Primary Adrenocortical Tumors in Autopsy Records -A Survey of “Cumulative Reports in Japan” from 1973 to 1984-
Shunzo KOBAYASHI, Hirotaka İWASE, Kohji MATSUO, Hideki FUKUOKA, Yukashi ITo and Akira-MASAOKA
ABSTRACT: All cases of primary adrenocortical tumors, including those found incidentally, recorded in the Pathological Autopsy Case Annuals of Japan during a 12 year period from 1973 to 1984 were surveyed. Age- and sex-specific incidences of lesions were estimated from the population, mortality and autopsy statistics for the same period. There were 101 adenomas, 77 of which were presumed to be non-functional, and 222 carcinomas. The age-specific distribution profiles of both the benign and malignant tumors showed single peaks in the sixties and could not be distinguished from one another. The estimated age-specific distribution of morbidity of the non-functional adenomas showed a peak at about 10 years younger than that found in the autopsy records, although it was again similar to that of carcinoma derived from various clinical reports. The morbidity of the non-functional adenomas per 100,000 population was almost equal to that of breast cancer in Japan, being highest in the fifties age group with more than 4,000 people a year being suggested to have adenoma in this age bracket.
KEY WORDS: adrenocortical carcinoma, adrenocortical adenoma, au- topsy, incidentaloma
INTRODUCTION
Hypertension, hypopotacemia or such spe- cific physical appearances as central obesity or virilization have been the main reasons for physicians performing examinations to uncover functional adrenal tumors. On the other hand, whether benign or malignant, non-functional adrenocortical tumors gen- erally remain undetected until they have
reached a relatively large size. The prognosis for adrenocortical carcinoma has thus been very poor, due to the highly malignant char- acteristics resulting partly from a delay in diagnosis.1-3 Recently, however, the acciden- tal or incidental detection of adrenal masses has been increasing with the introduction of routine diagnostic procedures for abdominal disorders and an improvement in tech- nology, especially in the availability of new imaging techniques.4-6 Since the involved patients generally do not show symptoms of excess hormone secretion or tumor invasion, indications for surgery based on a differen- tial diagnosis between carcinoma and adeno- ma have been controversial. Therefore, a more detailed analysis of either clinical or
The Second Department of Surgery, Nagoya City University Medical School, Nagoya 467, Japan.
Reprint requests to: Shunzo Kobayashi, MD, The Second Department of Surgery, Nagoya City University Medical School, Kawasumi-1, Mizuho-cho, Mizuho- ku, Nagoya 467, Japan
epidemiological features is required to assist in constructing appropriate diagnostic pro- cedures.
The difficulty, however, lies in the fact that only small numbers of clinical cases of non- functional adrenocortical adenomas are available in individual institutions.7 The pre- sent authors thus investigated all cases of primary adrenocortical tumors recorded in the Pathological Autopsy Case Annuals of Japan during the 12 year period from 1973 to 1984.8
MATERIALS AND METHODS
All cases of primary adrenocortical tumors, including those found incidentally, recorded during the 12 year period from 1973 to 1984 in the Pathological Autopsy Case Annuals of Japan, were surveyed. Age- and sex-specific incidences of adenomas were estimated from the respective age- and sex-specific statistics for the population, mortality and autopsy data of the same period.8,9
RESULTS
Among 321,847 recorded autopsy cases, 101 adrenocortical adenomas and 222 car- cinomas were found and, of the carcinoma cases, 142 were male and 80 female. Twenty- three cases of adenoma were functional and
the remaining 74 were recorded as tumors coexisting with other diseases without any information suggestive of excess hormone secretion. While the sex distribution of car- cinoma was unequal, being higher in males than females in every decade, the same was not evident for adenoma (Table 1).
The age distributions of adenoma and carcinoma showed similar profiles with a peak in the sixties and deviated towards younger ages for functional adenomas viewed separately (Fig. 1).
The number of autopsies in each age group did not correlate with the number of mortalities and only a few cases of over 70 years were examined. Therefore, the age- and sex-specific autopsy rates per 100,000 mortalities differed (Fig. 2).
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| Age | Carcinoma | Func-Ade | Non-Func-Ade | Total-Ade | ||||||||
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| M | F | T | M | F | T | M | F | T | M | F | T | |
| -19 | 2 | 12 | 14 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 |
| 20 | 5 | 5 | 10 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 |
| 30 | 8 | 7 | 15 | 2 | 5 | 7 | 1 | 2 | 3 | 3 | 7 | 10 |
| 40 | 27 | 9 | 36 | 3 | 4 | 7 | 4 | 2 | 6 | 7 | 6 | 13 |
| 50 | 22 | 16 | 38 | 2 | 3 | 5 | 17 | 4 | 21 | 19 | 7 | 26 |
| 60 | 37 | 18 | 55 | 1 | 3 | 4 | 10 | 13 | 23 | 11 | 16 | 27 |
| 70 | 37 | 8 | 45 | 0 | 0 | 0 | 13 | 6 | 19 | 13 | 6 | 19 |
| 80- | 4 | 5 | 9 | 0 | 0 | 0 | 4 | 0 | 4 | 4 | 0 | 4 |
| T | 142 | 80 | 222 | 8 | 15 | 23 | 50 | 28 | 79 | 58 | 43 | 101 |
M, male; F, female; T, total; func-ade, functional adenoma; non-func-ade, non-functional adenoma; total-ade, total adenoma
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Notable differences between males and females were also observed in the average age- and sex-specific distributions of mor- tality and population during the 12 year period (Fig. 3).
The age-specific distribution of non-func- tional adenoma correlated with an increase
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in the death rate until the seventies (Fig. 4).
The estimated age-specific morbidity per 100,000 population increased more gradually until the forties with a jump to the fifties and declining thereafter (Fig. 5).
More than 4,000 people a year in the fifties age bracket were suggested to have the tumor, the respective number for people aged between 40 and 50, being estimated at about 2,500 (Fig. 6).
DISCUSSION
The differences, if any, between the age- specific distributions of carcinomas and adenomas will provide information to help establish the differential diagnosis of these tumors. According to reports of clinical cases, the average age at the initial diagnosis of carcinoma was 36 years for women and 48 years for men3 and, although functional cases are considered more likely to occur at a
younger age, the age-specific distribution profile of non-functional carcinomas peaked in the fifties.10-12 In this study, however, the average age of women with carcinoma was about 50 years while that of men was 59 years, with a peak being observed in the sixties. Thus, the age-specific distribution of carcinoma in clinical cases is suggested to shift by about 10 years younger than that in autopsy cases.
There has been controversy regarding the histological diagnosis of malignancy for ad- renocortical tumors.13,14 The diagnosis of carcinoma supported by only a few histologi- cal findings did not correlate with patient prognosis, and therefore, it is difficult to rule out the possibility that some of the cases recorded as carcinoma in these Annuals in fact had adenomas. This possibility was also suggested by the reported high malignancy of adrenocortical carcinomas, with 5 and 10 year survival rates of 30 per cent and 10 per cent, respectively.15 On the other hand, the clinical study of age-specific distribution for non-functional adenomas has been difficult due to the small numbr of reports.
Performing a statistical analysis of cumula- tive autopsy cases is difficult because of the variation in diseases and the specialities of each hospital. The development of malig- nant diseases, especially forms that are diffi- cult to diagnose and treat, could be a strong stimulus for autopsy by physicians. Adreno- cortical carcinoma is one such disease, how- ever, since non-functional adrenocortical adenomas are not fatal and would not there- fore be the key reason for deciding upon an autopsy, incidentally detected cases at autopsy may reflect the absolute rates. Of the adenomas recorded in the Annuals, func- tional tumors were mainly found in persons younger than forty while almost all the remaining cases were found incidentally at autopsy without any clinical record of symp- toms suggesting excess hormone secretion. These cases were therefore tentatively con- sidered as non-functional adenomas for the purposes of this report.
The age-specific distribution of non-func- tional adenoma demonstrated a marked in- crease from the fifties onwards following estimation by the autopsy rates. Although the age-specific distribution profile for non-func- tional adenoma showed the same pattern as that for carcinoma, with a peak in the sixties in the autopsy records, the estimated age- specific morbidity per 100,000 population increased with a jump to the fifties. There- fore, the specific age bracket in which these adenomas are most likely to develop is suggested to be the fifties, although it is also conceivable that the majority develop before the age of 60 and that only a few will arise thereafter. The average annual numbers of patients with adenomas in each age group were also estimated by the age- and sex- specific distribution per population. More than 4,000 people a year in the fifties age bracket were suggested to have the tumor. Thus, notwithstanding the small number of clinical reports, the peaks and profiles of the age-specific distribution of both clinical and autopsy cases having adenoma were well correlated.” These data also suggest the existence of similar profiles for the age- specific distribution between carcinoma and adenoma in clinical cases. Thus, the age- specific distribution profiles of both adeno- mas and carcinomas cannot be distinguished with enough accuracy by both pathological and clinical analyses.
The estimated morbidity of non-functional adenoma is almost next to that of breast cancer in Japan. Concerning the supposedly higher incidence than that based on clinical reports, incidental detection of non-functio- nal adrenocortical tumors will obviously in- crease with the introduction of routine ab- dominal imaging examinations.16,17 The early detection of carcinoma will also increase under these circumstances, although the age of the patient at first examination offers no useful information for making a differential diagnosis between benign and malignant disease. Therefore, more detailed analyses of the clinical features of both types of tumors
should be performed to cast light on the indications for surgery.
(Received for publication on May 15, 1990)
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