Staging colorectal cancer with the TNM 7: The presumption of innocence when applying the M category

Abstract

One of the main changes of the current TNM-7 is the elimination of the category MX, since it has been a source of ambiguity and misinterpretation, especially by pathologists. Therefore the ultimate staging would be better performed by the patient's clinician who can classify the disease M0 (no distant metastasis) or M1 (presence of distant metastasis), having access to the completeness of data resulting from clinical examination, imaging workup and pathology report. However this important change doesn't take into account the diagnostic value and the challenge of small indeterminate visceral lesions encountered, in particular, during radiological staging of patients with colorectal cancer. In this article the diagnosis of these lesions with multiple imaging modalities, their frequency, significance and relevance to staging and disease management are described in a multidisciplinary way. In particular the interplay between clinical, radiological and pathological staging, which are usually conducted independently, is discussed. The integrated approach shows that there are both advantages and disadvantages to abandoning the MX category. To avoid ambiguity arising both by applying and interpreting MX category for stage assigning, its abandoning seems reasonable. The recognition of the importance of small lesion characterization raises the need for applying a separate category; therefore a proposal for their categorization is put forward. By using the proposed categorization the lack of consideration for indeterminate visceral lesions with the current staging system will be overcome, also optimizing tailored follow-up.

Full text

Giacomo Puppa, Graeme Poston, Per Jess, Guy F Nash, Kenneth Coenegrachts, Axel Stang
Staging colorectal cancer with the TNM 7th: The
presumption of innocence when applying the M category
Giacomo Puppa, Service de Pathologie Clinique, Hôpitaux Uni-
versitaires de Genève, 1211 Geneva, Switzerland
Graeme Poston, Department of Surgery, Aintree University
Hospitals, Liverpool L9 7AL, United Kingdom
Per Jess, Department of Surgery, Roskilde Hospital, University
of Copenhagen, 2200 Copenhagen, Denmark
Guy F Nash, Department of Colorectal Surgery, Poole General
Hospital, Poole BH15 2JB, United Kingdom
Kenneth Coenegrachts, Department of Radiology, AZ St.-Jan
Brugge-Oostende AV, B-8000 Bruges, Belgium
Axel Stang, Department of Oncology, Hematology and Palliative
Care, Asklepios Hospital Hamburg-Barmbek, 22291 Hamburg,
Germany
Author contributions: Puppa G and Stang A designed the study
and wrote the paper; Puppa G and Coenegrachts K provided the
images from their departments; Poston G, Jess P, Nash GF and
Coenegrachts K revised the text for important intellectual con-
tent.
Correspondence to: Giacomo Puppa, MD, PhD, Service de
Pathologie Clinique, Hôpitaux Universitaires de Genève, 1, rue
Michel Servet, 1211 Genève,
Switzerland. giacomo.puppa@hcuge.ch
Telephone: +41-22-3724956 Fax: +41-22-3724924
Received: June 25, 2012 Revised: August 18, 2012
Accepted: September 19, 2012
Published online: February 28, 2013
Abstract
One of the main changes of the current TNM-7 is the
elimination of the category MX, since it has been a
source of ambiguity and misinterpretation, especially
by pathologists. Therefore the ultimate staging would
be better performed by the patient’s clinician who can
classify the disease M0 (no distant metastasis) or M1
(presence of distant metastasis), having access to the
completeness of data resulting from clinical examina-
tion, imaging workup and pathology report. However
this important change doesn’t take into account the
diagnostic value and the challenge of small indetermi-
nate visceral lesions encountered, in particular, during
radiological staging of patients with colorectal cancer.
In this article the diagnosis of these lesions with mul-
tiple imaging modalities, their frequency, significance
and relevance to staging and disease management are
described in a multidisciplinary way. In particular the
interplay between clinical, radiological and pathological
staging, which are usually conducted independently, is
discussed. The integrated approach shows that there
are both advantages and disadvantages to abandoning
the MX category. To avoid ambiguity arising both by
applying and interpreting MX category for stage assign-
ing, its abandoning seems reasonable. The recognition
of the importance of small lesion characterization raises
the need for applying a separate category; therefore a
proposal for their categorization is put forward. By us-
ing the proposed categorization the lack of considera-
tion for indeterminate visceral lesions with the current
staging system will be overcome, also optimizing tai-
lored follow-up.
© 2013 Baishideng. All rights reserved.
Key words: Colorectal cancer; Staging; Indeterminate
lesions; Imaging; Metastases
Puppa G, Poston G, Jess P, Nash GF, Coenegrachts K, Stang A.
Staging colorectal cancer with the TNM 7th: The presumption of
innocence when applying the M category. World J Gastroenterol
2013; 19(8): 1152-1157 Available from: URL: http://www.
wjgnet.com/1007-9327/full/v19/i8/1152.htm DOI: http://dx.doi.
org/10.3748/wjg.v19.i8.1152
INTRODUCTION
Stage Ⅳ colorectal cancer (CRC) is no longer considered
a single entity[1] and after several proposals for stratify-
ing it[2,3] the current TNM-7 subdivides the M1 category
into M1a (metastasis conned to one organ: liver, lung,
EDITORIAL
Online Submissions: http://www.wjgnet.com/esps/
wjg@wjgnet.com
doi:10.3748/wjg.v19.i8.1152
1152 February 28, 2013
|
Volume 19
|
Issue 8
|
WJG
|
www.wjgnet.com
World J Gastroenterol 2013 February 28; 19(8): 1152-1157
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
© 2013 Baishideng. All rights reserved.

ovary, non-regional lymph node(s) and M1b (metastasis
in more than one organ or the peritoneum): accordingly
stage Ⅳ is subdivided in IVA (Any T, Any N, M1a) and
IVB (Any T, Any N, M1b)[4]. Population-based studies
demonstrate that the prognosis for surgically resected
stage Ⅳ disease is near identical for that of patients fol-
lowing potentially curative surgery for stage Ⅲ disease[5].
The prognosis and treatment options (including in-
creasingly used multimodality approaches) within the M1
stages depend largely on the extent and distribution of
the metastases. Therefore, the current staging will be able
to take into account improvements that have been made
in surgical techniques for resectable metastases, and the
impact of modern chemotherapy on rendering initially
unresectable CRC liver metastases operable, while at the
same time distinguishing between patients with a chance
of cure at presentation and those for whom only pallia-
tive treatment is possible[3].
An other major change with the new TNM-7 is that
the category ‘‘MX: Distant metastasis cannot be assessed’’
has been eliminated[4].
In this report, the change with the TNM-7 is dis-
cussed in a multidisciplinary setting and the diagnostic
significance of small indeterminate visceral lesions en-
countered during radiological staging of patients with
colorectal cancer is presented.
The resulting problems, in particular the ambiguities
for stage assigning when applying the MX category and
the risk of inaccurate staging and follow-up planning
because of its elimination, are discussed. A proposal is
presented for the categorization of such small, indeter-
minate visceral lesions.
CHANGE WITH THE TNM FROM THE
PATHOLOGIST POINT OF VIEW
There are basically two reasons for MX elimination.
Firstly the MX category has been a source of misin-
terpretation, especially by pathologists (i.e., pMX) who
“may assign MX, meaning that they cannot assess distant
metastasis”[6]. This is a clinical, not pathological assess-
ment. “If there are no obvious signs of metastasis, M0
or cM0 classifications are appropriate. In other words,
once clinically examined, a patient is M0 until proven
otherwise”[6] in analogy with the legal right Presumption
of Innocence.
The second reason is that assigning the MX category
prevents stage grouping by American cancer registries[6].
The elimination of MX allows only two categories,
M0 (cM0): no distant metastasis and M1 (cM1 or pM1):
distant metastasis[4] utilizing imaging and/or pathological
assessment[7].
This goes against the TNM rule of assigning the X
category, since the proper use of X is to denote the ab-
sence or uncertainty of assigning a given category[8] but
importantly these are two different situations.
A similar clinical-pathological context is encountered
when applying the R classification (R for residual as
descriptor of ‘‘tumour remaining in the patient’’ after
primary surgical resection): the assignment of the R clas-
sication must be performed “by a designated individual
who has access to the complete data”[9].
Despite extensive clinical assessment of treatment
results and careful pathologic examination, in some cases
the presence of residual tumour cannot be assessed: the
RX category applies[9,10].
If the pathologist hasn’t access to the preoperative
clinico-radiological work-up, he/she can do only a lim-
ited staging (pT and pN), in the dark about these clinical
data.
As an accurate pathological examination is the pre-
requisite for a prognostic staging and a tailored patient
treatment, the enhanced search for additional prognostic
factors applies in particular cases (problems with resec-
tion margins assessment; involvement of the peritoneum
and/or adjacent structures or organs; suspicion for vas-
cular invasion; few lymph nodes recovered; pericolonic
tumour deposits)[11,12].
In this setting, patient characteristics, treatment-rel-
ated features and disease extension as evaluated both dur-
ing surgery and preoperatively are all relevant informa-
tion.
In other words, the stage grouping, as well the risk
assessment of patients belonging to the same stage, are
better performed in the multidisciplinary setting than
considered in isolation.
RADIOLOGICAL STAGING
The major task of radiological staging is the exclusion
(cM0) or detection (cM1) of metastases, particularly
in the liver and/or the lung. The most frequently used
imaging modalities for staging of CRC cancer patients
are ultrasonography (US), computed tomography (CT),
magnetic resonance imaging (MRI), and positron emis-
sion tomography (PET)/CT (PET/CT)[13]. In the past
10 years, important advances have been made within all
four techniques. While some (CT and PET/CT) will give
patient specic information regarding abnormal masses
and increased tissue metabolic activity throughout the
body, others (MRI) will yield organ (liver) specific in-
formation and allow characterization of specic abnor-
malities to differentiate benign from malignant lesions.
However, no single modality will diagnose all metastases,
and the optimal imaging strategy to classify cM0 or cM1
depends on the clinical context, the organ site investi-
gated, and the individual aims of oncologic care.
With the introduction of multidetector row CT
(MDCT) scanning, CT imaging will continue to play the
dominant role in the radiological staging of CRC pa-
tients[14]. Improved MDCT technologies have resulted in
increased CT detection of small (< 1 cm) indeterminate
lesions in the lung and/or liver (in around 10%-40% of
CT CRC staging examinations)[15-20].
1153 February 28, 2013
|
Volume 19
|
Issue 8
|
WJG
|
www.wjgnet.com
Puppa G
et al
. A proposal for categorization of small, indeterminate visceral lesions

A major drawback of MDCT is that its ability to de-
tect small lesions has outstripped its ability to character-
ize them. Although most tiny lung and/or liver lesions
detected on CT staging of CRC patients are benign
(Figure 1), 10%-20% of CT-indeterminate lung and/or
liver lesions do develop into definite metastases (Fig-
ure 2)[17,18,20,21]. The M stage of CRC patients with CT-
indeterminate lung and/or liver lesions, therefore, would
require the category MX (“X” meaning uncertainty).
Regarding the definite diagnosis of whether or not
these lesions are benign or malignant, consideration
should include the T stage and the nodal status of the
primary tumour and the distribution patterns of lesions
as the probability of malignancy of small lung or liver
lesions depends on the stage of the primary tumour (T
stage) and the nodal status (N stage)[17,18].
Further evaluation with complementary imaging
modalities is needed in patients with small CT-indeter-
minate lesions if a change of M staging would alter the
treatment. In the thorax, additional PET/CT may be
helpful in the differentiation of a single < 1 cm pulmo-
nary lesion, but it may not be efcient when more than
one small lesion is found on MDCT examination. In the
liver, US may be the primary modality of choice in cases
of advanced liver metastases, whereas contrast-enhanced
US[22] MRI[23,24] and/or US-CT fusion imaging tech-
1154 February 28, 2013
|
Volume 19
|
Issue 8
|
WJG
|
www.wjgnet.com
C
B
A
Figure 1 Example of a small lesion which proved to be benign after
follow-up. A: Two small (< 10 mm) indeterminate focal liver lesions (white ar-
row) on contrast-enhanced computed tomography; B: Corresponding magnetic
resonance imaging (MRI), images showing a T2w Turbo Spin Echo sequence
with fat suppression. Two clearly hyperintense focal liver lesions (white arrow)
are displayed compatible with simple liver cysts; C: Corresponding MRI images
showing a T2w Turbo Spin Echo sequence without fat suppression. Two clearly
hyperintense focal liver lesions (white arrow) are displayed compatible with
simple liver cysts.
Figure 2 Example of a small lesion which proved to be malignant after
follow-up. A: Positron emission tomography (PET)/computed tomography
negative (PET-cold) focal liver lesion (white arrow) in a patient who received
chemotherapy in the past; B: Corresponding T1w Gradient Echo magnetic reso-
nance imaging (MRI) image before injection of contrast agent shows a rather
hypo-intense focal liver lesion (white arrow); C: Corresponding T1w Gradient
Echo MRI image in the venous phase after injection of contrast agent shows a
hypo-intense focal liver lesion with ring-enhancement compatible with an (active)
malignant focal liver lesion (colorectal cancer liver metastasis) (white arrow).
C
B
A
Puppa G
et al
. A proposal for categorization of small, indeterminate visceral lesions

1155 February 28, 2013
|
Volume 19
|
Issue 8
|
WJG
|
www.wjgnet.com
CONCLUSION
Advantages and disadvantages of the revised TNM
classication of metastatic status
Disease management for CRC has evolved in recent
years into a multidisciplinary setting and is essentially
based on tumour stage.
Cancer staging represents the operational basis for
choosing the most appropriate therapy and for evaluat-
ing the efficacy of different therapeutic methods; it is
an essential component of patient care, cancer research,
and control activities, even in light of the impressive
progress that has been attained in the elds of clinical
strategies and molecular medicine.
The TNM system is subjected to continuous updat-
ing through an ongoing expert review of existing data.
Proposals for changes are made in different situ-
ations, including when the classification is poorly ac-
cepted, poorly used, or criticized in the literature[27]: here
comes the decision for MX category elimination[6].
As the MX category results in ambiguity (lack of in-
formation or uncertainty in assigning a given category)
both in applying and in interpreting it for stage assign-
ing, it seems reasonable to abandon it.
This is also in accord with the general rule of the
niques[25] may complement the initial CT information in
candidates for liver resection.
Follow-up CT imaging may be a reasonable approach
in patients in whom a change of M staging would alter
the clinical management, as malignant lesions would be
expected to grow but benign lesions less so.
During restaging after neoadjuvant chemotherapy,
besides the complete clinical remission (disappearance
on CT, ycM0) achieved in a small number of patients
with metastases (mainly in CRC lung or liver metas-
tases), small lesions, suspected as being residual tumour
may be encountered (Figure 3): the difculties in inter-
preting these lesions are made harder by the response to
chemotherapy which may impact on the sensitivity of
preoperative imaging studies in identifying all sites of
disease[26].
Either chemotherapy itself, or the fatty infiltration
it commonly causes, can affect the ability of CT to ef-
fectively restage patients, resulting in both false negative
and false positive results; thus, in patients with known
hepatic steatosis, or in patients receiving neo-adjuvant
chemotherapy, liver MRI is often recommended for stag-
ing or restaging of hepatic disease[14].
However, only pathologic examination can determine
the actual nature of these lesions (Figure 4).
CBA
L
2
2
1
R
2
0
1
L
2
2
1
R
2
1
3
L
I
R
S
Figure 3 Restaging the liver after neoadjuvant therapy in a patient with multiple liver metastases from rectal cancer. A: On computed tomography (CT) before
intravenous contrast, all the metastases disappeared except for a small lesion suspicious of residual disease (white arrow); B: Corresponding CT after intravenous
contrast showing the challenging lesion (white arrow); C: Also on magnetic resonance imaging the lesion (white arrow) remains suspicious for malignancy providing
indication for a liver resection.
Figure 4 Pathological examination of the resected liver specimen corresponding to the lesion indicated by the white arrow in gure 3. A: Gross specimen:
on cut the macroscopic examination shows a star-like whitish lesion; B: At histology (hematoxylin and eosin, x 100) only brosis and inammation are seen indicating
a complete response to chemotherapy.
BA
Puppa G
et al
. A proposal for categorization of small, indeterminate visceral lesions

1156 February 28, 2013
|
Volume 19
|
Issue 8
|
WJG
|
www.wjgnet.com
TNM system which states that, “if there is doubt con-
cerning the correct category to which a particular patient
should be allotted (T, N, or M), then the lower (i.e., less
advanced) category should be used”[8].
However, the increased detection of small indetermi-
nate lesions due to improved imaging technologies, par-
ticularly with MDCT imaging[20], suggests that a separate
category is needed.
This is to avoid the application of M0 category to all
indeterminate/suspicious lesions, with consequent re-
duced diagnostic accuracy and staging errors.
Proposal
Cancer patients with small indeterminate lesions (e.g., in
the lung and/or liver) are at risk of developing metas-
tases and therefore need continued follow-up with imag-
ing. The TNM staging system uses an extensive number
of prexes and sufxes, as additional descriptors, their
presence indicating cases needing separate analysis[4] and
ongoing investigation. We propose to add a sufx (e.g.,
iPUL, iHEP) to cM0 to indicate the presence of "small
indeterminate lesions" considered to be benign but to be
surveyed on further follow-up imaging to conrm that
they are benign by their unchanged size and radiologic
characteristics.
REFERENCES
1 Poston G, Adam R, Vauthey JN. Downstaging or downsiz-
ing: time for a new staging system in advanced colorectal
cancer? J Clin Oncol 2006; 24: 2702-2706 [PMID: 16782909
DOI: 10.1200/JCO.2006.05.8404]
2 Nagashima I, Takada T, Nagawa H, Muto T, Okinaga K.
Proposal of a new and simple staging system of colorectal
liver metastasis. World J Gastroenterol 2006; 12: 6961-6965
[PMID: 17109517]
3 Poston GJ, Figueras J, Giuliante F, Nuzzo G, Sobrero AF,
Gigot JF, Nordlinger B, Adam R, Gruenberger T, Choti MA,
Bilchik AJ, Van Cutsem EJ, Chiang JM, D’Angelica MI. Ur-
gent need for a new staging system in advanced colorectal
cancer. J Clin Oncol 2008; 26: 4828-4833 [PMID: 18711170
DOI: 10.1200/JCO.2008.17.6453]
4 Sobin LH, Gospodarowicz MK, Wittekind CH. TNM Classi-
cation of Malignant Tumors. New York: Wiley-Blackwell,
2009
5 Morris EJ, Forman D, Thomas JD, Quirke P, Taylor EF, Fair-
ley L, Cottier B, Poston G. Surgical management and out-
comes of colorectal cancer liver metastases. Br J Surg 2010;
97: 1110-1118 [PMID: 20632280 DOI: 10.1002/bjs.7032]
6 Sobin LH, Compton CC. TNM seventh edition: what’s new,
what’s changed: communication from the International
Union Against Cancer and the American Joint Committee
on Cancer. Cancer 2010; 116: 5336-5339 [PMID: 20665503
DOI: 10.1002/cncr.25537]
7 Jessup JM, Gunderson LL, Greene FL, Washington MK,
Compton CC, Sobin LH, Minsky B, Goldberg RM, Ham-
ilton SR. 2010 Staging System for Colon and Rectal Carci-
noma. Ann Surg Oncol 2011; 18: 1513-1517 [DOI: 10.1245/
s10434-010-1360-1]
8 Greene FL, Brierley J, O’Sullivan B, Sobin LH, Wittekind
C. On the use and abuse of X in the TNM classification.
Cancer 2005; 103: 647-649 [PMID: 15612025 DOI: 10.1002/
cncr.20808]
9 Wittekind C, Compton CC, Greene FL, Sobin LH. TNM
residual tumor classification revisited. Cancer 2002; 94:
2511-2516 [PMID: 12015777 DOI: 10.1002/cncr.10492]
10 Puppa G, Bortolasi L, Colombari R, Sheahan K. Residual
tumor (R) classification in colorectal cancer: reduced, ex-
panded, or not uniform? Arch Pathol Lab Med 2011; 135: 288;
author reply 289 [PMID: 21366444]
11 Puppa G, Sonzogni A, Colombari R, Pelosi G. TNM staging
system of colorectal carcinoma: a critical appraisal of chal-
lenging issues. Arch Pathol Lab Med 2010; 134: 837-852 [PMID:
20524862]
12 Puppa G. TNM staging system of colorectal carcinoma:
surgical pathology of the seventh edition. Diagn Histopathol
2011; 17: 243-262 [DOI: 10.1016/j.mpdhp.2011.03.006]
13 Bipat S, van Leeuwen MS, Comans EF, Pijl ME, Bossuyt
PM, Zwinderman AH, Stoker J. Colorectal liver metastases:
CT, MR imaging, and PET for diagnosis--meta-analysis.
Radiology 2005; 237: 123-131 [PMID: 16100087 DOI: 10.1148/
radiol.2371042060]
14 Grand DJ, Beland M, Noto RB, Mayo-Smith W. Optimum
imaging of colorectal metastases. J Surg Oncol 2010; 102:
909-913 [PMID: 21165992 DOI: 10.1002/jso.21656]
15 Kronawitter U, Kemeny NE, Heelan R, Fata F, Fong Y.
Evaluation of chest computed tomography in the stag-
ing of patients with potentially resectable liver metastases
from colorectal carcinoma. Cancer 1999; 86: 229-235 [PMID:
10421258]
16 McIntosh J, Sylvester PA, Virjee J, Callaway M, Thomas
MG. Pulmonary staging in colorectal cancer--is computer-
ised tomography the answer? Ann R Coll Surg Engl 2005; 87:
331-333 [PMID: 16176690 DOI: 10.1308/003588405X60579]
17 Brent A, Talbot R, Coyne J, Nash G. Should indetermi-
nate lung lesions reported on staging CT scans influ-
ence the management of patients with colorectal cancer?
Colorectal Dis 2007; 9: 816-818 [PMID: 17931171 DOI:
1463-1318.2007.01229.x]
18 Christoffersen MW, Bulut O, Jess P. The diagnostic value
of indeterminate lung lesions on staging chest computed to-
mographies in patients with colorectal cancer. Dan Med Bull
2010; 57: A4093 [PMID: 20175945]
19 Grossmann I, Klaase JM, Avenarius JK, de Hingh IH, Mast-
boom WJ, Wiggers T. The strengths and limitations of rou-
tine staging before treatment with abdominal CT in colorec-
tal cancer. BMC Cancer 2011; 11: 433 [PMID: 21982508 DOI:
10.1186/1471-2407-11-433]
20 McQueen AS, Scott J. CT staging of colorectal cancer: what
do you nd in the chest? Clin Radiol 2012; 67: 352-358 [PMID:
22169348 DOI: 10.1016/j.crad.2011.10.005]
21 Lim GH, Koh DC, Cheong WK, Wong KS, Tsang CB. Na-
tural history of small, “indeterminate” hepatic lesions in
patients with colorectal cancer. Dis Colon Rectum 2009;
52: 1487-1491 [PMID: 19617765 DOI: 10.1007/DCR.0013-
e3181a74d5e]
22 Wilson SR, Burns PN. Microbubble-enhanced US in body
imaging: what role? Radiology 2010; 257: 24-39 [PMID:
20851938]
23 Motosugi U, Ichikawa T, Nakajima H, Sou H, Sano M, Sano
K, Araki T, Iino H, Fujii H, Nakazawa T. Imaging of small
hepatic metastases of colorectal carcinoma: how to use su-
perparamagnetic iron oxide-enhanced magnetic resonance
imaging in the multidetector-row computed tomography
age? J Comput Assist Tomogr 2009; 3 3: 266-272 [PMID:
19346857 DOI: 10.1097/RCT.0b013e31817f5c82]
24 Coenegrachts K. Magnetic resonance imaging of the liver:
New imaging strategies for evaluating focal liver lesions.
World J Radiol 2009; 1: 72-85 [PMID: 21160723 DOI: 10.4329/
wjr.v1.i1.72]
25 Stang A, Keles H, Hentschke S, Seydewitz C, Keuchel M,
Puppa G
et al
. A proposal for categorization of small, indeterminate visceral lesions

1157 February 28, 2013
|
Volume 19
|
Issue 8
|
WJG
|
www.wjgnet.com
Pohland C, Dahlke J, Weilert H, Wessling J, Malzfeldt E.
Real-time ultrasonography-computed tomography fusion
imaging for staging of hepatic metastatic involvement in pa-
tients with colorectal cancer: initial results from comparison
to US seeing separate CT images and to multidetector-row
CT alone. Invest Radiol 2010; 45: 491-501 [PMID: 20458251
DOI: 10.1097/RLI.0b013e3181ddd3da]
26 Charnsangavej C, Clary B, Fong Y, Grothey A, Pawlik TM,
Choti MA. Selection of patients for resection of hepatic
colorectal metastases: expert consensus statement. Ann Surg
Oncol 2006; 13: 1261-1268 [PMID: 16947009 DOI: 10.1245/
s10434-006-9023-y]
27 Gospodarowicz MK, Miller D, Groome PA, Greene FL,
Logan PA, Sobin LH. The process for continuous improve-
ment of the TNM classication. Cancer 2004; 100: 1-5 [PMID:
14692017 DOI: 10.1002/cncr.11898]
P- Reviewer Sipos F S- Editor Gou SX L- Editor O’Neill M
E- Editor Zhang DN
Puppa G
et al
. A proposal for categorization of small, indeterminate visceral lesions