MALIGNANT GIANT-CELL TUMORS OF THYROID GLAND
S. W. BERKHEISER, M.D.
Department of Laboratories of the Guthrie Clinic, Robert Packer Hospital, Sayre, Pennsylvania
Giant-cell carcinomas of the thyroid gland are not especially rare, since they
usually comprise from 4 to 10 per cent of the various histologic types of thyroid
malignancy (Clute and Warren, 2 Horn et al.,h and Smith et al.12). Recently in a
review of a series of thyroid carcinomas 2 unusual variants of giant-cell tumor
were observed. Both were originally thought to be giant-cell carcinomas of the
thyroid gland, but further study revealed several interesting features seldom
reported.
REPORT OF CASES
Case 1
Clinical data. A 65-year-old white man was admitted to the Robert Packer Hospital
October 8, 1947, because of a lump in the right side of the neck which produced difficulty in
swallowing. He was known to have had a goiter for 30 years, but 2 months prior to admission
the mass increased rapidly in size.
On physical examination the right lobe of the thyroid gland was found to be enlarged to
3 times normal size, and was nodular and firm. Roentgenograms of the chest disclosed
several dense shadows, 2 cm. in diameter, in the right middle and lower lobes. These were
thought to be metastatic tumors. There was no involvement of the skeletal system. Laboratory findings were within normal limits.
The right lobe and isthmus of the thyroid gland were resected on October 15, 1947. The
right lobe was replaced by a firm nodular tumor that was adherent to the adjacent neck
structures. The neoplasm had infiltrated posteriorly to the esophagus. The left lobe was
of average size and was not involved by tumor.
Postoperatively, the patient received irradiation therapy (1200 r) to the thyroid region,
and he was discharged on the eighth hospital day. He was readmitted December 26, 1947,
because of difficulty in breathing and swallowing.
Examination disclosed recurrence of the tumor at the former site of the right lobe of
the thyroid gland, which was firm and fixed. Roentgenograms showed numerous metastatic
lesions throughout both lung fields, but no evidence of bone involvement. Treatment was
largely supportive, and the patient died 5 days after the second hospital admission.
Autopsy. The principal autopsy findings were as follows: The region of the
right lobe of the thyroid gland was occupied by a firm grayish yellow neoplasm,
which measured 10 by 7 by 3 cm., and weighed 50 Gm. The right anterior
cervical as well as the deeper lymph nodes were enlarged and contained similar
tumor. The right external jugular vein and the superficial thyroid veins contained grossly visible tumor thrombi. Both lungs contained numerous discrete
metastatic nodules varying from 2 to 7 cm. in greatest diameter. Similar metastatic lesions were also present in the right eighth and ninth ribs. The left lobe
of the thyroid gland was small and firm, but not involved.
Histopathology. Sections of the tumor removed at operation disclosed a bizarre
type of giant-cell carcinoma with 2 definite cell types. One type consisted of
Received for publication August 17, 1953.
Dr. Berkheiser is Assistant Pathologist.
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pleomorphic spindle cells with irregular hyperchromatic nuclei and occasional
atypical mitoses. The other type was characterized by large multinucleated
cells with abundant eosinophilic cytoplasm. These cells had numerous, small,
uniform, vesicular nuclei that tended to be arranged centrally. The number of
nuclei varied from about 20 to 60 (Fig. 1). Atypical mitoses were not present in
the giant cells. These cells had a strong resemblance to the multinucleated giant
cells usually observed in benign giant-cell tumor of bone. In many regions the
giant cells had a definite relationship to vascular spaces, and in some instances
appeared to lie within endothelial-lined spaces. The recurrent thyroid tumor
observed at autopsy and the metastatic lesions had a similar histologic picture
(Fig. 2).
Sections of the operative specimen together with representative autopsy
sections were submitted to the Committee on Thyroid Cancer of the American
Goiter Association. The consensus was that the tumor represented a giant-cell
carcinoma of the thyroid gland.6
Case 2
Clinical data. A 77-year-old woman was admitted to the hospital October 8, 1948, because of a lump in the neck, which had been present for 1 year. The lump had increased in
size rapidly, and had become tender 6 months prior to admission. There was a 10-pound loss
in weight over the same period. Her history disclosed that she had hypertension and Parkinson's disease for the last 10 years.
°
On physical examination the right lobe of the thyroid gland was found to be enlarged
and firm. The right external jugular vein was markedly dilated. Roentgenograms showed
substernal extension of the right lobe of the thyroid gland with tracheal compression. There
was no evidence of bony metastasis. Shortly after admission the patient developed a daily
spiking temperature that did not respond to antibiotic therapy. Laboratory studies showed
an anemia with a red blood cell count of 2,500,000, hemoglobin of S.O Gm. per 100 ml., and a
leukocytosis of 18,000. She received multiple whole blood transfusions, but died 1 month
after admission, before exploration of the thyroid gland could be performed.
Autopsy. The main autopsy finding was marked enlargement of the thyroid
gland, which weighed 225 grams. The right lobe was replaced by a large tumor
mass, 11 cm. in diameter, firm, gray-brown and slightly nodular. The capsule
was partially intact but some extension into the left lobe and into the adjacent
neck structures was noted. The trachea, right carotid and right subclavian
arteries were compressed by the tumor. Both lungs contained numerous metastatic nodules, the largest of which measured 1.5 cm. in diameter. Metastases
were also present in the regional cervical lymph nodes, stomach and pancreas.
There was no involvement of the skeletal system.
Hislopalhology. The tumor, originating in the right lobe of the thyroid gland,
demonstrated an unusual pattern. It was characterized by numerous multinucleated giant cells of a different nature than those observed in the first case.
The distinguishing cells were large and irregular, with bizarre nuclei. Numerous
cells were racquet-shaped, others resembled a ribbon or strap (Fig. 3), and there
were a number of vacuolated giant cells. The cytoplasm of these cells was
granular and eosinophilic, but cross-striations were not seen with the routine
hematoxylin and eosin stain. The stroma was dense and fibrous with occasional
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large zones of necrosis. Clumps of tumor cells were present in several of the
capsular veins. In a few regions transitions from poorly differentiated epithelial
cells to a definitely sarcomatous type of growth was noted. The metastatic lesions
demonstrated an identical histologic pattern as the primary thyroid tumor.
Representative sections of the thyroid and the metastatic lesions were submitted to the Committee on Thyroid Cancer of the American Goiter Association.
Three of the 5 consultants concurred in a diagnosis of giant-cell carcinoma of
the thyroid gland. Two consultants differed in the interpretation of this tumor.
One classified the lesion as sarcoma, possibly myogenic in origin. The other
consultant thought it was consistent with squamous carcinoma with giant cells,
imitating fibrosarcoma and rhabdomyosarcoma.6
Since the exact type of giant-cell tumor in the latter case was uncertain, it
was decided to study it further by specific histologic technics. Multiple sections
of the original thyroid tumor, as well as the metastatic lesions, were stained by
Masson-Goldner, Mallory's phosphotungstic acid hematoxylin and Heidenhain's
iron hematoxylin methods. Each of these technics demonstrated within the
cytoplasm of the multinucleated giant cells definite cross-striations of the type
usually observed in rhabdomyosarcoma (Fig. 4). The cytoplasm of some of the
ribbon- and racquet-shaped cells had a granular cytoplasm with imperfect and
irregular cross-striations. Other cells demonstrated fine longitudinal fibrils.
DISCUSSION
True sarcomas of the thyroid gland may occur but are extremely rare. Smith13
and Hebbel3 have shown that many of the pleomorphic giant-cell tumors
formerly diagnosed as sarcomas were actually carcinomas.
According to Rather 10 the most common type of giant-cell carcinoma of the
thyroid gland is one that is characterized by multinucleated cells with irregular
and distorted nuclei, intermixed with smaller anaplastic spindle cells. This
variety is most likely to be mistaken for fibrosarcoma. Rather11 has also
emphasized the occurrence of another giant carcinoma of the thyroid gland that
bears a striking morphologic resemblance to benign giant-cell tumor of bone.
This variety is extremely uncommon, since he was able to find only 3 cases in
the literature. Only 1 of these, however, was substantiated by autopsy. Rather 11
reported an additional case, and discussed in detail the origin of the multinucleated cells in the giant-cell tumors of bone and thyroid gland. He found
that these cells were related to vascular channels, and that in many instances
they appeared to originate directly from the inner lining of the channels.
Identical features were observed in our first case. Sections of the primary
FIG. 1 (left upper). Case 1. Giant-cell carcinoma of the thyroid gland showing typical
multinucleated giant cells closely associated with vascular channels. H. and E. X 450.
FIG. 2 (right upper). Case 1. Metastasis to lung of giant-cell carcinoma of thyroid gland.
Note intimate association of giant cells to vascular channels. H. and E. X 190.
FIG. 3 (left lower). Case 2. Photomicrograph displaying numerous racquet-shaped giant
cells. Ribbon and strap forms are also numerous. Heidenhain's iron hematoxylin stain.
X 100.
FIG. 4 (right lower). Case 2. Large giant cell with cross-striations in the cytoplasm,
characteristic of rhabdomyosarcoma. Masson-Goldner trichrome stain. X 560.
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GIANT-CELL TUMORS OF THYROID GLAND
FIGS.
1-4
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thyroid tumor were compared with sections of benign giant-cell tumors of the
femur and fibula, and were found to be quite similar. There was a definite
relationship of the multinucleated giant cells to vascular channels in both the
thyroid and bone tumors. This relationship was maintained in the metastatic
lesions, and was especially prominent in the lungs (Fig. 2).
Histologically, the tumor in the second case closely resembles a rhabdomyosarcoma. It fulfills the criteria established by Stout14 necessary for that diagnosis,
namely: the presence of strap- or racquet-shaped cells, the presence of crossstriations in the cytoplasm, and the presence of large vacuolated giant cells.
Survey of the literature reveals scant information concerning tumors of the
latter type originating in the thyroid gland. Hirsch4 described a malignant
mixed tumor of the thyroid gland that contained large spindle cells with crossstriations. This tumor produced metastases to the neck, trunk and bones.
Portmann 7 listed 1 case of rhabdomyosarcoma of the thyroid gland among 220
cases of thyroid cancer. Neither of these authors presented detailed descriptions
or photomicrographs of the tumors.
Since the development of malignant mesoblastic tumors of the thyroid gland
is extremely rare, the origin of the rhabdomyosarcoma from thyroid gland in
the second case might seem questionable. Congenital teratomas of the thyroid
gland with striated muscle components have been reported more frequently
(Bale,1 Potter, 8 and Pusch and Nelson9). The origin of the rhabdomyosarcoma
of the thyroid gland might possibly be explained on the basis of embryonal
misplacement of striated muscle.
Whatever the site of origin, however, the giant-cell tumors of the thyroid
gland form an important group because of their uniformly poor prognosis. These
tumors invariably cause death of the patient within a year of the time of diagnosis. From the standpoint of treatment they are also important because of their
lack of response to irradiation. Surgery is of little value, since most of these
tumors progress rapidly and are usually far advanced before the patient seeks
help.
SUMMARY
Two unusual giant-cell tumors of the thyroid gland are presented: one, a
giant cell tumor resembling giant-cell tumor of bone; the other, a highly malignant rhabdomyosarcoma which has seldom been recognized or reported.
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