treatment and prognostic factors of papillary thyroid microcarcinoma

Treatment and prognostic factors of papillary thyroidmicrocarcinoma

Giordano, D.,* Gradoni, P.,* Oretti, G.,* Molina, E.� & Ferri, T.*

*Department of Otorhinolaryngology, University Hospital of Parma, Parma, and �Department of Pharmacology,

University of Parma, Parma, Italy

Accepted for publication 28 December 2009

Clin. Otolaryngol. 2010, 35, 118–124

Objective: To discuss the prognostic factors and out-

comes of treatment in patients diagnosed with papillary

thyroid microcarcinoma.

Design: Retrospective observational case review.

Setting: Department of Otorhinolaryngology of the

tertiary referral teaching hospital of Parma.

Participants: Ninety-seven patients diagnosed with

PTMC and surgically treated between January 1998 and

December 2007.

Main outcome measures: Clinical and histopathological

characteristics of the study group were identified and

statistically analysed.

Results: No cancer-related deaths were registered. Inci-

dence of recurrent disease was 9% after a 43 month mean

follow-up (range 12–120). Univariate analysis detected that

metastases in neck lymph nodes at diagnosis (p = 0.025),

a tumour >5 mm in size (p = 0.011), the presence of bilat-

eral tumoural foci (p = 0.007), the presence of capsular

invasion (p = 0.001), and the presence of vascular invasion

(p = 0.004) were related to recurrent disease. On multi-

variate analysis, the presence of bilateral tumoural foci

(p = 0.030), and the presence of capsular invasion (p =

0.005) were significantly related to tumour recurrence.

Conclusion: The prognosis for patients with papillary

thyroid microcarcinoma in this series was excellent, with

a 100% survival rate and minimal surgical-related mor-

bidity. Nevertheless, approximately 10% of patients

developed recurrent disease; aggressive treatment may be

justified depending on the presence or absence of

prognostic risk factors.

Papillary thyroid microcarcinoma (PTMC) is defined by

the World Health Organisation as a papillary thyroid can-

cer measuring 10 mm or less in maximum diameter.1

Data regarding its incidence have been published in

autopsy and surgical series. Nowadays, it is estimated that

it accounts for up to 30% of all papillary thyroid can-

cers,2,3 although marked geographic differences in inci-

dence rates have been noted.4

Most PTMCs are clinically indolent and detected inci-

dentally during histopathological examination of thyroid-

ectomy specimens for benign thyroid diseases. Advances

in ultrasonography-guided fine-needle aspiration biopsy

(us-FNAB) have resulted in a marked increase in the

number of patients diagnosed with PTMC.3

Predictors of relapse or persisting disease are quite well

established in conventional papillary thyroid carcinoma,

but they have not been consistently identified in PTMC.5

Generally, it is known that this distinct subset of papil-

lary thyroid cancer, based on size itself, offers an excellent

prognosis. Nevertheless, the debate goes on regarding the

optimal treatment for this disease. The low biological

aggressiveness and the rarity of distant metastases tend to

justify a less aggressive therapeutic approach than that

required for other papillary thyroid cancers.6 On the

other hand, some authors emphasise the fact that in some

patients PTMC may have a biological and clinical behav-

iour that is similar to conventional papillary thyroid car-

cinoma.7,8

The debate is partly favoured by the lack of literature

supporting randomised comparative trials for treatment

of PTMC. In fact, the low incidence of PTMC makes it

impractical to perform randomised comparative trials, so

that the proposed management policies are based on per-

sonal retrospective experiences.

In this study, we discuss the results of our treatment

protocol and characterise the clinical and histopathologi-

cal factors of prognostic significance in patients diagnosed

with PTMC.

Correspondence: Davide Giordano, Department of Otorhinolaryngology,

University Hospital of Parma, via A. Gramsci 14, 43100 Parma, Italy.

Tel.: 0039 (0)521 703532; fax: 0039 (0)521 290455; e-mail: davidegiord-

[email protected]

OR

IG

IN

AL

AR

TI

CL

E

118 � 2010 Blackwell Publishing Ltd • Clinical Otolaryngology 35, 118–124

Patients and methods

Ethical considerations

The Unified Human Research Committee of the district

of Parma approved the retrospective review of medical

records. The data were collected and analysed in an anon-

ymous form.

Participants and data collection

Charts of patients surgically treated for thyroid cancer in

the Department of Otorhinolaryngology at the tertiary

referral teaching hospital of Parma, during the period

between January 1998 and December 2007, were reviewed

retrospectively. Inclusion criteria were adult age, standard

total thyroidectomy, and histopathological diagnosis of

PTMC according to the World Health Organisation crite-

ria.1 Exclusion criteria were familial cancer, previous thy-

roid or parathyroid surgery, previous neck surgery,

previous neck irradiation.

The patients’ medical records were examined for age,

sex, treatment, clinical and histopathological characteris-

tics, and complications. Preoperative assessments were

based on clinical examination, measurement of serum

thyroid hormones, calcitonin, serum thyroid-stimulating

hormone, serum thyroglobulin, serum anti-thyroglobulin

antibodies, us-FNAB, and flexible fiberoptic laryngoscopy.

All patients were followed up at 3, 6 and 12 months

after surgery, and than yearly. Follow-up consisted of

clinical examination, neck ultrasonography, measurement

of serum thyroid hormones, serum thyroid-stimulating

hormone, serum thyroglobulin, and serum anti-thyro-

globulin antibodies.

The treatment outcome was taken as the endpoint of

statistical analysis, and was established during the last fol-

low-up visit.

Patients who died from cancer-related disease and those

with serum thyroglobulin levels higher than 2 ng ⁄ mL, in

the presence or absence of macroscopically recurrent dis-

ease, where considered to have an unfavourable outcome.

The latter patients were considered to be living with the

disease. Tumour recurrence was defined as new evidence

of regional nodal metastases, local recurrence, and distant

metastases occurring more than 6 months after successful

primary therapy. Foci of recurrent disease were investi-

gated by current imaging modalities.

Favourable outcome was established in the presence of

serum thyroglobulin levels equal to or lower than

2 ng ⁄ mL, in the absence of detectable serum anti-thyro-

globulin antibodies, and the patients free of hormonal

therapy. Such patients were considered to be disease-free.

Statistical analysis

The following characteristics were considered for statisti-

cal analysis:

1 Clinical: age (£45 years versus >45 years), gender (male

versus female), mode of diagnosis (non-incidental versus

incidental), clinically detectable neck metastases at time

of diagnosis (cN0 versus cN+), adjuvant radioiodine abla-

tion therapy (yes versus no).

2 Histopathological: size of tumour at its greatest dimen-

sion (£5 mm versus >5 mm), focality (unifocal versus

multifocal versus bilateral), presence of capsular invasion

(yes versus no), presence of vascular invasion (yes versus

no), histopathological subtype (usual variant, follicular

variant, tall cell variant, sclerosant variant, Hurthle cell

variant), histopathological evidence of autoimmune thy-

roid disease (Hashimoto, Graves, none).

Univariate analysis was performed with the Pearson

Chi-square test, and Fisher Exact test as appropriate. Sta-

tistically significant results obtained at univariate analysis

were submitted to Multivariate Logistic Regression. The

observed differences were statistically significant at a

p < 0.05 level. SPSS software (SPSS 13, Inc. Chicago, IL)

was used for statistical analysis.

Results

Clinical findings

Out of 179 patients diagnosed with papillary thyroid can-

cer, 97 of them (54%) met the inclusion criteria. The

study cohort consisted of 30 males (31%) and 67 females

(69%), with a male ⁄ female ratio of 1 ⁄ 2.2. The mean

patient age at surgery was 52 years (range: 25-80 years,

SD: 14). Patients were younger than 45 in 33 cases

(34%), and older than 45 in 64 cases (66%).

Fifty-one patients (53%) were diagnosed with ‘inciden-

tal’ PTMC, on the basis of routine histopathological

examination of the thyroid specimen after surgery for

benign thyroid disease.

Forty-six patients (48%) were diagnosed with ‘non-

incidental’ PTMC on the basis of preoperative us-FNAB.

In eight of them (8%) metastases in the central compart-

ment neck lymph nodes were detected by ultrasonogra-

phy.

All patients included in the study (100%) underwent

standard total thyroidectomy. Concomitant central com-

partment neck lymph node dissection was performed in

eight (8%) out of 97 patients.

All patients (100%) received L-thyroxin postopera-

tively to suppress thyroid-stimulating hormone (TSH)

secretion.

Papillary thyroid microcarcinoma 119

� 2010 Blackwell Publishing Ltd • Clinical Otolaryngology 35, 118–124

An iodine-131 whole body scan was performed after

surgery. Radioiodine therapy was administered to 73 out

of 97 patients (75%).

The diagnosis of neck lymph node metastases was sig-

nificantly correlated with tumour recurrence (p = 0.025;

OR: 8.3; CI: 1.6–43.3) at univariate analysis.

Table 1 summarises clinical characteristics of the study

group.

Histopathological findings

All patients in the study (100%) had a histopathological

diagnosis of PTMC. The size of the thyroid cancer was

5 mm or less in 38 patients (39%), and larger than 5 mm

in 59 patients (61%).

The histopathological subtypes encountered were the

usual variant in 39 patients (40%), the follicular variant

in 40 (41%), the tall cell variant in 14 (14%), the sclero-

sant variant in three (3%), and the Hurthle cell variant in

one patient (1%).

Papillary thyroid microcarcinoma was unifocal in 63

patients (65%), multifocal in 17 (18%), and bilateral in

17 (18%). Capsular invasion was present in 26 patients

(27%). Vascular invasion was found in 15 patients (16%).

Histopathological evidence of autoimmune thyroid dis-

ease was depicted in 35 of 97 patients, (32%) of which 25

cases suggested Hashimoto disease, while 10 cases sug-

gested Graves disease.

Eight out of 97 patients (8%) underwent central com-

partment neck lymph node dissection. Histopathological

examinations confirmed the presence of neck lymph node

metastases detected preoperatively.

Tumour size >5 mm (p = 0.011; OR: 6.6; CI: 0.8–

54.9), presence of bilateral tumoural foci (p = 0.007, OR:

7.9, CI: 1.9–33.8), presence of capsular invasion

(p = 0.001, OR: 12.7, CI: 2.4–66.3), and presence of

vascular invasion (p = 0.004; OR: 9.8; CI: 2.2–42.4) were

significantly related with tumour recurrence at univariate

analysis. Table 2 summarises histopathological findings of

the study group.

Recurrence and survival

The mean follow-up for the 97 patients enrolled in the

study was 43 months (range 12–120). No incidents of

bilateral vocal fold palsy were registered. The overall

incidences of various complications were: transient uni-

lateral recurrent laryngeal nerve palsy in three patients

(3%), transient hypocalcaemia in 16 patients (17%), and

definitive hypoparathyroidism in five patients (5%).

No cancer-related deaths were registered. The overall

incidence of recurrent disease was 9%. Three patients (3%)

developed thyroid bed recurrence and four (4%) had neck

lymph node recurrence. They successfully underwent revi-

sion surgery, without complications, and then received ra-

dioiodine therapy. These patients achieved complete

Table 1. Univariate analysis of clinical characteristics of the study group

Characteristics Patients (n)

Outcome

p OR (95% CI)Favourable Unfavourable

Age (years) 0.5 NS –

£45 33 29 4 –

>45 64 59 5

Gender 0.5 NS –

Males 30 26 4

Females 67 62 5

Diagnosis 0.3 NS –

Non-incidental 46 40 6

Incidental 51 48 3

cN+ at diagnosis 0.025* 8300 (1.6–43.4)

No 89 83 6

Yes 8 5 3

Radioiodine therapy 0.1 NS –

No 24 24 0

Yes 73 64 9

*p < 0.05.

cN+, clinically positive lymph node; NS, not significant; OR, odds ratio; CI, confidence interval.

120 D. Giordano et al.


clinical remission with negative serum thyroglobulin levels

by the last follow-up visit.

One (1%) had a distant recurrence in the skull. After

radioiodine therapy administration the patient achieved a

complete clinical remission with negative serum thyro-

globulin levels at the last follow-up visit.

Persistently elevated serum thyroglobulin levels without

macroscopic evidence of recurrent disease on imaging

studies were registered in one patient (1%).

The presence of bilateral tumoural foci (p = 0.030, OR:

6.6, CI: 1.2–36.7), and of capsular invasion (p = 0.005,

OR: 11.8, CI: 2.1–66.3) were significantly related to

tumour recurrence at multivariate analysis (Table 3).

Discussion

Comparisons with other studies

As a result of improvements in us-FNAB and refinements

in histopathological criteria, neoplastic thyroid lesions

which are too small to be palpated are diagnosed with

increased frequency.9 PTMC accounts for 54% of patients

diagnosed with thyroid cancer at our institution from

1998 to 2007. Although incidental PTMC still represents

the most common mode of diagnosis in our series, pre-

operative detection of PTMC accounts for an important

amount of patients reported in this series.

The optimal management of PTMC remains contro-

versial, ranging from conservative treatment to more

aggressive options.3,10,11 As the prognosis of PTMC is

Table 3 Multivariate analysis of clinical and histopathological

characteristics of the study group

Characteristics p OR (95% CI)

cN+ at diagnosis 0.74 NS –

Tumour size >5 mm 0.9 NS –

Presence of

bilateral foci

0.03* 6.6 (1.2–36.7)

Presence of capsular

invasion

0.005** 11.752 (2.1–66.3)

Presence of vascular

invasion

0.1 NS –

*p < 0.05; **p < 0.01.

cN+, clinically positive lymph node; NS, not significant; OR,

odds ratio; CI, confidence interval.

Table 2. Univariate analysis of histopathological characteristics of the study group

Characteristics Patients (n)

Outcome

p OR (95% CI)Favourable Unfavourable

Tumour size 0.011* 6.7 (0.8–54.9)

£5 mm 38 38 0

>5 mm 59 50 9

Focality 0.007** 7.9 (1.9–33.7)

Unifocal 63 60 3

Multifocal 17 16 1

Bilteral 17 12 5

Capsular invasion 0.001** 12.7 (2.4–66.2)

No 71 69 2

Yes 26 19 7

Vascular invasion 0.004** 9.8 (2.2–42.4)

No 82 78 4

Yes 15 10 5

Histopathological subtype 0.5 NS –

Usual variant 39 37 2

Follicular variant 40 36 4

Tall cells variant 14 12 2

Sclerosant variant 3 2 1

Hurtle cell variant 1 1 0

Autoimmunity 0.2 NS –

No 62 54 8

Hashimoto 25 24 1

Graves 10 10 0

*p < 0.05; **p < 0.01.

NS, not significant; OR, odds ratio; CI, confidence interval.



considered to be excellent, death or even a low inci-

dence in recurrence of this curable disease become unac-

ceptable. The majority of PTMC recurrences are

locoregional, in the thyroid bed, and in the neck lymph

nodes. Recurrence occurs in 0–11% of patients, mostly

during the first 10 years of follow-up.5,12–14 Rare cases

of distant metastases have also been reported.15 In this

study, the recurrence rate was 9% after a mean

43 month follow-up.

High rates of multifocal and bilateral PTMC are largely

reported, and seem to be associated with increased risk of

locoregional recurrence, when compared with unifocal

cancers.5,11 This is important when planning surgery.

Standard total thyroidectomy, being a more radical pro-

cedure than lobo-isthmusectomy, eliminates the fre-

quently observed multifocal or bilateral disease, thus

reducing the need for further operations. Another major

advantage of this procedure is the possibility of monitor-

ing serum thyroglobulin levels in order to promptly

detect recurrent disease which is very useful since Hay

reported that recurrent disease can be observed even

30 years after treatment.12

Although the prognostic value of lymph node status

with regard to tumour recurrence is well documented

in patients with PTMC 12,16, its significance in predict-

ing survival is debated. In the present series, neck

lymph node metastases have been encountered in the

central compartment. This resulted to be related with

tumour recurrence. Lateral neck lymphadenopathy

would suggest a more extensive involvement. Neverthe-

less, on the basis of our data prognostic relevance of

lateral neck metastases cannot be assessed. We perform

lymph node dissection when there is cervical lymphade-

nopathy detected either preoperatively or intraoperative-

ly, especially when postoperative radioiodine therapy is

planned. Central, or modified lateral neck dissection

when there is more extensive lymphadenopathy, yields

useful informations about the extent of tumour in

PTMC.

Radioiodine therapy was been administered in the

presence of poor prognostic factors such as older age

(>45 years), capsular invasion, multifocal or bilateral

foci, lymph node metastases, and the sclerosant variant.

The rationale for this option consists in the dual bene-

fit of reducing recurrence rates, and facilitating post-

operative follow-up by measuring serum thyroglobulin

levels.9

Some authors 5,14 have reported no prognostic advan-

tage in administrating radioiodine therapy after total thy-

roidectomy for PTMC. In this study, radioiodine therapy

administrated to patients with poor prognostic factors

showed no advantage at univariate analysis.

The prognostic factors of significance in this study have

been grouped into clinical and histopathological. As

reported by Pellegriti et al.,17 the presence of lymph node

metastases at presentation was related with tumour recur-

rence. In the present series, preoperative neck ultrasonog-

raphy detected lymph node metastases with great

accuracy. However, because only eight out of 97 patients

(8%) underwent neck lymph node dissection, it is possi-

ble that the incidence of lymph node metastases was

underestimated. As reported by Pellegriti et al.,17 and

Yamamoto et al.,18 our data showed that the presence of

vascular or capsular invasion was related to tumour

recurrence at statistical analysis.

Concerning dimensions of the tumours, our study

showed that a PTMC >5 mm was related with tumour

recurrence. This is in agreement with other studies 17,19

that correlated progressively increasing frequency of

signs of tumour aggressiveness (multifocality, bilateral-

ism, extrathyroidal invasion, lymph node involvement,

distant metastases) with increasing tumour size at pre-

sentation. In this study, we evaluated the multifocality

and bilateralism of tumoural foci separately. Interest-

ingly, at univariate analysis, our data showed that the

presence of bilateral foci, rather than the multifocality

of PTMC was significantly related with tumour recur-

rence.

Strengths of the study

Predictors of relapse or persisting disease are well estab-

lished in conventional papillary thyroid carcinoma,

although they have not been consistently identified in

PTMC.5

In our opinion, the lack of consensus may be due to

the heterogeneity of the various series presented. In par-

ticular, the varying extents of surgery and patient recruit-

ing over a long time-span may be important features that

can alter the accuracy of statistical analysis.

In this study, analysis of prognostic factors has been

conducted by a retrospective collection of a fairly homo-

geneous consecutive cohort of patients from a single

institution. Given the rarity of this condition the study

involved a relatively small number of patients accrued

over a short time-span. We can therefore confirm a high

degree of uniformity in clinical, ultrasonographic, and

histopathological diagnostic criteria.

Surgical interventions were undertaken by the same

operator (T.F.), using the same technique. This is of some

importance because the extent of surgery may influence

the analysis of prognostic factors. In fact, when lobectomy

is performed much information is lost, because the evalu-

ation of tumoural foci in the controlateral lobe cannot be



assessed. Moreover, the relevance of post-surgery moni-

toring of serum thyroglobulin levels cannot be evalu-

ated.17 As the patients included in our study underwent

standard total thyroidectomies, we were able to com-

pletely evaluate prognostic factors and perform a uniform

statistical analysis.

In this study, the prognosis of patients diagnosed with

PTMC was found to be excellent, with a 100% survival

rate and a minimal surgical-related morbidity. Regard-

less, a non-negligible part of patients (9%) may develop

recurrent disease. Most recurrences can be successfully

treated with further revision neck surgeries, and radioio-

dine therapy 11 albeit recurrent disease may exhibit

more aggressive behaviour.7,12 Revision surgery is rela-

tively safe in the hands of experienced surgeons, but, it

must be kept in mind that this procedure may be tech-

nically difficult. Obviously, avoiding an additional surgi-

cal procedure is preferable both for the patient and the

surgeon.

In agreement with data reported in the literature,4,10

our findings suggest that initial treatment of PTMC

should not differ from treatment of patients affected by

conventional papillary thyroid cancer. Concomitant cen-

tral compartment neck dissection should be performed

when cervical lymphadenopathy is discovered either

preoperatively or intraoperatively. Initial treatment

should be aggressive in order to avoid recurrence of

this potentially curable disease. Standard total thyroid-

ectomy with neck lymph node dissection, may represent

an adequate surgical strategy for the treatment of

patients diagnosed with PTMC. In the presence of poor

prognostic factors, radioiodine therapy should be part

of the treatment, because it facilitates postoperative fol-

low-up.

Limitations of the study

This study has some limitations. This is a retrospective

report on a relatively small number of patients without a

comparison group undergoing a different treatment

option. The fact that there is only one type of treatment

being studied limits the extent to which this study will

answer the question. Moreover, follow-up is relatively

limited, so the recurrence rates reported in the study may

vary in the future.

Given the rarity of this condition and the fact that

multiple treatment strategies exist, it is important that

development of scientifically validated outcome measures

become mandatory for documenting treatment efficacy

and durability. Finally, further randomised studies involv-

ing a greater number of patients with longer follow-up

are warranted to clarify the debate.

Keypoints

• Since the prognosis of papillarythyroid micro-

carcinoma is considered to be excellent, death or

even a low incidence in recurrence of this curable

disease become unacceptable. Aggressive treatment

may be justified depending on the presence or

absence of prognostic risk factors.• Standard total thyroidectomy, being a more radical

procedure than lobo-isthmusectomy, eliminates the

frequently observed multifocal or bilateral disease.• Lymph node dissection should be performed when

cervical lymphadenopathy is detected either preopera-

tively or intraoperatively, especially when postopera-

tive radioiodine therapy is planned.• Radioiodine therapy, administered in the presence of

poor prognostic factors, may play a role in reducing

recurrence rates, and facilitating postoperative follow-

up by measuring serum thyroglobulin levels.• On multivariate analysis the presence of bilateral

tumoral foci and the presence of capsular invasion

were significantly related to tumour recurrence.

Conflict of interest

None to declare.

References

1 Hedinger C., Williams E.D. & Sobin L.H., eds. (1988) Histologic

typing of thyroid tumors. In International Histological Classifica-

tion of Tumors, No. 11, pp. 1–18. World Health Organization,

Geneva.

2 Bramley M.D. & Harrison B.J. (1996) Papillary microcarcinoma

of the thyroid gland. Br. J. Surg. 83, 319–325

3 Ito Y., Uruno T., Nakano K. et al. (2003) An observation trial

without surgical treatment inpatients with papillary microcarci-

noma of the thyroid. Thyroid 13, 381–387

4 Chow S.M., Law S.C.K., Chan J.K.C. et al. (2003) Papillary mi-

crocarcinoma of the thyroid – prognostic significance of lymph

node metastasis and multifocality. Cancer 98, 31–40

5 Mazzaferri E.L. & Jhiang S.M. (1994) Long term impact of ini-

tial surgical and medical therapy of papillary and follicular thy-

roid cancer. Am. J. Med. 97, 418–428

6 Ito Y., Tomoda C., Uruno T. et al. (2004) Papillary microcarci-

noma of the thyroid: how should it be treated? World J. Surg.

28, 1115–1121

7 Rodriguez J.M., Moreno A., Parrilla P. et al. (1997) Papillary

thyroid microcarcinoma: clinical study and prognosis. Eur.

J. Surg. 163, 255–259

8 Piersanti M., Ezzat S. & Asa S.L. (2003) Controversies in papillary

microcarcinoma of the thyroid. Endocrin. Pathol. 14, 183–191

9 Sakorafas G.H., Giotakis J. & Stafyla V. (2005) Papillary thyroid

microcarcinoma: a surgical perspective. Cancer Treat. Rev. 31,

423–438



10 Orsenigo E., Beretta E., Fiacco E. et al. (2004) Management of

papillary microcarcinoma of the thyroid gland. EJSO 30, 1104–

1106

11 Baudin E., Travagli J.P., Ropers J. et al. (1998) Microcarcinoma

of the thyroid gland. Cancer 83, 553–559

12 Hay I.D., Grant C.S., van Heerden J.A. et al. (1992) Papillary

thyroid microcarcinoma. A study of 535 cases observed in a

50 year period. Surgery 112, 1139–1146

13 Hubert J.P., Kiernan P.D., Beahrs O.H. et al. (1980) Occult pap-

illary carcinoma of the thyroid. Arch. Surg. 115, 394–398

14 Appetecchia M., Scarcello G., Pucci E. et al. (2002) Outcome

after treatment of papillary thyroid microcarcinoma. J. Exp.

Clin. Cancer Res. 21, 159–164

15 Strate S.M., Lee E.L. & Childers J.H. (1984) Occult papillary car-

cinoma of the thyroid with distant metastases. Cancer 54, 1093–

1100

16 Sugitani I. & Fujimoto Y. (1999) Symptomatic versus asymp-

tomatic papillary thyroid microcarcinoma: a retrospective analy-

sis of surgical outcome and prognostic factors. Endocr. J. 46,

209–216

17 Pellegriti G., Scollo C., Lumera G. et al. (2004) Clinical behavior

and outcome of papillary thyroid cancers smaller than 1.5 cm in

diameter: study of 299 cases. J. Clin. Endocrinol. Metab. 89,

3713–3720

18 Yamamoto Y., Maeta T., Izumi K. et al. (1990) Occult papillary

carcinoma of the thyroid. A study of 408 autopsy cases. Cancer

65, 1173–1179

19 Roti E., Rossi R., Trasforini G. et al. (2006) Clinical and histo-

logical characteristics of papillary thyroid microcarcinoma:

results of a retrospective study in 243 patients. J. Clin. Endocri-

nol. Metab. 91, 2171–2178



treatment and prognostic factors of papillary thyroid microcarcinoma

Documents