The document discusses surgical margins in head and neck cancers. It reports that studies have defined an adequate margin as >=5mm and found higher recurrence and lower survival rates with margins <5mm. Mucosal tissue can shrink by 20-25% after resection. While clear margins are >5mm, close margins are generally defined as <=5mm. Even with margins of 5-7mm, patients without adjuvant therapy require close follow-up due to genetic changes that may remain in histologically normal margins.

1. Cut margins in head and neck cancers
• Most studies that specifically define margin
distance use a somewhat arbitrary definition of
=>5 mm to define margin adequacy.
• Chen et al4 reported on 270 consecutive patients
with carcinoma of the oral cavity, oropharynx,
hypopharynx, and larynx, using a defined 5- mm
margin standard. Locoregional recurrence and 5-
year disease-free survival rates were 55% and 7%,
versus 17% and 39%, for patients with
inadequate versus adequate margins,
respectively

2. • Gallo et al27 reported on 253 patients treated
by supracricoid partial laryngectomy, which
included 42 patients with supraglottic cancers.
Here, they defined "positive margins" as
cancer or dysplasia <5 mm, although they
did not further clarify the degree of dysplasia.

3. • Canine studies have demonstrated that
tongue mucosa contracts more than deep
tongue muscle after resection (24.8% vs
20.9%).
• The only study to address margin shrinkage in
patients with head and neck cancer appears to
have measured only mucosal contraction,
which was on the order of 20% to 25%.

4. • These figures providesome rough "rule of
thumb" for surgeons. Surgeons need to place
20% to 25% more tissue between the tumor
and "the blade" to achieve a particular margin
distance.
• Tissue formalin fixation and paraffin
embedding will also add to tissue shrinkage,
but to a lesser degree, on the order of 10%.

5. • Although what is a clear margin and what is an
involved one are intuitive, what lies between
involved and clear, commonly defined as
‘close’, is a concept that is much less clear.
• In general, the National Comprehensive
Cancer Network (NCCN) defines R close as B5
mm without distinction for any subsite in
HNSCC.

6. • Broder’s "grading system," on the basis of the degree
of tumor keratinization, was perhaps the first attempt
at microscopically predicting tumor behavior
• Tumor worst patterns of invasion (WPOI) can be
classified asaggressive if carcinomas contain either
small tumor islands (15 cells) that are separate from
but close to themain tumor mass (WPOI type 4), or
worse yet, if the tumor satellites are dispersed (WPOI
type 5). TheseWPOI have been validated as significant
prognosticators of outcome

7. • First described in 1953, this somewhat
controversial idea is that HNSCCs arise from a
"field" of genetically damaged or
"condemned" mucosa.

8. • The presence of morphologicallyintact but
genetically damaged cells would seem to explain
certain distressing patterns of HNSCC behavior
such as local tumor recurrence after
seemingly"complete" surgical resection with
"negative" margins. A growing lack of confidence
in the pathologist’s ability to recognize the
presence and extent of the neoplastic process in
patients at risk for HNSCC has accelerated a
search for novel biomarkers in the recognition
and treatment of HNSCC, particularly in the
evaluation of surgical margins.

9. • Liao et al. [9, 10] analyzed the survival in oral cavity squamous cell
carcinomas, in relation to pathological margins. They found that, in SCC of
the buccal mucosa, adequate pathological margins are deemed to play a
crucial role in ensuring satisfactory local control and they stated that the
presence of pathological margins B4 mm (close) is an independent
predictor of poor local control and should be treated with adjuvant RT. In
their experience, a close margin B4 mm was an independent risk factor for
local control both for patients treated with surgery alone and for those
treated with surgery plus adjuvant therapy [9]. However, in another article
published by the same authors, they concluded that the optimal
pathological margin for oral cavity squamous cell carcinomas should be[7
mm. Thus, despite a cut-off of 7 mm being the most reliable in their
experience, they concluded that in the case of margins of 4–5 mm,
patients must receive adjuvant therapy, and that for patients who did not
receive postoperative adjuvant therapy, even in the presence of
pathological margins of 5–7 mm, close follow-up examination is
recommended [

10. • Indeed, the presence of genetically altered
cells can be detected in histologically normal
mucosal margins with a variety of strategies
for detecting genetic alterations including
TP53 mutations, loss of heterozygosity,
promoter hypermethylation, eIF4E proto-
oncogene overexpression, and mitochondrial
DNA mutations.

11. • For carcinomas of the glottic larynx, narrow
margins of just 1 to 2 mm seem adequate.
Within the oral cavity 5 mm represents the
most commonly used margin standard.

12. • Based on the best literature evidence
currently available with regard to HNSCC, and
summarizing the data analyzed, the authors
conclude that, in vocal cord surgery, a close
margin could be considered as =<1 mm, in the
larynx as =<5 mm, in the oral cavity as =<4
mm and in the oropharynx as =<5 mm.

13. • Surgical margin affects locoregional control in
such a way that, narrower the surgical margin,
the greater the difference in locoregional control
after treatment. Patients with surgical margin ≤3
mm had a statistically significantly higher risk for
locoregional failure than those with surgical
margin more than 3mm . Recurrence rates for
patients with margins of 3 to 4 mm were identical
to those observed for patients with margins of
5mm . Acc. to Wong LS et al a margin of ≥5mm –
clear,1–5mm – close, <1mm – involved.

14. • Histologically normal margins may harbor underlying
genetic changes, which increase the risk of recurrence.
Genetic alterations identified in HNSCC included over-
expression of eIF4E , TP53 and CDKN2A/P16
proteins.Other alterations included promoter
hypermethylation of CDKN2A/P16 and TP53 mutations.
In addition, promoter hypermethylation of CDKN2A,
CCNAI and DCC was associated with decreased time to
head and neck cancer recurrence. A gene signature can
accurately predict which patients with OSCC are at a
higher risk of disease recurrence