Teratomas comprise the most common extragonadal germ
cell tumors in childhood (1). Teratomas of the neck in adults
are extremely rare. The tumors of the head and neck account
for 5% of all benign and malignant germ cell tumors and for
6% of all teratomas, where the most common sites of involve-
ment are the soft tissue of the neck, thyroid, superficial facial
structures, oral cavity, nasopharynx, and orbit (1, 2). Most
teratomas involving the thyroid are benign and occur in chil-
dren. We report a case of primary malignant thyroid terato-
ma in a 31-yr-old female. To our knowledge, this is the first
case of malignant teratoma with a primitive neuroectoder-
mal tumor component in the thyroid in Korea.
A 31-yr-old woman presented to our clinic with a two-
month history of a fast growing non-tender mass in the neck.
No pertinent past medical illness or family history was pre-
sent. On physical examination, a large hard and fixed mass
was palpated in the central neck, mostly occupying the thy-
roid gland. The laboratory findings were unremarkable, and
her thyroid function was normal. The computed tomogra-
phy scanning of the neck showed a 7.0×5.5 cm solid het-
erogeneous enhancing mass arising in the right lobe of thy-
roid gland (Fig. 1). It was invading beyond the thyroid gland
and extended down to the anterior mediastinum. The trachea
and right sternocleidomastoid muscle were deviated to the
left. The supraclavicular, highest mediastinal, and bilateral
prevascular lymph nodes were all enlarged. The largest lymph
node was over 2.5 cm at the levels II and III.
The F-18-FDG positron emission tomography (PET) scan
showed a huge hypermetabolic mass in the right thyroid gland
with multiple hypermetabolic lesions in the neck and in the
prevascular area of mediastinum. Fine needle aspiration slides
revealed diffusely scattered oval to spindle shaped atypical
cells with rare eosinophilic amorphous material suggesting
poorly differentiated carcinoma possibly consistent with me-
dullary carcinoma. She underwent total thyroidectomy with
bilateral modified radical neck dissection. The tumor was
penetrating the thyroid capsule and was invading the adja-
cent tissue involving the right recurrent laryngeal nerve. The
upper portion of the sternum was cut to dissect the inferior
portion of right thyroid. The lymph nodes along the chain
were removed after the sheaths of the common carotid, and
internal jugular vein were opened. The postoperative period
was uneventful except transient hypocalcemia. On the third
day of operation, the total serum calcium level was 6.7 mg/
dL with a ionized calcium level of 0.88 mM/L. Calcium was
replaced by oral medication.
Eunyoung Kim, Tae Seok Bae,
Youngmee Kwon, Tae Hyun Kim,
Ki-Wook Chung, Sun Wook Kim,
Jungsil Ro, Eun Sook Lee
Research Institute and Hospital, National Cancer
Center, Goyang, Korea
Address for correspondence
Eun Sook Lee, M.D.
Center for Breast Cancer, National Cancer Center,
809 Madu-1-dong, Ilsan-gu, Goyang 411-769, Korea
Tel : +82.31-920-1633, Fax : +82.31-920-1759
E-mail : firstname.lastname@example.org
J Korean Med Sci 2007; 22: 568-71
Copyright � The Korean Academy
of Medical Sciences
Primary Malignant Teratoma with a Primitive Neuroectodermal Tumor
Component in Thyroid Gland
: A Case Report
Teratomas comprise the most common extragonadal germ cell tumors in childhood.
Most teratomas involving the thyroid are benign and occur in children. However,
the adult cases reported are mostly malignant and commonly arise in the thyroid.
We report a case of a 31-yr-old female with a huge neck mass. Pathologic examina-
tion revealed it to be malignant teratoma composed of primitive neuroepithelial tis-
sue with primitive neural tubes and loose myxoid to fibrous immature mesenchymal
stroma. The patient underwent extensive evaluation of the thyroid gland with com-
puted tomography (CT) scan and positron emission tomography (PET) scan, which
revealed no evidence of metastatic disease. She underwent total thyroidectomy
with bilateral modified radical neck dissection, intensive chemotherapy and radio-
therapy. At 22-months of follow-up, the patient has remained euthyroid and showed
no evidence of recurrence. This is the first case, to our knowledge, of malignant
thyroid teratoma with a exuberant primitive neuroectodermal tumor component in
Key Words : Malignant Teratoma; Thyroid Neoplasm; Thyroid Disease
Received : 29 September 2005
Accepted : 9 March 2006
Malignant Thyroid Teratoma
On gross examination, the mass was occupying most of the
right lobe of thyroid gland with a ill-defined border, measur-
ing 7.5×5.0×4.7 cm. The cut surface was grayish white,
hemorrhagic, and necrotic with focal cystic changes. Many
lymph nodes were grossly involved by the tumor (Fig. 2).
The microscopic examination showed that the tumor was
mainly composed of primitive neuroepithelial tissue with
primitive neural tubes and loose myxoid to fibrous immature
mesenchymal stroma (Fig. 3). The normal thyroid follicles
were intermingled or adjacent to the tumor. The tumor cells
were pleomorphic and partly necrotic with hyperchromatism
and frequent mitotic figures (4-6/10 high power fields). A
Fig. 1. Computed tomography (CT) scan of malignant teratoma.
A 7.0×5.5 cm mass is observed within the right anterior neck.
The trachea and right sternocleidomastoid muscle are deviated
to the left.
Fig. 3. Microscopic findings of malignant teratoma. The tumor is
mainly composed of primitive neuroepithelial cells and neural tu-
bules (H&E stain, ×100).
Fig. 4. Microscopic findings. Mature cartilage is also noted within
the primitive neuroepithelial tissue (H&E stain, ×100).
Fig. 2. Gross finding of malignant teratoma. The mass is mainly
located in the right lobe of thyroid with extrathyroidal extension
and multiple lymph node involvement.
E. Kim, T.S. Bae, Y. Kwon, et al.
multitude of small cystic spaces was lined by mature squa-
mous or glandular epithelium. Islands of mature cartilage
were noted within the primitive neuroepithelial tissue (Fig.
4). Metastases were present in 25 of total 58 lymph nodes,
where metastatic components were only composed of a prim-
itive neuroepithelial component. The tumor cells were posi-
tive for synaptophysin, focally positive for cytokeratin, neu-
rofilament, desmin, and CD99 on immunohistochemical
staining. The primitive neuroepithelial component comprised
more than 4 in low power magnification fields (×4 objec-
tive with a ×10 ocular, using bvx.), which thus was catego-
rized as malignant teratoma according to the Thompson et
al.’s criteria (3).
After she recovered from the surgery, she was placed on
an intensive chemotherapy according to the National Can-
cer Institute protocol reported by Grier et al. (4). She received
14 cycles of chemotherapy consisting of VAC (vincristine 2
mg, doxorubicin 75 mg/m2, cyclophosphamide 1,200 mg/
m2, every 3 weeks), alternate with IE (ifosfamide 1,800 mg/
m2with mesna, and etoposide 100 mg/m2for five days by
After the completion of the 10th cycle of chemotherapy,
she received external beam radiation therapy (EBRT) with a
total dose of 55.8 Gy, 5 days/week. The treated volume in-
cluded the thyroid bed, cervical lymph nodes, and upper
mediastinum. Upon completion of radiation therapy, she
received further chemotherapy. Dactinomycin at 1.25 mg/
m2replaced doxorubicin. The patient completed total 17
cycles of chemotherapy. Dose reductions along with granu-
locyte colony-stimulating factor and erythropoietin supports
She has been remains free of disease for 22 months after
Malignant teratoma of the thyroid in adult was first report-
ed by Lurje in 1908, who described a case of a 53-yr-old wo-
man (5). By 1999, nineteen cases of malignant teratoma of
the thyroid had been reported in the medical literature, em-
phasizing the aggressive clinical course of the disease (1). After
then, 3 cases have been reported (2, 6, 7). There were a pre-
dominance of primitive neuroepithelial component within
mature squamous or glandular epithelial components and
mature cartilage in our case.
Malignant thyroid teratoma is an aggressive tumor, with a
short median survival (median, 8 months) after surgery with-
out postoperative chemotherapy. The commonly used drugs
are the same agents effective in the treatment of germ cell
tumors (6, 8, 9). It usually consists of bleomycin, cisplatin,
and etoposide (BEP) protocol alone or in combination with
other agents aimed to treat the sarcomatous component. The
most common agents included are vincristine, cyclophos-
phamide and actinomycin-D (2, 6).
Chen et al. reported a 32-yr-old woman with malignant
thyroid teratoma who underwent a simple lobectomy of the
thyroid (8). She received chemotherapy of BEP and was still
alive without evidence of disease after 6.7 yr. No further local
radiotherapy or operation was arranged.
Djalilian, et al. reported a 33-yr-old woman with malignant
thyroid teratoma who underwent 5 cycles of chemotherapy
with vinblastin, ifosfamide, and cisplatin (1). After 3 further
cycles of carboplatin and etoposide, the patient underwent
autologous bone marrow stem cell transplant. She did well
with evidence of stable disease in the lungs at 21 months from
the diagnosis but died of metastatic teratoma. Recently, high-
dose chemotherapy in combination with autologous stem
cell transplant has been found to be effective in prolonging
the survival in some patients with gonadal germ cell tumors
Jayaram et al. treated a malignant teratoma of the thyroid
with predominantly neuroepithelial differentiation with sur-
gery alone (7). She died after 15 months with metastases to
liver, vertebra, paraaortic and paracaval lymph nodes.
Craver et al. reported a 15-yr-old black girl with a malig-
nant thyroid teratoma with exuberant primitive neuroecto-
dermaltumor components. There were bilateral nodal involve-
ment and mediastinal extension (6). She was treated with an
aggressive combination chemotherapy of BEP and radiation.
Further chemotherapy included vincristin, actinomycin-D,
and cyclophosphamide alternating with ifosfamide and eto-
poside for six cycles. These agents were included to treat the
sarcomatous component. Presently there is no residual dis-
ease 16 months after the diagnosis.
Kushner et al. treated 36 patients with poor-risk primi-
tive neuroectodermal tumor (12). The P6 protocol consists
of high-dose cyclophosphamide, doxorubicin, and vincristine.
The protocol achieved excellent pathological or clinical res-
ponses in 34 patients and partial responses in two patients.
All six patients with metastatic disease limited to lungs
achieved a complete response and did not relapse for the fol-
low-up period of 7 to 36 months.
Primary thyroid malignant teratoma is rare. For teratomas
of other sites with primitive neuroectodermal tumor compo-
nents, the suggestion is to tailor the chemotherapy regimens
known to be effective in the treatment of the transformed
histology, after complete surgical resection (13). Most of
chemotherapeutic agents chosen for malignant teratomas of
the thyroid have been selected and established for teratomas
of other origins (10, 11). Therefore, we decided to adminis-
ter an intensive chemotherapy regimen according to the NCI
protocol INT-0091 (4). Grier et al. compared the 49 weeks
of standard chemotherapy consisting of doxorubicin, vincris-
tine, cyclophosphamide and dactinomycin to chemotherapy
alternating with ifosfamide and etoposide in primitive neu-
roectodermal tumor (Ewing’s sarcoma) patients. They con-
cluded that for nonmetastatic patients, the 5-yr disease free
Malignant Thyroid Teratoma Download full-text
survival (69% vs. 54%) and overall survival (72% vs. 61%)
were superior in the later group. We used the combination
chemotherapy altering with ifosfamide and etoposide for this
specific patient of primary malignant teratoma with a prim-
itive neuroectodermal tumor component.
Some investigators have reported the role of EBRT for resid-
ual tumor tissues (5). Although EBRT has frequently been
used, its role in front-line therapy is not clear. Locoregional
control at the time of recurrence seems to provide short-term
palliation. We opted for the radiation treatment in this patient
in light of the extensiveness of the disease and the residual
microscopic disease after the surgery.
It is suggested that patients with primary malignant ter-
atoma of the thyroid should be managed according to their
major malignant component. The complete surgical excision
and extensive chemotherapy are recommended for most pa-
tients with primary malignant teratoma (1, 6). As for the
exuberant primitive neuroectodermal tumor component in
this particular case with an extensive involvement of the sur-
rounding soft tissue and lymph nodes, best clinical outcome
could be obtained with intensive multidisciplinary therapies
consisting of complete excision, chemotherapy and radiation
therapy to the lesion.
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