IMPORTANCE OF TUMOR

THICKNESS AND DEPTH OF

INVASION IN NODAL
INVOLVEMENT AND PROGNOSIS
OF ORAL SQUAMOUS CELL
CARCINOMA
DR. ISHITA SINGHAL
MDS FIRST YEAR
INDEX

• SQUAMOUS CELL CARCINOMA

• TNM STAGING

• INTRODUCTION

• DISCUSSION

• RESULTS

• REFERENCE ARTICLES

• CONCLUSION

• REFERENCES
SQUAMOUS CELL CARCINOMA
It is the most common malignant
epithelial tissue neoplasm of the
oral cavity.
It is derived from the stratifi ed
squamous epithelium.
Since oral squamous cell
carcinomas constitute bulk of the
oral malignancies (above 90 %) it
is thus commonly referred to as
Oral Cancer.

Rajendran, Arya, and Shivapatha Sundaram. Shafer's Textbook of Oral Pathology. 2012.
 PRIMARY TUMOR [T]
T CATEGORY T CRITERIA
TX Primary tumor cannot be assessed
Tis Carcinoma in situ
Tumor< 2 cm , < 5 mm depth of invasion (DOI)
T1
DOI is depth of invasion and not tumor thickness.
Tumor < 2 cm, DOI > 5 mm and < 10 mm
T2
or tumor > 2 cm but < 4 cm, and < 10 mm DOI
T3 Tumor > 4 cm or any tumor > 10 mm DOI
T4 Moderately advanced or very advanced local disease
Moderately advanced local disease
(lip) Tumor invades through cortical bone or involves the inferior alveolar nerve, floor of mouth, or
skin of face (i.e., chin or nose).
T4a (oral cavity) Tumor invades adjacent structures only (e.g., through cortical bone of the mandible or
maxilla, or involves the maxillary sinus or skin of the face)
Note: Superficial erosion of bone/tooth socket.
(alone) by a gingival primary is not sufficient to classify a tumor as T4.
Very advanced local disease
T4b Tumor invades masticator space, pterygoid plates, or skull base and/or encases the internal carotid
artery
Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 REGIONAL LYMPH NODE – CLINICAL [cN]

N CATEGORY N CRITERIA

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

Metastasis in a single ipsilateral lymph node,

N1
3 cm or smaller in greatest dimension and ENE(-)
Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension
and ENE(-);
N2 or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and
ENE(-);
or in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, and ENE(-)

Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension,
N2a
and ENE(-)

N2b Metastasis in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension, and ENE(-)

Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, and
N2c
ENE(-)
Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 REGIONAL LYMPH NODE – CLINICAL [cN]

N CATEGORY N CRITERIA

Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-);

N3
or metastasis in any node(s) and clinically overt ENE(+)

N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-)

N3b Metastasis in any node(s) and clinically overt ENE(+)

A designation of “U” or “L” may be used for any N category to indicate metastasis above the lower
NOTE border of the cricoid (U) or below the lower border of the cricoid (L).
Similarly, clinical and pathological ENE should be recorded as ENE(-) or ENE(+)

Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 REGIONAL LYMPH NODE – PATHOLOGICAL [pN]

N CATEGORY N CRITERIA

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

Metastasis in a single ipsilateral lymph node,

N1
3 cm or smaller in greatest dimension and ENE(-)

Metastasis in a single ipsilateral lymph node- 3 cm or smaller in greatest dimension and ENE(+);
or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-);
N2 or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and
ENE(-);
or in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, ENE(-)

Metastasis in single ipsilateral or contralateral node 3 cm or smaller in greatest dimension and ENE(+);
N2a
or single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-)

N2b Metastasis in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension and ENE(-)

Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and
N2c
ENE(-)
Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 REGIONAL LYMPH NODE – PATHOLOGICAL [pN]

N CATEGORY N CRITERIA

Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-);

N3 or in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+);
or multiple ipsilateral, contralateral or bilateral nodes any with ENE(+)

N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-)

Metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+);
N3b
or multiple ipsilateral, contralateral or bilateral nodes any with ENE(+)

A designation o f “U” or “L” may be used for any N category to indicate metastasis above
NOTE the lower border o f the cricoid (U) or below the lower border of the cricoid (L) Similarly,
clinical and pathological ENE should be recorded as ENE(-) or ENE(+)

Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 DISTANT METASTASIS

M CATEGORY M CRITERIA

M0 No distant metastasis

M1 Distant metastasis

Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 PROGNOSTIC STAGE GROUPS
THEN THE STAGE
WHEN T is.. AND N is.. AND M is..
GROUP is..
T1 N0 M0 I

T2 N0 M0 II

T3 N0 M0 III

T1, T2, T3 N1 M0 III

T4a N0, N1 M0 IV A

T1, T2, T3, T4a N2 M0 IV A

ANY T N3 M0 IV B

T4b ANY N M0 IV B

ANY T ANY N M1 IV C
Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 CHARACTERISTICS OF LIP AND ORAL CAVITY TUMORS

A.EXOPHYTIC B.ULCERATED C.ENDOPHYTIC

Gress DM, Edge SB, Greene FL, et al. Principles of cancer staging. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
 INTRODUCTION
As OSCC grows, it invades the
surrounding tissue and
metastasizes to regional neck
nodes. With reference to the TNM
staging system, when dealing
with large lesions (T3 and T4), or
preoperative N-positive, neck
disease–positive neck nodes, the
authors substantially agree in
recommending treatment
including the neck nodes.
However, there are still many
doubts concerning the best way
to approach neck disease in the
case of early-stage lesions (T1
and T2).
• Part of the problem with a “wait and see” approach is that patients
aff ected by upper aerodigestive tract (UADT) SCC with negative nodes
at the time of presentation (N 0 ) have a high risk of harbouring occult
node metastases.

• And this can be proved only by postoperative histologic node

examination; the clinical aspects and preoperative tests are not
completely reliable.

• Elective neck dissection provides pathologic information on the status

of neck nodes, thus helping to determine the need for additional
therapy, and can also remove undetectable cancer cells lodged in the
lymph vessels.

• However, many patients might not need such treatment, and,

furthermore, it does have an associated morbidity and may remove or
destroy a natural barrier to cancer spread.
• The reliable parameters to be applied as predictors of neck node
metastasis and prognosis can be divided into:
1. Epidemiologic parameters (age, sex, race, alcohol, and / or tobacco
intake)
2. Clinical parameters (T classifi cation, TNM stage, site)
3. Histologic parameters (perineural invasion, perivascular invasion,
infl ammatory exudate, grading, pattern of invasion, tumor thickness )
• If these parameters were signifi cantly related to the presence of
occult metastases or to the subsequent development of regional
recurrences, they could be helpful when deciding on the regional
treatment of stage I–II OSCC.
• However, to date, management of the clinically negative neck in early
SCC of the oral cavity is still a controversial issue.
• The increasing depth of invasion and the microvascular proliferation
caused by neoplastic growth might determine proximity to blood
vessels and lymphatics, thus facilitating the tumour's ability to
metastasize.
• Moreover, it has been observed that it is more diffi cult for tumor
emboli to form in the small-caliber lymphatics of superfi cial areas
than in the wider lymphatics of deeper tissue.
DISCUSSION
As stated by Moore et al, depth
of invasion and tumor thickness
are not the same, and a
distinction has to be made,
even though many authors use
these two terms synonymously.
Thickness Measurement
• “Depth of invasion” means the extent of cancer growth into the
tissue beneath an epithelial surface.
• If the epithelium is destroyed, some investigators reconstruct a
surface line and measure from this line.
• However, the depth of invasion is sometimes expressed by referring to
the microscopic, anatomic deep structures that are reached, rather
than by referring to objective micrometre measurements in
millimetres.
• In this case, congruence among pathologists is less readily achieved,
because a series of subjective assessments are needed to determine
the level of invasion.
• Thickness concerns the entire tumor mass; an objective parameter is
needed, and it can be obtained using an ocular micrometre.
• The proximity to blood vessels and lymphatics is what determines an
increased risk of nodal metastases developing in as much as it
facilitates the tumour ’s ability to expand.
• Therefore, the actual mass that is present beneath the theoretical
reconstruction of a basement membrane of the tumor is considered
(depth of invasion) rather than thickness of the entire tumor.
1. The fi rst important factor to be considered is the diffi culty in
measuring both depth of invasion and tumor thickness.
2. With regard to depth of invasion, a series of subjective assessments
are needed, whereas in tumor thickness objective measurement is
undertaken.
• Breslow defi ned strict criteria for measuring cutaneous melanoma
(i.e., from the deepest point of invasion to the top of the granular cell
layer of the overlying epidermis, excluding keratin, parakeratin, and
infl ammatory exudates).

• If the lesion is ulcerated, the ulcer base serves as the reference point.

• However, he reported two main problems: poor sampling and variation

in apparent thickness because of the variable angle of sectioning.

• In articles concerning oral carcinoma, maximum tumor thickness was

most often evaluated with an optical micrometre with various
measurement techniques, depending on whether the mucosal surface,
the tumor surface, or the ulcer base was chosen as the starting point.
• Some authors adopted the technique developed by Breslow and
measured vertically starting from the tumor surface or the base of the
ulcer base.

• In those cases in which the tumor was exophytic, the most perpendicular
section was measured from the tip of the papilla to the maximal depth.

• Other authors likely used the same technique, but it is not clear whether
they excluded keratin, parakeratin, and infl ammatory exudates.

• Alternately, an imaginary line indicating the level of the adjacent intact

mucosa or of the basal membrane can be considered the starting point
for measuring the thickness of the tumor into the underlying tissue to
the deepest point of invasion.
• Moore et al used the technique proposed by Breslow, as well as a
second measurement obtained from an imaginary “ normal mucosal
line” for comparison.
• They found that longer survival of most patients with verrucous
cancer correlated better with thickness as measured from the line of a
“basement membrane constructed through the tumor ” than with
the entire thickness of the exophytic tumor.
• Analogously, Urist et al and Woolgar and Woogar et al considered
thickness as the entire tumor measurement and depth as the amount
from the surrounding normal mucosa.
• With regard to cup-shaped tumors, Frierson and Cooper made several
radially oriented measurements and took into consideration the
largest one.
• Giacomarra et al, affi rmed that “tumor thickness is commonly used
as a synonym of depth of invasion and indicates the part of the
tumor situated under the line of the basal membrane ” compared
with authors who adopted the technique proposed by Breslow that
measures tumor thickness from either the tumor surface or from the
base of the ulcer.
• It must be pointed out that it is not always easy to distinguish the
exact technique that was used in each study. Most of the authors did
not clearly explain the measurement techniques they used.
• Bundgaard et al refer to the “stage of invasion / depth”, but it is not
clear whether this is an objective parameter or the description of the
anatomic structure that was reached by the tumor.
• Moore et al reported the possibility of reconstructing a “ normal
mucosal line” as the basement membrane line in case of exophytic
and /or verrucous tumors.
• Ambrosch et al alone interpreted it as the basement membrane line,
whereas Woolgar et al used the surface line of the surrounding
healthy mucosa.
• It must be pointed out that no fi gures were used to clarify Moore et
al’s concept.
• Most likely, the diff erence between the basement membrane line or
the surrounding healthy mucosa line is more theoretical than practical
because of the limited thickness of healthy epithelium.
• Breslow stated the need to study the entire step-sectioned lesion, at 1
to 2 mm intervals, to fi nd the maximal thickness.
• Thus, tumor thickness has generally been evaluated on the basis of
the surgical excision specimen.
• The usefulness of this parameter may be limited if accurate
measurement can only be achieved after resecting the lesion.
• Because pathologic tumor thickness is being used, so decisions
regarding management of the neck must be put off until pathology
resection reports are available, thus delaying neck treatment.
• Conversely, it could be useful to preoperatively obtain this parameter
to plan more appropriate therapy.
• The relationship between tumor thickness in biopsy and subsequent
surgical specimens was retrospectively investigated to determine
whether any predictive information on fi nal specimen thickness could
be obtained.
• Many authors evaluated the biopsy specimens by diff erent site of the
lesions and measurement techniques.
• The reliability of non-invasive techniques has also been investigated.
Fixation of the tissue for paraffi n-embedded sections invariably leads
to shrinkage, and, therefore, correlating such measurement to an in
vivo technique could be problematic.
• Simple clinical palpation seems to be unreliable, inaccurate, and
inconsistent, and although some authors used this method to obtain
tumor thickness measurements, there are no studies demonstrating
its usefulness.
• Shintani et al found intraoral ultrasonography reliable in 24 cases of
carcinoma of the tongue. On histologic sections, tumor thickness was
measured from the surface of the tumor to the maximal depth.
Discordance was observed among most of the tumors that were thicker
than 20 mm was ascribed to tissue shrinkage caused by formalin
fi xation, whereas lesions that were thinner than 10 mm were quite
similar. The advantage of intraoral ultrasonography is:
1. It is rapid and easily repeated.
2. It allows the observer to distinguish the tumor mass from the
surrounding tissue.
3. It was more reliable than CT and MRI when dealing with very thin
lesions.
• It can be quite uncomfortable for patients, resulting in pain and gag
refl ex. It is also observer dependent.
RESULTS
The measurements listed in the
survival and relapse-free
survival (RFS) columns refer to
the thickness values that
showed signifi cant
improvement.
• First, it must be said that the lack of standard sampling,
measurement techniques, and cut off values makes it quite impossible
to compare the studies found in the literature.
• Although most authors substantially agree that tumor thickness is a
signifi cant parameter for predicting nodal metastasis development and
for survival, the cut off thickness is really quite variable, ranging from
1.5 mm to 10 mm. It is unclear why the studies have reached such
inconsistent results with reference to the cut off measurement point.
• Mohit-Tabatabai et al and Spiro et al were the fi rst authors to apply
Breslow’s hypothesis regarding the link between nodal involvement
and tumor thickness to OSCC.
• Mohit-T et al planned a retrospective study based on 84 patients with
stage I–II SCC of the fl oor of the mouth.

• All the histologic slides were blind reviewed by expert pathologists, who
examined maximum tumor thickness, grading, and infl ammatory
reaction.

• The authors evaluated three thickness ranges (<1.5 mm, from 1.6 to
3.5 mm, and >3.6 mm ) and found a metastases incidence of 2%, 35%,
and 60%, respectively.

• Statistical analysis revealed a signifi cant link between thickness and

metastasis in tumors >1.5-mm thick.

• As a consequence, they suggested performing modifi ed neck dissection

in cases of tumor thickness >1.5 mm and with no clinical nodal
evidence.
• Spiro et al retrospectively analyzed 92 patients with T1–T2–T3
disease who had been surgically treated for carcinoma of the tongue /
fl oor of the mouth and who had been followed up for at least 24
months.

• Some of them also underwent elective neck dissection on clinically

negative necks.

• Using univariate and multivariate analysis, they found a signifi cant

diff erence when they chose a cut off thickness of 2 mm, both for
locoregional recurrences and survival.

• Finally, he considered elective neck dissection appropriate for N 0 oral

cancer when the thickness of the primary tumor exceeded 2 mm,
because the risk of metastasis approached 40% in his study.
• Hosal et al decided to use a cut off point of 9 mm, but they assessed
carcinomas of any stage and found signifi cance only for the presence
of nodal involvement at presentation, but not for locoregional
recurrences.

• Woolgar found a signifi cant increase in nodal metastases and a

worsening of survival for thickness of T2 lesions exceeding 8 mm.

• Al-Rajhi et al found better relapse-free and disease-specifi c survival

rates for thickness measuring less than 10 mm in stage I–II
carcinoma, but no signifi cance was found at a 5 mm cut off.

• Among the article reviewed, very few authors used multivariate

analysis to substantiate the importance of tumor thickness in
patients with stage I–II carcinoma who had been surgically
treated for the primary tumor alone.
• Asakage et al carried out a longitudinal, retrospective study on 44
patients aff ected with stage I–II cancer of the tongue, who only
underwent hemi glossectomy, with no treatment for regional nodes.
• Tumor thickness was measured according to the technique described
by Breslow.
• Univariate and multivariate statistical analysis were applied.
• They found that a 4-mm cut off was signifi cant with regard to the
development of nodal metastasis–free and disease-free survival.
• Thus, they suggested planning radical neck dissection on patients with
stage I or II lesions thicker than 4 mm and having a G2–G3 Broder ’s
grading.
• Kurokawa et al studied 50 patients aff ected with carcinoma of the
tongue and found a signifi cant increase in regional recurrences and a
worsening of overall survival for tumor thickness exceeding 4 mm.
• Only few authors failed to fi nd a link between tumor thickness and
nodal involvement or survival.
• Berdugo et al (2018) stated that in the oral tongue, the level of the
basement membrane of the closest adjacent normal mucosa is
probably better represented by an arcuate rather than a straight line,
especially when the line is drawn through two points, i.e., normal
mucosa on both sides of carcinoma.
• Brown et al examined the data of 87 patients with primary tumors of
the tongue /fl oor of the mouth.

• They had not been selected on the basis of tumor stage, but had been
followed up for at least 24 months.

• Univariate and multivariate statistical analyses revealed that only

tumor thickness greater than 3 mm was a signifi cant parameter for
better survival, whereas it was not for regional recurrence.

• The lack of inclusion criteria regarding tumor stage meant that they
only included seven of 87 cases with tumor thickness measuring less
than 2 mm.
• In any case, none of Brown et al’s seven patients had regional
metastases or died of disease, thus the authors suggested elective
treatment of the neck when tumor thickness measured less than 2
mm.
• They also pointed out some of the problems related to measuring
tumor thickness, the main one being the diff erence in complexity
when measuring tumor thickness in melanoma lesions (as described
by Breslow) compared with measuring thickness in mucosal tumors,
where there is often no mucosal surface on the slide to use as a
reference point.
• Moreover, only prospective studies can avoid the problems related to
the lack of strict guidelines for processing the samples and measuring
tumor thickness.
• Close et al studied 43 patients with stage II or greater
oral /oropharyngeal carcinoma who underwent resection of the
primary tumor and simultaneous neck dissection as initial treatment.
• They adopted 5 mm and 10 mm as cut off values but failed to fi nd a
link between tumor thickness and regional involvement.
• It must be pointed out that they had a very small number of early-
stage lesions, with only nine of 43 stage II tumors, and only 12 of 43
lesions measuring less than 5 mm.
• This may have reduced the impact of the tumor thickness parameter
in predicting nodal metastases.
• Morton et al reviewed the data of 26 patients treated for early-stage
tongue carcinoma.

• None had nodal clinical evidence, and the maximum diameter of the
tumor was 30 mm (T1 and T2).

• All patients only underwent primary tumor surgical therapy, with a

follow-up range of 12 to 60 months.

• They analyzed several parameters, such as grading, thickness,

vascular invasion, perineural invasion, infl ammatory reaction, and
resection border involvement, and related them to the development of
nodal metastases.
• Measurements were made from the base of the overlying epithelium
or from the base of the ulcer to the deepest extent of the tumor.
• They found no relationship between tumor thickness and nodal
metastasis or survival in patients whose tumors of the tongue were
less than 30 mm in diameter.
• They believed that tumor thickness became more important when
larger (T2–T4) tumors were taken into consideration.
• Conversely, they found perineural invasion to be a signifi cant
parameter.
• Gluckman et al analyzed the tumor thickness of 43 patients who had
been surgically treated for tongue /fl oor of the mouth carcinoma with
a minimum follow-up of 48 months.
• All lesions were T1 classifi cation.
• They evaluated the presence of nodal involvement and the clinical
outcome as well.
• They grouped patients on the basis of “nonaggressive” tumors or
“aggressive” tumors.
• They tested several parameters on the excision specimens but found
no link between tumor thickness and clinical course.
• Yamazaki et al presented a large group of patients with tongue cancer
(254 cases, stage I–II) treated with radical radiation therapy alone
and with follow-up ranging from 36 to 288 months.
• They failed to fi nd any link between tumor thickness and regional
recurrence, but it must be pointed out that because no excision
specimens were available, tumor thickness was preoperatively
detected by palpation.
• Of course, this kind of measurement has great inter examiner
unpredictability; however, it has not yet proved to be reliable.
• Giacomarra et al studied 61 subjects with tumors of any stage from
various sites of the oral cavity and oropharynx, who underwent
surgery on tumor and nodes.
• They found a link between thickness (7 mm) and nodal metastases,
regardless of N status but not with occult metastases in the N 0 neck.

• It must be pointed out that in this study the term “ thickness” is

considered a synonym for “depth of invasion”, which indicates the
part of the tumor below the line of the basal membrane.
• These authors did not clearly explain the technique they used to
measure thickness. Furthermore, even though the study population
included any stage of tumors, multivariate analysis was not used.
• Williams et al studied 66 patients with T1–3 N0 carcinoma of the
tongue /fl oor of the mouth (follow-up ranging from 5–102 months)
and found a signifi cant link between tumor thickness greater than 4
mm and regional recurrence but not with survival.

• Some patients in this study also underwent elective neck dissection at

the time of primary tumor excision.

• Matsuura et al evaluated 173 patients with stage I–II carcinoma of

the tongue that had been treated with interstitial brachytherapy
associated with external irradiation in some cases.

• In a follow-up of at least 24 months, they found a link between tumor

thickness greater than 8 mm and regional recurrences but not with
survival. Thickness was measured by palpation and contact
ultrasonography.
• De Visscher et al found a link with regional recurrences but not with
local ones, which were more likely related to the large tumor size and
to surgical margins containing carcinoma cells.
• Martinez-Gimeno et al demonstrated the prognostic reliability of
tumor thickness and developed a weighted scoring system based on
the relative importance of the predictive value of each factor for the
risk of regional recurrences.
• A cut off score was set to determine the need for radical neck
dissection.
• Po Wing et al tried to apply the Martinez-Gimeno score to stage I–II
carcinoma of the tongue.

• This was based on data from mixed groups of tumors of diff erent
stages from both the oral cavity and the oropharynx.

• Multivariate analysis revealed that when both the Martinez-Gimeno

score and tumor thickness were included, only tumor thickness was an
independent factor for predicting regional involvement.

• Repeating univariate analysis of the Martinez-Gimeno score with

tumor thickness taken out demonstrated that there was no longer a
signifi cant link. This suggests that the predictive value of that scoring
system in early-stage carcinoma of the tongue was mainly related to
tumor thickness.
• Tumuluri et al studied the proliferating cell density at the invasive
tumor front and compared it with some known prognostic factors,
including tumor thickness. They found a higher Ki-67 labelling index
in tumors with an infi ltrating depth of invasion greater than 5 mm.
• Rahima et al tested the prognostic signifi cance of perineural invasion
(PNI) in oral and oropharyngeal carcinoma. The depth of invasion was
found to be linked to PNI, local recurrence, and survival, whereas it
was not signifi cant for regional recurrence or development of distant
metastases.
• Wenzel et al analyzed 115 patients treated for advanced-stage ( at
least T2) OSCC. They found no discriminatory relation between
horizontal size and depth of invasion versus the pattern of metastatic
lymph node disease, because they were both similarly related to the
intranodal or extra-nodal spread.
• Studies of prognostic factors in patients with head and neck cancers
almost invariably seem to recommend that the staging system should
be changed or that a prospective, randomized trial is needed to clarify
the issue once and for all.
• Howaldt et al proposed a modifi ed pTNM staging in which three cut
off s of tumor thickness (5 mm, 10 mm, and 20 mm) were combined
with the greatest tumor dimension to obtain the pT classifi cation.
They based their proposal on the fi ndings in 806 patients in the large
Dosak tumor registry in Germany.
REFERENCE ARTICLES
• Tan WJ et al (2012) that tumors with pathological invasion depth ≥ 4 mm
were 3.3 times more likely to suff er from local recurrence compared with
tumors of invasion depth < 4 mm.
• Ghazi N et al (2018) stated that the increasing DOI and the microvascular
proliferation caused by neoplastic growth might determine proximity to
blood vessels and lymphatic channels, thus facilitating the metastatic
process. He also said that DOI and T T are strong and independent
predictors of metastatic neck lymph nodes and this fi nding has also been
confi rmed by metanalytic studies.
• Moe J et al (2019) stated that DOI in intraoperative frozen sections has an
accuracy of 96.8% and may be reliably used as a clinical tool to determine
the need for END in early-stage OCSCC.
• Chang WC et al (2019) determined that survival prognosis for patients with
a pN0 status, should include all adverse features. In contrast, extra nodal
extension was the most important prognostic factor for patients with a pN+
status.
• Berdugo et al (2019) stated that a proactive assessment and
reporting of DOI on diagnostic biopsies or documentation of factors
limiting DOI measurement (e.g., fragmentation, lack of intrinsic
tongue musculature, absence of normal mucosa ) may minimize the
need to re-review the diagnostic biopsy when glossectomy reveals no
or minimal residual carcinoma.
CONCLUSION
Growing evidence in the
literature shows that tumor
thickness is a reliable parameter
for predicting regional node
involvement and patient survival
in OSCC. The substantial
agreement among authors,
despite the lack of comparable
study groups, of measurement
techniques, and cut off values
paradoxically enforced its
reliability. Further studies are
clearly awaited to reach a
consensus on these topics to
develop therapy protocols that
are also based on this parameter.
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