Journal of Surgical Oncology

EDITORIAL
Patterns of Invasion as Major Prognostic Factors in Cancer of the Oral Cavity
ASHOK R. SHAHA, MD, FACS*
Memorial Sloan-Kettering Cancer Center, New York, New York

Editorial on the article: Predictors of Prognosis for Squamous Cell

Carcinoma of the Tongue by Thiagarajan et al.
Dr. Thiagarajan and his colleagues from the Tata Memorial hospital
in Mumbai have described their experience with predictors of prognosis
in squamous cell carcinoma of the oral tongue. They have identied
those tumor related prognostic predictors that can have major inuence
in the decision making for adjuvant radiotherapy and overall outcome.
In a short period of 31/2 years the authors have identied 586 patients
eligible for the study. Follow up information was available in 85% of
the patients. The recurrence of the disease was noted in 31% of the
patients. Their follow up is short, median, and mean follow up of 18 and
22 months, respectively. The authors have concluded that the perineural
invasion signicantly affected disease free survival and also tumor
thickness of more than 11 mm signicantly affected the overall
survival. The authors have concluded that other than nodal metastasis,
tumor related factors like thickness and perineural invasion are adverse
prognostic factors and can inuence survival. They used these two
important prognostic factors in patients with early stage oral cancer
who may potentially benet from postoperative adjuvant radiation
therapy.
This is an interesting manuscript of identifying the histopathological
prognostic factors based on extended review of the histopathology in
relation to perineural invasion and tumor thickness. There have been
several publications in the past about the tumor thickness and generally
greater than 4 mm is considered to be having adverse effect especially in
relation to microscopic nodal metastasis. The depth of 4 mm is generally
used as a cutoff for consideration of elective nodal dissection. The
authors experience of 11 mm clearly indicates much more aggressive
tumor with possibly high incidence of nodal metastasis, and local
recurrence. Perineural invasion and lymphovascular invasion or
lymphovascular emboli are also considered to be adverse prognostic
features. The perineural invasion has been classied into intratumoral,
peripheral, and extratumoral. A committed and involved pathologist
who will study the histopathology in greater details in view of these
prognostic factors is very critical.
The size of the nerve is quite important, as minor unnamed
microscopic intratumoral nerve involvement may not be as critical as
larger nerve involvement. Bernier et al.[1] included perineural invasion
and lymphovascular emboli as adverse pathological features and showed
benets from postoperative adjuvant chemoradiotherapy. There
continues to be considerable debate as to the role of postoperative
chemoradiotherapy in prognostically adverse features such as positive
margins and multiple positive nodes or extranodal spread. The EORTC
study by Bernier et al.[1] and RTOG study by Cooper et al. showed
clearcut impact of the use of postoperative chemoradiation therapy,
however, one must need to keep in mind the high incidence of
complications related to severe mucositis, neutropenia, and pharyngeal

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stricture are directly related to aggressive postoperative chemoradiation

therapy.
In the treatment details, the authors have mentioned about the use of
selective nodal dissection levels IIII in 250 cases, while 321 patients
underwent modied neck dissection. Only four patients underwent neck
dissections level IIV. Clearly, in view of the higher incidence of level
IV nodal metastasis as shown by Byers [2] from MD Anderson in
patients with cancer of the oral tongue, majority of the head and neck
surgeons will generally consider adding excision of level IV nodal group
along with supraomohyoid or selective nodal dissection. However,
interestingly, the bulk of their patients underwent only selective nodal
dissections level IIII. It is also interesting as an institutional policy that
the patients who underwent selective nodal dissections level IIII
underwent pathological evaluation within the operating theatre complex
and doubtful nodes were subjected for frozen section. If the frozen
section was positive the remaining level IV and V nodes were cleared.
This is a unique practice at Tata Memorial hospital since the majority of
the other major cancer institutions do not use frozen section in selective
nodal dissection and Im not sure adding resection of level IV and
level V nodes where the incidence of nodal metastasis is very low is
indicated. The majority of these patients will receive postoperative
radiation therapy in any case. Nodal metastasis at level V in oral tongue
cancer has prognostically very poor outcome. The authors have
identied prognostic factors to the survival and nodal metastasis as
age, clinical Tstage and pathological Tstage, clinical and pathological
nodal stage, extracapsular spread, perineural invasion, and tumor
thickness. In multivariate analysis the authors have identied age,
perineural invasion, Tstage, tumor thickness as important factors
affecting nodal metastasis. While factors affecting overall survival are
reported as age, pathological Tstage, tumor thickness and extra
capsular spread.
The understanding of the patterns of invasion of the primary tumor is
very important. BrandweinGensler[3] has studied extensively the
patterns of invasiveness and invasive front in patients with cancer of the
oral cavity. She has described the worst prognostic indicators as invasive

Conict of interest: None.

*Correspondence to: Ashok R. Shaha, MD, FACS, Professor of Surgery
Head and Neck Service, Memorial SloanKettering Cancer Center, 1275
York Avenue, New York, NY 10065. Fax: 12127173302. Email:
shahaa@mskcc.org
Received 31 january 2014; Accepted 3 February 2014
DOI 10.1002/jso.23582
Published online in Wiley Online Library
(wileyonlinelibrary.com).

Ashok R. Shaha

front of the tumor and tumor islands. She has divided the tumor margins
into ve subgroups.
(1)
(2)
(3)
(4)
(5)

Pushing border.
Fingerlike growth.
Large separate islands, more than 15 cells per island.
Small tumor islands, 15 cells or fewer per island.
Tumor satellites.

The worst pattern of invasion is type 4 and 5, exhibiting tumor

islands. She has also dened lymphocytic host response and perineural
invasion as important pathological features. Based on these
histopathological criteria, she has assigned scoring rank and based on
this, she has been able to divide the patients into low, intermediate and
high risk. This model is very important in certain critical decision
making in relation to adjuvant therapy in low stage oral cavity cancer.
The information provided by BrandweinGensler[3] is very critical
and several other authors have reported similar experience such as
Golusi!nski et al.[4] The identication of the tumor islands is extremely
critical as there is a high incidence of local recurrence in this group of
patients and they may be beneted with postoperative radiation therapy
even at an early stage. Generally, Stage I and II oral cavity cancers are
treated with single modality such as appropriate surgery with negative
margins. However, the tumor prognostic features are important as
patients with worst prognostic indicators may have high incidence of
local recurrence and subsequent mortality. Whether postoperative
radiation therapy can prevent such occurrences remains unclear,
however, this may be one of the important indications of the use of

Journal of Surgical Oncology

adjuvant postoperative radiation therapy in early stage cancer of the oral

tongue. Once the tumor inltrates from the oral tongue to the muscularis
of the tongue, the tumor may percolate through the interstices of the
muscles of the oral tongue, which may lead to diffuse tumor islands and
high incidence of local recurrence. This pattern of invasiveness may be
different between oral tongue, buccal mucosa, and the gum.
The information provided by Thiagarajan and DCruz[5] is an
important addition to our understanding of histopathological predictors
of prognostic factors in cancer of the oral cavity, nodal metastasis and the
use of adjuvant radiation therapy in the early stages of oral cancer.

REFERENCES
1. Bernier J, Cooper JS, Pajak TF, et al.: Dening risk levels in locally
advanced head and neck cancers: A comparative analysis of
concurrent postoperative radiation plus chemotherapy trials of the
EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:843
850.
2. Byers RM: A word of caution: The skip metastases. Head Neck
1995;17:359360;No abstract available.
3. BrandweinGensler M, Teixeira MS, Lewis CM, et al.: Oral
squamous cell carcinoma: Histologic risk assessment, but not margin
status, is strongly predictive of local diseasefree and overall survival.
Am J Surg Pathol 2005;29:167178.
4. Szybiak B, Trzeciak P, Golusi!nski W: Role of extended histological
examination in the assessment of local recurrence of tongue and oor
of the mouth cancer. Rep Pract Oncol Radiother 2012;17:319323.
5. Predictors of prognosis for squamous cell carcinoma of the tongue by
Thiagarajan et al. JSO to ll.