Aug 4, 1984 - phenomenon and psammoma bodies. The signifi- cance of histopathologically confirmed lymph node metastases (pN+) was also analysed for ...
Acta Radiologica Oncology 24 (198s) Fasc.
I
FROM T H E DEPARTMENTS OF ONCOLOGY, OTORHINOLARYNGOLOGY AND CYTODIAGNOSTICS, UNIVERSITY HOSPITAL, S-22185 LUND, SWEDEN.
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PROGNOSTIC FACTORS O F PAPILLARY, FOLLICULAR AND MEDULLARY CARCINOMAS OF THE THYROID GLAND Retrospective multivariate analysis of 216 patients with a median follow-up of 11 years J. TENNVALL, A.
BIORKLUND,
T.
MOLLER,
Abstract Various prognostic factors have been tested in multivariate analyses of 216 patients with papillary, follicular or medullary thyroid carcinomas without initial distant metastases. The median follow-up time was 11 years. The patient’s sex was not found to be a significant predictor. Age at diagnosis seemed to be an important predictor for papillary as well as for follicular carcinomas, but when deaths in intercurrent disease were estimated, marked cellular atypia and tumour invasion beyond the thyroid capsule proved to be more important predictors. For medullary carcinomas tumour invasion beyond the thyroid capsule was the only significant predictor.
Thyroid carcinomas constitute a heterogeneous group of tumours with widely varying prognoses. A large number of possible prognostic factors have been discussed for the papillary, follicular and medullary carcinomas occurring in the thyroid. They have, however, only been tested as independent predictors of survival in the great majority of studies found in the literature. It is well known that there is great co-variation between several of these variables, but only three studies have analysed the possible interdependence between different prognostic factors (2, 21, 23). One of these investigations is a multivariate analysis of 507 patients by the EORTC Cooperative Group (2) which, however, does not separately ana2-858101
J. RANSTAMand M.
AKERMAN
lyse the different histologic types. The median follow-up was also rather short (40 months). WANEBO et coll. (23) analysed some parameters for 153 patients with well-differentiated carcinomas with a longer period of follow-up. The justification of a long follow-up is that late recurrence of differentiated carcinomas is not unusual (12, 18, 19). The multivariate analysis done in the third study (21) tested the EORTC prognostic index on 226 patients with differentiated thyroid carcinomas who had a median follow-up exceeding 1 I years. During that investigation it was found desirable to make a separate analysis for each histologic sub-group due to their varying biologic behaviour, but also due to certain microscopic qualities specific for each group. No such studies have been performed earlier, so far as is known to the authors. The aim of the present investigation was therefore to identify variables for papillary, follicular and medullary carcinomas in order to predict the prognosis of survival for each histologic group.
Material and Methods
The material consisted of 262 patients with histopathologically confirmed differentiated thyroid carAccepted for publication 4 August 1984.
17
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18
J . TENNVALL, A . BIORKLUND, T. MOLLER, J . RANSTAM AND M . AKERMAN
cinomas referred to the Department of Oncology, University Hospital, Lund, during the years 1955-1972. The follow-up period was concluded in May, 1981. The median observation time was thus 1 1 years, and 26 per cent of the patients have been observed at least 15 years, which justifies the construction of survival curves up to 15 years. The female/male ratio was 3/1. The median age was 49 years (range 8-83). Primary assessment included radiologic examination of the lungs and the axial skeleton, as well as a postoperative scintigraphy of the neck and a longitudinal scan of the whole body. If signs of metastases were demonstrated within two months after operation, distant metastases were considered as initially present. Follow-up data were usually obtained during the first 10 years postoperatively from examinations at the Department and after that, usually from examinations at other hospitals in the region, or from questionnaires by mail. Histopathologic examinations. Histologic material from 29 patients could not be obtained; it was thus possible to re-evaluate microscopic slides from only 233 patients. Excluded from further analysis were also 7 patients with tumours reclassified as benign, and 10 patients with distant metastases at diagnosis, due to the small number of patients with this variable in each subgroup. A total of 216 patients with differentiated thyroid carcinomas thus form the basis for this analysis. All microscopic slides were re-examined by the same pathologist (M .A.). Re-examination was performed on the original slides. There was great variation in the number of slides from case to case. From some carcinomas, only one or 2 slides had been cut, from others 8 to 10. When the original slides were found to be of technically inferior quality, new slides were prepared from existing tissue blocks. The pathologist had no knowledge of the clinical course of the disease for each specific patient. The histologic reclassification was made according to the WHO histologic typing of thyroid tumours (9). In the re-evaluation of the papillary and follicular carcinomas marked cellular atypia (MA) was noted. MA was considered present when the following observations were made: In papillary carcinomas, the papillary structures lacked the characteristic monostratified epithelium, the epithelial cells were multilayered and unevenly
distributed, there was a marked variation in cellular and nuclear size and shape, and nuclei were chromatin-rich with unevenly distributed chromatin. Multinucleated cells were occasionally seen. ‘Ground glass’ nuclei were missing. Follicular carcinomas with MA also showed considerable variation in cellular and nuclear size and shape. The nuclei had coarse, unevenly distributed chromatin and prominent nucleoli. The typical follicular structures were replaced by solid masses of cells or of a trabecular pattern. In spite of the multivaried appearance of the medullary carcinoma, from the carcinoid-like to the tumour consisting of pleomorphic and bizarre cells, MA was considered present when the chromatin pattern was very irregular and hyperchromatic, the nucleoli prominent and the mitotic activity high. Seven patients initially classified as having follicular carcinomas were at re-examination classified as cases of follicular adenoma. The diagnosis of follicular carcinoma used the same criteria as have recently been described (10) that is evidence of invasion either into the capsule, into blood vessels, or into adjacent thyroid tissue. Only 29 patients had an occult carcinoma (lo mm) pN+ (UICC) Diffusely growing non-encapsulated follicular carcinomas (FCD) Marked cellular atypia Ground glass Psammoma bodies Azkanazy cells Vascular invasion
I0 mm)
Male sex
>10 mm
pT4
PN +
MA
-
-0.100 (0.119)
Tumour invading beyond thyroid capsule (pT4)
0.282 (10mm
pT4
FCD
Az+
MA
Vascular invasion
Age Male sex
-0.224 (0.054)
-
Non-occult tumour ( > l o mm)
-0.068 (0.314)
0.176 (0.103)
0.196 (0.080)
0.071 (0.307)
-0.019 (0.446)
Follicular carcinoma, diffusely growing (FCD)
0.033 (0.409)
0.010 (0.473)
0.229 (0.049)
(0.001)
Marked cellular atypia (MA)
0.029 (0.419)
-0.043 (0.380)
0.107 (0.222)
0.321 (0.010)
0.080 (0.285
Azkanazy cells (Az+)
0.297 (0.015)
-0.050 (0.360)
0.165 (0.120)
-0.014 (0.462)
-0.263 (0.029)
-0.133 (0.171)
Vascular invasion
0.027 (0.424)
0.162 (0.124)
0.212 (0.063)
0.214 (0.062)
0.073 (0.303)
0.214 0.062)
Tumour invading beyond
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thyroid capsule (pT4)
0.425
-
-
-0,182 (0.096)
-
- Negative correlation.
Table 4 Significant negative prognostic variables for surviuat in papillary, follicular and medullary carcinonzas. Mulfiuariute analysis
Histologic type
Negative prognostic factor
Relative risk
Coefficient*
p-value
Papillary carcinoma n = 141
Age at diagnosis Marked cellular atypia
10.60** 4.35
0.0944 1.4721
t0.00005 0.0361
Follicular carcinoma n=49
Age at diagnosis Marked cellular atypia Tumour with invasion beyond thyroid capsule
10.80** 3.74 2.83
0.0952 1.3199 1.0400
