Case Report

Polypoid non-neural
Volume 23
2024
e243202

granular cell tumor of the

oral cavity: case report
and literature review
Larissa Abbehusen Couto1 , Daiana Cristina Pereira
Santana1 , Ianna Josefa Valeska de Aniz Castro1 ,
Roberto Almeida de Azevedo2 , Flávia Caló de
Aquino Xavier3 , Jean Nunes dos Santos3 , Águida
Cristina Gomes Henriques Leitão3*

1
Dentistry and Health Postgraduate Aim: To report a case of non-neural granular cell tumor
Program, School of Dentistry,
Federal University of Bahia, Brazil.
(NN-GCT), an uncommon neoplasm, with only six studies
worldwide describing cases involving the oral cavity.
2
Department of Oral and
Maxillofacial Surgery, School of Methods: A 26-year-old male patient with an erythematous,
Dentistry, Federal University of firm, polypoid nodule in the floor of the mouth that exhibited
Bahia, Brazil.
areas of ulceration and mild bleeding to the touch. A biopsy
3
Dentistry and Health Postgraduate was performed to aid in the diagnosis. Results: Based on
Program, Laboratory of Oral and
Maxillofacial Pathology, School the histopathological and immunohistochemical results
of Dentistry, Federal University of (vimentin +, CD68 +, S100 -), the diagnosis was compatible
Bahia, Brazil.
with S100-negative (primitive polypoid non-neural) granular
cell tumor. No recurrence was observed over two years of
follow-up. Conclusion: The diagnosis of NN-GCT is extremely
challenging because this tumor shares histological and
immunophenotypic features with many benign and malignant
Corresponding author: tumors. Although oral NN-GCT may exhibit unusual and
Águida Cristina Gomes Henriques
atypical histological features, it has an indolent behavior.
Leitão
Address: Av. Araújo Pinho, nº 62, Thus, until more cases of oral involvement are reported,
Canela, Salvador, Bahia, Brasil. complete resection and close follow-up are recommended.
CEP: 40100-150
School of Dentistry, Federal Keywords: Granular cell tumor. S100 proteins.
University of Bahia
E-mail: [email protected] Immunohistochemistry. Mouth neoplasms.
Telephone: +55 71 99293-0304

Editor: Dr. Altair A. Del Bel Cury

Received: April 22, 2023

Accepted: July 12, 2023

http://dx.doi.org/10.20396/bjos.v23i00.8673202 Braz J Oral Sci. 2024;23:e243202 1

 Couto et al.

Introduction

Granular cell tumor (GCT) was described for the first time by Abrikossof in 1926.
It is defined as a neural tumor composed of round and/or spindle-shaped cells with
pink granular cytoplasm as a result of the abundant presence of intracytoplasmic
lysosomes. GCT is a common benign mesenchymal neoplasm that is mostly found in
the head and neck region, especially the tongue1. The strong reactivity of GCT to S100
protein suggests a relationship of the histogenesis of these tumors with perineural
cells, particularly Schwann cells2.
In contrast to typical or conventional GCT, non-neural granular cell tumor (NN-GCT)
is an uncommon neoplasm3. Clinically, this tumor manifests as an asymptomatic
swelling with a nodular, exophytic, and erythematous appearance, similar to pyogenic
granuloma4. Non-neural GCT was described in 1991 by LeBoit et al.5 as a ‘primitive pol-
ypoid granular cell tumor’ characterized by well-delimited borders, expansive growth,
a polypoid configuration, and the presence of a larger number of mitoses and nuclear
pleomorphism when compared to conventional GCT. In addition, NN-GCT does not
exhibit immunoreactivity to S100 protein3-5.
We found 15 articles in the English language literature that document cases or case
series of NN-GCT (3–17) and only six describe cases involving the oral cavity3,4,6-9. This
study reports a case of oral NN-GCT with atypical histopathological characteristics.
Its clinical, histopathological and immunohistochemical features, as well as possible
differential diagnoses, are discussed.

Clinical case
a 26-year-old African American man without comorbidities, a non-smoker and
social drinker, was seen with a 5-cm asymptomatic, pedunculated polypoid nod-
ule in the lingual gingiva that extended to the floor of the mouth and had been
present for approximately 3 months. The lesion was located between teeth 35
and 44, had a firm consistency, was erythematous, and exhibited areas of ulcer-
ation, with mild bleeding to the touch (Figure 1A). The involved teeth showed slight
mobility when manipulated. Radiographic examination revealed an intact lamina
dura and the absence of signs suggestive of bone and dental erosion (Figure 1B).
The clinical diagnosis was pyogenic granuloma. Surgery was performed under
local anesthesia. The lesion was completely excised at its base while preserving
the involved teeth. The material was sent for anatomopathological analysis. The
surgical wound was closed by first intention without complications. The stitches
were removed on postoperative day 7. There were no signs of infection or dehis-
cence. Macroscopic analysis showed a polypoid appearance, smooth surface, and
firm consistency (Figure 1C). Histopathological examination revealed fragments
of a mesenchymal benign neoplasm characterized by the proliferation of sheets
of large oval or polygonal cells with abundant eosinophilic granular cytoplasm
(Figure 2A), associated with the proliferation of spindle-shaped cells, sometimes
arranged in a storiform pattern (Figure 2B). The cytoplasmic granules were PAS
positive (Figure 2C). Some tumor cells contained a vesicular nucleus and promi-

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 Couto et al.

nent nucleoli, as well as typical and atypical mitotic figures (Figure 2D). Moderate
pleomorphism and areas with hyperchromatic cells were also observed (Figure 2E).
There were small foci of necrosis in the center (Figure 2F) and on the top of the
tumor. Lymphovascular, perineural, and muscular invasion were absent. The lesion
was lined with epithelium without atypia and showed an extensive area of ulcer-
ation (Figure 2G). The stroma was intensely vascularized and exhibited areas of
an intense mixed inflammatory infiltrate associated with ulceration. Although the
lesion was well circumscribed, it lacked a capsule.

A B

Figure 1. Clinical presentation of non-neural granular cell tumor (A-C). A – Erythematous, polypoid,
nodular lesion with foci of superficial ulceration located in the lower alveolar ridge and floor of the mouth.
B – Preoperative panoramic radiograph showing no signs of bone or dental involvement. C – Macroscopic
view of the lesion showing a polypoid appearance and smooth surface.

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 Couto et al.

A B

C D

E F

Figure 2. Histopathological features of non-neural granular cell tumor (A-G). A – Proliferation of large oval
and polygonal cells with abundant eosinophilic granular cytoplasm. B – Proliferation of spindle-shaped
cells. C – Cytoplasmic granules of PAS-positive granular cells. D – Tumor cells with a vesicular nucleus,
prominent nucleoli, and mitotic figures. E – Hyperchromatic and pleomorphic tumor cells. F – Necrotic
foci in the center of the tumor. G – Extensive area of ulceration on the tumor surface.

Regarding immunohistochemical features, tumor cells were positive for vimentin

(100%) (Figure 3A) and CD68 (>80%) (Figure 3B). Positive staining for smooth muscle
actin (SMA) was detected in less than 30% of the tumor cells and was present espe-
cially in the spindle cell component (Figure 3C). The tumor cells were negative for
S100 (Figure 3D), HHF35, CD34, AE1/AE3, HMB45, CD56, and Melan A. Staining for
Bcl-2 was rare and positive expression of p53 and Ki-67 was observed in less than 5%
of tumor cells (Figure 3E).

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 Couto et al.

A B

C D

Figure 3. Immunohistochemical features of non-neural granular cell tumor (A-E). A – Tumor cells showing
100% positivity for vimentin B – Tumor cells showing > 80% positivity for CD68. C – Tumor cells showing
< 30% positivity for smooth muscle actin. D – Absence of S100 immunoreactivity. E – Positive Ki-67
staining in 5% of tumor cells.

The diagnosis was S100-negative (primitive polypoid non-neural) GCT. The patient
has been followed up for 2 years and shows no signs or symptoms of recurrence of
the tumor. The teeth are preserved (Figure 4A and 4B).

Figure 4. Postoperative follow-up (A-B). A – Clinical presentation after 1 year of follow-up. Note the
normal colored mucosa and the absence of tooth mobility in the lower arch and signs of recurrence.
B – Postoperative panoramic radiograph (1 year) showing preserved bone and dental contours and no
signs of recurrence.

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 Couto et al.

Discussion
Since its first description, a diverse and unusual histopathology of NN-GCT has been
reported. Synonyms such as primitive GCT, dermal GCT or S100-negative GCT repre-
sent attempts of classifying this tumor, particularly after LeBoit et al.5 demonstrated
negative staining for proteins of different lineages, especially S100 protein. This fact
differentiates NN-GCT from conventional GCT. The latter is of neural origin, more spe-
cifically Schwann cells, as indicated by the reactivity to S100 protein, i.e., its histogen-
esis is better established3,6.
Only eight cases of NN-GCT of the oral cavity have been reported in the literature
(Table 1). The mean age of these cases varied widely and there was a higher fre-
quency in males (5 cases) than females (3 cases). The most common clinical pre-
sentation was a painless nodule that was similar in color to the adjacent mucosa or
erythematous. An ulcerated surface was sometimes observed. Tumor size ranged
from 0.3 to 3.8 cm. The lip was the most affected site, followed by the cheek mucosa,
palate, tongue, and alveolar ridge. In the present case, the tumor was located in
the attached gingiva, extending to the floor of the mouth, and was larger than the
cases reported in the literature. It appeared as a painless, erythematous polypoid
nodule with foci of ulceration, similar to pyogenic granuloma, in agreement with the
published studies.

Table 1. Demographic data and clinical characteristics of nine case of non-neural granular cell tumor
(S100 negative) of the oral cavity.
Age Size Recurrence/
Author Sex Site Clinical appearance
(years) (cm) metastasis

Painless, pedunculated,
Gingiva/floor
Present case 26 M 3.8 ulcerated, erythematous, firm No
of the mouth
polypoid nodule

Basile and Woo, Sessile, erythematous, firm

4 F - Lower lip No
2003 nodule

Chaudhry and
55 F 1.1 Upper lip Painless nodule No
Calonje, 2005

Chaudhry and
43 F 0.3 Upper lip Painless nodule No
Calonje, 2005

Lerman and Alveolar Ulcerated, erythematous nodule

43 M - No
Freedman, 2007 ridge with irregular borders

Polypoid mucosa-colored
Solomon and
12 M 1 Tongue nodule on the ventral surface of No
Velez, 2015
the tongue

Rawal and Painless, erythematous

19 M 0.9 Hard palate No
Dodson, 2017 polypoid nodule

Rawal and Painless, ulcerated polypoid

64 M 1 Oral mucosa No
Dodson, 2017 nodule with a history of trauma

Ulcerated, mucosa-colored
Mejía et al.,
47 M 1.3 Lower lip exophytic nodule in the mucosa No
2019
and semimucosa of the lower lip
M: male; F: female.

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 Couto et al.

Primitive polypoid GCT of the skin described by LeBoit et al.5 or dermal NN-GCT3
exhibits unique histological features such as exophytic and polypoid nodular growth
lined with stratified pavement epithelium without atypia. Neoplastic cell proliferation
is well delimited and consists of round, polygonal or spindle-shaped cells with abun-
dant granular cytoplasm that stains intensely with PAS. The nucleus of the tumor cells
is vesicular or hyperchromatic and significantly larger and more variable when com-
pared to conventional GCT. Prominent nucleoli are also found. The presence of vari-
ably shaped typical mitotic figures and lymphatic invasion have also been reported.
A mild inflammatory infiltrate can be present but necrotic foci have not been detected3,5.
The characteristics of the present case were similar to tumors of the skin. However,
some features not previously described by LeBoit et al.5 or Chaudhry and Calonje3
were observed in the present case, such as proliferation of spindle-shaped cells in a
storiform pattern, atypical mitotic figures, and areas of necrosis. We believe that the
areas of necrosis detected in the present case are related to a reduction in blood cir-
culation to the cells due to the large size of the tumor.
The first case of NN-GCT of the oral cavity dates back to 2003 and was reported by
Basile and Woo7. The histology of the tumor present in the lower lip of a 4-year-old girl
was consistent with the description of LeBoit et al.5 (Table 2) and the authors added
the presence of spindle cell proliferation in a storiform pattern and myxoid areas.
Similarly, most of these morphological features were observed in the present case,
including the storiform pattern of proliferating spindle-shaped cells. Two years later,
Chaudhry and Calonje3 published a series of 11 cases of NN-GCT, with only two involv-
ing the oral cavity (upper lip). In both cases, a painless nodule was observed in women
with mean age of 50 years, which exhibited the same unusual histology (Table 2).
Lerman and Freedman6 reported the case of a 43-year-old man who had a tumor with
an ulcerated, erythematous surface and irregular borders. The authors described the
same histological findings as Chaudhry and Calonje3. Thus, the present case shows
additional characteristics, including a biphasic proliferation pattern and the presence
of atypical mitotic figures and necrotic foci.

Table 2. Histopathological features of nine cases of non-neural granular cell tumor (S100 negative) of
the oral cavity.
Cell Typical Atypical Tissue
Author Polypoid Ulceration Pleomorphism Necrosis
shape mitosis mitosis invasion
Present case Yes Yes Moderate S, O, P Yes Yes No Yes
Basile and
Yes No Focal Varied Low No No No
Woo, 2003
Chaudhry and
Yes No Focal S and O Low No No No
Calonje, 2005
Chaudhry and
No No Moderate S and O Low No No No
Calonje, 2005
Lerman and
Freedman, No Yes Yes S and O Yes No No No
2007
Solomon and
Yes No No - No No No No
Velez, 2015
Continue

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 Couto et al.

Continuation
Rawal and
Yes Yes No S, O, P High No No No
Dodson, 2017
Rawal and
Yes Yes No S, O, P High No No No
Dodson, 2017
Mejía et al.,
Yes Yes No - Low No Muscle No
2019
S: spindle shaped; O: oval; P: polygonal.

Eight years later, Solomon and Velez9 reported the case of a 12-year-old boy with a
mucosa-colored nodule on the ventral surface of the tongue. Microscopically, pat-
terns similar to those seen in conventional GCT were found, i.e., the nodule did not
exhibit unusual histological patterns or mitotic figures (Table 2) as observed in pre-
vious studies3,6,7 and in the present case. However, the immunohistochemical pat-
tern was positive for vimentin and CD68 and negative for S100, CD56, CD34, SMA,
CD1a and CD163, among other markers. Within this context, Solomon and Velez9
suggested that S100-negative GCT is a benign process similar to conventional GCT
and that conventional GCT is associated with a wide range of clinical and histolog-
ical features. Thus, the need to distinguish NN-GCT (S100-negative GCT) as a new
entity must be evaluated.
Rawal and Dodson4 added two cases with an erythematous, painless polypoid
nodule. One nodule measuring 0.9 cm occurred in the palate of a 19-year-old male
patient and the other measuring 1 cm occurred in the oral mucosa of a 64-year-old
man. The histological findings included the proliferation of well-circumscribed oval,
polygonal or spindle-shaped cells arranged in nests, sheets, and fascicles. These
cells exhibited abundant PAS-positive eosinophilic granular cytoplasm and a vesicu-
lar nucleus with prominent nucleoli, as well as typical mitotic figures and prominent
vascularization, in agreement with the present case. However, the three features
identified in our case and mentioned above (atypical mitotic figures, a second pat-
tern of cell growth, and necrosis) were also absent in the NN-GCT described by
Rawal and Dodson4 (Table 2).
The most recent case of NN-GCT (S100 negative) of the oral cavity was that reported
by Mejía et al.8 in a 47-year-old man who exhibited an exophytic, ulcerated lesion in
the mucosa and semimucosa of the lower lip. The maximum diameter was 1.3 cm.
Microscopic analysis revealed the presence of an ulcerated polypoid lesion charac-
terized by the proliferation of cells with granular cytoplasm and homogeneous nuclei,
with a low percentage of mitoses and without cellular atypia, very similar to the case
described by Solomon and Velez9 but different from the present case (Table 2).
Despite the rarity of NN-GCT, it is now possible to characterize and to define criteria for
its diagnosis based on the clinical and histopathological data that have been published
over the years. Exophytic polypoid growth, an erythematous color or color similar to
the adjacent mucosa, and an ulcerated surface are clinical features that resemble
pyogenic granuloma and that characterize NN-GCT (Table 1). Regarding histopatho-
logical features, the proliferation of PAS-positive oval, polygonal or spindle-shaped

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 Couto et al.

cells that exhibit nuclear pleomorphism, prominent nucleoli, and an increased num-
ber of mitotic figures are common findings (Table 2). Over the years, the histological
description of this pathology may become more robust and characteristics seen less
frequently in oral lesions may be added.
With respect to the immunophenotypic characterization of NN-GCT, some immuno-
histochemical markers have been recommended to aid in its diagnosis. The absence
of S100 immunoreactivity has been observed since the first description of NN-GCT
until the most recent publication. However, strong and diffuse positivity for NKI/C3
(CD63) and CD68 has been reported in six of the nine cases of the oral cavity, as well
as positive vimentin immunoreactivity in five cases. Negative staining for proteins
of cell lines with distinct differentiation such as HMB45, Melan A, SMA, cytokeratin
(AE1/AE3), CD56, HHF35, and neuron-specific enolase (NSE) is also observed. Table 3
shows an immunohistochemical panel of markers used by several authors, including
this case report, for the characterization and diagnosis of NN-GCT of the oral cavity.

Table 3. Immunoreactivity in nine cases of non-neural granular cell tumor (S100 negative) of the oral cavity.
AE1/
Author PAS Vimentin CD68 CD63 S100 NSE HHF35 HMB45 CD56 Melan A SMA
AE3
Present case + + + NT - NT - - - - - +
Basile and
- + - + - - NT - NT NT - NT
Woo, 2003
Chaudhry and
NT NT + + - NT NT - - NT - -
Calonje, 2005
Chaudhry and
NT NT + + - NT NT - - NT - -
Calonje, 2005
Lerman and
Freedman, NT + + + - NT NT - - NT - +
2007
Solomon and
NT + + NT - NT NT NT NT - NT -
Velez, 2015
Rawal and
+ NT NT + - NT NT NT - NT NT -
Dodson, 2017
Rawal and
+ NT NT + - NT NT NT - NT NT -
Dodson, 2017
Mejía et al.,
NT + + NT - - NT NT NT + NT NT
2019
NT: not tested; +: positive; -: negative.

Analysis of the immunohistochemical panel reveals a mesenchymal origin of the

granular tumor cells involved in the histogenesis of NN-GCT, as demonstrated by
positive staining for vimentin and negative staining for cytokeratins AE1/AE3. The
immunopositivity for S100 protein in conventional GCT supports the neural his-
togenesis of this tumor; however, the cases initially described by LeBoit et al.5
were negative for S100, as were the nine cases reported in the studies included in
the present review3,4,6-9. In addition to negative S100 immunoreactivity, Basile and
Woo7 reported negative immunostaining for NSE, a fact that rules out a neural
origin and explains the nomenclature of NN-GCT. The present study supports the

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 Couto et al.

non-neural origin by showing negative immunostaining for CD56 (a neuronal cell

adhesion molecule expressed on the surface of neurons and glial cells), a known
marker of neural tumors10.
In the present case, 80% of granular cells were positive for CD68. The same was
reported for five of the nine cases shown in Table 23,6,8,9. CD68 is a marker related
to histiocytic differentiation and is also associated with the presence of lysosomes.
However, the expression of CD68 associated with the absence of CD163 (a more
specific protein for histiocytic differentiation) proved that it should not be consid-
ered a histiocytic/macrophage lineage4. Another marker that has shown significant
positive expression in the literature is NKI/C3 (CD63). This marker is related to cells
of melanosomal origin and has been associated with a higher lysosomal content.
However, despite positivity in NN-GCT, the same studies reported negative immuno-
reactivity for other melanoma-related proteins such as HMB45 and Melan A3,4,6,7,11, as
also observed in the present case. These data reinforce a high content of lysosomes
in granular cells and do not indicate histiocytic or melanocytic differentiation.
Electron microscopy analysis of the neoplastic granular cells present in NN-GCT and
conventional GCT reveals different complex lysosomal structures11,12 that explain
the high expression of lysosomal membrane-associated markers such as CD68 and
NKI/C3 (CD63). These two markers have been cited in some studies on NN-GCT of
the skin and oral cavity3,6,11,12. According to Basile and Woo7, overexpression of lyso-
somes in mesenchymal neoplasms can occur in four situations: 1) degenerative/
reactive phenomena in mesenchymal tumors with a well-defined origin; 2) primary
nerve sheath tumors such as conventional GCT; 3) hamartomas and/or degenerative
phenomena without a defined origin such as congenital epulis; 4) S100-negative pol-
ypoid tumor of the skin and mucosa with a nonspecific nature of degenerative granu-
lar cells, like the case reported here.
Focal staining of SMA was observed in 30% of the tumor cells, especially in the spin-
dle-cell component. This feature has also been described by Lerman and Freedman6
and can be explained by the proliferation of spindle-shaped cells arranged in a typical
storiform pattern with entrapment of collagen, as reported in the first case involving
the oral cavity7. Smooth muscle tumors can also exhibit alterations in granular cells;
however, although positive for SMA, the tumor cells were negative for HHF35, a spe-
cific muscle actin marker13.
Taken together, the available data indicate that the histogenesis of the present case,
as well as of the oral NN-GCT cases reported in the literature, is not well defined due
to the lack of expression of specific proteins in the two growth patterns, i.e., granu-
lar and spindle-shaped cells. There seems to be consensus among the authors of
the studies included in this review regarding the positive expression of NKI/C3 and
CD68, markers that only indicate a high lysosomal content in granular cells. Within
this context, the diagnosis of NN-GCT becomes extremely challenging because this
tumor shares histological characteristics with different tumors and because of the
possible presence of atypia. Furthermore, since there is no expression of specific
proteins that are important for the identification of other pathologies, the diagnosis
is made by exclusion.

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 Couto et al.

For the differential diagnosis, the exclusion process involves the correlation between
clinical, histopathological, and immunohistochemical features since a range of
benign and malignant oral lesions contain eosinophilic granular cells. Considering
histopathological and immunohistochemical features, the following pathologies
must be included: conventional GCT (similar morphology but S100 positive); con-
genital epulis of the newborn (also S100 negative but the lesion is congenital and
has specific clinical characteristics); verruciform xanthoma (CD68 positive and
S100 negative but NKI/C3 and CD163 positive); granular cell leiomyoma (positive
for SMA and other muscle proteins); melanoma (positive for NKI/C3, S-100, HMB45,
and Melan A); atypical fibroxanthoma (S100 negative and CD68 and SMA positive);
cellular neurothekeoma (positive for NKI/C3, negative for S100, can also be positive
for SMA); granular cell variants of PEComa (negative for S100 and positive for SMA,
HMB45, and Melan A), and benign fibrous histiocytoma (granular cells positive for
NKI/C3 and CD68 and negative for S100 and SMA)4,14,15.
In view of the unusual histological findings of benign neoplasms such as necrosis
and atypical mitotic figures, it was important to include atypical and malignant GCT
in the possible differential diagnoses. Fanburg-Smith et al.12 considered six criteria to
be important for the diagnosis of conventional malignant GCT: presence of necrosis,
population of spindle-shaped tumor cells, vesicular nucleus with prominent nucle-
oli, high mitotic activity, increased nuclear cytoplasmic ratio, and pleomorphism.
The authors suggested classifying conventional GCTs as benign (meeting none of
the criteria and focal pleomorphism), atypical (one or two criteria), and malignant
(three or more criteria). In the following years, other authors proposed classifica-
tions in an attempt to simplify the decision regarding the nature of conventional GCT.
Nasser et al.16 suggested the classification of CGT as a benign tumor; however, in the
presence of necrosis and/or mitosis, the tumor will be classified as uncertain malig-
nant potential. Machado et al.15 modified the classification of Fanburg-Smith et al.12
and recommended the denomination of GCT without metastatic potential for benign
and atypical tumors and GCT with increased risk of metastasis for tumors with histo-
logical patterns indicative of malignancy.
When these criteria are applied to the classical NN-GCT described by LeBoit et al.5, the
tumor would be classified as malignant since it possesses three malignancy-related
criteria according to Fanburg-Smith et al.12, as uncertain malignant potential by
Nasser et al.16, and as increased risk of malignancy by Machado et al.15. However, only
three of the 45 reported cases of skin NN-GCT had regional lymph node metastasis.
Nevertheless, the authors reiterate that NN-GCT is an uncommon neoplasm with a
benign behavior and regional metastases are extremely rare17-19. Thus, we believe that
the classification proposed by Fanburg-Smith et al.12 for conventional GCT would not
be adequate for NN-GCT.
Considering the possible differential diagnosis with malignant GCT, we also per-
formed immunohistochemical analysis of Bcl-2, p53, and Ki-67. The observation of
high indices (> 10%), especially for Ki-67 and p53, has been associated with a higher
risk of malignancy in conventional GCT12. In the present study, the expression of these
markers was low (< 5% of tumor cells). This finding may be related to the benign
nature of the pathologies, showing low cell proliferation indices.

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 Couto et al.

In view of the above considerations, the best denomination for the present case would
be atypical NN-GCT. We believe that the use of the term atypical is appropriate in this
case because of the identification of distinct and unusual microscopic features when
compared to those reported for NN-GCT, including the presence of atypical mitotic
figures and necrotic areas. These characteristics reinforce the need for a more rigor-
ous follow-up of the patient.
We hope that this study contributes to a better understanding and characterization
of oral NN-GCT. Despite some atypical histological features and the lack of an estab-
lished histogenesis, this tumor has a completely indolent behavior. Only eight cases
of oral NN-GCT have been documented so far and it remains uncertain whether the
biological behavior of skin NN-GCT can be extrapolated to oral tumors. Therefore,
until a substantially larger number of cases of oral involvement have been reported,
complete resection and rigorous follow-up are recommended.

Acknowledgement
We thank the state funding agency Fundação de Amparo À Pesquisa do Estado da
Bahia (FAPESB) and Conselho Nacional de Desenvolvimento Científico e Tecnológico
(CNPq) for the fellowships granted to the students involved in this study.

Data availability
Datasets related to this article will be available upon request to the corresponding
author.

Author contribution
Larissa Abbehusen Couto: analysis and interpretation of data for the work; drafting
the work. Daiana Cristina Pereira Santana: acquisition, of data for the work; drafting
the work. Ianna Josefa Valeska de Aniz Castro: analysis of data for the work.
Roberto Almeida de Azevedo: acquisition, of data for the work; revising it critically
for important intellectual content. Flávia Caló de Aquino Xavier: analysis and inter-
pretation of data for the work; revising it critically for important intellectual contente.
Jean Nunes dos Santos: analysis and interpretation of data for the work; revising
it critically for important intellectual content. Águida Cristina Gomes Henriques
Leitão: Substantial contributions to the conception and design of the work; analysis
and interpretation of data for the work; revising it critically for important intellectual
content; Final approval of the version to be published. All authors agreement to be
accountable for all aspects of the work in ensuring that questions related to the
accuracy or integrity of any part of the work are appropriately investigated and
resolved. All authors actively participated in the manuscript findings and have revised
and approved the final version of the manuscript.

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