Current Health Sciences Journal Vol. 50, No.

3, 2024 July-September

Original Paper
Epidemiological and Histopathological Features of
Oral Squamous Cell Carcinoma-A Retrospective Study
IONUŢ-OCTAVIAN ILIE1, OTILIA CLARA MĂRGĂRITESCU2,
ALEX EMILIAN STEPAN3, RALUCA NICULINA CIUREA3,
MIRELA MARINELA FLORESCU3, CRISTINA MUNTEANU4,
MIRCEA ŞERBĂNESCU5, CLAUDIU MĂRGĂRITESCU2
1PhD student, Department of Morphopathology, University of Medicine and Pharmacy of Craiova, Romania
2Department of Neurosurgery, University of Medicine and Pharmacy of Craiova, Romania
3Department of Morphopathology, University of Medicine and Pharmacy of Craiova, Romania
4Department of Oral and Maxillofacial Surgery, University of Medicine and Pharmacy of Craiova, Romania
5Medical Informatics Department, University of Medicine and Pharmacy of Craiova, Romania

ABSTRACT: Oral Squamous Cell Carcinoma (OSCC) it was reported to be the 6th on the list of human
malignant neoplasms responsible for high morbidity and mortality worldwide. We conducted a retrospective
study between 2009-2019, investigating 50 such cancers hospitalized and diagnosed during this period in our
institution. The purpose of the study was to establish a clinical-morphological profile of this type of cancer developed
in the geographical area served by our institution. The epidemiological study highlighted the predominance of cases
in men over 50 years old, mainly affecting the tongue, followed by the lips and oral floor. The histopathological study
showed the prevalence of conventional cases of OSCC (70%) and the rest of the cases belonging to rarer forms
(acantholytic-18%, verrucous-6%, basaloid-4% and sarcomatoid-2%). In terms of the degree of differentiation, the
moderately differentiated cases prevailed (64%) and according to the TNM clinical stage, most cases were diagnosed
in stage II (36%) and IV (26%). 70% of investigated cases presented muscle invasion and 38% perineural invasion.
Our investigation highlighted the existence of particular morpho-clinical profiles depending on the tumor topography.
Thus, tumors developed at the tongue level reached the maximum frequency in the 6th decade of life, being absent
in the 8th decade and most often associated muscle invasion and perineural invasion, being diagnosed in advanced
pTNM stages.

KEYWORDS: Epidemiology, Histopathology, Oral cavity, Oral squamous cell carcinomas.

Despite the progress achieved in the last
Introduction period of time, the showing up of improved
In the European demographic space, diagnostic techniques, the discovery of new
malignant neoplasms of the head and neck therapies, as well as new management protocols
amount to 4% of all cancers. In 2012, there were for head and neck cancer, the prognosis of these
approximately 140,000 new cases of oral patients still remains reserved, not changing
squamous cell carcinoma and around 63,500 significantly in the last three decades, the 5-year
deaths due to this form of oral malignancy [1]. survival rate remains around 50-60% [4].
According to the latest statistics provided by Over time, numerous studies have been
GLOBOCAN regarding malignant neoplasms of carried out regarding the identification of the
the oral cavity and lips, this form of cancer is the most feasible prognostic, clinical and
sixth most common worldwide, reporting for the histopathological parameters of oral squamous
year 2020, approximately 377,713 new cases of cell carcinomas, highlighting as more important:
oral squamous cell carcinoma and around tumor size, lymph nodal and distant
177,757 deaths due to them [2]. dissemination status (pTNM clinical staging),
Squamous cell carcinoma of the mucosa of along with the histopathological evaluation of
the oral cavity has an exceptional morbidity and the perineural/ lymphovascular invasion and,
mortality considering the many functions in respectively, of the status of the resection
which this mucosa participates. Thus, the 5-year margins.
survival in localized clinical forms of the disease Considering the aforementioned, the main
is between 75-84%. In advanced clinical forms aim of the study is to outline a particular
accompanied by metastasis, the survival over the epidemiological and histopathological profile of
same period of time is 20% (location: floor of oral squamous cell carcinomas diagnosed and
the oral cavity) and 36% (location: tongue) [3].

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Ionuţ-Octavian Ilie et al. - Epidemiological -Histopathological Features of Oral Squamous Cell Carcinoma

treated in the County Emergency Clinical written informed consent regarding their
Hospital of Craiova No. 1, in the last decade. participation in the study.

Materials and Methods Results

The present study was carried out by Based on our research, from the
analyzing 50 cases of oral squamous cell histopathological perspective, the conventional
carcinoma, between 2009-2019, of some well-differentiated form of oral squamous cell
patients hospitalized in the Oro-Maxillo-Facial carcinomas (OSCC) most often appeared like
Surgery Clinic and diagnosed invasive islands of malignant Malpighian cells.
histopathologically in the Pathology Laboratory In our casuistry the conventional well-
of the County Emergency Clinical Hospital No. differentiated squamous cell carcinoma
1 of Craiova. developed to the following locations: lip, oral
The study of the medical records of the floor, tongue, alveolar ridge and intermaxillary
targeted patients allowed us to collect commissure. In addition, the conventional
epidemiological data, among which we retained: moderate differentiated squamous carcinomas,
age, gender, topography of tumor lesions (jugal beside the mentioned locations, it appeared on
mucosa, oral floor, tongue, gingival mucosa, the gingival mucosa and on the palate.
palatal fibromucosa, oropharynx), pTNM The definitory characteristic of the well-
staging, dominant clinical appearance of the differentiated form is that the tumor proliferation
tumor lesions, the presence or absence of achieves nearly completely the cytoarchitecture
clinically detectable nodal metastases, as well as of normal Malpighian epithelium, but what is
data related to the local and regional extension still remaining as obvious as that, are the
of the tumor. Last but not least, the detailed attributes of malignancy such as: dyskeratosis of
study of the medical records allowed us to the tumor cells, keratin pearls development,
extract some precious data regarding certain invasion to such an extent in the superficial
essential risk and promoters factors of this oral underlying stroma, the polarity of the epithelial
pathology: the status of oral hygiene, inadequate cells tends to get lost, the basement membrane
working conditions and vicious habits. of the lip mucosa broke apart and this
We collected from the records of the phenomenon contributed to the extent of
Pathology Laboratory of the same hospital the invasion, atypical cells are minimal and the
corresponding histopathological data of these nuclear-cytoplasmic ratio is in favor of the
patients, such as: the histopathological subtype nucleoli (Figure 1A).
of oral squamous cell carcinoma according to Furthermore, the form of conventional well-
the WHO criteria [5], the degree of malignancy, differentiated lip squamous cell carcinoma from
the presence and absence of bone invasion, the our case history, developed exclusively to males
presence and absence of muscular invasion and (4 cases) with ages between 72 and 86 years-old,
perineural invasion, the presence and absence of from rural area, who had as vicious habits, risk
lymph node metastases, the pattern of tumor and promoter factors smoking, long-term
invasion, histological grading systems [6,7], exposure to UV rays and bad oral hygiene. The
pTNM staging, the presence and absence of other 28 cases of conventional carcinomas in
areas of necrosis and inflammatory infiltrate, the male patients had other topography. As medical
presence and absence of vascular invasion and history, only one of them was diagnosed with
areas of ulceration, association or not of some diabetes type II and high blood pressure, the
precancerous lesions and last but not least the other two did not mention any known medical
status of the resection margins. history. The tumors’ diameters were between
The collected data were entered into an Excel 2-5cm. The stages pTNM they were diagnosed
and we analyzed them statistically using SPSS in were IVA for two of them and stage III and II
software version 12 and descriptive statistical for the remaining two male patients with the
methods that present the quantitative variables in same form and location. Concerning the tumors’
the form of absolute and relative frequencies. To invasive behavior, they all invaded the muscle in
compare the variables, the Chi square test was the forementioned cases. With regard to female
used, with p<0.05. patients with conventional oral squamous cell
The study was approved by the Ethics and carcinoma, their number was of 3 cases and the
Deontology Committee of the University of locations were the lip one case, the tongue and
Medicine and Pharmacy of Craiova, palate, each with one case. Their ages ranged
(no. 198/18.10.2022) and all patients signed a between 48 and 74 years and they had as risk

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and promoter factors: smoking, alcohol as risk factors smoking, alcohol consumption
consumption and bad oral hygiene. From their and bad oral hygiene. One of the forementioned
medical history we retained a few pathologies, patients of 69 years, had multiple pathologies,
not primary correlated with the malignant including: coronary cardiopathy, virus C
lesions, such as: otomastoiditis, treated hepatitis, obstructive hypertrophic cardiopathy
tuberculosis, hyperlipidemia, high blood and angina pectoris. The diameters of the tumor
pressure grade III. masses were between 1-7cm.
The variant of verrucous OSCC was Histopathologically, we observed the insular
diagnosed in three cases, all male patients with aspect of the neoplastic proliferation which
ages ranging from 52 years to 67 years, all exhibited the pseudoglandular spaces in the
located on the lips. These patients had as risk central part as a consequence of the acantholysis
and promoter factors the consumption of process (Figure 2A).
alcohol, smoking and bad oral hygiene. Through Concerning the attributes of conventional
one of the patients’ medical history, we found poor differentiated carcinomas, we can say that
the following pathologies, non-related directly the cytoarchitecture of the lesion no longer
with the malignancy: ischemic stroke, high resemblance to the normal squamous epithelium,
blood pressure, operated gastric ulcer and aortic in the microenvironment of the tumor the
insufficiency. The diameters of the neoplasms immature cells are predominant, there is
were between 2 and 4cm and the pTNM stages minimal or even absent keratinization and the
of these cases were III for one of them and mitoses are abundant, atypical and typical
respectively, I for the other two. From the (Figure 2B). Also, these forms tend to be more
histopathological perspective, we noticed that aggressive beginning to invade the perineural
the neoplastic proliferation was ample in area and minor salivary glands (Figure 2C,
keratosis and parakeratosis, with an acanthotic Figure 2D).
squamous epithelium accomplishing the so From these cases of poor differentiated
called “church spires” aspect (Figure 1B). squamous carcinomas, arose as a particular
The features of Malpighian epithelium in pattern of malignancy, the basaloid form which
conventional moderate differentiated carcinomas appeared to two male patients, one of 58 years
are not so evident because the attributes of old and respectively 69 years old the other one.
malignancy become more and more obvious: Both of these cases occurred to the oral floor
there are few keratin pearls formation or mucosa. These patients did not mention having
singular cell keratinizations, the nuclear any of the risk and promoter factors, aside the
pleiomorphism is extending and the number of bad oral hygiene, and the same situation goes for
mitosis is increasing (Figure 1C). The lesions the medical history where they did not relate
placed and developed on the tongue almost any. The diameters of the neoplasms were 4cm
constantly presented the invasion of underlying for the first case, with pTNM stage IVA and
striated muscle fiber bundles (Figure 1D) and in 3cm for the second one, with pTNM stage II.
one case located on the oral floor it presented Histopathologically speaking, the neoplastic
vascular invasion (Figure 1E), these features proliferations were consisted of cubic and
marking the changing in aggressiveness. As cylindrical cells, which had tachychromatic
another marker of aggressiveness, we also nuclei and “palisaded” array (Figure 2E).
spotted locoregional lymph node metastases on a Also, as a particular form of poor
case located on the oral floor, too (Figure 1F). differentiated carcinoma there was one case of
The acantholytic form of oral squamous cell sarcomatoid pattern, diagnosed to a male patient
carcinomas, as a particular form of moderate of 65 years of age, located alike basaloid forms
differentiated squamous carcinoma, were found on the oral floor mucosa. The case belongs to
in a total number of 9 cases, from which 6 cases pTNM stage III and had 2/3cm in diameter.
in male patients and 3 cases in female patients, From the histopathological perspective there
with their ages in the interval of 40 and 80 years. were blended areas of conventional squamous
Four of the six male patients developed this carcinoma with malignant neoplastic
form on the oral floor, respectively the proliferation with spindle cell morphology
remaining cases, 1 on the tongue and 1 on the (Figure 2F).
lip. By approaching the same trait in female Our study included the analysis of 50 patients
cases, we observed that two of them formed with oral squamous cell carcinoma (OSCC),
these carcinomas on the tongue and one on the 35 (70%) from rural areas and 15 (30%) from
lip. In these patients’ instance, we can remember urban areas, with an average age of diagnosis of

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Ionuţ-Octavian Ilie et al. - Epidemiological -Histopathological Features of Oral Squamous Cell Carcinoma

60.82±11.61 years, with a variation between the analysed cases, 15 cases (30%) were well
39 and 86 years old. Most cases of oral differentiated (G1), 32 cases (64%) were
squamous cell carcinomas were diagnosed in moderately differentiated (G2) and 3 cases (6%)
male patients, 44 of the cases (88%) and the were poorly differentiated (G3) (Table 1, Figure
remaining 6 cases were diagnosed in female 1, Figure 2). The most prevalent pTNM stage
patients (12%), resulting a gender ratio of 7.33:1 was stage II, 18 cases (36%) (Table 1). At the
in favor of male patients (Table 1). Their most time of diagnosis, 6 patients (12%) presented
frequent locations are on the tongue 15 cases detectable metastases on clinical examination, in
(30%), 14 cases on the lip (28%), 14 cases on 41 patients (82%) they were absent, and
the oral floor (28%), on the alveolar ridge 3 patients (6%) presented reactive lymph nodal
3 cases (6%), at the level of the palate 2 cases hypertrophies. Muscular invasion was present in
(4%), at the level of the gingival mucosa and 35 cases (70%) and absent in 15 cases (30%),
intermaxillary commissure 1 case each (2% perineural invasion present in 19 cases (38%)
each) (Table 1). The tumor formations presented and absent in 31 cases (62%) and lymphatic
the following macroscopic clinical aspects: invasion present in 6 cases (12%) and absent in
ulcerative in 27 cases (54%), ulcerative and 44 cases (88%) (Table 1, Figure 2). The
exophytic lesions in 15 cases (30%) and resection margins of the tumor fragments were
exophytic lesions in 8 cases (16%) (Table 1). invaded in 23 cases (46%) and not invaded in
The sizes of the tumor lesions were between 27 cases (54%) (Table 1). The histopathological
1and 7cm, with an average of 2.87±1.25cm. The analysis of the 50 cases of OSCC showed that
most frequently encountered histopathological more than half of them were classified in the
subtypes were: conventional 35 cases (70%), Bryne grade II (38 cases=76%), and the rest in
acantholytic 9 cases (18%), verrucous 3 cases the Bryne grade I (8 cases=16%) and in the
(6%), basaloid 2 cases (4%) and sarcomatoid 1 Bryne grade III (4 cases=8%) (Table 1).
case (2%) (Table 1, Figure 1, Figure 2). Among
Table 1. Clinical and histopathological parameters of OSCC.

Features Parameters No. of cases Percentage %

Gender Females 6 12%
Males 44 88%
Locations Lip 14 28%
Tongue 15 30%
Oral floor 14 28%
Alveolar ridge 3 6%
Gingival mucosa 1 2%
Intermaxillary commissure 1 2%
Palate 2 4%
Macroscopic aspect Ulcerative 27 54%
Ulcerative and exophytic 15 30%
Exophytic 8 16%
Resection margins Invaded 23 46%
Uninvaded 27 54%
Degree of G1 15 30%
differentiation G2 32 64%
G3 3 6%
pTNM staging I 9 18%
II 18 36%
III 10 20%
IVA 13 26%
Histopathological Conventional 35 70%
subtype Acantholytic 9 18%
Verrucous 3 6%
Basaloid 2 4%
Sarcomatoid 1 2%
Muscular invasion Present 35 70%
Absent 15 30%
Perineural invasion Present 19 38%
Absent 31 62%
Lymphatic invasion Present 6 12%
Absent 44 88%
Bryne grade I 8 16%
II 38 76%
III 4 8%

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Figure 1. Oral Squamous Cell Carcinoma (OSCC). A. Lip with conventional well-differentiated SCC,
neoplastic proliferations with squamous epithelial architecture and dyskeratosis with keratin pearls
formation. HE staining, 100x; B. Lip with verrucous SCC, neoplastic proliferation with abundant keratosis
and parakeratosis in an acanthotic squamous epithelium accomplishing the “church spires” appearance.
HE staining, 25x; C. Tongue with conventional moderate-differentiated SCC, neoplastic proliferation with
obvious malignancy appearances and few keratin pearls formation. HE staining, 100x; D. Tongue with
conventional moderate-differentiated SCC, invading the underlying striated muscle fiber bundles.
HE staining, 200x; E. Oral floor with conventional moderate-differentiated SCC, with vascular invasion.
HE staining, 200x; F. Oral floor with conventional moderate-differentiated SCC, developing locoregional
lymph node metastases. HE staining, 25x.

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Figure 2. Oral Squamous Cell Carcinoma (OSCC). A. Alveolar ridge with acantholytic SCC, characteristically
having the presence of pseudoglandular spaces in the central part of insular neoplastic proliferations
created by acantholysis process. HE staining, 25x; B. Tongue with conventional poor-differentiated SCC, the
neoplastic proliferations do no longer resembles squamous epithelium, keratinization is minimal and nuclear
atypia are evident. HE staining, 200x; C. Tongue with conventional poor-differentiated SCC, with perineural
invasion. HE staining, 100x; D. Tongue with conventional poor-differentiated SCC, invading minor salivary
glands. HE staining, 200x: E. Oral floor with basaloid SCC, in which the neoplastic cells at the periphery of
the proliferations have a basaloid morphology (cubic-cylindrical cells with little cytoplasm and
tachychromatic nuclei) and have a "palisaded" arrangement. HE staining, 100x; F. Oral floor with
sarcomatoid SCC, in which there were areas of conventional squamous carcinoma mixed with foci of
malignant neoplastic proliferation with spindle cell morphology. HE staining, 100x.

The statistical analysis highlighted that the developed at the level of the oral floor had a
distribution of cases according to age and linear distribution, with a sharp decrease in the
location shows the following trends: cases 8th decade; in the case of gingival mucosa, after
located at the level of the tongue reached the the age of 50 years, the distribution of cases was
maximum frequency in the 6th decade of life, also linear. The differences between these
being absent in the 8th decade; cases located on distributions are statistically significant
the lip showed an increase in incidence with according to Fisher's Exact test, which indicated
aging, with a peak in the 8th decade; cases a p value of 0.0131 (Figure 3A).

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Figure 3. Oral Squamous Cell Carcinoma (OSCC)- statistical analysis. A. The distribution of cases stratified
by age and location; B. The distribution of perineural invasion stratified by location; C. The distribution of
muscular invasion stratified by location; D. Linear regression analysis showing the influence of tumor
grading on Bryne score of the investigated cases.

Regarding perineural invasion, we observed a Otherwise, we could not establish statistically

greater tendency for tumors located on the significant correlations between the main
tongue to be associated with this parameter morphoclinical investigated parameters.
compared to those located on the lips
(χ²=4.2086, p <0.05) (Figure 3B). In addition, Discussions
tumors located on the tongue and lips more Regarding the topographic point of reference,
frequently showed muscular invasion compared carcinomas of the oral cavity were ranked
to those in other locations, with high statistical globally as the 18th to the 26th most common
significance (χ²=16.9161, p<0.01) (Figure 3C). form of human cancer [8].
Regarding the association with the Bryne According to some studies, the highest rate of
grade, we observed that the second Bryne grade cases of oral squamous cell carcinoma was
occurs much more frequently in the investigated observed in France, Croatia, Hungary, Sri Lanka
cases, regardless of location. Also, this grade and Melanesia. Over the years, there has been an
was found more frequently in young people increased incidence of oral cancer in South Asia,
(≤50 years), while Bryne grade I was seen more as well as oral and nasopharyngeal cancer in
often in older people, but the difference was not Southeast Asia [9].
statistically significant. From the point of view of the topography of
In addition, multiple regression analysis cancerous lesions, India, Bangladesh, Pakistan
showed that the degree of differentiation is the and Sri Lanka presented about 1/3 of the
only variable that significantly influences the malignant neoplasms developed in the oral
Bryne grade (p=0.007). This significance was cavity [10].
also confirmed by linear regression, which had a In accordance with other researches, in the
p=0.004, with an intercept of 8.46 and a United States of America there was a
coefficient of 1.42 (Figure 3D). stabilization, even a decrease in the cases of oral
Although we can not speak of statistical and pharyngeal cancer for both genders in most
significance between the stage and lymphatic decades of life, between the years 1973-2003
invasion, we noticed the tendency of the [9].
presence of invasion exclusively in the advanced In addition, according to another study, an
pathological stages (III and IVA). upward trend was noticed for lip cancers in
Caucasian individuals living in the equatorial

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Ionuţ-Octavian Ilie et al. - Epidemiological -Histopathological Features of Oral Squamous Cell Carcinoma

region, with long-term exposure to an increased this, we also identified the following
proportion of ultraviolet rays being the main histopathological subtypes: acantholytic (18%),
contributing factor [11]. verrucous (6%), basaloid (4%) and sarcomatoid
Based on extensive studies, a mortality peak (2%). This analysis of the morphoclinic
was remarked among men of Italian and French parameter corresponds to data highlighted by
nationality during the 1980s, which began to Ciucă FI et al. [19] who identified more than
decline only after 1990 [12]. half of the cases (53.7%) as belonging to the
However, there was a constant increase in the conventional subtype and Inaut AF et al. [20]
parameter previously mentioned in Belgium, who identified over 90% of the cases as
Greece, Denmark, Scotland and Portugal [13]. belonging to the same conventional
According to our research, OSCC histopathological subtype.
predominantly affected men, 88% of the The degree of differentiation of oral
analysed cases and only 12% were diagnosed in squamous cell carcinomas most common in our
women, an aspect also supported by other case series is represented by the moderately
studies [1,14,15]. differentiated forms, totaling 32 cases (64%),
The demographic distribution by place of being followed by the well-differentiated forms
origin highlighted that 35 (70%) of the (30%) and finally by the poorly differentiated
diagnosed patients came from the rural area and ones (6%). At the same time, our study
the difference of 15 cases (30%) from the urban highlighted the fact that most of the resection
area. Harris JA et al. [16], in a similar study margins were not invaded (54%) by the
published in 2020, highlighted a similar aspect carcinomas, the percentage difference being
regarding this epidemiological parameter, represented by the invaded resection margins.
demonstrating that over 80% of the patients Studies and specialized literature highlight
came from rural areas. The average age of similar aspects as follows: according to a study
diagnosis in our study was 60.82 years, an conducted in 2024, the majority were
aspect supported by a statistical study carried moderately differentiated forms of oral
out in the USA between 2003-2007, by squamous cell carcinomas (52.5%) [20] and at
Altekruse SF et al. [17], which claims that the the same time, in accordance with a study
average age of diagnosis of cancer of the oral conducted in 2018, most of the resection
cavity and pharynx is 62 years. margins were uninvaded (76%) [19].
Daroit NB et al. [18], according to a research Our study, regarding pTNM staging,
carried out in 2023 on a large group of patients, highlights that the predominant stage is
found that from a topographical point of view, represented by stage II (36%), followed in
oral malignant neoplasms developed and descending order by stage IVA (26%), stage III
affected in most cases the tongue, following (20%) and stage I (18%). By comparing with the
them in second place the oral floor. Following specially designed literature, there is a slight
the analysis carried out in our research, we change in the trend of this parameter over time,
reached the same results, the most frequent the parallel being made with the study carried
localization of cases of oral squamous cell out by Ciucă FI et al. in 2018 [19], where the
carcinomas being at the level of the tongue, 30% most frequent pTNM stage was represented by
of the cases, being followed in second place by stage III (37.04%), with a small percentage
the oral floor and the lip, each of these two difference followed by stage II (33.33%), and on
locations statistically contributing 28% of cases. the last two places ranking stage IV (16.67%)
Regarding the macroscopic clinical aspect of and stage I (12.96%).
the lesions, ulcerative lesions were predominant, By following the statistical analysis carried
54% of the cases analyzed and diagnosed, the out in our study, we observed the following
same thing was highlighted by Daroit NB et al. aspects: oral squamous cell carcinomas
[18] in the study they realized, where 484 (49%) developed on the tongue reached a maximum
of the cases had the same macroscopic frequency in the 6th decade of life, and in the
appearance. 8th decade they were absent; regarding the cases
The histopathological analysis of the cases developed at the level of the lips, they presented
studied by us highlighted that the most common a maximum incidence in the 8th decade of life;
morphopathological subtype of oral squamous carcinomas developed from the mucosa of the
cell carcinomas was represented by the oral floor showed a sudden decrease in
conventional subtype, with a number of 35 cases incidence in the 8th decade of life, otherwise
(70%) from the total case history. Apart from having a linear distribution, similar to

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carcinomas developed from the gingival mucosa Conclusions

which after the age of 50 years showed the same The results of our investigation indicate the
linear distribution. After carrying out the Exact prevalence of casuistry among men, with an
Fisher test, it emerged that the differences average age of diagnosis around 61 years, more
between the previously mentioned distributions frequent developed in the tongue, followed by
are statistically significant (p=0.0131). In lip and oral floor. Histopathologically prevailed
general, it is considered that tongue cancer the conventional type of OSCC, moderately
predominates in men over 50 years old [21], but differentiated (G2), much more frequently with
studies of the last decade indicate an increase in pTNM stage II, almost two thirds showing
the incidence among young people and muscle invasion and 38% perineural invasion.
especially among women [22]. Particularly for cases with tongue localization,
Regarding the invasive nature of OSCC, we we found a maximum incidence in the 6th
observed a greater tendency for tumors decade of life, most cases presenting muscle
developed on the tongue to be associated with invasion and perineural invasion and advanced
perineural invasion, compared to those clinical stages at the time of diagnosis. It seems
developed on the lips (χ²=4.2086, p<0.05). The that for OSCC, tumor topography influences the
vast majority of studies highlighted the fact that clinical behavior and the morphological profile,
in oral cancer, perineural invasion is associated dictating different therapeutic strategies to be
with a poor prognosis and its presence is taken in such patients.
considered a clinical indication for radiotherapy
and systemic treatment [23,24,25]. References
Recently, Huang Q et al., showed that 1. Capote-Moreno A, Brabyn P, Munoz-Guerra MF,
Sastre-Perez J, Escorial-Hernandez V, Rodriguez-
lymphovascular and perineural invasions are Campo FJ, Garcia T, Naval-Gias L. Oral
independent negative prognostic factors for squamous cell carcinoma: epidemiological study
tongue cancer, patients with lymphovascular and risk factor assessment based on a 39-year
and/or perineural invasion may have series. Int. J. Oral Maxillofac. Surg, 2020, 49:
1525-1534.
significantly poorer overall survival [26]. 2. Alexandra C, Andrei N, Mihaela M, Eugenia P.
In addition, we noticed that muscular Predictive Factors in the Appearance and
invasion appeared with a much higher frequency Evolution of Squamous Cell Carcinomas of the
in tumors from the tongue and lips, compared to Oral Cavity. Medicina, 2022, 58 (5):570.
tumors from other locations, an aspect that had a 3. Christina McC, Alex K, Marco AM, Iona TL, Tanya
J, Grace B. Oral Squamous Cell Carcinoma
high statistical significance (χ²=16.9161, Associated with Precursor Lesions. Cancer Prev
p<0.01). Literature studies indicate that in Res, 2021, 14(9):873-883.
OSCC the muscle invasion can be used as a 4. Tiwana MS, Wu J, Hay J, Wong F, Cheung W,
prognostic parameter, cases with skeletal muscle Olson RA. 25 year survival outcomes for
squamous cell carcinomas of the head and neck:
invasion have a poor prognosis and the degree of population-based outcomes from a Canadian
muscle invasion increases as the degree of tumor province. Oral Oncol, 2014, 50:651-656.
differentiation decreases [27]. 5. Johnson N, Franceschi S, Ferlay J, Ramadas K,
For tongue OSCC it seems that the pattern of Schmid S, MacDonald DG, Bouquot JE, Slootweg
muscle invasion plays an important role in the PJ. Squamous cell carcinoma. In: Barnes L,
Eveson JW, Reichart P, Sidransky D (Eds.): World
progression of the disease, the local recurrence Health Organization classification of tumours:
being higher in patients with muscle invasion pathology and genetics of head and neck tumours.
[28]. IARC, 2005, Lyon, 168-175.
After performing the multiple regression 6. Bryne M, Koppang HS, Lilleng R, Kjærheim A.
Malignancy grading of the deep invasive margins
analysis, we noticed that the only variable that of oral squamous cell carcinomas has high
significantly influences the Bryne grade is prognostic value. The Journal of pathology, 1992,
represented by the degree of tumor 166 (4):375-381.
differentiation (p=0.007). The previously 7. Anneroth G, Batsakis J, Luna M. Review of the
mentioned significance was also confirmed by literature and a recommended system of
malignancy grading in oral squamous cell
the linear regression, which had a p=0.004, with carcinomas. European Journal of Oral Sciences,
an intercept of 8.46 and a coefficient of 1.42. 1987, 95 (3):229-249.
The literature indicates Bryne's grading system 8. PĂtru A, Şurlin V, MĂrgĂritescu C, CiucĂ E,
as the best in in predicting the outcome of MĂrgĂritescu OC, Camen A. Palate Squamous
Cell Carcinomas:A Ten-Year Single Institute
OSCC and this is mainly due to the fact that it Experience. Curr Health Sci J, 2020, 46(4):358-
takes into account the tumor morphology from 370.
the invasion front [29,30].

10.12865/CHSJ.50.03.08 419
Ionuţ-Octavian Ilie et al. - Epidemiological -Histopathological Features of Oral Squamous Cell Carcinoma
9. Newell Johnson W, Prasanna J, Hemaltha AA, 21. Warnakulasuriya S. Global epidemiology of oral
Amarasinghe K. Squamous cell carcinoma and and oropharyngeal cancer. Oral Oncol, 2009,
precursor lesions of the oral cavity: epidemiology 45(4-5):309-316.
and aetiology. Periodontology 2000, 2011, 57(1): 22. Patel SC, Carpenter WR, Tyree S, Couch ME,
19-37. Weissler M, Hackman T, Hayes DN, Shores C,
10. Sankaranarayanan R. Oral cancer in India: an Chera BS. Increasing incidence of oral tongue
epidemiologic and clinical review. Oral Surg Oral squamous cell carcinoma in young white women,
Med Oral Pathol, 1990, 69:325-330. age 18 to 44 years. J Clin Oncol, 2011,
11. Moore SR, Allister J, Roder D, Pierce AM, Willson 29(11):1488-1494.
DF. Lip cancer in South Australia, 1977-1996. 23. Binmadi N, Alsharif M, Almazrooa S, Aljohani S,
Pathology, 2001, 33:167-171. Akeel S, Osailan S, Shahzad M, Elias W, Mair Y.
12. Tanaka S, Sobue T. Comparison of oral and Perineural Invasion Is a Significant Prognostic
pharyngeal cancer mortality in five countries: Factor in Oral Squamous Cell Carcinoma: A
France, Italy, Japan, UK and USA from the WHO Systematic Review and Meta-Analysis.
Mortality Database (1960-2000). Jpn J Clin Oncol, Diagnostics, 2023, 13:3339.
2005, 35:488-491. 24. Cooper JS, Zhang Q, Pajak TF, Forastiere AA,
13. Bosetti C, Bertuccio P, Levi F, Lucchini F, Negri E, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak
La Vecchia C. Cancer mortality in the European AJ, Rotman M, Lustig R, Ensley JF, Thorstad W,
Union 1970-2003, with a joinpoint analysis. Ann Schultz CJ, Yom SS, Ang KK. Long-term follow-up
Oncol, 2008, 19:631-40. of the RTOG 9501/intergroup phase III trial:
14. Leite AA, Leonel ACLS, Castro JFl, Carvalho EJA, postoperative concurrent radiation therapy and
Vargas PA, Kowalski LP, Perez DEC. Oral chemotherapy in high-risk squamous cell
squamous cell carcinoma: a clinicopathological carcinoma of the head and neck. Int J Radiat
study on 194 cases in northeastern Brazil. A Oncol Biol Phys, 2012, 84(5):1198-1205.
cross-sectional retrospective study. Sao Paulo 25. Sher DJ, Adelstein DJ, Bajaj GK, Brizel DM,
Med J, 2018, 136(2):165-169. Cohen EEW, Halthore A, Harrison LB, Lu C,
15. Alves AM, Correa MB, Karine DS, Maria LAA, Ana Moeller BJ, Quon H, Rocco JW, Sturgis EM,
CUV, Ana PNG, Adriana E, Sandra BCT. Tishler RB, Trotti A, Waldron J, Eisbruch A.
Demographic and Clinical Profile of Oral Radiation therapy for oropharyngeal squamous
Squamous Cell Carcinoma from a Service-Base cell carcinoma: Executive summary of an ASTRO
Population. Brazilian Dental Journal, 2017, 28(3): Evidence-Based Clinical Practice Guideline. Pract
301-306. Radiat Oncol, 2017, 7(4):246-253.
16. Harris JA, Hunter WP, Hanna GJ, Treister NS, 26. Huang Q, Huang Y, Chen C, Zhang Y, Zhou J, Xie
Menon RS. Rural pacients with oral squamous cell C, Lu M, Xiong Y, Fang D, Yang Y, Hu W, Zheng
carcinoma experience better prognosis and long- F, Zheng C. Prognostic impact of lymphovascular
term survival. Oral Oncology, 2020, 111:1-7. and perineural invasion in squamous cell
17. Altekruse SF, Kosary CL, Krapcho M, Neyman N, carcinoma of the tongue. Sci Rep, 2023, 13(1):
Aminou R, Waldron W, Ruhl J, Howlader N, 3828.
Tatalovich Z, Cho H, Marrioto A, Eisner MP, Lewis 27. Chatterjee S, Devi A, Kamboj M, Narwal A, Anand
DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb R, Bhola R. The road less travelled: Skeletal
DG, Edwards BK. SEER Cancer Statistics muscle invasion in oral squamous cell carcinoma.
Review, 1975-2007. National Cancer Institute, J Oral Biol Craniofac Res, 2022, 12(5):516-521.
Bethesda MD, 2010, 423-431. 28. Chandler K, Vance C, Budnick S, Muller S. Muscle
18. Daroit NB, Martins LN, Garcia AB, Haas AN, Dal invasion in oral tongue squamous cell carcinoma
Moro Maito FL, Rados PV. Oral cancer over six as a predictor of nodal status and local
decades: a multivariable analysis of a recurrence: just as effective as depth of invasion?
clinicopathologic retrospective study. Brazilian Head Neck Pathol, 2011, 5(4):359-363.
Dental Journal, 2023, 34(5):115-124. 29. Thamilselvan S, Pandiar D, Krishnan RP,
19. Ciucă FI, Mărăşescu PC, Matei M, Florescu AM, Ramalingam K, Pavithran P. Comparison of
Mărgăritescu C, Petrescu SMS, Dumitrescu CI. Broder's and Bryne's Grading System for Oral
Epidemiological and Histopathological Aspects of Squamous Cell Carcinoma with Lymph Node
Tongue Squamous Cell Carcinomas- Metastases and Prognosis: A Scoping Review.
Retrospective Study. Current Health Science Cureus, 2024, 16(1).
Journal, 2018, 44(3):211-224. 30. Wagner VP, Webber LP, Curra M, Klein IP,
20. Inaut AF, Jose MAU, Jose MSP, Cintia CP, Irene Meurer L, Carrad VC, Martins MD. Bryne's
LIM, Xabier MM, Andres BC, Jose AL, Abel GG. grading system predicts poor disease-specific
Epidemiological, clinical and prognostic analysis of survival of oral squamous cell carcinoma: a
oral squamous cell carcinoma diagnosed and comparative study among different histologic
treated in a single hospital in Galicia (Spain): a grading systems. Oral Surg Oral Med Oral Pathol
retrospective study with 5-year follow-up. Med Oral Radiol, 2017, 123(6):688-696.
Oral Patol Oral Cir Bucal, 2024, 29(1):36-43.

Corresponding Author: Otilia Clara Mărgăritescu, Department of Neurosurgery, Faculty of Medicine,

University of Medicine and Pharmacy of Craiova, Petru Rareş Street, 200349 Craiova, Romania,
e-mail: omargaritescu@yahoo.com

420 10.12865/CHSJ.50.03.08