Abstract: Granular cell tumor (GCT) is an uncommon tumor of soft tissue, and rarely occurs in thyroid. In this article, we report the FNAC results and pathological analysis of a 14-year-old female who presented with a painless mass in the right lobe of thyroid gland. A resection of the right lobe and isthmus of thyroid were applied after cells with abundant strong eosinophilic cytoplasma, indistinct border and inconspicuous nucleolus were found in the FNAC of the mass. Postoperative pathology and immunohistology helped diagnosis the lesion as thyroid GCT. Differential diagnosis from five diseases and cell types were performed and a review of all eleven papers reporting thyroid GCT was provided

Lixin Guo

Qianrui Li

Qijun Chen

Sheyu Li

Yong Jiang

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Int J Clin Exp Pathol 2014;7(8):5186-5191
www.ijcep.com /ISSN:1936-2625/IJCEP0001004
Case Report 
Fine needle aspiration cytology of a granular cell tumor 
arising in the thyroid gland: a case report and  
review of literature
Qijun Chen1, Qianrui Li2, Lixin Guo1, Sheyu Li2, Yong Jiang1
1Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 2Department of 
Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China
Received June 4, 2014; Accepted July 24, 2014; Epub July 15, 2014; Published August 1, 2014
Abstract: Granular cell tumor (GCT) is an uncommon tumor of soft tissue, and rarely occurs in thyroid. In this article, 
we report the FNAC results and pathological analysis of a 14-year-old female who presented with a painless mass 
in the right lobe of thyroid gland. A resection of the right lobe and isthmus of thyroid were applied after cells with 
abundant strong eosinophilic cytoplasma, indistinct border and inconspicuous nucleolus were found in the FNAC 
of the mass. Postoperative pathology and immunohistology helped diagnosis the lesion as thyroid GCT. Differential 
diagnosis from five diseases and cell types were performed and a review of all eleven papers reporting thyroid GCT 
was provided.
Keywords: Fine needle aspiration cytology, granular cell tumor, thyroid gland
Granular cell tumor (GCT) is an uncommon 
tumor of soft tissue which could occur in many 
locations. The most common site is known to 
be the tongue [1], while GCTs of the thyroid 
gland have been rarely reported. Here we 
reported the fine needle aspiration cytology 
(FNAC) result of a patient with GCT of the thy-
roid gland and reviewed relevant literatures.
Case report
A 14-year-old Chinese female presented to our 
hospital complaining of a painless mass in the 
neck for more than three months. She denied 
dysphagia, nausea, vomiting or dyspnea. Phy- 
sical examination revealed I° thyroid enlarge-
ment. A non-tender, smooth, firm, and irregular 
mass with a diameter of 2 cm was palpated in 
the right lobe, which was movable when 
swallowing. 
A thyroid ultrasound revealed a hypoechoic 
nodule (2.4 cm x 1.9 cm x 1.7 cm) in the right 
lobe with undefined margin, irregular shape 
and non-uniform density. Several anechoic 
nodules were detected in both lobes. It sug-
gested a potential carcinoma in the right lobe 
and nodular goiters in other areas.
Accompanied by ultrasound guided thyroid fine 
needle aspiration, short-spindle and round-
shaped cells with abundant strong eosinophilic 
cytoplasma and indistinct border were observed 
in the smears and cell blocks. The nuclei were 
round or oval, with inconspicuous nucleolus. No 
colloid or scattered lymphocytes were found 
(Figures 1, 2). As FNAC indicated a tumor 
couldn’t be excluded, and surgery was suggest-
ed to remove this mass.
During surgery, a solid mass of a size 3.3 cm x 
3.2 cm x 2.6 cm was removed from the right 
lobe of thyroid, invading the right cricothyroid 
muscle. The section of the mass was grey. As 
no suspected mass was suggested in the left 
lobe, the right lobe and isthmus of thyroid were 
resected.
Post-surgical pathology observed tumor cells 
distributing as patchy or nests, with undefined 
margin from the normal tissue. The tumor cells 
were large, uniformly-shaped, often presented 
in round, polyhedral or spindle shapes. The 
Granular cell tumor in thyroid gland
5187 Int J Clin Exp Pathol 2014;7(8):5186-5191
tumor cells had abundant cytoplasm filled with 
eosinophilic granules, and appeared as syncy-
tial clusters with indistinct border. The nucleus 
of the tumor cells was small, round, oval, occa-
sionally spindle in shape, with inconspicuous 
nucleolus. No nuclear division was detected 
(Figures 3, 4). 
Immunohistochemistry showed the tumor cells 
were positive for S-100, CD68, and NSE in both 
cytoplasm and nucleus, while uniformly nega-
tive with TTF1, TG, and calcitonin (Figures 5-7). 
On the basis of morphology and immunopheno-
type, the lesion was diagnosed as GCT in the 
thyroid. No recurrence was observed one year 
after surgery.
Discussion
Clinical features and pathogenesis
GCT could occur in patients of all ages. Previous 
studies reported GCT occurring in patients 
between 11 to 85 years old but most common-
ly in middle-aged women of 40 to 50 years old 
[2]. GCT could occur all throughout the human 
body, such as tongue, skin, subcutaneous tis-
sue, breast, esophagus, stomach, and larynx 
[3-7]. But tongue is considered as the most 
common site. Thyroid GCT is very rare, with a 
Figure 1. FNAC smears observed abundant cells dis-
tributing as sheets. Short-spindle and round- shaped 
cells were observed, with abundant strong eosino-
philic cytoplasma. HEX400.
Figure 2. Cell blocks observed tumor cells with abun-
dant strong eosinophilic cytoplasma. The nuclei were 
round or oval. HEX400.
Figure 3. Tumor cells distributed as patchy or nests, 
pushing surrounding normal thyroid tissue, with un-
defined margins. HEX100.
Figure 4. The tumor cells were large and often pre-
sented in round, polyhedral or spindle shapes. They 
had abundant cytoplasma filled with eosinophilic 
granules. The nucleus of the tumor cells was small, 
with inconspicuous nucleolus. HEX400.
Granular cell tumor in thyroid gland
5188 Int J Clin Exp Pathol 2014;7(8):5186-5191
PubMed search result of merely 11 cases 
(shown in Table 1) [8-18]. Most of the cases 
were young female (10 out of 11) between 11.5 
and 47 years old, with the diameter of tumor 
between 8 mm to 42 mm. Most of them pre-
sented as painless mass. Five of the 11 
patients underwent FNAC before surgery, one 
of which was found with atypical cell morphol-
ogy but the final diagnosis was all based upon 
histopathology [14-18].
The genesis of GCT has been argued and later 
confirmed to be Schwann cells in the neurolem-
ma via immunohistochemistry and electronic 
microscope. Tumor cells in this case were 
S-100, NSE and CD68 positive, consistent with 
which from the source of Schwann cells.
Pathological diagnosis
The preoperational FNAC results of this patient 
were consistent with those of the five reported 
cases [14-18]. The tumor cells were large in 
shape, syncytial, with abundant eosinophilic 
granular cytoplasm and indistinct order. Nuclei 
of the cells were polymorphic, presenting in 
round, oval, or spindle shapes. Nucleolus was 
inconspicuous. It has been difficult to make the 
diagnosis of GCT via cytology before surgery. 
And differential diagnosis should be made from 
the following diseases and cell types.
Firstly, Hürthle cell tumor and dysplastic nod-
ules should be differentiated. Hürthle cells are 
generally larger, with round nucleus, and granu-
lar pink cytoplasm. The cell boarders are usu-
ally well-defined. In lesions derived from Hürthle 
cells metaplasia, lymphocytes can be observed 
in the background, and the nucleolus is usually 
predominant. Hürthle cell tumor can be classi-
fied into large and small pleomorphism. Large 
pleomorphism presents as loosely attached 
and obviously enlarged Hürthle cells with rich 
granular cytoplasm, the nuclear size of which is 
various with difference between cells of more 
than two times. Large nucleolus can be observ-
able in this type. Small pleomorphism presents 
as loosely attached Hürthle cell cluster with the 
size of cells and cytoplasm varying from giant 
Figure 5. Immunohistochemistry showed the tumor 
cells were positive for S-100 in both cytoplasma and 
nucleus. DABX200.
Figure 6. Immunohistochemistry showed the tumor 
cells were positive for NSE in both cytoplasma and 
nucleus. DABX200.
Figure 7. Immunohistochemistry showed the tumor 
cells were positive for CD68 in both cytoplasma and 
nucleus. DABX200.
Granular cell tumor in thyroid gland
5189 Int J Clin Exp Pathol 2014;7(8):5186-5191
cells with abundant cytoplasm and large nucle-
olus to uniform small cells with high nuclei-
cytoplasm ratio. A mixture of large and small 
cells can be seen in some cases [19].
Secondly, macrophages with high nuclei-cyto-
plasm ratio are often observed in benign follic-
ular nodular cystic changes of thyroid. However, 
macrophages are often less viscous than GCT 
cells, with vesicular nucleus and foamy cyto-
plasm, usually containing tawny hemosiderin.
Thirdly, cells of the eosinophilic subtype of 
medullary thyroid carcinoma can be diagnosed 
from a presentation of rough karyosome, pro-
truding nucleolus and intranuclear inclusions, 
and pink-stained amyloid substance around 
tumor cells. Moreover, positive immunohisto-
chemical staining for synaptophysin, chromo-
granin A, CEA and calcitonin is of diagnostic 
significance [17].
Fourthly, non-neoplastic follicular cells are uni-
formly small, with distinct cell borders and oval 
uniform nuclei with a size similar to lympho-
cytes [14, 15].
Fifthly, rhabdomyoma cells are presented with 
defined cell borders, striated cytoplasm and 
clear cellular background. Special staining and 
immunohistochemical staining results showing 
differentiation towards skeleton muscle can 
help differentiate the two diseases [20].
Cytological diagnosis of GCT should take the 
five cellular pathological changes into differen-
tiation. Although it is difficult to make the diag-
nosis of GCT via cytology independently, FNAC 
could potentially suggest the diagnosis of GCT 
before surgery. Cell blocks and immunohisto-
chemistry can give evidence to the differentia-
tion from GCT to other pathological changes.
Histopathologically benign granular cell tumors, 
as our current case, are presented with tumor 
cells distributing as patchy or nests, pushing 
normal thyroid tissue with an indistinct border. 
The tumor cells are large but polygonal, pre-
sented in round, polyhedral, or spindle shapes 
with indistinct borders. Some cells fuse togeth-
er with abundant cytoplasm and eosinophilic 
granules. The tumor cell nuclei are small, major-
ity of which present in round or oval shape, 
minority of which present in spindle shapes 
with inconspicuous nucleolus and no nuclear 
division.
Malignant GCT is rare. Non-malignant GCT in 
Thyroid gland was reported according to our 
knowledge. It presents as rapid in growth with a 
diameter larger than 5 cm. Early regional recur-
rence or metastasis is common. According to 
the histological diagnostic criteria established 
by Fanburg-Smith et al [21] and Wang et al [22], 
six items should be evaluated: necrosis, pres-
ence of spindle cells, presence of vesicular 
nucleus and large nucleolus, more than 2 
nuclear division per 10 HPF (more than 5 nucle-
ar division per 50 HPF according to Wang, et 
al.), high nuclei-cytoplasm ratio, and pleomor-
phism. Histological malignant tumor can be 
diagnosed if at least three items are matched. 
An atypical diagnosis is suggested if two items 
match. Benign pathological change is consid-
ered if at most one item is matched. An atypical 
Table 1. Granular cell tumors of thyroid reported to date
Reference Age/Gender
Macro-
scopic size Immunohistochemistry
Vladimir, et al [8] 21/M 1.8 cm “+” S-100, Calretinin; “-” AE1-3, Thyroglobulin, TTF1, Inhibin-A
Baloch, et al [9] 47/F 2.5 cm “+” S-100; “-” TTF1, Thyroglobulin, Calcitonin, Chromogranin
Milias, et al [10] 43/F 2.5 cm “+” S-100, CD68, Vimentin, Laminin, NSE; “-” AE1/3, CAM5.2, EMA, CEA, Calcitonin, SMA
Paproski, et al [11] 23/F 1.5 cm “+” S-100; “-” Thyroglobulin, Electron microscopy
Mahoney, et al [12] 11.5/F 1.5 cm “+” S-100; “-” Thyroglobulin, calcitonin, chromograninA, EMA, vimentin, ER, PR
Chang, et al [13] 12/F 1.4 cm “+” S-100, vimentin; “-” Thyroglobulin, TTF-1, ChromograninA, Synaptophysin, Calcitonin, 
Cytokeratin
Bowry, et al [14] 36/F 0.8 cm “+” S-100, CD68, Calretinin, Inhibin A, NSE; “-” AE1/3, CK7,TTF1, Thyroglobulin, Synapto-
physin, Chromogranin A, Calcitonin
Min, et al [15] 24/F 1.8 cm “+” S-100, CD68, NSE; “-” GFAP, TTF-1
Cimino-Mathews, et al [16] 28/F 3.0 cm “+” S-100, CD68; “-” Thyroglobulin, TTF-1, Calcitonin
Harp, et al [17] 27/F 4.2 cm “+” S-100, CD68; “-” Synaptophysin, Chromogranin
Singh, et al [18] 11/F 3.5 cm “+” S-100
Current report 14/F 3.3 cm “+” S-100, CD68, NSE; “-” Thyroglobulin, TTF-1, Calcitonin
Granular cell tumor in thyroid gland
5190 Int J Clin Exp Pathol 2014;7(8):5186-5191
GCT case has been reported with spindle tumor 
cell shape, increased nuclei-cytoplasm ratio 
and conspicuous nucleolus [16]. On the basis 
of histological features and immunophenotype, 
our case was diagnosed as benign GCT.
Treatment
According to our knowledge, all reported thy-
roid GCTs are benign and grow slowly. Surgery 
was used in all reported cases. Excellent prog-
nosis was observed after local excision. 
Surgery is also the main treatment of benign 
GCT in other sites according to previous reports. 
A good prognosis is supposed by complete 
remove of the tumor. Regarding malignant 
GCTs, wide local excision combining with 
regional lymph node dissection if necessary 
are adapted currently. Clinical outcomes could 
hardly be improved by radiotherapy or chemo-
therapy [23]. Follow-up is necessary, especially 
for those with the risk of reoccurrence and 
metastasis.
In conclusion, thyroid GCT is rare but usually 
benign. All diagnosis of reported cases is made 
according to histopathology. However, cytology 
is potentially diagnostically significant due to its 
specific characteristics in the future.
Acknowledgements
We thank Dr. Jingqiang Zhu from Department of 
Thyroid and Breast Surgery, West China 
Hospital, Sichuan University for giving surgical 
treatment to the patient. This work is support-
ed by the Research Supporting Project from 
Science and Technology Department of Sichuan 
Province (No. 2013SZ0093) and the Scientific 
Research Project of Health Department of 
Sichuan Province (No. 120203).
Disclosure of conflict of interest
None.
Address correspondence to: Dr. Yong Jiang, Depar- 
tment of Pathology, West China Hospital, Sichuan 
University, 37 Guoxue Road, Chengdu, Sichuan, 
China, 610041. Tel: (86) 189-8060-1965; E-mail: 
brave.heart@163.com; Dr. Sheyu Li, Department of 
Endocrinology and Metabolism, West China Hos- 
pital, Sichuan University, 37 Guoxue Road, Chengdu, 
Sichuan 610041, China. Tel: (86) 131-9487-4843; 
E-mail: lisheyu@gmail.com
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Case Report Fine needle aspiration cytology of a granular cell tumor arising in the thyroid gland: a case report and review of literature

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Case Report Fine needle aspiration cytology of a granular cell tumor arising in the thyroid gland: a case report and review of literature

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