Anaplastic Carcinoma of the Thyroid

A Clinicopathologic Study of 121 Cases

Y. S. Swamy Venkatesh, MRCP (UK),* Nelson G. Ordonez, MD,t
Pamela N. Schultz, RN, MS,* Robert C. Hickey, MD,$
Helmuth Goepfert, MD,§ and Naguib A. Samaan, MD, PhD, FRCP”

One hundred twenty-one cases of anaplastic carcinoma of the thyroid treated at

M. D. Anderson Cancer Center, Houston, were reviewed. Anaplastic carcinoma is a
rapidly growing neoplasm with a dismal prognosis. The mean survival of our
patients was 7.2 10 months. A significant percentage of our patients (35%)had
areas of well-differentiated thyroid carcinoma elsewhere, supporting the hypothesis
that anaplastic thyroid carcinoma arises from preexisting well-differentiated
thyroid carcinoma. Twenty-four of 30 tumors analyzed (84%)stained for keratin, 28
(93.3%)stained for vimentin, and ten (33%) stained for epithelial membrane
antigen. Younger patients lived longer than older patients, and patients whose
disease was earlier-stage at presentation responded better than patients with
metastases at presentation. Radical surgery alone did not significantly increase
survival duration over less radical surgery. The role of multimodality therapy
needs further evaluation. Cancer 66:321-330,1990.

A NAPLASTIC THYROID CARCINOMA accounts for

5% to 14% of primary malignant thyroid neo-
plasm^.'-^ In contrast to papillary and follicular thyroid
carcinoma, anaplastic carcinoma is one of the most ag-
gressive neoplasms affecting humans. This is exemplified
by a 5-year survival rate of 7.1% and a mean survival
period of 6.2 months seen in a previous review from The
University of Texas M. D. Anderson Cancer Center,
Houston, Texas.4
This study involves one of the largest series of patients
with anaplastic thyroid carcinoma. In it we review the
cases of 121 patients whose anaplastic thyroid carcinoma
was treated at M. D. Anderson Cancer Center between
From the *Section of Endocrinology, Department of Medical Spe-
cialties, and the Departments of tPathology, $General Surgery,and $Head
and Neck Surgery, The University of Texas M. D. Anderson Cancer
Center, Houston, Texas.
Supported by the Nancy D. Carmichael Estate for Cancer Research
and the Robert V. Davidson Estate for Cancer Research, Houston, and
the Caduceus Foundation, New York.
The authors thank Hazel Dalton, HT, Thomas Brooks, HT, and Elsa
Ramos, HT, for their technical assistance and Rosa M. Quiroz for typing
the manuscript.
Address for reprints: Naguib A. Samaan, MD, PhD, Chief, Section of
Endocrinology, Box 15, The University of Texas M. D. Anderson Cancer
Center, 15 15 Holcombe Boulevard, Houston, TX 77030.
Accepted for publication January 9, 1990.
1950 and 1987 and describe the immunocytochemical
features of 30 tumors. The response to treatment and fac-
tors affecting prognosis are analyzed, and the long-term
survivors are characterized.
Materials and Methods
We reviewed the records of all patients who had a his-
tologically proven diagnosis of anaplastic thyroid carci-
noma and were treated at M. D. Anderson Cancer Center
between 1950 and 1987. All the slides were reviewed by
one author (N.G.O.). For each patient the clinical pre-
sentation, clinical course, and modes of treatment were
noted. The patients were then divided into two groups,
“initial anaplastic” and “transformed anaplastic.” The
initial anaplastic group comprised patients in whom an-
aplastic carcinoma was diagnosed at the time of their first
presentation. The transformed anaplastic group com-
prised those who received a diagnosis of well-differentiated
thyroid carcinoma at presentation and developed ana-
plastic carcinoma at a later date. Anaplastic carcinoma
was found on histologic examination of tissue from re-
current tumor.
The stage of disease at presentation was determined
retrospectively. “Gland only” indicates that tumor was
confined to the thyroid gland. “Gland and nodes” signifies

32 1
322 CANCERJuly 15 1990 Vol. 66

tumor involving the thyroid gland and the regional lymph
nodes. If the tumor involved the thyroid gland, the re-
gional nodes, and the adjacent soft tissue structures it was
classified as “gland and nodes and neck” disease. “Distant
disease” denotes evidence of metastases outside the neck
area. Survival figures were calculated from the time of
tissue diagnosis. Surgery performed was identified as total
thyroidectomy, subtotal thyroidectomy, lobectomy, or
biopsy. Total thyroidectomy denoted removal of both
lobes and the isthmus and only a small rim of tissue was
left around the parathyroid glands and recurrent laryngeal
nerve on the side that was free of disease. Excision of one
entire lobe, the isthmus, and a portion of the other lobe
was considered subtotal thyroidectomy. Lobectomy in-
dicates removal of one entire lobe. Anything less than
excision of an entire lobe was considered a biopsy.
Survival data were analyzed from the time of tissue
diagnosis. Only those patients who died as a result of an-
aplastic carcinoma were categorized as deaths due to the
disease; deaths from other causes were censored, and the
patients were categorized as survivors until the time of
death. The chi-square test, mean f standard deviation,
and Student’s t test were used to compare survival status
among the various groups.
Immunohistochemical studies were performed on 30
tumors from which sufficient material was available. The
immunostaining procedure was performed on formalin-
fixed, paraffin-embedded tissue sections using the avidin-
biotin-peroxidase complex (ABC) method of Hsu and
colleague^.^ The specimens were cut 3 to 4 pm thick, de-
paraffinized in xylene, and rehydrated in descending
grades (100% to 70%) of ethanol. To enhance the im-
munostaining of some antibodies, the sections were di-
gested in 0.1% protease (type XIV; Sigma Chemical Co.,
St. Louis, MO) in phosphate-buffered saline, pH 7.6, for
30 minutes; for the remaining antibodies, this step was
omitted because the enzymatic treatment would produce
a detrimental effect on the immunostaining.
Use of digestion is specified by antibody in Table 1.
Endogenous peroxidase activity was blocked by 10 min-
utes’ treatment with 3% hydrogen peroxide in absolute
methanol. Sections were then incubated in a humid
chamber with the primary antibodies (Table 1) for I hour
at room temperature. This procedure was followed by
immunoperoxidase staining using ABC Elite kits (Vector
Laboratories, Burlingame, CA). To minimize background,
monoclonal antibodies were preincubated with normal
horse serum and polyclonal antibodies with normal goat
serum ( 1:10 dilution). The immunostaining was devel-
oped using 3-amino-9-ethylcarbaole as a chromogen. The
slides were counterstained with Mayer’s hematoxylin. To
evaluate the specificity of the antibodies and the effect of
enzymatic digestion on the immunostaining, positive and
negative control tissue sections were stained as described
elsewhere.6
Results
Age and Sex
The ages of the 121 patients in this study ranged from
24 to 9 1 years (mean, 6 1.3 f 1 1.2 years). Only four pa-
tients were younger than 40 years of age. Fifty-four were
men and 67 were women.

TABLEI . Primary Antibodies, Their Source, Dilution, and Enzymatic Treatment

Enzymatic
Antibody Source Animal (type) Dilution digestion

Antivimentin Dako Corporation Mouse (MoAb) 1:25 No

Santa Barbara, CA
Anti-CEA Hybritech Mouse (MoAb) 1: 1,000 No
San Diego, CA
EMA Dako Corporation Mouse (MoAb) 1 :20 Yes
Santa Barbara, CA
Anti-keratin (AI/A3) Boehringer-Mannheim Mouse (MoAb) 1:300 Yes
Indianapolis, IN
Antithyroglobulin Ortho Diagnostics Rabbit (PAb) 1:3 No
Raritan, NJ
MSA (HHF35) Enzo Biochem Mouse (MoAb) 12300 No
New York, NY
Anticalcitonin Immunonuclear Rabbit (PAb) 1:2,000 Yes
Stillwater, MN
Anti-FVII1R:Ag Dako Corporation Rabbit (PAb) 1:200 Yes
Santa Barbara, CA
Antidesmin Dako Corporation Mouse (MoAb) 1:lO Yes
Santa Barbara, CA

CEA: carcinoembryonic antigen; EMA: epithelial membrane antigen; MoAb: monoclonal antibody; PAb: polyclonal antibody.
MSA: muscle-specific actin; FVII1R:Ag: Factor VIII-related antigen;
No. 2 CARCINOMA OF THE THYROID *
ANAPLASTIC Venkatesh et al. 323

Symptoms at Presentation
The patients could be placed into four different cate-
gories: ( 1) patients with previous differentiated carcinoma
whose disease, after remaining stable for several years,
suddenly became fulminant; (2) patients with long-stand-
ing histologically undiagnosed goiter who experienced
sudden rapid growth of the goiter; (3) patients without
previous thyroid disease who had a rapidly growing neck
mass; and (4) patients who had widespread metastatic dis-
ease diagnosed at excision of metastases or postmortem.
Table 2 summarizes the number of patients in each group.
A rapidly enlarging neck mass with or without a pre-
vious goiter was the most common mode of presentation,
present in 78 of the 12 1 patients. Compressive symptoms
including dysphagia and dyspnea were seen in 42 of the
I2 1 patients. None of the patients had hypothyroidism
or hyperthyroidism.

Metastases
Metastases occurred in 64 (53%) of the patients. The
lung was the most common site of metastases (88%) fol-
lowed by the bones (1 5%).

Pathologic Findings
Histologically, the tumors consisted of an admixture
of spindle cells and pleomorphic giant cells. When the
tumors were predominantly spindle, the cells had a sar-
comatoid appearance, often arranged in fascicles resem-
bling fibrosarcoma or in a storiform pattern similar to
that of malignant fibrous histiocytomas (Fig. 1). In other
cases, the tumor was composed predominantly of large
anaplastic cells containing single or multiple hyperpyk-
notic nuclei and eosinophilic cytoplasm that, on occasion,
presented a rhabdoid-like appearance (Fig. 2). Approxi-
mately 20% of the tumors had areas of squamous differ-
entiation, but keratin pearl formation was not seen (Fig.
3). Numerous multinucleated, benign-appearing, osteo-
clast-like cells were present in five cases (Fig. 4). Hem-
orrhage, necrosis, and inflammation were common find-
ings in all tumors. Forty-six tumors contained residual
foci of well-differentiated carcinoma (35 papillary, seven
follicular, and four Hiirthle cell tumors).
TABLE2. Clinical Presentation of Patients
Grow No. Percent
Transformed anaplastic 21 17.4
Rapid increase in the size
of long-standing goiter 13 10.7
Rapidly growing neck mass 78 64.5
Metastatic disease 13
FIG. 1 . Spindle cell growth pattern mimicking soft tissue sarcoma
(H & E, X200).
Immunocytochemical Results
Twenty-four of the 30 tumors studied (80%) reacted
for keratin. In nine of these cases, the staining occurred
in over 50% of the cells. In most cases, the staining was
evenly distributed throughout the cytoplasm, especially
in the spindle cells (Fig. 5). In two tumors (Patients 3 and
13), the staining pattern was characterized by paranuclear
globular inclusions that reacted for both keratin and vi-
mentin (Figs. 6A and 6B). Light microscopic analysis
showed that these tumors were composed of giant cells
having rhabdoid features characterized by eosinophilic
cytoplasm and eccentric nuclei (Fig. 2).
Twenty-eight tumors stained for vimentin. The staining
pattern for this cell marker was similar to that for keratin.
Twenty-two tumors (73%)coexpressed both intermediate
filaments, often in the same cells (Figs. 6A and 6B). Four
cases presented with residual papillary carcinoma (Patients
2, 5, 22, and 27). All four reacted for keratin in the well-
differentiated carcinoma areas, but only two stained in
324 July 15 1990
CANCER Vol. 66

reactivity for keratin occurred only in the spindle, not in

the multinucleated osteoclast-like, cells. The immuno-
histochemical results of the 30 primary tumors are sum-
marized in Table 3. Metastases from the lung and cervical
lymph nodes from two patients were also studied and
showed reactivity only for vimentin.

Other Observations
Four patients had histories of irradiation to the head
and neck area, and one patient had been treated for hy-
perthyroidism with radioactive iodine several years earlier.
Second malignancies were noticed in four patients.
Adenocarcinoma of the stomach, endometrial carcinoma,
melanoma, and Hodgkin’s disease were present in one
patient each.

Survival
Since 108 patients (89%) have died of anaplastic car-
cinoma, survival was analyzed according to mean & stan-

FIG. 2. Giant cell pattern. The cells have abundant eosinophilic cy-
toplasm and eccentric nuclei (H & E, X300).

the anaplastic areas. No reactivity for vimentin in the

residual well-differentiated carcinomas was seen in any of
the four cases.
Immunostaining for epithelial membrane antigen
(EMA) occurred in ten (33%) tumors. All of these also
reacted for keratin. In general, in these tumors, fewer cells
reacted for EMA, the former marker, than for keratin.
The immunostaining tended to occur along the cell
membrane (Fig. 7).
Focal reactivity for thyroglobulin (1% to 5% of cells)
was obtained in three cases. No entrapped normal thyroid
or low-grade carcinoma was revealed in serial sections
stained for this marker in these cases. Three additional
tumors, two of which were squamous, stained for carci-
noembryonic antigen (CEA) (Fig. 8). No reactivity was
seen for calcitonin, desmin, muscle-specific actin, or Fac-
tor VIII-related antigen in any of the cases.
One of the tumors presented numerous multinucleated
osteoclast-like cells (Patient 26). Numerous spindle cells FIG. 3. portion of an anaplastic carcinoma having a squamoid ap-
in this tumor stained for both vimentin and keratin, but pearance (H & E, ~ 2 0 0 ) .
No. 2 ANAPLASTIC
CARCINOMA
OF THE THYROID - Venkatesh et al. 325

Table 5 summarizes these data. These two groups were

statistically similar according to sex distribution and mean
age at diagnosis. Of the initial group, 88% have died,
whereas 95% of the transformed group have died. This
difference is not statistically significant, nor were their
lengths of survival different. The surgery performed most
often in both groups was total thyroidectomy. The inci-
dence of radiotherapy was similar. The extent-of-disease
parameter could not be analyzed owing to the definition
of the transformed group. Chemotherapy was adminis-
tered significantly more often to the transformed group,
and the incidence of distant metastases was significantly
higher in the transformed group.
Patients were also grouped into long-term or short-term
survivors. Long-term survivors were defined as patients
living longer than 24 months. The long-term survivors
*
were significantly younger at diagnosis (54.1 13.7 years)
than were the short-term survivors (63.9 ? 10.5 years, P
< 0.01) and had significantly less disease at diagnosis ( P
< 0.03). The long-term survivors received total and sub-

FIG.4. Numerous osteoclast-like giant cells intermixed with spindle

tumor cells (H & E, X200).

dard deviation (SD) of length of survival. Only those who

have died are included in this analysis. The mean k SD
survival duration of these patients is 7.2 f 10 months.
The lengths of survival according to the prognostic vari-
ables are summarized in Table 4. Men and women had
similar survival durations. The mean k SD age at diag-
nosis of the patients was 6 1.3 f 1 1.2 years. The younger
the patient at diagnosis, the longer he survived (r = -0.29,
P < 0.01). If the disease was confined to the neck, the
patient’s mean survival was longer than if his disease had
spread beyond the neck area (8.1 ? 10.7 years versus 3.3
f 3.7 years, P < 0.001). Patients also survived longer if
their treatment was total or subtotal thyroidectomy and
if they received radiotherapy, chemotherapy, or both;
however, type of treatment did not make a statistically
significant difference.
We compared the prognostic variables of patients whose
presenting histologic diagnosis was anaplastic carcinoma
with those whose diagnosis Of well-differentiated carci- FIG.5. Anaplastic carcinoma showing positive reaction for keratin in
noma was later transformed into anapiastic carcinoma. squamoid areas of the tumor (ABC, x200).
326 CANCERJuly 15 1990 Vol. 66

FIGS.6A AND 6B. (A) Immunocytochemical preparation of the same tumor as case illustrated in Figure 2 (Patient 2) showing reactivity for keratin
in a globoid-like pattern. (B) Immunopreparation for vimentin demonstrating reactivity for vimentin in a staining pattern similar to that of keratin
(ABC, X300).

total thyroidectomies more often, but the difference be-
tween their surgery and that of the short-term survivors
was not statistically significant. The effect of the prognostic
variables is summarized in Table 6.
Thirteen patients were still living at the time of the
study, after 3, 15, 16, 43, 44, 61, 72, 73, 155, 175, 232,
243, and 3 13 months, respectively. Ten of the 12 long-
term surviving patients received combined radiotherapy
and chemotherapy postoperatively.
Discussion
The age and sex characteristics of our patients resemble
those found in other ~ e r i e s . Carcangiu
~-~ et ~ 1and
. Shvero
~ entiated carcinoma elsewhere. Williams has suggested that
et u L , ~however, found a higher prevalence of the tumor
in men than we did,
The incidence of anaplastic carcinoma in the US ranges
from 5% to 14% of the thyroid cancer al-
though it differs geographically and is higher in areas of
endemic goiter.”
Most cases of anaplastic carcinoma occur in elderly
patients. Only four patients in our series were younger
than 40 years. Three of these presented with anaplastic
carcinoma, whereas the remaining patient initially had a
papillary carcinoma which later transformed into ana-
plastic. The anaplastic tumors in all four cases were made
of a mixture of spindle and giant cells. Another case of
anaplastic carcinoma occurring in a young person was
’’
reported by Albores-Saavedra el al. in a 22-year-old pa-
tient. The classic presentation of a rapidly enlarging neck
mass was seen in 64% of our patients.
Twenty-one patients in our series initially had a diag-
nosis of differentiated thyroid carcinoma. Seven of them
had received prior radioactive iodine treatment, but none
had received any other form of radiotherapy. A significant
percentage of our patients (30%) had foci of well-differ-
radiation may play a role in anaplastic transformation.”
Radioactive iodine has also been suggested to increase the
rate of anaplastic transformation of differentiated thyroid
cancer.I3-l6 However, Tubiana et al. report no cases of
anaplastic transformation of differentiated thyroid car-
cinoma among 359 patients treated with external-beam
radiation or radioactive iodine.” Nine of our patients in
the transformed anaplastic group had received no radio-
active iodine.
No. 2 ANAPLASTIC
CARCINOMA
OF THE THYROID * Venkatesh et al. 327

in normal endometrium22 as well as in a wide variety of

epithelial neoplasms, especially adenocarcinomas of the
e n d o m e t r i ~ m , serous ~ ~ . ~ ~carcinomas of the
renal cell carcinoma^,^^.^^ anaplastic carcinomas of the
t h y r ~ i d , ' * . ' ~large
, ~ ' cell carcinomas of the lung,28%29 sar-
comatoid carcinomas of the breast,30and spindle cell car-
cinomas of both the urinary bladder3' and aerodigestive
tra~t.~~.~~
Coexpression of vimentin and keratin occurred in 73%
of the tumors in the current series. These results are com-
parable with those reported in other series (17.5% to
100%).'8,27,34,35 Six of the tumors from our patients reacted
for vimentin but not for keratin. Since none of these tu-
mors reacted for any of the mesenchymal markers (des-
min, muscle-specific actin, or Factor VIII-related antigen)
used in this study but all had the characteristic morpho-
logic features of anaplastic carcinomas of the thyroid, we
believe that these cases also were anaplastic carcinomas.
The reasons why they did not stain for keratin are not
clear but could be multiple, including the degree of tumor
differentiation, inactivation of the antigen due to pro-

FIG. 7. Immunoperoxidase preparation demonstrating peripheral

staining pattern for epithelial membrane antigen (ABC, X300).

Immunocytochemical results of this study indicate that

immunocytochemical study can assist in differentiating
anaplastic thyroid carcinoma from other neoplasms with
which they can be confused, i.e., various types of sarco-
mas, melanomas, and some anaplastic large cell lympho-
mas. The fact that keratin reactivity was present in 80%
of the tumors tested and that those tumors that expressed
EMA and CEA also reacted for keratin indicates that ker-
atin is the single most useful epithelial marker for the
diagnosis of anaplastic thyroid carcinoma. These results
are in agreement with those obtained by other^^^'*-^^ who
found keratin in 40% to 100%of the cases studied, indi-
cating that most anaplastic thyroid neoplasms can be re-
garded as true carcinomas despite their sarcoma-like ap-
pearance.
Although early studies indicated that vimentin was a
marker for mesenchymal differentiation and that the im-
munocytochemical demonstration of this intermediate
filament would allow for the differentiation between car-
FIG.8. Immunostaining preparation from Patient 15. The reactivity
cinomas and sarcomas?' this Concept is no longer tenable. for carcinoembryonic antigen is localized in the squamoid portions of
Coexpression of keratin and vimentin has been reported the tumor (ABC, X200).
328 July 15 1990
CANCER Vol. 66

TABLE3. Immunocytochemical Results for 30 Cases of Anaplastic different groups can be explained, at least in part, by dif-
Thyroid Carcinoma ferences in the type of antibodies to the thyroglobulin
Patient used. A case in point is the recent study by de Micco et
no. Pattern Ker Vim EMA CEA Thy ~zl.,~'who reported reactivity for thyroglobulin in 17% of
the anaplastic carcinomas stained with a polyclonal an-
I Giant cell 0 3+ 0 0 0
2 Giant cell 4+ 4f 0 0 I+ tibody and one stained with monoclonal antibodies,
3 Spindle and giant 0 3+ 0 0 0 whereas 50% to 67% of the same tumors reacted with
cell three other monoclonal antibodies used in that study.
4 Spindle cell I+ 3+ 0 0 If
5 Giant cell 0 4+ 0 0 0 Alternatively, because of the frequent association be-
6 Spindle and giant 0 3+ 0 0 0 tween foci of well-differentiated forms of thyroid carci-
cell noma and entrapment of normal thyroid epithelium
7 Spindle cell I+ 4f 0 0 0
8 Spindle cell I+ 4+ 0 0 0 within areas of anaplastic carcinoma, thyroid colloid and
9 Spindle and giant I+ 4+ 0 0 0 thyroglobulin may have been phagocytized by anaplastic
cell tumor cells and, therefore, responsible for the high fre-
10 Spindle and giant 0 4f 0 0 0
cell quency of positivity for thyroglobulin reported in some
II Spindle and giant 3+ I+ If 0 0 studies.
cell Anaplastic thyroid carcinomas containing numerous
12 Spindle and giant 2f I f 0 0 0
cell multinucleated, benign-appearing, osteoclast-like cells like
13 Squamoid 4+ 2+ 0 0 0 those found in five of the tumors in this series are well
14 Giant cell I+ 2+ 0 0 0 recognized as a pattern known to occur in a minority of
15 Squamoid 4+ 0 3+ 2+ 0
16 Spindle, giant cell, 2+ 4+ I+ 0 0 cases. The fact that we were able to demonstrate reactivity
and squamoid for keratin in the spindle and anaplastic giant tumor cells
17 Spindle and giant 2+ I+ 3+ 0 0 but not in the benign-looking, osteoclast-like cells in the
cell
18 Squamoid 4f 3f I+ 0 0 only tumor in which immunocytochemical studies were
19 Spindle and giant I f 4+ 0 0 0 performed appears to support light-microscopic and elec-
cell tron-microscopic evidence suggesting that these cells are
20 Giant cell 2+ 4+ 0 0 0
21 Spindle and giant I f 3+ I+ 0 0 not tumoral but may represent nonneoplastic mesenchy-
cell ma1 elements attracted by the tumor, perhaps through
22 Giant cell 0 4+ 0 0 0 some secretion of cancer cells.7
23 Squamoid 3+ 3+ 3+ It 0
24 Giant cell 2+ 4 f 0 0 0 Although some immunocytochemical studies44have
25 Squamoid 4+ 2+ 3+ 0 0 indicated that a large percentage of anaplastic tumors of
26 Spindle and giant 2f 2f 0 0 0 the thyroid are medullary carcinomas, and therefore C -
cell
27 Spindle and giant 2+ 0 2+ 0 0 cell-derived neoplasms, the lack of immunoreactivity for
cell
28 Squamoid 3+ I+ I+ 0 0
2+ 2+ 0 0 I+ 4. Prognostic Variables and Their Effect on Survival
TABLE
29 Giant cell
30 Spindle and giant 3+ 2+ 0 I+ 0
cell No. of Survival
patients (mb) P
Ker: keratin; Vim: vimentin; EMA: epithelial membrane antigen; CEA: Sex
carcinoembryonic antigen; Thy: thyroglobulin; 0: no reaction; 1+: 1%- Female 59 6.8? 11.1
25% positive cells; 2+: 26%-50%; 3+: 5 1 7 ~ 7 5 % ;4 f : >75% positive 20.9
Male 49 6.7 2 7.8
cells. Extent of disease*
Neck area 60 8.1 * 10.7 <o.oo I
longed fixation, or the inability of the antibodies used in
Distant metastasis 28 3.3 * 3.7
Surgery*
the study to identify certain cytokeratin polypeptides. Total thyroidectomy and
Reactivity for thyroglobulin is almost invariably de- subtotal thyroidectomy 39 8.9 k 12.8 >0.1
Lobectomy and biopsy 49 4.7 _t 4.3
tected in well-differentiated tumors of the thyroid, but Radiotherapy
inconsistently detected in poorly differentiated carcino- Yes 44 8.5 k 11.8 >o.2
mas, especially anaplastic carcinoma^.^^-^^ Although some No 64 5.5 ? 7.8
Chemotherapy
investigator^^,^^ have been unable to identify reactivity Yes 46 7.3 k 11.0
for thyroglobulin in any of the cases studied, others have No 62 5.4 *5.4
>0.2
reported immunoreactivity for this marker in up to 70% Chemotherapy and
radiotherapy 30 9.1 k 13.0 >o.l
of their cases.8,34,40-43
The results of this study indicated No chemotherapy or
that immunostaining for thyroglobulin was of little or no radiotherapy 48 4.8 k 7.8
value for diagnosing anaplastic thyroid carcinomas. It is * Patients with transformed anaplastic carcinoma were excluded from
possible that the discrepancies in the results obtained by this analysis.
No. 2 ANAPLASTICCARCINOMA OF THE THYROID - ve/'enkate.Yhet a/. 329
TABLE
5. Initially Anaplastic and Transformed Anaplastic Patient Groups

Initial anaplastic Transformed anaplastic

(100 patients) (2 1 patients)

Variable No. Percent No. Percent P value

Men 43 43 12 57 >0.3
Women 57 57 9 43
Age (yr) 63.1 * 11.6 59.4 f 10.8 >0.2
Died 88 88 20 95 >0.4
Length of survival (mo) 6.5 t 9.3 7.8 f 11.3 >0.6
Surgery
Total thyroidectomy 47 47 14
Subtotal thyroidectomy 8 8 2 67
20.1
Lobectomy 30 30 5 10
Biopsy 25 25 0 24
Irradiation 51 51 7 33 <0.2
Chemotherapy 46 46 18 86 <0.00 1
Distant metastases 47 47 17 81 <0.01

calcitonin in any of the tumors studied in this series does
not support that observation. In our opinion, as well as
that of others, anaplastic giant and spindle cell forms of
medullary carcinomas of the thyroid can occur but are
extremely rare.'8.45-48
Results of treatment were dismal. More radical surgery
did not provide a significant advantage over less radical
surgery. Interestingly, ten of the 12 long-term survivors
received combined multimodality treatment including
combination chemotherapy and radiotherapy. Kim and
Leeper report complete tumor regression in eight of their
nine patients treated who underwent combination che-
, ~ ~ Tallroth et al. report
motherapy and r a d i ~ t h e r a p yand
a complete remission in four of their 34 patients after
combination chemotherapy and radi~therapy.~' However,
comparing the long-term survivors (> 24 months) and
the short-term survivors with regard to age, sex, extent of
disease, type of surgery, and use of radiotherapy or che-
motherapy reveals that the only significant differences be-
tween the two groups were in the age at presentation and
the extent of disease at presentation: the long-term sur-
vivors were significantly younger at presentation and had
less disease.
The role of combined multimodality treatment for an-
aplastic carcinoma needs to be further evaluated pro-
spectively. Patients in the initially anaplastic group also
survived longer than those in the transformed anaplastic
group, but the difference was not statistically significant.
Our data suggest that patients with transformed anaplastic
carcinoma behaves no differently from initially diagnosed
anaplastic carcinoma.
In conclusion, we find that anaplastic carcinoma is as-
sociated with a dismal prognosis but that combined mul-
timodality therapy may offer hope of long-term survival,
particularly in younger patients with less disease at the
time of diagnosis.

TABLE6. Short-Term and Lone-Term Survivors

Short-term survivors (104 Long-term survivors

patients) (17 patients)
Characteristics No. Percent No. Percent P valiie

Men 47 45 8 47
Women 57 55 9 53 >0.9
Age (yr) 63.9 f 10.5 54.1 t 13.7 <0.0 1
Extent of disease
Gland only 9 9 5 29
Gland t nodes 8 8 3 18
Gland + nodes t neck 53 51 7 41 >0.03
Distant metastases 34 33 2 12
Surgery
Total thyroidectomy 39 38 9 53
Subtotal thyroidectomy 7 7 3 18
Lobectomy 30 29 5 >O. 1
29
Biopsy 28 27 0
Radiotherapy 45 43 11 65 >0.2
Chemotherapy 45 43 11 65 >0.2
Transformed 18 17 3 18 >0.9
3 30 CANCERJuly 15 1990
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