ORIGINAL ARTICLE

Clinical and Histological Differences in Anaplastic

Thyroid Carcinoma
J. M. Rodriguez,1 A. Piñero,1 S. Ortiz,1 A. Moreno,1 J. Sola,2 T. Soria,1 R. Robles1 and P. Parrilla1
From the 1Department of Surgery and 2Department of Pathology, Virgen de la Arrixaca University Hospital, Murcia, Spain

Eur J Surg 2000; 166: 34–38

ABSTRACT
Objective: To report our experience in patients with anaplastic thyroid carcinoma and try to establish differences between cases
in which the histological study showed that there was an associated thyroid carcinoma and those that were strictly anaplastic or
pure.
Design: Retrospective study.
Setting: University hospital, Spain.
Subjects: 14 patients with anaplastic thyroid cancer treated over a period of 26 years; 7 presented with associated thyroid
tumours and 7 were pure.
Mean outcome measures: Clinical data (age, sex, symptoms), treatment, histological study (associated thyroid disease, spread,
involved lymph nodes) and follow-up.
Results: 13 of the 14 tumours had spread locally. 5 patients were treated by total thyroidectomy, 3 subtotal thyroidectomy, 5
excision of the tumour, and 1 patient had a biopsy alone. There were associated thyroid tumours in 7 cases: 2 follicular, 2 tall
cell papillary, 1 solid papillary, 1 medullary and 1 Hürthle cell tumour. 12 patients died. Another 2 are still alive having
survived 61 and 70 months respectively, both with associated anaplastic cancers (follicular and solid). The mean survival was
14 months (24 for associated anaplastic carcinoma and 4 for pure anaplastic carcinoma).
Conclusion: There is a subgroup of anaplastic cancers in which a better differentiated thyroid carcinoma coexists with the
anaplastic carcinoma. The prognosis in this subgroup is better than that for primary pure anaplastic carcinoma.
Key words: thyroid, anaplastic carcinoma, prognosis, associated carcinoma.

INTRODUCTION Arrixaca” University Hospital in Murcia: 210 papillary

Unlike other thyroid carcinomas anaplastic thyroid
carcinoma is one of the most aggressive known, with a
mean survival of 6–15 months (3, 4, 18). Despite
combined treatments with radiotherapy and chemother-
apy there has been little progress in its management
and control. One of the current topics of discussion is
its relation to other thyroid tumours, for it has been
suggested that it could be a transformed pre-existing
thyroid carcinoma (12, 14, 16, 18, 19). We can, how-
ever, discern a subgroup in which the two tumours are
associated, which suggests the possibility of an early
diagnosis; this is fundamental in a tumour of such
aggressiveness.
In this paper we analyse the clinicopathological
features in 14 patients with anaplastic thyroid carcino-
ma. We have differentiated between two groups of
patients depending on whether or not they had a second
thyroid carcinoma.
PATIENTS AND METHODS
Between 1970 and 1996, 322 patients with thyroid
carcinoma were operated on at the “Virgen de la
(65%), 50 follicular (16%), 48 medullary (15%), and
14 anaplastic (4%).
We made a detailed retrospective study of those with
anaplastic tumours and recorded: clinical data (age,
sex, symptoms); complementary studies (chest radio-
graphy (n = 14), ultrasonography (n = 8), gammagra-
phy studies (n = 7), tomography (n = 4), laryngoscopy
(n = 5), bronchoscopy (n = 2) and fine-needle aspira-
tion biopsy (FNA) (n = 10); surgical treatment (total
thyroidectomy, subtotal thyroidectomy, lobectomy,
resection of the tumour (when the resection was less
than a total lobectomy), biopsy alone; and the extent of
lymph node dissection); and histological data (diag-
nosis made following the morphological criteria
described by Carcangiu et al. (3) and Rosai (13), the
patients being divided into two groups—pure or
primary tumours (those with anaplastic tumour in the
whole of the specimen studied) and associated or
“transformed” tumours (presenting with typical areas
of anaplastic carcinoma interspersed with areas of
another thyroid carcinoma; in no case was there a
microcarcinoma). In four cases, the pathologist in-
corporated immunohistochemical techniques for diag-
nosis. The TNM classification was also recorded.

 2000 Scandinavian University Press. ISSN 1102–4151 Eur J Surg 166

 Anaplastic thyroid carcinoma 35

Table I. Details of 14 patients with anaplastic thyroid carcinoma

History of Mean
Case Age thyroid TNM Type of Chemo- Radio- survival
No. (years) Sex disease classification Operation tumour therapy therapy (months)
1 22 Female No T2 Total thyroidectomy Associated No No 61 (alive)
2 88 Female Goitre T4N1 Total thyroidectomy Associated Yes No 5
3 60 Female Goitre T4N1 Total thyroidectomy Associated Yes No 4
4 54 Male No T4M1 Total thyroidectomy and Associated Yes No 11
tracheostomy
5* 64 Female Nodule T4 Excision of tumour Primary No No 2
6 74 Female Goitre T4 Biopsy Primary No No 5
7 66 Female No T4 Subtotal thyroidectomy Primary No Yes 4
8* 45 Male Nodule T4N1 Excision of tumour Primary No Yes 8
9 50 Male No T4 Excision of tumour Primary No No 3
10 64 Female Goitre T4 Total thyroidectomy Primary No No 3
11 58 Female No T4N1M1 Excision of tumour and Primary No No 2
tracheostomy
12* 72 Female Nodule T4M1 Excision of tumour and Associated No No 12
tracheostomy
13 58 Male No T4N1 Total thyroidectomy Associated Yes No 70 (alive)
14 35 Female No T4N1 Total thyroidectomy Associated Yes No 9

* Subtotal thyroidectomy 4, 13, and 7 years before, respectively, for papillary cancers.

Finally, we recorded follow-up data: recurrences,
distant metastases, mortality, and survival. Mortality
was considered only in patients who died of their
anaplastic tumours.
The results of the two groups were compared with
Fisher’s exact test.
RESULTS
The overall mean age of the patients was 63 years
(range 22–88). Only two were aged under 45 years old,
and seven were over 60. Ten of the 14 were women.
Seven patients had a previous history of thyroid
disease: four had had goitres for over 30 years and
three had been operated on for papillary cancers 4, 7,
and 13 years previously. Four of the patients had been
treated with thyroxine (three of those who had had
previous thyroid surgery and one with a goitre that had
not been operated on). The three patients who had been
operated on had bilateral subtotal thyroidectomy, and
all were given subsequent treatment with 131I.
The most common and frequent features were

Fig. 1. There are

different-sized follicles
on the left and on the
right a wide area of
large-cell anaplastic
carcinoma with a
lymphocytic and
metaplastic reaction
(haematoxylin and
eosin, original
magnification 250).

Eur J Surg 166

36 J. M. Rodriguez et al.

Table II. Causes of death of the patients with anaplastic thyroid carcinoma
Case no. Histological type
1 Follicular
4 Follicular
12 Papillary—tall cell
13 Papillary—solid
14 Papillary—tall cell
2 Hürthle tumour
3 Medullary
5 Primary
6 Primary
7 Primary
8 Primary
9 Primary
10 Primary
11 Primary
Survival (months) Outcome
61 Alive and disease-free
11 Died, bone metastasis at 8
12 Died, bone and lung metastasis at 6
70 Alive, reoperated on 5 times for nodal metastases
9 Died, jugular bleeding after recurrence of tumour
5 Died, respiratory insufficiency after recurrence of tumour
4 Died, respiratory insufficiency after recurrence of tumour
2 Died, respiratory insufficiency after recurrence of tumour
5 Died, respiratory insufficiency
4 Died, recurrence of tumour and nodal metastases
8 Died, recurrence of tumour and nodal metastases
3 Died, respiratory insufficiency after recurrence of tumour
3 Died, recurrence of tumour
2 Died, cerebral metastases

cervical masses (n = 12), dysphonia (n = 8), dysphagia DISCUSSION

(n = 6), dyspnoea (n = 5) and cervical pain (n = 4). The
rest of the clinical data are shown in Table I.
Thyroid ultrasonography showed a solid mass in
three and a mixed solid-cystic mass in five. FNA
cytology was diagnostic in three out of 10 patients. The
diagnosis in the remaining patients was: papillary
cancer (n = 5), follicular proliferation (n = 1) and
colloid nodule (n = 1).
At the time of operation, 13/14 tumours had spread
locally (six involving the recurrent laryngeal nerve and
seven tracheal invasion), six had nodal metastases and
two distant spread (lung and skeletal). Operations and
treatment are shown in Table I.
The histopathological study showed another thyroid
carcinoma in 7/14 (Table II). The two patients who
were alive at the time of writing had associated or
transformed tumours (follicular and solid, Fig. 1), and a
mean survival of 24 months, compared with the 4
months of the primary or pure group. The overall mean
survival was 11 months (Table III).
Anaplastic carcinoma makes up 6% of our thyroid
cancers, an incidence lying between the 2.7% and 15%
reported (3, 6, 14, 18). The clinical features of our
patients were similar to those of other series, with a
predominance of women and a mean age between 60
and 70 years; they presented with rapidly developing
thyroid tumours and symptoms of local compression
(4, 16, 18). Anaplastic thyroid cancer is rare in patients
aged under 40 years, although it has been documented
by Carcangiu et al. and Venkatesh et al. (3, 18). There
were two two patients aged 22 and 35 years in our
series. The disease may present in an unusual manner
(fever, local inflammatory signs, nodal metastases, and
distant metastases), and can constitute a medical
emergency, as in four of our patients (acute respiratory
insufficiency (n = 3) and serious bleeding (n = 1)). Pre-
operative diagnosis may not be easy: in this series, FNA
was useful in only 30% of the cases in which it was
done. Incision biopsy may be useful in cases of doubt.

Table III. Treatment according to histological type (n = 7 in each group)

Primary Associated
Mean age (years) 60.1 55.5
Female: Male 5/2 5/2
Pre-existing thyroid disease 4 3
Treatment:
Total thyroidectomy/Subtotal thyroidectomy/ Resection/Biopsy 0/2/4/1 5/1/1/0
Associated thyroiditis 4 0
Staging:
T2/T4/N1/M1 0/7/2/1 1/6/4/2
Mean survival (months) 3.8 18*

* p < 0.05

Eur J Surg 166


Half our series (7/14) had a history of previous
thyroid disease, and Demeter et al. found this associa-
tion in 76% of their patients (13/17) (4). This evidence
has been used to support the hypothesis that it may
derive from transformation of a well-differentiated
thyroid tumour (2, 3, 12–14, 19). This reported asso-
ciation varies between 13% and 89% (1, 19). In our
study, half had associated thyroid carcinomas, papil-
lary being the most common, but we also discovered
single examples of medullary and Hürthle cell carci-
noma (9). Our data, therefore, support the hypothesis
on the origin of certain types of anaplastic tumours,
such that well-differentiated papillary carcinoma parti-
cularly might be slowly transformed into other vari-
eties of less differentiated papillary cancers, such as tall
cell and insular, the malignancy of which seems
intermediate, finally to degenerate into a totally
undifferentiated form (8, 11). More unusual is the
association between medullary and anaplastic carcino-
ma, as in one of our cases. This may be explained by
the fact that no differentiation was possible, although in
this case the process was less evident. However, this
possible origin or evolution is difficult to illustrate or
confirm.
Adequate treatment of anaplastic thyroid carcinoma
is still controversial. Radical surgery seems to have lost
support because it is not able to control the local
progress of the disease or improve survival (5, 7, 15,
17). Currently, combined therapy (surgery ‡ radiother-
apy ‡ chemotherapy or radiotherapy ‡ chemotherapy)
seems to be the best form of management, as indicated
by the results of Ekman et al., Schlumberger et al. and
Tennvall et al. (5, 15, 17). However, resection may
often be necessary to reduce the tumour mass and
ensure a free airway (10). In the light of our results,
surgery seems to be worthwhile in the transformed
group.
The mean reported survival ranges from 6 to 15
months, similar to that found in our series (14 months).
Usually all the patients die before a year is up, although
there are isolated patients who have survived over 5
years (1, 4, 18). These were possibly cases of trans-
formed tumours, where, as in our study, the response to
treatment and survival is better. Other factors involved
in the poor prognosis of anaplastic tumours are: age
over 65 years, previous history of thyroid disease,
presence of chronic lymphocytic thyroiditis, dyspnoea,
and distant metastases (4, 7, 18). We found no differ-
ences between either group with regard to age or
previous thyroid disease, but there was a difference in
the association of lymphocytic thyroiditis (no cases in
the transformed group), operation (total thyroidectomy
in five of the seven transformed cases compared with
resection in the primary cases) and tumour staging.
None of these differences was significant. We also
Anaplastic thyroid carcinoma 37
noted the presence of thyroiditis in certain cases that
was associated with the tumoural process. As far as
survival is concerned, the transformed cases had
considerably higher survival than the primary cases
(24 compared with 4 months, respectively). Two
patients were alive at 70 and 61 months, respectively,
(aged under 60 years, with no previous history of
thyroid disease, treated with total thyroidectomy and
with an associated tumour).
In conclusion, our study shows that we can define a
subgroup of anaplastic thyroid cancer that probably
originates from a pre-existing thyroid carcinoma with
typical biological behaviour, and in which aggressive
surgery is possible and improves survival. The prog-
nosis of transformed anaplastic cancers is better than
that of primary cancers.
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Address for correspondence:
Jose M. Rodriguez, M.D.
Department of Surgery
Virgen de la Arrixaca University Hospital
ES-30120 Murcia
Spain