Volume 5 • Issue 4 • 1000238
J Cytol Histol
ISSN: 2157-7099 JCH, an open access journal
Research Article Open Access
Diaz-Cano, J Cytol Histol 2014, 5:4
DOI: 10.4172/2157-7099.1000238
Short Communication Open Access
Multicentric Papillary Thyroid Carcinoma: Stratification for Treatment
Salvador J. Diaz-Cano*
Department of Histopathology, King’s College Hospital and King’s Health Partners, London, United Kingdom
*Corresponding author: Salvador J. Diaz-Cano, King’s College Hospital,
Dept of Histopathology, Denmark Hill, London, Greater London, SE5 9RS,
United Kingdom, Tel: +44 20 3299-3041 Fax: +44 20 3299-3670; E-mail:
sdiaz-cano@nhs.net
Received December 18, 2013; Accepted March 29, 2014; Published March 31,
2014
Citation: Diaz-Cano SJ (2014) Multicentric Papillary Thyroid Carcinoma:
Stratifcation for Treatment. J Cytol Histol 5: 238. doi:10.4172/2157-
7099.1000238
Copyright: © 2014 Diaz-Cano SJ. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Abstract
Tumor stage is the main prognosticator of differentiated thyroid carcinomas, but it needs further stratifcation for
multicentric neoplasms (most frequently papillary thyroid carcinomas, PTC), which frequently present as foci smaller
than 1cm and are considered by default as high-risk tumors. Not all cases of multicentric PTC should be considered
of high risk and they should be stratifed to avoid unnecessary radioiodine ablation in selected cases. Currently,
there are known variables for this stratifcation: size and number of tumor foci, clonal patterns, and specifc markers
of aggressive behaviour (infltrative growth, BRAF mutation). In a near future, the identifcation of a gene expression
pattern associated with a higher risk of recurrence would allow us to focus more aggressive treatment appropriately.
Keywords: Tyroid; Papillary carcinoma; Multicentric; Treatment
stratifcation
Abbreviations: miRNA: Micro RNA; PTC: Papillary Tyroid
Carcinoma
Short Commentary on Early Multicentric PTC
Te treatment of papillary thyroid carcinoma (PTC) has
signifcantly changed recently and it is mainly based on surgery and
radioiodine ablation, the latter for high-risk patients only [1-4].
However, this treatment is currently subjected to extensive review
especially for low risk carcinomas. Two main factors have contributed
to this review: the increased incidence of secondary neoplasms afer
radioiodine treatment and the efciency demonstrated by low dose
treatment [4,5]. Cancer treatment selection depends on patient
stratifcation according to risk for a given tumor, but it is particularly
challenging for patients with low-risk thyroid cancers because of the
slow growth of such tumors. Tumor stage is the main prognosticator
of diferentiated thyroid carcinomas, but it needs further stratifcation
for multicentric neoplasms (most frequently PTC), which frequently
present as foci smaller than 1cm and are considered by default as high-
risk tumors. Microscopic PTCs (<1.0 cm) are considered a subset
of PTCs that behave more benign. Tey follow an indolent course
and carry an excellent prognosis. Distant metastases and mortality
rates were reported to be less than 0.5% [6]. However, some authors
suggest that there exists a subgroup of microscopic PTCs that can be
aggressive, requiring therapeutic management similar to larger tumors
[7]. Unfortunately, within this set of patients, prognostic factors have
not been well defned. However, in recent years some specifc markers
for aggressiveness were identifed, including sizes larger than 5 mm,
multifocality, tumor extension beyond the parenchyma, lymph node
involvement, tumor non-incidentally discovered, and the extent of
primary surgery [7-10].
Currently, both biologic and pathologic variables provide a
reliable basis for risk stratifcation of early stage thyroid cancer.
Intratumor heterogeneity is at the foundation of tumor progression
and it correlates with the tumor volume and multicentricity [11]: the
potential to metastasize increase directly with primary size (the main
element for T staging), and multicentric neoplasms (expressed by (m)
in the T classifcation). Tese two key elements are the main general
prognosticators used to plan any adjuvant radioiodine treatment.
Although multicentric PTCs are not stratifed further considering
that the presence of multicentricity provides a risk for all patients, no
statistical diference in cancer mortality has been observed between the
ablated and nonablated groups of patients with multicentric PTC [12],
most likely refecting the lack of selection criteria.
Multicentricity is considered an expression of tumor heterogeneity,
the main driver of tumor progression by increasing the number of
diferent clones and therefore the probability of sub-clone development
with additional acquired capabilities [11]. Multicentric PTC is more
frequently detected due to improved diagnostic methods. More than
70% of microscopic PTCs are diagnosed incidentally (in specimens of
the thyroid removed for benign thyroid disease) and it is responsible
for the 2.4x increase in incidence of diferentiated thyroid carcinoma
[13]. Multiple foci have been reported in approximately 7-56% of
microscopic PTCs [6,14]. A number of clinical studies showed that
patients with ≥ two foci had higher recurrence rate and cancer mortality
than those with unifocal PTMCs [6,12]. Moreover, multifocality is
an independent risk factor for metastases [15]. It was demonstrated
that cases with positive lymph nodes had a higher risk of recurrence
[13]. Hence, multifocal PTMCs have been considered to have a poor
prognosis requiring radioiodine ablation and close surveillance within
the frst year. Patients with multicentric microscopic PTC need to
be treated as highrisk patients, which partially explain the increase
in the proportion of patients receiving radioactive iodine [5,16]. Te
recurrence rate increases signifcantly in cases with ≥ 5 foci, which
frequently undergo
131
I ablation [12]. As all foci are governed by the
volume growth criteria expressed below, the clinical signifcance
given to each focus must be linked to its size and a demonstrable
evidence of diferent cellular progenitor. Terefore, the stratifcation
of patients with multicentric tumors would require considering both
the size of each focus, the number of foci, and a sensible application
of clonality tests (such as X-chromosome inactivation and fractional
allelic loss assays) [17]. An appropriate use of these markers serves to
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ISSN: 2157-7099