Case 1 -
Rhabdoid Tumor of Thyroid
Sylvia L. Asa
University Health Network
Toronto, ON, Canada
Click on each slide thumbnail image for an enlarged view
This 66-year-old woman presented with a neck nodule. She had a history of a long-standing goiter.
She was euthyroid; the goiter had been painless and non-tender. She had noted a sudden and rapid
increase in size of her right neck in the preceding few weeks and she complained of dysphagia, dyspnea
and hoarseness. On examination she had an assymetrical large goiter with a fixed 6 cm right nodule. She
underwent thyroidectomy. The right lobe measured 6 x 5 x 5 cm and weighed 60 grams. It was multinodular
with obvious infiltrating tumor. The left lobe weighed 6 grams and measured 4 x 3 x 1 cm with multiple
small nodules measuring up to 5 mm in diameter.
Case 1 - Figure 1 - The thyroid contains an invasive solid tumor.
Case 1 - Figure 2 - The tumor is composed of a solid growth of neoplastic cells with focal inflammation, predominantly around vascular channels.
Case 1 - Figure 3 - The tumor cells are large and discohesive.
Case 1 - Figure 4 - The tumor cells have abundant cytoplasm with cytoplasmic inclusions; nuclear pleomorphism is prominent.
Case 1 - Figure 5 - Tumor cells have eccentric nuclei with prominent nucleoli and occasional binucleate cells are identified
Histologic, Immunohistochemical and Molecular Findings
Histological examination showed an invasive, highly cellular neoplasm, involving the entire right
lobe, with focal geographic necrosis, areas of hemorrhage and extrathyroidal invasion into skeletal
muscle. Microscopic foci of malignancy were detected in the left lobe. The tumor was predominantly
composed of a solid growth of large discohesive neoplastic cells with abundant cytoplasm, cytoplasmic
inclusions and eccentric nuclei with prominent nucleoli; this was a typical rhabdoid tumor. At the
periphery, there were sclerotic areas where this lesion merged with irregular follicles lined by cells
with atypical nuclei that had features of papillary carcinoma. By histology, it could not be determined
if this represented reactive changes in surrounding thyroid tissue.
Immunohistochemical staining showed immunoreactivity in rhabdoid cells for low molecular weight
cytokeratins, vimentin, sarcomeric actin and myoglobin. Immunostains for desmin, smooth muscle actin and
S100 protein were negative in tumor cells but stained normal components of surrounding tissues. The
atypical cells at the periphery of the lesion were immunoreactive for thyroglobulin, cytokeratin 19 and
TTF-1. Stains for p53 were negative throughout. Ki67 labeled more than 90% of tumor cells.
For molecular studies, RNA was extracted from the neoplastic tissue, reversed transcribed into cDNA,
then amplified, using primers specific for RET/PTC1 and RET/PTC3 fusion genes . In all
tumor samples examined, including blocks with atypical follicles and blocks of pure rhabdoid tumor,
RET/PTC 3 fusion transcripts were detected, indicating the presence of a RET/PTC3 gene rearrangement in
rhabdoid tumor cells.
The patient rapidly developed local recurrence with massive mediastinal lymph node metastases. She
received external beam radiotherapy to the neck and mediastinal area with a total dose of 60 Gray over
one month, but the disease progressed and the patient died one month later. The apparent cause of death
was a severe mediastinal syndrome with possible pulmonary thromboemboli. Autopsy was not performed.
Rhabdoid Tumor of Thyroid
Rhabdoid tumor is a very aggressive neoplasm first described by Beckwith et al in 1978 as a variant of
renal Wilm's tumor in children  . Subsequently, rhab doid tumors have been described in
; they can occur at any age
and always exhibit
aggressive behavior with a tendency to develop early metastasis . They have a poor
prognosis due to lack of responsiveness to radio- and chemotherapy. Morphological findings in this tumor
include the presence of large pleomorphic cells with abundant cytoplasm, typical eosinophilic inclusions
and eccentric nuclei with distinct nucleoli. The immunohistochemical profile of rhabdoid tumor cells may
vary from case to the next: immunoreactivity for vimentin, myogenic markers, keratins, markers of smooth
muscle lineage, neuron specific markers and S100 have been reported
findings in these cells include the presence of whorled cytoplasmic filaments
with rhabdoid features are considered to represent a final pathway of dedifferentiation of neoplasms
derived from multiple cell types, including tumors of neuroectodermal, myogenic, histiocytic, melanocytic
and epithelial origin
Primary rhabdoid tumor of thyroid gland is a very rare neoplasm. To the best of our knowledge, six
cases have been reported in the recent literature
. All seven cases including this one
occurred in women whose ages ranged from 38 to 69 years (mean age 51.8 years). All had extrathyroidal
extension of tumor at the time of diagnosis, and all had local and distant recurrence. The disease has
been uniformly rapidly lethal. These features confirm thyroid rhabdoid tumor to be a highly aggressive
neoplasm, with a mean survival similar to that of anaplastic thyroid carcinoma. Indeed, rhabdoid tumors
and anaplastic carcinomas of thyroid exhibit similar clinical, morphological and immunohistochemical
features. Both are rare thyroid tumors that occur in older patients, both invade extrathyroidal tissues
and surrounding structures, both give rise to cervical adenopathy and distant metastases, and both have
very high mortality with a mean survival of 6 months. Both tumors are wholly or partially composed of
undifferentiated cells that may exhibit immunohistochemical or ultrastructural features of epithelial
Anaplastic carcinoma usually arises by dedifferentiation of a pre-existing differentiated carcinoma
. Origin of rhabdoid tumor from thyroid follicular epithelium has also been
suggested. In our case, rhabdoid cells showed immunohistochemical evidence of both epithelial and muscle
differentiation but thyroglobulin and TTF-1 were negative; in other cases reported, thyroglobulin was
detected in the rhabdoid component  . In all cases reported, there has been evidence of
differentiated follicular or papillary neoplasia admixed with the rhabdoid component. One could argue
that reactive changes in adjacent parenchyma can mimic malignancy  , and in our case, this
possibility was raised. To address this, we carried out molecular studies using a marker that is
specific for papillary carcinoma of thyroid, RET/PTC  .
In our case, a RET/PTC3 rearrangement was detected in blocks of tissue containing both the atypical
cells at the periphery of the dominant tumor and in blocks with rhabdoid tumor only. This finding
confirms the presence of underlying papillary carcinoma and indicates a direct relationship of the
rhabdoid tumor to this differentiated component. This finding provides firm evidence that rhabdoid tumor
derives from a pre-existing differentiated papillary thyroid carcinoma.
In conclusion, the clinicopathological features supported by new molecular findings suggest that
rhabdoid tumor of thyroid should be considered a variant of anaplastic carcinoma.
The author thanks Dr. Maria Letizia Lai of Cagliari, Italy for contributing this case.
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