10.14639/0392-100X-N2185
Objectives. To quantify tumour size and margin shrinkage due to formalin fixation in head and neck cancer specimens and determine its effect on tumour staging and margin clearance. Methods. Tumour specimens were measured immediate post-resection and at 24 hours after fixation. Tumour was measured in 2 dimensions and one margin was measured. Shrinkage was categorised as &lt; 10%, 10-20%, and &gt; 20%. Effect of shrinkage on tumour stage and margin clearance were evaluated. Results. A total of 50 specimens were analysed. The tumour AP (Anterior Posterior) and SI (Superior Inferior) measurements showed significant shrinkage with a mean difference of 22.93% and 21.69% respectively. &gt; 20% shrinkage was noted in 78% of AP and 58% of SI measurements. Margins showed a mean difference of 25.61%. 84% of margins demonstrated &gt; 20% shrinkage. In all, 46.7% of T3 and 23% of T2 tumours pre-fixation were downstaged to T2 and T1, respectively, post-fixation. Conclusions. Formalin fixation alone can be responsible for significant shrinkage of tumour and margin dimensions in head and neck specimens. It is suggested that decisions regarding the treatment plan should be made on clinical staging of primary tumour rather than pathological staging. In addition, post-excision pre-fixation margins should be considered for treatment planning.
text/xml
1827-675X
2185
en
Sushmitha Kabekkodu
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
neoplasm staging
Effect of formalin fixation on tumour size and margins in head and neck cancer specimens
Text.Serial.Journal
https://www.actaitalica.it/
42
Head and neck
2022-11-23
2022-06-17
2022-12-13
2022-12-13
434-440
1
Sushmitha Kabekkodu
2022/11/23
10.14639/0392-100X-N2185
434
Department of Otorhinolaryngology and Head and Neck Surgery, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India
1827-675X
neoplasm staging
en
440
Effect of formalin fixation on tumour size and margins in head and neck cancer specimens
https://www.actaitalica.it/article/download/2185/869
42
ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42:434-440; doi: 10.14639/0392-100X-N2185




Head and neck


Effect of formalin fixation on tumour size
and margins in head and neck cancer specimens
Effetto della fissazione in formalina sulle dimensioni e sui margini tumorali dei pezzi
operatori della testa e del collo
Kshithi K, Vikrant Kamboj, Suja Sreedharan, Vijendra Shenoy S, Thripthi Rai, Sushmitha Kabekkodu
Department of Otorhinolaryngology and Head and Neck Surgery, Kasturba Medical College, Mangalore, Manipal Academy of Higher
Education, Manipal, India


SUMMARY
Objectives. To quantify tumour size and margin shrinkage due to formalin fixation in head
and neck cancer specimens and determine its effect on tumour staging and margin clear-
ance.
Methods. Tumour specimens were measured immediate post-resection and at 24 hours af-
ter fixation. Tumour was measured in 2 dimensions and one margin was measured. Shrink-
age was categorised as < 10%, 10-20%, and > 20%. Effect of shrinkage on tumour stage and
margin clearance were evaluated.
Results. A total of 50 specimens were analysed. The tumour AP (Anterior Posterior) and
SI (Superior Inferior) measurements showed significant shrinkage with a mean difference
of 22.93% and 21.69% respectively. > 20% shrinkage was noted in 78% of AP and 58%
of SI measurements. Margins showed a mean difference of 25.61%. 84% of margins dem-
onstrated > 20% shrinkage. In all, 46.7% of T3 and 23% of T2 tumours pre-fixation were
downstaged to T2 and T1, respectively, post-fixation.
Conclusions. Formalin fixation alone can be responsible for significant shrinkage of tu-
mour and margin dimensions in head and neck specimens. It is suggested that decisions
regarding the treatment plan should be made on clinical staging of primary tumour rather
than pathological staging. In addition, post-excision pre-fixation margins should be consid-
ered for treatment planning.                                                                    Received: June 10, 2022
                                                                                                Accepted: August 25, 2022
KEY WORDS: head and neck neoplasms, formaldehyde, margins of excision, neoplasm
staging                                                                                         Correspondence
                                                                                                Suja Sreedharan
RIASSUNTO                                                                                       Department of Otorhinolaryngology and Head and
Obiettivi. Quantificare la riduzione delle dimensioni del tumore e dei margini di resezione     Neck Surgery, Kasturba Medical College Hospital,
conseguente alla fissazione in formalina nei tumori della testa e collo e valutare il suo im-   Attavar, Mangalore, Karnataka, India PIN 575001
                                                                                                E-mail: suja.sreedharan@manipal.edu
patto sulla stadiazione del tumore e lo stato dei margini.
Metodi. I pezzi operatori sono stati misurati nell’immediato postoperatorio e dopo 24 ore
di fissazione. Sono stati misurati il tumore in due dimensioni ed un margine di resezione.        How to cite this article: Kshithi K, Kam-
La contrazione è stata classificata come < 10%, 10-20%, > 20%. È stata poi analizzato             boj V, Sreedharan S, et al. Effect of formalin
l’effetto della contrazione sullo stadio del tumore e lo stato dei margini.                       fixation on tumour size and margins in head
Risultati. In totale sono stati analizzati 50 casi. Le misure AP (anteroposteriore) e SI (su-     and neck cancer specimens. Acta Otorhi-
periore-inferiore) hanno mostrato una riduzione significativa con una differenza media ri-        nolaryngol Ital 2022;42:434-440. https://doi.
                                                                                                  org/10.14639/0392-100X-N2185
spettivamente di 22,93 e 21,69%. Una contrazione maggiore del 20% è stata registrata nel
78% delle misure AP e nel 58% delle SI. I margini hanno dimostrato una differenza media
                                                                                                © Società Italiana di Otorinolaringoiatria
del 25,61%. Nell’84% dei casi il margine ha mostrato una riduzione superiore al 20%. Il         e Chirurgia Cervico-Facciale
46.7% dei tumori classificati pre-fissazione T3 e il 23% dei T2 sono stati classificati dopo
la fissazione rispettivamente T2 e T1.
                                                                                                               OPEN ACCESS
Conclusioni. Nei tumori della testa e collo, la fissazione in formalina può causare una
contrazione significativa delle dimensioni del tumore e della distanza dal margine di rese-     This is an open access article distributed in accordance with
                                                                                                the CC-BY-NC-ND (Creative Commons Attribution-Non-
zione. Suggeriamo che le decisioni terapeutiche si basino sulla stadiazione clinica piuttosto   Commercial-NoDerivatives 4.0 International) license. The
che sulla patologica. Inoltre, i margini dovrebbero essere valutati subito dopo la resezione    article can be used by giving appropriate credit and mentio-
prima della fissazione.                                                                         ning the license, but only for non-commercial purposes and
                                                                                                only in the original version. For further information: https://
PAROLE CHIAVE: tumori testa e collo, formaldeide, margini di resezione, stadiazione             creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                            Tumour and margin shrinkage due to formalin




Introduction                                                       the procedures carried out included wide local excision, with
                                                                   or without hemi-mandibulectomy (for buccal mucosal and
Head and neck cancers, including cancers arising from the
                                                                   tongue malignancies), whereas wide local excision was per-
oral cavity, oropharynx, hypopharynx and larynx, are the
                                                                   formed for lip lesions. All resections were carried out by en-
sixth most common type of cancer worldwide and a leading
                                                                   suring a minimum 1 cm margin circumferentially from the tu-
cause of cancer-related deaths 1. Multidisciplinary manage-
                                                                   mour border, assessed by visual inspection and palpation. The
ment strategies are cornerstones for achieving optimal ther-
                                                                   mucosal and skin incisions were placed using scalpel and the
apeutic outcomes in cancers of the head and neck region.
                                                                   rest of the tumour excision was completed using electrocau-
However, surgery remains the mainstay of therapy for oral
                                                                   tery. Patient details including age, gender, tumour site, tumour
cancers 2. The ultimate aim of surgical resection is adequate
                                                                   size, clinical TNM staging, pathological TNM staging and the
clearance of tumour 3. Positive or close margins may neces-
                                                                   surgical procedure undertaken were recorded. Patients who
sitate the addition of adjuvant therapy like chemotherapy or
                                                                   were switched to a non-surgical treatment modality (because
radiation therapy to the treatment protocol.
                                                                   of poor performance scales) and who had previously under-
In addition to tumour margin, adjuvant treatment is also
dictated by tumour size which determine the classification         gone chemotherapy or radiotherapy or both were excluded
of tumours into different T stages. A reduction in tumour          from the study.
size in the pathology report will understage the tumour and
the patient may be deprived of adjuvant therapy with dis-          Measurement
astrous consequences. Hence, accurate measurements of              Tumour size measurements were undertaken using a digital
tumour dimensions and margins are paramount in the man-            caliper with a resolution of 0.1 mm and accuracy of ± 0.2 mm.
agement of patients with head and neck cancer.                     Initial tumour measurements were taken immediately after
Prior to histopathological analysis, specimens are preserved       excision of the surgical specimen. For tumour measurement,
in formalin, which is the most common fixative used by             the anteroposterior (and superoinferior) margins were record-
many laboratories. Various studies have reported a change          ed based on the sutures already placed at the tumour margins
in tumour dimensions and margin measurements due to                for tumour orientation. For measurement of margins, in most
formalin fixation. Specimens from colorectal, oesophageal          of cases, the anterior margin was chosen but in 3 cases where
and breast tumours have demonstrated significant shrink-           this was not possible, e.g. oral cavity tumour involving the
age of both tumour dimensions and tumour free margins 4-8.         angle of mouth, another prominent margin was arbitrarily
Studies on head and neck cancer specimens also have noted          chosen for measurement. The margin was marked by placing
shrinkage, but the results are not uniform and the degree          a suture to identify the exact site for second measurement. Af-
of shrinkage showed wide variations (10-25%)for tumour             ter marking, specimens were stored in 10% neutral buffered
margins and 3-24% for tumour dimensions 9-12. In addition,         formalin for 24 hours and the measurements were repeated
the number of studies are sparse and there is only one in-         by the same observer using the same reference points. The
vestigation that has evaluated the effect of formalin fixation     measurements were then tabulated and compared.
on both tumour and margin measurement 9.
Our study was aimed at determining the effects of formalin         Results
fixation on tumour dimensions as well as margin measure-
ments, and to evaluate the discrepancies between clinical          50 consecutive patients with head and neck cancer who ful-
and pathological tumour staging caused by formalin fixation.       filled the selection criteria and underwent wide local resec-
                                                                   tion for primary tumours were included in the study. Patient
                                                                   characteristics are listed in Table I.
Materials and methods
Subjects                                                           Tumour shrinkage
50 patients with oral cavity malignancy managed with surgi-        The AP and SI dimensions measured before and after fixation
cal resection of the primary tumour in a 2-year period were        were compared (Tab. II). Tumour shrinkages were classified
included in the study. A detailed history was obtained and a       into 3 categories: < 10, 10-20 and > 20%. A mean difference
thorough clinical examination of the head and neck region          of 22.93% was observed in AP measurements with 78% of the
was conducted. Contrast-enhanced CT scan was obtained in           specimens demonstrating shrinkage of > 20%. For SI meas-
all cases to identify the extent of the lesion and the malignan-   urement, the mean difference was 21.69 with 58% of patients
cy was proven by pre-operative biopsy. Tumours belonging           showing a shrinkage of more than 20 percent. When pre- and
to Stage I to IV were included in study as long as en bloc         post-fixation values were compared for AP and SI dimensions
resection was possible. Depending on the extent of tumour,         the difference in the means were highly significant (Tab. III).



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Table I. Demographic data, site of cancer, surgical treatment of primary can-     specimen margins that were > 5 mm (clear) were converted
cer site, clinical T stage and pathological T stage.                              to 1-5 mm (close) post-fixation. Pre- and post fixation val-
 Variable                                        Number of patients (n = 50)      ues were compared and found to be highly significant.
 Age
    < 40 years                                          7 (14%)                   Comparison of shrinkage by sub-site
    40-60 years                                         34 (68%)                  Upon comparison, the shrinkage of tumour dimension was
    > 60 years                                          9 (18%)                   found to be highest with tongue (27.43% AP and 26.82%
 Gender                                                                           SI) followed by lip (27.03% AP and 23.91% SI) and buccal
    Male                                                32 (64%)                  mucosa (22.15% AP and 20.72% SI) and the values were
    Female                                              18 (36%)                  highly significant (Tab. IV). However, for margin measure-
 Ethnicity                                                                        ment, there was no significant difference in the percentage
    Indian                                                                        of shrinkage between the three sub-sites (Tab. V).
 Location
    Buccal mucosa                                       37 (74%)                  Pre-fixation versus post-fixation stage
    Tongue                                              10 (20%)
                                                                                  On comparison of pre-fixation to post-fixation stage, down-
                                                                                  staging of the tumours was seen, especially for stage T3
    Lip                                                  3 (6%)
                                                                                  tumours (Fig. 1). Of the 15 tumours staged T3 pre-fixation,
 Type of surgery
                                                                                  7 tumours (46.7%) were down-staged to T2 post-fixation.
    Wide local excision                                 22 (44%)
                                                                                  In addition, 3 of 13 tumours (23%) staged T2 pre-fixation
    Wide local excision+ marginal                        3 (6%)
    mandibulectomy                                                                were down-staged to T1 post-fixation. Tumours staged T4a
    Wide local excision+                                21 (42%)
                                                                                  did not demonstrate any change in staging post-fixation.
    hemimandibulectomy
    Hemiglossectomy                                      4 (8%)                   Discussion
 Clinical T stage
                                                                                  According to the 2020 GLOBOCAN estimates 1, world-
    T1                                                   1 (2%)
                                                                                  wide, head and neck cancer accounts for more than 1.5 mil-
    T2                                                  13 (26%)
                                                                                  lion cases and 500,000 deaths annually. In Southern Asian
    T3                                                  15 (30%)                  countries, cancers of the lip and oral cavity have a high
    T4a                                                 21 (42%)                  prevalence and is a leading cause of cancer death among
 Pathological T stage                                                             men in India and Sri Lanka. This high frequency can be
    T1                                                   4 (8%)                   attributed to the widespread consumption of tobacco in var-
    T2                                                  17 (34%)                  ied forms in these regions.
    T3                                                  8 (16%)                   Among the treatment options currently available, surgery
    T4a                                                 21 (42%)                  is a key modality in management of head and neck cancer.
                                                                                  Although chemotherapy and radiotherapy are established
                                                                                  treatment modalities for head and neck cancer, oral cancers
Margin shrinkage                                                                  are mainly managed by surgical resection, with non-surgi-
Margin measurements demonstrated a mean difference of                             cal modalities being reserved for adjuvant therapy.
25.61% between pre- and post-fixation values (Tab. II).                           In head and neck cancer, the main aim of surgery with cu-
These results were significant and 84% of margins de-                             rative intent is to achieve an R0 resection, i.e. microscopic
creased by more than 20% post-fixation (Tab. III). 28 of the                      tumour clearance. Inadequate excision margins have an ad-


Table II. Shrinkage of tumour (anterior posteriorx and superior inferiory dimensions) and tumour margins, when classified into 3 groups; < 10, 10-20 and > 20%.
                                                                                                Parameter
                                                            APx                                    SIy                         Margin measurement
                                                   N              Percentage              N              Percentage             N              Percentage
 Shrinkage (%)              < 10%                 0                  .0%                 0                  .0%                  0                .0%
                            10-20%                11                22.0%                21                42.0%                 8               16.0%
                             > 20%                39                78.0%                29                58.0%                42               84.0%




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Table III. Mean pre- and post-fixation anterior posteriorx, superior inferiory dimensions and tumour margins.
 Parameter                             N       Mean (cm)          Std. deviation        Mean difference      S.D. of difference                           Change (%)           P-value
 APx                                  Pre     50           4.98                   1.98                     1.14                        0.46                   22.93             0.000
                                      Post    50           3.84                   1.62
 SIy                                  Pre     50           3.56                   1.51                     0.77                        0.35                   21.69             0.000
                                      Post    50           2.79                   1.23
 Margin measurement                   Pre     50           1.27                   0.35                     0.33                        0.12                   25.61             0.000
                                      Post    50           0.95                   0.25
The difference between means, the Standard Deviation (S.D.) of the difference and the P-value of the statistical test (Student T test) applied are shown in the table. Std.: Standard.




Table IV. Mean shrinkage of anterior posteriorx, superior inferiory tumour dimensions and tumour margins for different sites (Buccal mucosa, Lip and Tongue).
 Parameter           Diagnosis                             N           Mean           Std.          Mean            S.D of        Difference       P-value
                                                                        (cm)       deviation     difference       difference          (%)
 APx                    Buccal mucosa              Pre              37            5.24              2.16              1.15               0.53              22.15              0.000
                                                   Post             37            4.10              1.74
                             Tongue                Pre              10            4.36              1.01              1.17               0.17              27.43              0.000
                                                   Post             10            3.19              0.86
                                Lip                Pre               3            3.74              1.51              0.97               0.24              27.03              0.020
                                                   Post              3            2.78              1.29
 SIy                    Buccal mucosa              Pre              37            3.74              1.56              0.77               0.37              20.72              0.000
                                                   Post             37            2.97              1.26
                             Tongue                Pre              10            2.87              1.20              0.75               0.28              26.82              0.000
                                                   Post             10            2.12              0.94
                                Lip                Pre               3            3.72              1.52              0.86               0.28              23.91              0.034
                                                   Post              3            2.86              1.27
 Margin                 Buccal mucosa              Pre              37            1.28              0.38              0.32               0.12              24.75              0.000
 measurement                                       Post             37            0.96              0.28
                             Tongue                Pre              10            1.26              0.25              0.35               0.10              27.73              0.000
                                                   Post             10            0.91              0.16
                               Lip                 Pre              3             1.20              0.26              0.30               0.14              24.48              0.061
                                                   Post             3             0.90              0.13
The difference between means, the Standard Deviation (S.D.) of the difference and the P-value of the statistical test applied (Student t-test) are shown in the table. Significant p-values
are marked in bold. Std.: Standard




Table V. Comparison of shrinkage across the different subsites (buccal mucosa, lip and tongue).
           Parameter                                             N              Mean shrinkage                                      S.D. of shrinkage                   ANOVA p
                                                                                       (%)                                                  (%)
 Anterior posterior dimensions                  Buccal mucosa                37                       22.15                                 4.96                          0.006
                                                   Tongue                    10                       27.43                                 3.46
                                                     Lip                      3                       27.03                                 5.57
 Superior inferior dimensions                   Buccal mucosa                37                       20.72                                 5.03                          0.004
                                                   Tongue                    10                       26.82                                 4.21
                                                     Lip                      3                       23.91                                 5.38
 Margin measurement                             Buccal mucosa                37                       24.75                                 4.10                          0.124
                                                   Tongue                    10                       27.73                                 3.24
                                                     Lip                     3                        24.48                                 6.06
Comparison done by ANOVA and significant p values marked in bold. S.D.: Standard deviation.




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Kshithi K et al.




                                                                                gin dimensions post-fixation, but the findings were not uni-
                                                                                form in all studies. For instance, on breast cancer speci-
                                                                                mens, the studies by Yeap et al. 7 and Masooma et al. 8 noted
                                                                                significant tumour margin shrinkage post formalin fixation,
                                                                                while another study by Krekel et al. 17 contradicted this
                                                                                finding and showed no shrinkage in the breast specimens
                                                                                studied.
                                                                                Few studies have documented the effects of resection and
                                                                                formalin fixation on head and neck cancer specimens.
                                                                                These studies have taken two parameters into considera-
                                                                                tion: i) shrinkage of tumour and margins because of resec-
                                                                                tion; and ii) shrinkage because of fixation with formalin.
                                                                                Post-excision margin measurements were seen to shrink
Figure 1. Number of patients in the different T stages by clinical and patho-   by 14.9% in a study by Lauren et al. 9, while Mistry et
logical staging.
                                                                                al. 11 noted a mean loss of 22.7% in oral cancers (buccal
                                                                                mucosa and tongue cancer). Cheng El Fol et al. 10,18 dem-
verse effect on prognosis, apart from necessitating the addi-                   onstrated significant shrinkage in mucosal margins (up to
tion of post-operative adjuvant therapy 13. Studies have not-                   75%) when post fixation measurements were compared to
ed that inadequate surgical margins have a bearing on local                     pre-resection margins. A study by Lauren et al. 9 noted that
and regional recurrence, metastasis and death 14. However,                      although there was an overall mean shrinkage of tumour
there is considerable variation with regards to the definition                  size and tumour free margins of 10.7% and 11.3%, respec-
of positive, close and clear margins and various cut-offs of                    tively, in post-fixation specimens, most of the decrease in
2 mm, 5 mm, or 10 mm have been used to define adequate                          tumour size and tumour-free margins occurred between pre
margins within head and neck region 15. In this context, the                    and post-excision measurements. Post-fixation, the tumour
UK Royal College of Pathologists has issued guidelines for                      size further decreased by 4.7% and margin measurements
clear margins, close margins and positive margins for histo-                    by 3.7%, although neither of these discrepancies were sta-
logical clearance of > 5 mm, 1-5 mm and < 1 mm, respec-                         tistically significant. This study concluded that the decrease
tively 16. As margin status is important in defining adjuvant                   may be due to intrinsic tissue properties rather than the ef-
treatment, it is important not only to obtain adequate mar-                     fects of formalin.
gins but also to measure the margins accurately.                                Our study was mainly focused on specimens from buccal
In addition to surgical margins, tumour dimensions also                         mucosa, tongue and lip as these were the most common sites
need accurate measurements. Considering that the widely                         of cancer seen in our study. We focused on post-excision
used AJCC TNM classification system for head and neck                           pre-fixation and post-fixation measurements. We found that
cancer focuses on tumour dimensions in assigning T catego-                      margin measurements because of fixation changed in 84%
ry, it is important to measure the exact tumour dimensions,                     (42 of 50) of specimens by > 20%. Similar findings were
as variation can lead to either upstaging or down-staging                       reported by Pangare et al. 12 in their study on specimens of
of a tumour, which will have considerable therapeutic and                       oral squamous cell carcinoma from gingivobuccal sulcus
prognostic implications.                                                        where the average surgical margin shrinkages were 18.7%
Prior to histopathological analysis of surgical specimen,                       anteriorly, 14.9% posteriorly, 23.6% medially and 23.9%
the specimen has to be fixed. The commonly used method                          laterally.
is fixation with 10% neutral buffered formalin. In most                         Apart from measurement of resection margins, the anter-
laboratories, including ours, specimens are not processed                       oposterior tumour dimensions were also measured in our
immediately and the duration in formalin varies depend-                         study since variation in tumour size impacts the treatment
ing on the number of specimens received each day. In our                        plan. On comparison of tumour dimensions, it was noted
study, all the specimens were fixed in formalin for 24 hours                    that anteroposterior tumour dimensions decreased in all
prior to second measurement to avoid any variation in tis-                      50 specimens with 78% of the specimens demonstrating
sue exposure to formalin. The effect of formalin fixation                       shrinkage of > 20%. This is higher than what was reported
on tumour dimensions and tumour-free margins have been                          by Chen et al. 19 wherein the maximal diameter of speci-
studied on tissues from various sites like colorectal, breast,                  mens shrank by 1.5 mm (4.40%) after formalin fixation.
oesophageal and skin tumours 4-8. Some of these studies                         This low level of shrinkage could be due to the multiple
have documented significant shrinkage of tumour and mar-                        pathologies and sites examined in their study. Herein, the



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                                                                                           Tumour and margin shrinkage due to formalin




discrepancy of measurements led to underestimation of T            We suggest studies on other head and neck sites, including
staging in 8 patients (8%) when tumour size was consid-            but not limited to larynx, maxillary alveolus and hard pal-
ered for T staging (5 patients shifted from T3 to T2 and 3         ate. The anatomy in these sub-sites is diverse and would
patients from T2 to T1). A similar finding was observed in         warrant separate evaluation rather than extrapolation of
our study where a change in T category was noted post-             findings from other areas. Moreover, tumour margins and T
fixation in 10 cases (7 cases shifted from T3 to T2 and 3 pa-      staging are not the only factors which determine the neces-
tients shifted from T2 to T1). This apparent downstaging of        sity of adjuvant therapy; high risk or adverse risk factors
the tumour can have significant therapeutic and prognostic         such as multiple positive nodes or nodes with extracapsular
implications. For instance, a tumour that is pre-operatively       invasion, vascular/lymphatic/perineural invasion, oral cav-
assigned to T3 category will be a Stage III cancer as per the      ity cancers with positive level 4 or 5 nodes and poor differ-
AJCC classification. This patient would often require post-        entiation of primary tumour are established indications for
surgical adjuvant therapy in the form of radiotherapy owing        postoperative radiation in oral malignancies and need to be
to the higher risk of recurrence. A significant shrinkage in       considered when planning postoperative therapy 21.
tumour size that leads to downstaging of T category can
adversely affect the treatment plan in these patients with         Conclusions
denial of adjuvant treatment and consequently a higher
chance of recurrence. In addition, the documentation of            The findings of our study indicate that formalin fixation
close margins will require referral for adjuvant therapy,          can be responsible for significant shrinkage of tumour and
which could have been otherwise avoided. The medico-               margin dimensions in head and neck specimens. We sug-
legal implications of this clinico-pathological conundrum          gest that any deliberation on postoperative adjuvant therapy
cannot be ignored and requires resolution.                         should be made on clinical staging of the primary tumour
The shrinkage of tumour dimension in our study is higher           rather than pathological staging along with consideration
than what was documented by Chen et al. 19. Most of the            of other established clinical and pathological parameters
patients in our study had T3 or T4 tumours and almost all          which are at high risk for locoregional recurrence of can-
were heavy tobacco chewers. Whether these two factors              cer. In addition, post-excision pre-fixation margins should
can alter the intrinsic tissue properties and cause a higher       be considered for treatment planning.
degree of shrinkage is not known and requires further study.
The AJCC cancer staging manual specifies that the patholo-         Conflict of interest statement
gist should note potential alteration in tumour size caused by     The authors declare no conflict of interest.
fixation if it might affect staging and that up to 30% shrink-
age of soft tissues may occur in resected specimens after          Funding
formalin fixation 20. Furthermore, it mentions that pathologi-     This research did not receive any specific grant from funding
cal staging does not supplant clinical staging as the primary      agencies in the public, commercial, or not-for-profit sectors.
scheme. Also due to the complex anatomy of oral cavity
combined with restricted mouth opening (often seen in high         Author contributions
stage tumours or cases with coexistent oral submucous fibro-       Conceptualization: SS, VK. Methodology: SS, VK, KK.
sis), it is not always possible to accurately assess tumour size   Data collection and analysis: KK, VK, SS, VSS. Writing-
by clinical examination alone. From the findings of our study,     original draft: KK, VK, TR, SK. Writing-review and edit:
we contend that T staging of tumour for treatment should be        SS, VSS.
done by clinical examination and that margin measurement
should be done post-resection but before fixation.                 Ethical consideration
Another finding that was noted in our study was that there         This study was approved by the Institutional Ethics Com-
was a sub-site specific variation in the degree of shrinkage       mittee (Kasturba Medical College, Mangaluru) (approval
where the shrinkage of tongue tumours was higher in com-           number/protocol number IEC KMC MLR 10-19/498).
parison to other sub-sites. This could be due to the variation     The research was conducted ethically, with all study pro-
in intrinsic tissue properties at different sites. However, the    cedures being performed in accordance with the require-
margins did not show any subsite-specific discrepancy un-          ments of the World Medical Association’s Declaration of
like previous studies 10.                                          Helsinki.
Our study is limited by the number of sites that were evalu-       Written informed consent was obtained from each par-
ated, as most of the tumours were involving the buccal mu-         ticipant/patient for study participation and data publica-
cosa and tongue, with only three cases of lip malignancy.          tion.



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