Download Clear cell follicular adenoma of the thyroid: A case report

Clear Cell Follicular Adenoma of
the Thyroid:
A Case Report
Torill Sauer, M.D., F.I.A.C., and Reidar Olsholt,
M.D., Ph.D.
A case of clear cell follicular adenoma of the thyroid is presented.
The patient presented with a single, hyperactive nodule in the right
lobe. The cytologic features include cellular smears with numerous disrupted cells and a granular background. The cytoplasm
was abundant, pale grayblue vacuolated or granulated, but not
clear. Thyreoglobulin was demonstrated both histologically and
ultras~ructurally,confirming the follicular-cell derivation of the
tumor. Ultrastructurally, the cytoplasm was filled with empty,
membrane bound vacuoles. The clear cell change might represent
an artifact of formalin fixation and/or the parafin embedding
procedure. Diagn Cytopathol 1996 15: 124- 126.
@) 1996 Wiley-Lib\, Inc
Key Words: Clear cell; Thyroid; FNAC
We present a case of clear cell follicular adenoma of the
thyroid and demonstrate the cytologic features of this
tumor.
Clinical History
A 47-yr-old female presented at the ENT outpatient clinic
of Ullevaal Hospital with an asymptomatic, palpable nodule in the right thyroid lobe. The lesion was aspirated. The
cytologic findings were consistent with a follicular tumor.
A scintigramm (using the isotope 99mTc-pertecnetat)
of the thyroid revealed an enlarged right lobe with a hyperactive nodule occupying most of the lobe. The surrounding thyroid tissue and the left lobe was partly suppressed. The patient had normal thyroid function with
FT4 and TSH within normal range.
Because the cytologic diagnosis was consistent with a
neoplasm, a right thyroidectomy was performed. Histology showed a clear cell follicular adenoma. Follow-up has
been uneventful.
Follicular lesions are common findings when investigating
thyroid nodules by fine-needle aspiration cytology
(FNAC). Histologically they may represent a cellular
nodule in a goiter, a follicular adenoma, or a carcinoma.
Several variants exist as to growth pattern (follicular, trabecular, solid) and cell types (common, oxyphilic, and
Cytologic Findings
clear cell type).
The smears were cellular with partly disrupted cells, nuClear cell changes of the cytoplasm may occur in areas
merous naked nuclei, and a finely granular background.
of both follicular and papillary tumors, but pure clear cell
Sheets and follicular clusters were loosely cohesive with
differentiation is unusual. Chronic TSH overstimulaoccasional overlapping of nuclei (Fig. 1). Stromal fragtion has been suggested as a cause for this change due to
ments containing branching blood vessels and attached
hypertrophy and dilation of mitochondria or hypertrophy
epithelial cells were seen. Nuclei were uniformly round
of the Golgi apparatuses.
Accumulation of glycogen, lipid, and t h y r ~ g l o b u l i n ~ - ~and 2-3X the size of an erythrocyte. The chromatin
structure was homogenous. A single, round and mediumhas also been described. Other clear cell tumors such as
sized nucleolus was apparent. The cytoplasm was abunmetastatic renal cell cancer, parathyroid tumors and
dant, pale grayblue, with different sized vacuoles in the
hyperplasias, and clear cell variant of medullary carciGiemsa-stained smears and finely granulated in the
noma may mimic a primary follicular-derived tumor, both
Papanicolaou-stained smears (Fig. 2). Colloid material
cytologically and histologically, and demonstration of inwas not seen. Based on these findings, a primary diagnosis
tracellular thyroglobulin is essential for diagnosis.
of follicular tumor of the thyroid was given.
Received September 14, 1994. Accepted March 23, 1995.
From the Department of Pathology and the E N T Department, Ullevaal University Hospital, Oslo, Norway.
Address reprint requests to Torill Sauer, M.D., Department of Pathology, Ullevaal University Hospital, N-0407 Oslo, Norway.
124
Diagnostic Cytopathology, Yo1 15, No 2
Histologic Findings
Thyroidectomy specimen revealed a 2.2 cm diameter
tumor. A thin rim of compressed, normal thyroid tissue
@ 1996 WILEY-LISS. INC
THYROID FOLLICULAR ADENOMA
Fig. 1. Loosely cohesive epithelial cell clusters; abortive f o k u l a r structure (arrowheads) and fragile cytoplasm (PAP stain; magnification
surrounded the lesion. The tumor was well circumscribed
with a smooth, thin capsule and a rather soft consistency.
The cut surface was pale brown and homogeneous. Microscopically the pattern was mostly solid, but with areas of
follicular growth. The cells were large with a clear cytoplasm (Fig. 3). There was no evidence of vascular or capsular invasion. The tumor cells stained positive for intracytoplasmic thyroglobulin (Fig. 4) (APAAP method
with a fast red substrate).
Ultrastructurally, the cells were dominated by closely
lying, membrane bound, empty vacuoles (Fig. 5). Neuroendocrine granules were not found. EM immunostaining
for thyroglobulin showed positivity in moderate electrondense globules of the common follicular cell type. Acinic
structures containing
thyroglobulin POsitive granules within the colloid (Fig, 6).
X 250).
Fig. 4. Positive cytoplasmic staining for thyroglobulin (APAAP stain
with fast red substrate; magnification X 250).
Fig. 2. Finely vacuolated cytoplasm (Giemsa stain; magnification
x 500).
Fig. 3. Mainly follicular growth pattern; abundant clear cytoplasm
(H%E stain; magnification x 250).
Fig. 5. Ultrastructural empty membrane bound cytoplasmic vacuole; in
between normal appearing mitochondria (magnification X 5,700).
Diagnostic Cytopathology, Vol 15, No 2
125
SAUER AND OLSHOLT
with a dominant clear cell pattern. They may show several
cytologic characteristics reminiscent of follicular thyroid
lesions, such as microfollicular pattern, colloid-like structures and tissue fragments with branching vessels. Usually
they have a much coarser and irregular nuclear chromatin
pattern, 8-1 but demonstration of thyroglobulin is essential in order to differentiate a follicular cell derived tumor
from these lesions. This might mainly represent a problem
in histologic specimens, though, as the clear cell changes
are not appreciated in cytolologic smears.
Acknowledgments
Fig. 6. Thyroglobulin positivity within colloidal material in a follicular
lumen (magnification x 9,100; EM immunostaining with colloidal gold).
The authors are grateful to Dr. Fredrik Skjgwten for supplying the ultrastructural pictures, and Dr. Vibeke Engh
for reviewing the manuscript.
References
Discussion
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Cytomorphologically this lesion was a follicular tumor,
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not accumulated. In addition, the scintigraphic finding of
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