Oral Potentially malignant disorders and their

relationship with a cervical mass

N. SolanoA.B,E. Rivera, G. DuenesB, M. AtencioB

Oral and Maxillofacial Surgery Unit, Venezuela

A

Oral Surgery Post-Graduated program, School of Dentistry, Universidad del Zulia, Venezuela
B

ABSTRACT

Oral potentially malignant disorder (OPMD) is defined as an epithelial lesion or disorder that has an increased
risk for malignant transformation. The diagnosis of OMPD begins with a clinical examination, and, when
present, it is most commonly described as a white lesion (leukoplakia) or less often as a red lesion
(erythroplakia). These diagnoses are only clinical, and a definitive diagnosis must be determined through
biopsy and histopathology examination. The location of the mass, details surrounding its appearance, and
overall time course are important factors to help differentiate neoplastic disease from other possibilities in the
long differential diagnosis. The clinical evaluation of a persistent neck mass may also require imaging studies
or biopsy to establish the diagnosis. The objective of this study is to describe potentially malignant lesions in
the oral cavity and the degree of transformation in malignant lesions and their relationship with the appearance
of cervical masses.

INTRODUCTION

The oral cavity is lined by a mucous membrane (the oral mucosa) consisting of a stratified squamous
epithelium, which may or not be keratinized, and one underlying connective tissue layer, the own sheet. These
tissues have an adaptive capacity to modify their morphology, organization and structure as a defense
mechanism. To the point of creating macroscopic changes that are of great importance and that may have the
ability to be initial steps to malignant lesions, when combined with risk factors that can aggravate the clinical
picture and determine the variation in the evolution of the themselves.Oral potentially malignant disorder
(OPMD) is defined as an epithelial lesion or disorder that has an increased risk for malignant transformation.
The diagnosis of OMPD begins with a clinical examination, and, when present, it is most commonly described
as a white lesion (leukoplakia) or less often as a red lesion (erythroplakia). These diagnoses are only clinical,
and a definitive diagnosis must be determined through biopsy and histopathology examination1.

One of the most important factors that help define a specific diagnosis is the patient´s age. In general, three
age groups need to be considered: pediatric (<15 years), young adults (16 to 40 years of age), and older
adults (>40 years of age). Each of these age groups exhibits a certain relative frequency of disease
occurrence, which can help the clinician develop an appropriate diagnosis2-3. It is important to note the majority
of neck masses in the young pediatric population are more commonly inflammatory and congenital rather than
neoplastic4. Neoplasia, on the other hand, tends to vary in terms of anatomic location but is inclined to follow a
systematic pattern of lymphatic spread from the primary oropharyngeal site. In 5% to 10% of patients, the
primary source of the tumor is not readily apparent, and after a detailed, exhaustive physical examination
coupled with imaging studies and directed biopsies of oropharyngeal tonsillar tissue, the pharyngeal walls, and
the base of the tongue, approximately 1% to 2% remain carcinomas of unknown primary origin. 5-6This chapter
outlines a practical approach to the diagnosis and evaluation of adult patients with cervical neck masses. The
objective of this study is to describe potentially malignant lesions in the oral cavity and the degree of
transformation in malignant lesions and their relationship with the appearance of cervical masses.

ORAL POTENTIALLY MALIGNANT DISORDER (OPMD)

Oral potentially malignant disorder (OPMD) is defined as an epithelial lesion or disorder that has an increased
risk for malignant transformation.

Leukoplakias (OLK) were first reported in the literature in 1877. It is a clinical diagnosis defined by the World
Health Organization (WHO) as “a white patch or plaque that cannot be characterized clinically or pathologically
as any other definable lesion”. 7-8 A recent systematic review indicated the worldwide prevalence of oral
potentially malignant disorders (OPMDs) was 4.47% and that OLK was one of the most common at 4.11% 9.
Proliferative verrucous leukoplakia (PVL) is a particularly aggressive variant of OLKcharacterized by multifocal
lesions and a corrugated clinical appearance, and displays a particularly high MT rate of between 40% and
70%10.

Erythroplakia is defined as a potentially malignant disorder of the oral cavity that presents as a red patch of the
oral mucosa that cannot be diagnosed as any other definable lesion. The lesion cannot have traumatic,
vascular, or inflammatory causes. Although erythroplakia is rare, it has a much higher rate of malignant
transformation than other premalignant conditions, such as leukoplakia and submucous fibrosis. The reported
transformation rates range from 14% to 50%,11-12 times greater than the malignant transformation rates of
leukoplakic lesions13. Systematic reviews have shown a range of 1.3% to 34% of malignant transformation in
erythroplakic lesions in the global population14.The soft palate is the most common site for erythroplakia to
occur. Other common sites include ventral tongue, floor of mouth, and tonsillar pillars. Other areas of the
tongue are rarely affected15

Oral Lichen Planus (OLP), it is a mucocutaneous inflammatory condition that can manifest in a number of
ways. The most common is reticular type which has a white lacy appearance, other forms include erosive,
atrophic and plaque forms. The first reported case of oral squamous cell carcinoma developing in a patient
with OLP was in 2010 and since thattime a number of studies have reported on malignant transformation in
OLP. The malignant transformation rate in OLP is 0-5%16.

Oral Submucous Fibrosis (OSF)has an average MTR range of 7-30%17 and there are multiple etiologic factors
that have been linked to this disease and include vitamin deficiencies like iron and zinc, autoantibodies, and
the molecule capsaicin in chilies. However, the most predominant etiological factor in the literature with the
strongest link is the use of areca nut and its derived products that include betel quid and gutkha. Gutkha is a
grainy light brown substance that contains high concentrations of areca nut; it is combined with tobacco and
provides a central stimulation leading to higher addiction than chewing tobacco.1-18

Human papillomavirus (HPV) has been identified as a risk factor for the development of oral and
oropharyngeal19-20squamous cell carcinoma (OSCC, OPSCC). Wetzel & Wollenberg of up to 3%.
Histopathologic evidence has been seen in some instances of oral epithelial dysplasia. These lesions most
commonly present as leukoplakia, but erythroplakias and erythroleukoplakias have also been described.
Several subtypes exist of which 16 and 18 are deemed high risk for the development of OPSCC21-22. Two viral
oncoproteins derived from the HPV gene, E6 and E7, have been isolated and are necessary for the malignant
transformation to SCC. These oncoproteins exert their repressive effects on p53 and Rb tumor suppressor
activity respectively. The standard to confirm the presence of HPV in dysplastic oral lesions is through in situ
hybridization. The oral health professionals are responsible for the early diagnosis of lesions that can become
malignant and oral cancer in its earliest stages.There are several etiologic factors involved: tobacco (smoked
or chewed), drinking, diet, immunosuppression, viruses such as human papillomavirus (HPV), the presence of
premalignant lesions and, in discussion for some authors, local trauma factors.

It is known that oral epithelial dysplasia (OED) is often the precursor to OSCC. Oral dysplasia is diagnosed
histologically and defined by the W.H.O as a precancerous lesion of stratified squamous epithelium
characterized by cellular atypia and loss of normal maturation and stratification short of carcinoma in situ 23-24-25.
The presence and the grade of dysplasia contributes to the malignant transformation potential for all the above
(OPMD)23-26-27-28. OLP, OSF, OL and OE are the gross clinical manifestations of the accumulating microscopic
dysplastic changes of normal cellular architecture26, 29, 27, 30. However, PPOEL’s and clinically normal mucosa
can progress to OSCC without the presence of dysplasia. However, not all dysplastic lesions will progress to
OSCC29The overall MTR of OED in the literature can range from 6%-36% 30. Current variables in the literature
that affect the MTR are the site of the lesion; tongue and FOM being at the higher end of the MTR spectrum
along with the grade of the dysplasia23. There are conflicting reports with respect to grading severity being
correlated with MTR24, 31, 32. Primary squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT)
as it represents over 90% of primary malignancy in the head and neck33. A persistent neck mass in an adult
older than 40 years should raise a suspicion of malignancy. A neck mass in a young adult patient is more likely
to be an inflammatory, congenital, or traumatic process. The presenting neck mass should be carefully
examined by inspection and palpation. We present a box that indicates somecharacteristics of the injuries with
high suspicion of malignanity in the oral cavity(BOX1). The location of the mass, details surrounding its
appearance, and overall time course are important factors to help differentiate neoplastic disease from other
possibilities in the long differential diagnosis. The clinical evaluation of a persistent neck mass may also
require imaging studies or biopsy to establish the diagnosis 34. In this article, a management algorithm is
exposed in patients with cervical massin Maracaibo University Hospital. (BOX 3)

BOX 1 -BOX
CHARACTERISTICS OF THEOF
1 - CHARACTERISTICS INJURIES WITH HIGH
THE INJURIES WITHSUSPICION OF MALIGNITY
HIGH SUSPICION OF MALIGNANITY
DURATION: Injury that persist for more than two weeks
ERYTHROPLAKIA: Injury that is completely red or has a red dotted and white component
FIXATION: Injury that is adhered to adjacent structures
INDURATION: Injury and tissues that surround it and are film to palpation

BLEEDING: Injury that bleeds to a soft manipulation

GROWTH RATE: fast growing injury
ULCERATION: Injury that is ulcerated, or is present as an ulcer.
Hupp, J et al. Cirugía Oral y Maxilofacial Contemporánea. 6ta. Ed. 2014. Elsevier España.

BOX 2 First-Echelon Lymphatic Sites of Drainage of

the Head and Neck
Cervical lymphadenopathy is the presence of abnormal, usually enlarged, lymph nodes in the neck that can
represent the immune response of a transient pathologic process or worse: the progression of a malignant
disease. Cervical lymph nodes comprise one-third of the body’s lymphatic system and the drainage of the
head and neck follows a predictable pattern. The latest proposed anatomic classification, and the system most
widely used among head and neck surgeons, is the Robbins Classification, which delineates the neck into 6
levels based on lymphatic drainage.describes the significance of each level in the neck (BOX 2). A basic
understanding of neck levels will aid in localizing the primary site of malignant or infectious disease in the
presence of cervical lymphadenopathy. If there is a strong clinical suspicion of malignancy based on history,
like an older patient with B symptoms such as fever, night sweats, and weight loss who presents with a neck
mass, or based on examination, like a patient with a palatine tonsil mass and ipsilateral neck
lymphadenopathy, then a CT neck scan with contrast is recommended to rule out lymphoma and to rule out
metastatic carcinoma respectively in these two examples. CT will provide anatomic detail of bone and the soft
tissue of the neck and upper aerodigestive tract35

Approximately 65% of patients with cancer of the oropharynx or hypopharynx will demonstrate cervical
lymphadenopathy as the initial symptom prior to diagnosis26.The most common malignant neoplasm to present
as a neck mass in an adult is metastatic squamous cell carcinoma with the primary site in the upper
aerodigestive tract. In all patients older than the age of 40, squamous cell carcinoma should be considered,
and for those patients older than 60, the utmost suspicion should be of squamous cell carcinoma. The 30% of
adults who are diagnosed with head and neck cancer had cervical lymphadenopathy at their first clinic
visit36.This statistic should sway providers to be vigilant about enlarged cervical lymph nodes in the adult
population. In addition, a cystic neck mass requires careful diagnostic workup because nodal metastases of
both HPV-related oropharynx cancer and thyroid cancer can present with cystic variants, which may be all too
easily dismissed as a congenital lesion37

Algorithm for Work-up of a Neck Mass in Adults.

Maracaibo University Hospital
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In conclusion,identifying potentially malignant desordersin the oral cavity begins with through clinical
examination of the soft tissue in the oral cavity and assessment of the patient risk factors. There are injuries in
the oral cavity with high suspicion characteristic malignitythat indicate presence of an OPMD. It is confirmed
via biopsy and microscopic examination of the lesional tissue. malignancy must not be missed; therefore, the
evaluation of a neckmass in an adult should be a cautious one. The most probable diagnosis of a neckmass in
adults (age over 40) is very different than in children and even young adults(ages 20–40). Providers should
hone their history-taking and examination skills in orderto distinguish between the various causes of a neck
mass. Communicating pertinentinformation regarding the patient’s age, risk factors, presentation, and
physicalcharacteristics to colleagues in radiology and cytopathology will increase the likelihoodof coming to the
correct diagnosis. Skepticism about a benign pathologic resultis encouraged. Lastly, front line providers should
not hesitate to consult with orpromptly defer management to otolaryngology colleagues because most
patientswill require surgical intervention and a rising number will need comprehensivecancer care.

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