca BB, Latronico AC, Campos Carneiro P, Alves VA, et al. Adrenocortical carcinoma: clinical and laboratory observations Cancer 2000;88:711-36.  Back to cited text no. 7      
8.Wooten MD, King DK. Adrenal cortical carcinoma: Epidemiology and treatment with mitotane and a review of the literature. Cancer 1993;72:3145-55.  Back to cited text no. 8  [PUBMED]    
9.Lucon AM, Pereira MA, Mendonηa BB, Zerbini MC, Saldanha LB, Arap S. Adrenocortical tumors: results of treatment and study of Weiss's score as a prognostic factor. Rev Hosp Clin Fac Med Sao Paulo 2002;57:251-6.  Back to cited text no. 9      

Correspondence Address:
Manoj Jain
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226 014, UP
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.64325

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3]

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