Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma 2018 Update
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Szkolenie podyplomowe/Postgraduate education
Endokrynologia Polska
DOI: 10.5603/EP.2018.0014
Tom/Volume 68; Numer/Number 1/2018
ISSN 0423–104X
Guidelines of Polish National Societies Diagnostics
and Treatment of Thyroid Carcinoma 2018 Update
Polish Endocrine Society, Polish Society of Oncology, Polish Thyroid Association,
Polish Society of Pathologists, Society of Polish Surgeons, Polish Society of
Surgical Oncology, Polish Society of Clinical Oncology, Polish Society of
Radiation Oncology, Polish Society of Nuclear Medicine, Polish Society of
Paediatric Endocrinology, Polish Society of Paediatric Surgeons, Polish Society
of Ultrasonography
Barbara Jarząb1, Marek Dedecjus2, Dorota Słowińska-Klencka3, Andrzej Lewiński4, Zbigniew Adamczewski4,
Ryszard Anielski5, Maciej Bagłaj6, Agata Bałdys-Waligórska7, Marcin Barczyński8, Tomasz Bednarczuk9,
Artur Bossowski10, Monika Buziak-Bereza7, Ewa Chmielik11, Andrzej Cichocki12, Agnieszka Czarniecka13,
Rafał Czepczyński14, Janusz Dzięcioł15, Tomasz Gawlik1, Daria Handkiewicz-Junak1,
Kornelia Hasse-Lazar1, Alicja Hubalewska-Dydejczyk7, Krystian Jażdżewski16, Beata Jurecka-Lubieniecka1,
Michał Kalemba1, Grzegorz Kamiński17, Małgorzata Karbownik-Lewińska18, Mariusz Klencki3,
Beata Kos-Kudła19, Agnieszka Kotecka-Blicharz1, Aldona Kowalska20, Jolanta Krajewska1,
Aleksandra Kropińska1, Aleksandra Kukulska1, Emilia Kulik1, Andrzej Kułakowski21, Krzysztof Kuzdak22,
Dariusz Lange11, Aleksandra Ledwon1, Elżbieta Lewandowska-Jabłońska1, Katarzyna Łącka14,
Barbara Michalik1, Anna Nasierowska-Guttmejer23, Janusz Nauman9, Marek Niedziela24,
Ewa Małecka-Tendera25, Małgorzata Oczko-Wojciechowska1, Tomasz Olczyk1, Ewa Paliczka-Cieślik1,
Lech Pomorski26, Zbigniew Puch1, Józef Roskosz1, Marek Ruchała14, Dagmara Rusinek1,
Stanisław Sporny27, Agata Stanek-Widera11, Zoran Stojcev28, Aleksandra Syguła1, Anhelli Syrenicz29,
Sylwia Szpak-Ulczok1, Tomasz Tomkalski30, Zbigniew Wygoda1, Jan Włoch31, Ewa Zembala-Nożyńska11
1
Nuclear Medicine and Endocrine Oncology Department; M. Sklodowska-Curie Memorial Institute — Cancer Centre, Gliwice
Branch, Gliwice, Poland
2
Endocrine Oncology and Nuclear Medicine Clinic, M. Sklodowska-Curie Memorial Institute — Cancer Centre, Warsaw, Poland
3
Department of Morphometry of Endocrine Glands, Chair of Endocrinology, Medical University, Lodz
4
Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Polish Mother’s Memorial Hospital — Research
Institute, Lodz
5
Diagnostic and Therapeutic Unit, Boni Fratres Hospital; Cracow; Department of Disaster and Emergency Medicine Jagiellonian
University Medical College, Cracow
6
Department of Paediatric Surgery and Urology, Wroclaw Medical University, Wroclaw
7
Department of Endocrinology, Jagiellonian University Medical College, Cracow
8
Department of Endocrine Surgery, Third Chair of General Surgery, Jagiellonian University Medical College, Cracow
9
Department of Endocrinology and Internal Medicine, Medical University, Warsaw
10
Department of Paediatrics, Endocrinology, Diabetology with Cardiology Divisions, Medical University of Bialystok, Bialystok
11
Tumour Pathology Department, M. Sklodowska-Curie Memorial Institute — Cancer Centre, Gliwice Branch, Gliwice, Poland
12
Department of Surgical Oncology, M. Sklodowska-Curie Memorial Institute — Cancer Centre, Warsaw, Poland
13
Department of Oncological and Reconstructive Surgery M. Sklodowska-Curie Memorial Institute — Cancer Centre, Gliwice
Branch, Gliwice, Poland
14
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan
15
Department of Human Anatomy, Medical University of Bialystok, Bialystok
16
Genomic Medicine, Medical University of Warsaw, Warsaw
17
Department of Endocrinology and Isotope Therapy, Military Institute of Medicine, Warsaw
18
Department of Oncological Endocrinology, Medical University of Lodz
19
Department of Pathophysiology and Endocrinology, Division of Endocrinology, Medical University of Silesia, Katowice
20
Endocrinology Clinic, Holycross Cancer Centre, Kielce
21
Retired Professor of oncological surgery
22
Department of Endocrinological, General and Oncological Surgery, Medical University, Lodz
Barbara Jarząb, Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Institute — Cancer Centre,
Gliwice Branch, Gliwice, Wybrzeze Armii Krajowej 15, 44–101 Gliwice, tel.: +48 32 278 93 01, 93 39; e-mail: barbara.jarzab@io.gliwice.pl
34Endokrynologia Polska 2018; 69 (1)
23
Department of Pathomorphology, Central Clinical Hospital of MSWiA, Warsaw
24
Department of Paediatric Endocrinology and Rheumatology, 2nd Chair of Paediatrics, Poznan University of Medical Science,
Poznan
25
Department of Paediatrics and Paediatric Endocrinology, School of Medicine in Katowice, Medical University of Silesia, Katowice
26
Department of General and Oncological Surgery, Medical University, Lodz
27
Department of Dental Pathology, Medical University, Lodz
28
Oncological Surgery Clinic, Medical University of Silesia, Katowice
29
Department of Endocrinology, Metabolic Diseases and Internal Diseases, Pomeranian Medical University, Szczecin
30
Department of Endocrinology, Diabetology and Internal Diseases, Lower Silesian Hospital, Wroclaw
31
Specialistic Private Practice, Gliwice
Significant advances have been made in thyroid can- mendations that would be updated in the future (the
cer research in recent years, therefore relevant clinical next updating round being foreseen in 2018). Profes-
guidelines need to be updated. The current Polish sor Dedecjus led this discussion and later continued it
guidelines “Diagnostics and Treatment of Thyroid on-line, recording all changes proposed. At the same
Carcinoma” have been formulated at the “Thyroid meeting it was decided to supply the Polish recom-
Cancer and Other Malignancies of Endocrine Glands” mendations with medical justification, in line with the
conference held in Wisła in November 2015 [1]. Evidence-Based Medicine (EBM) approach [2]. This task
The Chair of the Scientific Committee, Professor Bar- was assigned to Professor Barbara Jarzab, who within
bara Jarzab, invited all scientific societies engaged in her team of collaborators found a group of co-authors
clinical management of thyroid carcinoma to delegate for this work. This group of co-authors consisted of the
their official representatives to participate as authors in following experts: Daria Handkiewicz-Junak, Agnieszka
updating these guidelines. In response, the following Czarniecka, Agata Bałdys-Waligórska, Ewa Chmie-
scientific societies prepared and accepted the updated lik, Jolanta Krajewska, Dagmara Rusinek, Małgorzata
guidelines: the Polish Endocrine Society, Polish Society Oczko-Wojciechowska, Beata Jurecka-Lubieniecka,
of Oncology, Polish Thyroid Association, Polish Soci- Tomasz Gawlik, Kornelia Hasse-Lazar, Michał Kalemba,
ety of Pathologists, Society of Polish Surgeons, Polish Agnieszka Kotecka-Blicharz, Aleksandra Kropińska,
Society of Surgical Oncology, Polish Society of Clinical Aleksandra Kukulska, Aleksandra Ledwon, Barbara
Oncology, Polish Society of Radiation Oncology, Polish Michalik, Tomasz Olczyk, Ewa Paliczka-Cieślik, Zbig-
Society of Nuclear Medicine, Polish Society of Paediatric niew Puch, Józef Roskosz, Aleksandra Syguła, Sylwia
Endocrinology, Polish Society of Paediatric Surgeons, Szpak-Ulczok, Zbigniew Wygoda, Emilia Kulik, Elżbieta
and the Polish Society of Ultrasonography. Lewandowska-Jabłońska, and Ewa Zembala-Nożyńska.
The Guidelines, prepared in a short time, were pub- It was decided to base the Polish recommendations on
lished in January 2016 by the Polish Journal of Endo- the ADAPTE system [3] used by the European Thyroid
crinology. However, in several instances, not only their Association (ETA) in their documents published over
style and clarity asked for improvement, but also new the years 2013–2017 [2, 3]. Within this system, each
developments and new evidence-based medical data recommendation is evaluated according to its strength
required reflection and modification of some of the rec- (Strength of Recommendation; SoR) — within grades
ommended procedures. Thus the need arose to update G1; or G2; (Table I), and an additional grade to evaluate
the entire content of these guidelines [1]. the quality of its supporting medical evidence. Thus, the
At the initiative of Professor Andrzej Lewinski, National ETA applies two evaluation criteria, with additional sub- PODYPLOMOWE
SZKOLENIE
Consultant in Endocrinology and President of the Polish divisions (cf. Table I). Within the Quality of Evidence
Thyroid Association, the Thyroid Cancer Guidelines (QoE) criterion, we have added a third, lowest, grade if
Group was formed in January 2017. This group, which our recommendation is based on the Polish consensus
included Professor Marek Ruchała, President of the — it is then labelled QoE: PolCon.
Polish Endocrine Society, and Professor Barbara Jarząb, We have also strived to supply each recommendation
President of the Polish Group for Endocrine Tumours with a reference to relevant literature, if available.
(PGNE), authorised Professor Marek Dedecjus, Presi- References were taken from a set of publications
dent of the Polish Society of Organ Biopsy, to invite as gathered by ATA experts [4] who applied EBM rules
co-authors recognised authorities in their relevant in their selection. If the recommendation relevant to
disciplines, to collaborate in updating these guidelines. the Polish conditions is covered by the recommenda-
The list of these experts as co-authors was approved by tions published by ATA, we quote the number of the
the whole collaborating group. relevant ATA recommendation. For example, ATA
The Authors Group met in Warsaw on April 26, 2017. GL R5 indicates that the subject is dealt with in ATA
At this meeting recommendations were selected which recommendation number five (R5). Those interested
urgently required correction and updating and recom- should refer to the ATA recommendations [4] and ATA
35Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma 2018 Update Barbara Jarząb et al.
Table I. Evidence-Based Medicine (EBM) system evaluating the strength of a recommendation [2, 3] (modified)
Strength of Recommendation (SoR) Clinical Interpretation
G1 Strong recommendation (for or against) concerns all This recommendation may be applied without any doubt. It will benefit
patients in most clinical conditions. Abiding by this most patients in practically all cases
recommendation is evidently advantageous to the patient
G2 Weak recommendation (for or against); an optimal This grade of a recommendation requires that analysis be performed by the
management may differ depending on the epidemiology acting clinician whether the patient is likely to benefit from its application. In
or on the patient’s clinical workout. Application of this this analysis the quality of supporting medical data needs to be considered
recommendation is to be decided by the acting clinician as well as the patient’s condition. The acting clinician should also correctly
appraise his or her competence to apply this recommendation
Quality of evidences (QoE)
+++ High quality data obtained from randomized clinical trials (RCT) or from unequivocal results of retrospective analyses directly concerning
the subject of recommendation
++ Moderate quality data obtained from studies judged by the EBM approach to be methodologically deficient or the conclusions of which
are equivocal or indirect
+ Low quality data based on case studies or on clinical observations only
PolCon Lack of direct data with regard to the conditions in Poland. The statement is based on a consensus reached via discussion among Polish
experts (the number of Polish experts in support of this statement is given in parentheses)
recommendations referring to medullary thyroid cancer 1.5. RET germline mutation carriage and/or high
(ATA GL MTC) [6]. serum calcitonin (Ct) concentration [6].
We also wish to remind the reader that the Polish rec- SoR: G1; QoE: +++; ATA GL MTC
ommendations established in November 2015 were de- 1.6. History of exposure to previous neck radiation [7].
veloped as a consensus based on the earlier-published SoR: G1; QoE: +++
Recommendations of the American Thyroid Association 1.7. Other suspicion of thyroid disease.
(ATA). These meticulously prepared recommendations SoR: G1; QoE: PolCon 62/62
(ATA GL) contained full references to published medical 1.8. Neck ultrasound is not a screening tool [8].
evidence. At the time, the Polish experts believed that SoR: G2; QoE: PolCon 62/62
reliance on ATA recommendations would be sufficient, 1.9. There is no sufficient evidence to recommend or
but a consensus should be reached as to which of these not to recommend screening neck ultrasound in
recommendations would apply in the Polish conditions. persons with a risk of familiar differentiated thy-
In our current update of the Polish recommendations roid cancer (DTC) arising from the follicular cell.
we were, however, aware that any oncological recom- SoR: G2; QoE: PolCon 62/62
mendations must be based on medical evidence. In the 1.10. Neck ultrasound together with physical ex-
currently published Update of these Recommendations amination is sufficient to exclude nodular goitre.
we were able to extend our 2016 Recommendations SoR: G1; QoE: PolCon 62/62
by adding the relevant medical evidence. We are also 2. Other useful diagnostic examinations in nodular
aware that future work on the Polish Recommendations goitre include:
will enable further, more accurate medical evidence 2.1. In every case of nodular goitre: TSH. If TSH is
PODYPLOMOWE
relevant to the Polish conditions, to be included. abnormal, assessment of serum fT4 or fT4/fT3
SZKOLENIE
is recommended [4].
I. Diagnostics of thyroid cancer SoR: G1; QoE: ++; ATA GL R2
2.2. Anti-thyroid peroxidase antibodies (TPOAb)
1. Indications for thyroid ultrasound [5]: and other anti-thyroid antibodies, depending
1.1. Nodular goitre or palpable thyroid nodule on experience of the particular centre.
SoR: G1; QoE: +++; ATA GL R6 SoR: G2; QoE: PolCon 61/62
1.2. Neck lymph node enlargement not related to 2.3. Assessment of serum calcitonin (Ct) concentra-
infection. SoR: G1; QoE: PolCon 62/62 tion is useful in diagnostics of nodular goitre,
1.3. Thyroid enlargement without any palpable but it is not recommended in every case, due
tumour. to low risk of medullary thyroid cancer (MTC).
SoR: G1; QoE: PolCon 62/62 However, Ct assessment is useful [6]:
1.4. Thyroid lesion detected by ultrasonography SoR: G2; QoE: ++; PolCon 62/62; ATA GL 4
performed due to other reasons or by other 2.3.1. If there is clinical suspicion of MTC, and in RET
imaging tools. mutation carriers [6].
SoR: G1; QoE: +++; ATA GL R6 SoR: G1; QoE: +++
36Endokrynologia Polska 2018; 69 (1)
2.3.2. To exclude MTC prior to planned thyroid sur- 3.1.9. Paresis of recurrent laryngeal nerves,
gery (see par. 3.3.1). particularly unilateral.
SoR: G2; QoE: PolCon 62/62 SoR: G1; QoE: + / PolCon 62/62
2.4. Assessment of serum thyroglobulin (Tg) is 3.2. Sonographic [5]:
not recommended, as it provides no essen- 3.2.1. Sonographic features suggesting prob-
tial information on suspected malignancy in ability of thyroid cancer metastases
a thyroid lesion. to cervical lymph nodes (see also par.
SoR: G1; QoE: ++; ATA GL R3 and R34 11.2.2) [1, 9].
2.5. 99mTc thyroid scan is recommended only if TSH SoR: G1; QoE: +++
is close to, or below the lower limit of normal 3.2.2. Thyroid capsule infiltration with or
range, in a patient with nodular goitre [9]. without infiltration of adjacent neck
SoR: G2; QoE: ++ structures.
2.6. Elastography is not routinely required in the SoR: G1; QoE: ++
assessment of thyroid lesions; however, it may 3.2.3. Microcalcifications inside the thyroid
be helpful in the selection of a thyroid lesion lesion.
amendable to fine-needle aspiration biopsy SoR: G1; QoE: +++ / PolCon 62/62
(FNAB) [10–12]. 3.2.4. Solid, hypoechoic tumour pattern.
SoR: G2; QoE: PolCon 62/62 SoR: G1; QoE: +++
2.7. MRI and CT are not routinely used in the 3.2.5. Tumour shape (taller than wider).
evaluation of thyroid nodules [9]. SoR: G1; QoE: + / PolCon 62/62
SoR: G1; QoE: PolCon 62/62 3.2.6. Irregular tumour margins.
2.8. FDG-PET-CT is not recommended in differen- SoR: G1; QoE: + / PolCon 62/62
tial diagnostics of thyroid nodules [9]. 3.2.7. Increased tumour vascularisation.
SoR: G1; QoE: +; ATA GL R5 and R18 SoR: G1; QoE: +
3. Features of increased malignancy risk in a thyroid IMPORTANT NOTICE! Sonographic
lesion, evaluated prior to FNAB: appearance of follicular neoplasms,
3.1. Clinical including thyroid carcinoma, often
3.1.1. Lymph node and/or distant metastases does not present the above-mentioned
(see par. 11.2) [8]. sonographic risk features — lesions have
SoR: G1; QoE: ++; ATA GL R9-R8 regular margins, they could be isoechoic
3.1.2. History of previous neck exposure to without microcalcifications.
radiation [7]. SoR: G1; QoE: +
SoR: G1; QoE: +++; ATA GL R2 and R20 4. Indications for FNAB of a thyroid lesion:
3.1.3. History of familial thyroid cancer (it 4.1. Thyroid lesion ≥ 1 cm in at least one dimen-
concerns MTC) [8]. sion and ≥ 5 mm in other dimensions, if
SoR: G2; QoE: +; ATA GL R1 there are no other lesions showing a higher
3.1.4. Clear tumour growth. Note that benign risk of malignancy (evaluated according to
lesions may grow at the same rate [5–8]. rules given in par. 3), which require FNAB
SoR: G1; QoE: PolCon 62/62 first — see par. 5 concerning multiple thyroid
IMPORTANT NOTICE: Rapid lesion lesions. PODYPLOMOWE
SZKOLENIE
enlargement (within a few weeks) may SoR: G1; QoE: PolCon 62/62; ATA GL R7 and
strongly suggest anaplastic thyroid cancer, R8
requiring urgent consultation by an oncol- 4.2. A thyroid lesion below 1 cm in the greatest di-
ogist and/or oncological endocrinologist. mension if clinical or sonography risk features
SoR: G1; QoE: PolCon 62/62 of malignancy are present and reliable FNAB
3.1.5. Hard nodule attached to neighbouring is possible.
tissues. SoR: G1; QoE: PolCon 62/62; ATA GL R8
SoR: G1; QoE: + 4.2.1. Sonography follow-up of a thyroid le-
3.1.6. Tumour over 4 cm in diameter. sion below 1 cm in the greatest dimen-
SoR: G1; QoE: + / PolCon 62/62; ATA GL R20 sion every 3–6 months, depending on
3.1.7. Nodule occurrence before 20 years of age. clinical risk, and postponement of FNAB
SoR: G1; QoE: + / PolCon 62/62 until tumour diameter reaches 1 cm, is
3.1.8. Nodule occurrence after 60 years of age. acceptable.
SoR: G1; QoE: + / PolCon 62/62 SoR: G1; QoE: PolCon 62/62; ATA GL R8
37Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma 2018 Update Barbara Jarząb et al.
4.3. Thyroid lesions, regardless of their diameter, if ultrasound examination, subject to rules given
lymph node or distant metastases from thyroid in par. 3, 4, and 5.
cancer, high calcitonin concentration or RET SoR: G1; QoE: ++
mutation carriage are present if reliable FNAB 6.3. Hot lesions, detected by FDG-PET, should
is possible. be initially evaluated by ultrasound. Further
SoR: G1; QoE: PolCon 62/62 management depends on the result of this ul-
5. Indications for FNAB in multifocal thyroid lesions [9]: trasound examination, subject to rules given in
5.1. The risk of thyroid cancer in a patient with par. 3, 4, and 5. However, FNAB of a hot thyroid
multifocal thyroid lesions and a single thyroid lesion on FDG-PET is obligatory [15, 16].
lesion are comparable [8]. SoR: G1; QoE: + / PolCon 62/62 ATA GL R5
SoR: G1; QoE: +++; ATA GL R21 6.4. Hot lesions, detected incidentally by 99mTcMIBI
5.2. The optimal strategy assumes selection of (a heart scan), should be initially evaluated by
thyroid lesions for FNAB depending on their ultrasound. Further management depends
malignancy risk (lesions presenting the highest on the result of this ultrasound examination,
risk features should undergo biopsy first) and subject to rules given in par. 3, 4, and 5.
carrying out biopsy in all lesions in which it is SoR: G1; QoE: ++ / PolCon 62/62
indicated, or in at least four lesions with the 7. FNAB of a thyroid lesion is not advised:
highest clinical and sonography risk features. 7.1. In lesions less than 5 mm in all diameters FNAB
SoR: G1; QoE: ++/PolCon 62/62 is not routinely recommended due to low clini-
5.3. If a negative FNAB result is obtained in all cal risk with exceptions given in par. 4.3.
lesions, selected as above, exclusion of malig- SoR: G1; QoE: PolCon 62/62
nancy risk may be considered with reasonable 7.2. In pure cystic lesions, according to sonography
probability. In cases of sequential biopsy proce- criteria.
dures all above-determined biopsy sites should SoR: G1; QoE: ++; ATA GL R8
be investigated within the following 3–6-month 7.3. In lesions showing spongiform appearance on
period, depending on risk assessment. ultrasound in at least 50% of the lesion volume.
SoR: G1; QoE: + / PolCon 62/62 SoR: G2; QoE: + / PolCon 62/62; ATA GL R8
5.4. If thyroid lesions are multiple, they have 7.4. In lesions that appear as autonomous on the
a similar sonographic pattern and do not pre- thyroid scan (so-called “hot nodule”) [9].
sent significant features of malignancy, FNAB SoR: G2; QoE: ++; ATA GL 22
of the biggest lesion only is acceptable [5]. 8. Cytological classification of lesions subjected to
SoR: G1; QoE: + / PolCon 62/62 FNAB should be based on NCI guidelines, referred
5.5. If diffuse changes in thyroid echostructure to the Bethesda System for Reporting Thyroid Cyto-
are present, indications for FNAB are relative pathology called “Bethesda Classification” in these
and FNAB may be taken only from a single “Recommendations” (Table II) [17, 18].
localisation. In such cases the National Can- SoR: G1; QoE: ++ / PolCon 62/62; ATA GL R9
cer Institute (NCI) accepts biopsy without 9. FNAB — execution and technique.
sonography guidance, particularly if thyroid 9.1. Requirements for ultrasound-guided FNAB
is clearly enlarged [9]. [5, 9].
PODYPLOMOWE
SoR: G1; QoE: + / PolCon 62/62 SoR: G1; QoE: PolCon 62/62; ATA GL R8 and R10
SZKOLENIE
5.6. Elastography may be helpful in the selection 9.1.1. Concerning all FNAB procedures [5].
of a lesion for FNAB; however, it is not obliga- SoR: G1; QoE: PolCon 62/62; ATA GL R6
tory [10–14] 9.1.2. Ultrasound-guidance is recommended
SoR: G1; QoE: PolCon 62/62 during biopsy of any thyroid lesion. It
6. Indications for FNAB after diagnosis of thyroid le- is not required in general thyroid en-
sion by other imaging modalities. largement with diffuse echostructure
6.1. Thyroid lesions, incidentally detected in ul- alterations with no clear lesions.
trasound performed for other reasons (such SoR: G1; QoE: PolCon 62/62
as Doppler ultrasound of carotid arteries), are 9.1.3. Ultrasound-guided FNAB is always re-
subject to rules given in par. 3, 4, and 5. quired if FNAB is repeated due previous
SoR: G1; QoE: ++ / PolCon 62/62 non-diagnostic result [4, 5].
6.2. Thyroid lesions, detected by CT or MRI, should SoR: G1; QoE: PolCon 62/62; ATA GL R10
be initially evaluated by ultrasound. Further 9.2. Written, informed consent is always required.
management depends on the result of this SoR: G1; QoE: PolCon 62/62
38Endokrynologia Polska 2018; 69 (1)
Table II. The 2017 Bethesda System for Reporting Thyroid Cytopathology [17, 18]
Category Recommended Risk of Risk of malignancy The risk of Cytological diagnoses included in
terminology malignancy considering NIFTP malignancy a particular category and other
as postoperative in Polish comments
outcome patients
I Nondiagnostic 5–10 5–10 5–10%* Clinical context should be considered
or
unsatisfactory
II Benign 0–3 0–3 < 1%* Nodular goitre
Thyroiditis, including chronic
inflammations
Hyperplastic nodule
Colloid nodule (lots of colloid, sufficient
cellularity)
Cytological findings suggest colloid nodule
(lots of colloid, insufficient cellularity)
Thyroid cyst
III Atypia of ~10–30 6–18 2.4–5.2% This category should be used in rare
undetermined cases when it is not possible to state a
significance precise cytological diagnosis
(AUS)
or Follicular
lesion of
undetermined
significance
IV Follicular 25–40 10–40 8.2–19% At least 25% of lesions belonging to
neoplasm this category are not neoplastic tumors
or (hyperplastic nodules, inflammation).
Suspicious This category should not be diagnosed
for a follicular when nuclear features of papillare thyroid
neoplasm cancer are present
V Suspicious for 50–75 45–60 75% This category involves:
malignancy — papillary thyroid cancer
— medullary thyroid cancer
— lymphoma
— metastatic carcinoma
— anaplastic thyroid cancer/vascular
sarcoma due to the presence of necrotic
tissues
VI Malignant 97–99 94–96 95–100%* This category involves:
— papillary thyroid cancer
— medullary thyroid cancer
— lymphoma
— metastatic carcinoma
— anaplastic thyroid cancer/ vascular PODYPLOMOWE
SZKOLENIE
sarcoma
*lack of Polish data — data given in the table are NCI data
10. Information, which should be provided in the re- 10.6. Data related to patient history (any primary
ferral form. cancer, exposure to neck irradiation, concomi-
10.1. First name, last name, and address of the refer- tant thyroid disorders).
ring physician. 10.7. Information related to administered treatment,
10.2. First name, last name of the patient or patient’s if relevant to interpretation of cytological
identification number. results.
10.3. Patient’s sex and age. 10.8. Data about any previous FNAB (date, lesion
10.4. Initial clinical diagnosis. location, diagnosis).
10.5. Lesion location and diameter. SoR: G1; QoE: PolCon 62/62
39Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma 2018 Update Barbara Jarząb et al.
11. Selection of lesion for FNAB: 12.3.4. Cyst liquid only.
11.1. The selection of the lesion for FNAB is based SoR: G1; QoE: ++
on ultrasound according to the following rules 13. Qualitative assessment of FNAB — clinical and
[8, 9]. radiological aspects [20].
11.1.1. The main criterion is not lesion diameter 13.1. Solid thyroid nodules.
but the presence of clinical and sono- 13.1.1. With cytological cellular features indi-
graphic features of malignancy risk [9]. cating suspicion of malignancy (cellular
SoR: G1; QoE: +++; ATA GL R8 atypia), a variant of Bethesda, class III
11.1.2. A large nodule requires several biopsies category. Diagnosis of cells suspected of
taken from different locations within the malignancy in a cytological smear must
nodule [19]. be given in the final FNAB report, even
SoR: G1; QoE: + / PolCon 62/62; ATA GL R if the number of cells is small (see point
11.1.3. A cyst should be drained. If any of its 12.3.2, 14.3.4.2.) [20].
solid part is present, FNAB is required. SoR: G1; QoE: + / PolCon 62/62
The liquid obtained by FNAB may un- 13.1.2. With inflammation [17, 19].
dergo centrifuging and precipitation to In this case the aspirate may contain
prepare a smear [5]. fewer follicular cells; therefore, fulfill-
SoR: G1; QoE: PolCon 62/62 ing the criterion of par. 12.3.1 is not
11.2. In the case of neck lymph node enlargement [5]. absolutely crucial. The criterion given in
11.2.1. If a thyroid nodule is accompanied by point 12.3.2 should then be considered.
the presence of a suspicious lymph SoR: G2; QoE: +
node, the lymph node should also un- 13.1.3. With large colloid amount.
dergo FNAB. The presence of a large colloid amount
SoR: G1; QoE: ++ is a reliable proof of a tumour being
11.2.2. Sonography features of suspected meta- benign, so FNAB may be diagnostic
static lymph node are: transversal diam- despite its poor cellularity [17].
eter greater than 5 mm, loss of hilar ar- SoR: G2; QoE: + / PolCon 62/62
chitecture, heterogenic echotexture with 13.1.4. With follicular hypertrophy and small
cystic areas, round shape, peripheral or colloid amount.
mixed vascularity, microcalcifications [9]. Criterion 12.3.1 is optimal, particularly
SoR: G1; QoE: +++ if fulfilled in one smear. However, ex-
12. Representativeness of FNAB. cessively restrictive requirements re-
12.1. Qualitative and quantitative assessment of the garding sample cellularity and quality
representativeness of a cytological aspirate is may increase the percentage of non-
obligatory [17]. diagnostic FNABs to 20% or higher [17].
SoR: G1; QoE: PolCon 62/62 SoR: G1; QoE: PolCon 62/62
12.2. Qualitative evaluation is expressed dichoto- 13.2. Cysts.
mously as satisfactory or unsatisfactory and 13.2.1. Pure cyst (sonography criterion): the
should consider the differences related to le- risk of cancer 1–4% [5, 9].
PODYPLOMOWE
sion type (see par. 13.1) [17]. Aspiration of a pure cyst very rarely
SZKOLENIE
SoR: G1; QoE: PolCon 62/62 involves cancer diagnosis. The use of
12.3. The following grading of quantitative assess- criterion 12.3.4 makes a clinically useful
ment is recommended: report possible. Adding the description
12.3.1. Diagnostic material: at least five groups “non-diagnostic material to fully exclude
of cells containing at least 10 well- appearance of cystic cancer ” may be
preserved follicular cells. It is necessary considered.
to consider the clinical context when SoR: G1; QoE: +
preparing this assessment. 13.2.2. According to this consensus, in such
SoR: G1; QoE: PolCon 62/62 cases FNAB of the solid part of the
12.3.2. Diagnostic material, in spite of its poor nodule should be performed.
cellularity (see par. 14.1). SoR: G1; QoE: PolCon 62/62
SoR: G1; QoE: PolCon 62/62 14. Recommended diagnostic terminology.
12.3.3. Non-diagnostic material, due to lack of, It is recommended that six classes of cytological
or small number of follicular cells. diagnosis be used, according to the Bethesda Clas-
SoR: G1; QoE: PolCon 62/62 sification [18, 20].
40Endokrynologia Polska 2018; 69 (1)
14.1. Non-diagnostic FNAB (Bethesda class I). equivocally indicate their benign char-
14.1.1. The FNAB result is defined as non-diag- acter or even if malignancy is suspected.
nostic if it does not fulfil representative- Pathologist’s comment is necessary.
ness criteria (see par. 12), considering the SoR: G1; QoE: PolCon 62/62
clinical-radiological context (see par. 13). 14.3.4. In many centres this category is divided
SoR: G1; QoE: PolCon 62/62; ATA GL R9 to two subcategories [4, 17]:
14.1.2. Non-diagnostic FNAB may be related to 14.3.4.1 The first one is a “follicular
three causes [5]: lesion of undetermined signifi-
14.1.2.1. Inadequate cellularity. cance — FLUS” — these lesions
14.1.2.3. Lack of follicular cells. are characterised by a highly
14.1.2.3. Incorrect sample fixation and cellular smear, the presence of
storage. rosette architecture, variability
SoR: G1; QoE: ++ of eosinophilic cytoplasm, and
14.2. Benign nodule (Bethesda class II). paucity of colloid.
This term represents final diagnosis of nodular SoR: G2; QoE: + / PolCon 62/62;
goitre, thyroiditis (acute, subacute, and auto- ATA GL R15
immune), a single hyperplastic, or a colloid 14.3.4.2 The second subcategory is
nodule. The risk of malignancy is minimal “Atypia of undetermined signifi-
[18, 21]. See also par. 24.2.2. cance — AUS” — strong nuclear
SoR: G1; QoE: +++ polymorphism, nuclear hetero-
14.2.1. The diagnosis of a “benign nodule” chromia, single grooves and nu-
formally involves also the diagnosis clear clearances, macronucleosis
of follicular adenoma; therefore, some in lesions, which have been
centres apply the statement “FNAB not subjected to any previous
negative with reference to malignancy” therapy. The AUS subcategory
or “non-malignant lesion”. The guide- indicates risk of malignancy
lines recommend the statement “benign at least two-times higher than
lesion” in such a case. that of the FLUS subcategory
SoR: G1; QoE: PolCon 62/62 and mainly concerns thyroid
14.2.2. FNAB smear should contain an ad- cells with features suggesting
equate number of cells. If the number papillary thyroid cancer (PTC).
of cells is too small and a repeated SoR: G2; QoE: + / PolCon
FNAB shows mainly colloid and also 62/62; ATA GL R15
few cells, the appearance of which does 14.3.5. The criteria that differentiate between
not suggest malignancy, the diagnosis categories “follicular lesion of undeter-
“cytological picture suggests a colloid mined significance” and “suspicious
lesion/nodule” is recommended. for a follicular neoplasm” are given in
SoR: G1; QoE: PolCon 62/62 Table III.
14.3. Follicular lesion of undetermined significance According to Polish data, the risk of
(Bethesda class III) [22, 23]. malignancy in follicular lesions of un- PODYPLOMOWE
SZKOLENIE
14.3.1. This diagnosis should be stated as rarely determined significance ranges between
as possible [17]. 2.4% and 5.2% [22–24]. So far, the vast
SoR: G1; QoE: PolCon 62/62 majority of such lesions in Poland were
14.3.2. This diagnostic category may be stated benign nodules or follicular neoplasms
after exclusion of the five remaining demonstrating low risk of malignancy.
Bethesda classes, to represent cytologi- Thereby, according to the authors
cal findings that fulfil neither qualita- of these guidelines the diagnosis of
tively nor quantitatively the “suspicious a follicular lesion of undetermined
for a follicular neoplasm” or “suspicious significance should not constitute in
for malignancy” criteria. itself an indication for surgery. It has
SoR: G2; QoE: + / PolCon 62/62 not yet been proven in Poland that this
14.3.3. Qualification of Bethesda class III may diagnosis significantly increases the risk
be related to sample limitations (low of malignancy compared with benign
cellularity, blood admixture, incorrect nodules [21, 23, 25].
fixation), if cellular features do not un- SoR: G2; QoE: + / PolCon 62/62
41Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma 2018 Update Barbara Jarząb et al.
Table III. Cytologic criteria for diagnosis of „follicular lesion of undetermined significance” „suspicion for a follicular neoplasm”
Feature Follicular lesion of undetermined Suspicious for a follicular
significance neoplasm
Hypercellular aspirate (subjective) Rather yes Yes
Prominent population of small arrangement Yes Yes
(groups, nests, rosets)
Sheets of follicular cells Might be seen No or single
Colloid in background Might be seen No or trace
Foamy macrophages Might be present No or single
Anisocytosis/anisokaryosis No or a little No
Lymphocytes/plasmatic cells No or single No
Oncocytes Non significant If > 75% of cells — there is a suspicion
for an Hurthle neoplasm
Oncocytes have prominent nucleoli
Anisocytosis of oncocytes
Oncocytes in spatial arrangements
Indication for surgery No Yes, after confirmation of the second
pathologist
Indication for a repeated FNAB Yes Rather no
14.3.6. If Bethesda III category is stated on the 14.4.3. “Suspicious for a Hurthle-cell neoplasm”
basis of abnormalities in a cell structure, (previously “suspicious for a oncocytic/
a higher risk of malignancy has to be oxyphilic neoplasm”; see also par. 14.4.8).
considered. SoR: G2; QoE: PolCon 62/62
SoR: G2; QoE: PolCon 62/62 14.4.4. The risk of malignancy of a lesion “sus-
14.3.7. Particular caution in interpretation is picious for a follicular neoplasm” in Po-
required in diagnosis of a follicular le- land is 8.2–19% [21, 25, 26] and depends
sion of undetermined significance in on the centre. Therefore, the decision
small lesions not exceeding 1 cm in any concerning surgery may be made with
dimension. reference to the centre’s experience.
SoR: G2; QoE: PolCon 62/62 SoR: G2; QoE: PolCon 62/62
14.3.8. Follicular lesion of undetermined signif- 14.4.5. The diagnosis of “suspicious for a fol-
icance constitutes a substitute diagnosis licular neoplasm” should be stated in
that requires further correction, in cor- cases when the pathologist anticipates
relation with clinical and sonographic the necessity of surgery and final histo-
features of the lesion during the next pathological diagnosis [17, 25].
FNAB (see par. 25). SoR: G1; QoE: +++
PODYPLOMOWE
SoR: G2; QoE: PolCon 62/62 14.4.6. Considering this diagnosis, the risk of
SZKOLENIE
14.4. Suspicious for follicular neoplasm (Bethesda cancer should be evaluated individually
class IV) [25, 26]. together with clinical-epidemiological
14.4.1. NCI recommends the statement “Suspi- factors [20, 26].
cious for follicular neoplasm” because SoR: G2; QoE: PolCon 62/62
25% of these nodules are not in fact 14.4.7. If the diagnosis “suspicious for a fol-
neoplasms [17]. Diagnostic criteria are licular neoplasm” is an indication for
given in Table III. surgery it should be confirmed by an-
SoR: G1; QoE: ++ other pathologist.
14.4.2. This class involves lesions previously SoR: G2; QoE: PolCon 62/62
known as either “follicular/oncocytic 14.4.8. This statement may reflect a final his-
neoplasm” or “follicular/oncocytic tu- topathological diagnosis of a follicular
mour ”. It should not involve lesions adenoma, follicular carcinoma, and
that show nuclear features of papillary follicular variant of papillary thyroid
thyroid cancer (see par. 14.4.8). carcinoma, and their oxyphilic variants.
SoR: G2; QoE: PolCon 62/62 However, it may also indicate a non-
42Endokrynologia Polska 2018; 69 (1)
neoplastic lesion such as a hyperplastic 14.5.3. Suspicion for MTC should be accom-
tumour showing a high cellularity or panied by serum calcitonin assessment
lymphocytic thyroiditis (in which distur- (basal Ct > 100 pg/mL allows MTC to
bances of cell structure are often present, be diagnosed with high probability) [6].
see par. 13.1.1). Therefore, the statement SoR: G1; QoE: +++ / PolCon 62/62; ATA
“suspicious for a follicular neoplasm”, GL MTC
recommended by NCI [18] is more 14.5.4. Suspicion for lymphoma requires
adequate than “follicular tumour ” or a second FNAB and flow cytometry [17].
“follicular neoplasm” (these statements SoR: G1; QoE: ++ / PolCon 62/62
may be used as clinical terms only, not as 14.6. Malignant tumours (Bethesda class VI) [17].
a cytological diagnosis) [20, 26]. 14.6.1. This category involves the diagnosis
—— We recommend using the term of papillary thyroid cancer, anaplastic
“Bethesda category IV” due to the thyroid cancer, or metastatic carcinoma.
difficulty in appropriate Polish SoR: G1; QoE: +++; ATA GL R12
translation. 14.6.2. MTC diagnosis and localisation of pri-
—— The diagnosis “suspicious for a fol mary focus of a metastasis from other
licular neoplasm” also involves cancer and lymphoma require immu-
a subclass “suspicious for Hurthle- nocytochemistry [17].
cell neoplasm”. SoR: G1; QoE: PolCon 62/62
—— Because the authors of a new WHO 14.6.3. In the diagnosis of Bethesda class VI,
classification accepted the evidence the decision about surgery is obvious.
that oxyphilic adenomas and carci- SoR: G1; QoE: PolCon 61/62 ATA GL R12
nomas are separate neoplasms and 15. FNAB report.
should not be treated any more as FNAB report should contain:
a variant of follicular neoplasms, 15.1. Information related to the nodule location and
the authors of current guidelines its features enabling its identification [9].
recommend the use of a “Hurthle SoR: G1; QoE: PolCon 62/62
neoplasm” category. To maintain 15.2. Information concerning FNAB representative-
consistency with Bethesda IV cat- ness, both qualitative and quantitative [20].
egory the diagnosis “suspicious SoR: G1; QoE: PolCon 62/62
for Hurthle-cell neoplasm” should 15.3. Description of cytological examination of each
be used. If a pathologist diagno- nodule assessed.
ses follicular cells with oxyphilic SoR: G1; QoE: PolCon 62/62
metaplasia (oncocytic) one should 15.4. Diagnostic conclusion that classifies FNAB
not use the term “Hurthle cells” to findings to one of six Bethesda classes (Table
facilitate an interpretation of cyto- II). See par. 16) [20].
logical diagnosis and differentiation SoR: G1; QoE: +++ / PolCon 62/62; ATA GL R9
between lesions suspicious for a ne- 15.5. IMPORTANT NOTICE: It is recommended that
oplasm and non-neoplastic lesions: a comment be attached to the FNAB report [17].
(ex. inflammatory lesions, showing SoR: G1; QoE: PolCon 62/62 PODYPLOMOWE
SZKOLENIE
oxyphilic metaplasia). 16. Unacceptable diagnostic terminology.
SoR: G2; QoE: PolCon 62/62 16.1. The following statement should be avoided:
14.5. Suspicious for malignancy (Bethesda class V). 16.1.1. “Atypical cells have not been found”,
14.5.1. Such a statement means that some fea- “bloody smear”, “malignancy features
tures of malignant tumours are present have not been found”.
but not all that would allow a diagnosis SoR: G1; QoE: PolCon 62/62
of malignancy. According to the Polish 16.1.2. All examples given in par. 16.1.1 should
data, the risk of cancer ranges between unequivocally evaluate whether the
50 and 75% [21, 27]. FNAB result is benign (Bethesda II) or
SoR: G1; QoE: + / PolCon 62/62 non-diagnostic (Bethesda I) [20].
14.5.2. Suspicion for papillary thyroid carci- SoR: G1; QoE: PolCon 62/62
noma most often concerns its follicular 16.1.3. One must not use the statement “FNAB
variant [17]. result may arouse suspicion for a fol-
SoR: G1; QoE: ++ / PolCon 62/62 licular tumour”.
SoR: G1; QoE: PolCon 62/62
43Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma 2018 Update Barbara Jarząb et al.
16.1.4. The statement given in par. 16.1.3 does 18.2.2. Low molecular weight heparin.
not provide the clinician with sufficient An eight-hour interval between the last
information about whether a patholo- dose of the drug and FNAB is necessary.
gist formally diagnoses “suspicious for SoR: G2; QoE: + / PolCon 62/62
a follicular neoplasm” or whether there 18.2.3. Dabigatran (Pradaxa).
are some data suggesting this diagnosis A 12-hour interval between the last dose
but not sufficient to support it. In such of the drug and FNAB is necessary.
cases the pathologist should consider SoR: G2; QoE: + / PolCon 62/62
whether or not to state a diagnosis of 18.2.4. Rivaroxaban (Xarelto).
“follicular lesion of undetermined sig- A 24-hour interval between the last dose
nificance”, which is clear for a clinician of the drug and FNAB is necessary.
because it gives information that the SoR: G2; QoE: + / PolCon 62/62
nodule requires further diagnostics. 18.2.5. Clopidogrel.
Additional information “suspicion for If, for cardiological reasons, drug with-
a follicular neoplasm is not excluded” drawal is contraindicated, FNAB is ac-
or “suspicion for a follicular neoplasm ceptable in a patient using clopidogrel
was considered but not all criteria are only if there is an absolute indication for
fulfilled” is also acceptable. FNAB. Replacement with a low molecu-
SoR: G1; QoE: PolCon 62/62 lar weight heparin is not justified due
17. FNAB reliability and limitations. to the differences in the mechanisms of
17.1. Differentiation between follicular carcinoma action of both drugs.
and adenoma on the basis of cytological ex- SoR: G2; QoE: + / PolCon 62/62
amination is not possible [20]. 18.2.6. Acceptable drugs:
SoR: G1; QoE: PolCon 62/62 —— Aspirin with doses < 0.3 g.
17.2. Because there is always a risk of a false nega- —— Non-steroidal anti-inflammatory
tive result of FNAB clinicians should evaluate drugs.
the presence of clinical features of malignancy SoR: G2; QoE: ++ / PolCon 62/62
indicating surgical treatment [21]. 19. FNAB complications [28].
SoR: G2; QoE: PolCon 62/62; ATA GL R23 and R24 19.1. Transient.
17.3. This risk is usually related to insufficient 19.1.1. Haematoma (prevention — compression
sample cellularity, incorrect aspiration, wrong of FNAB site following biopsy. If deeply
interpretation, or the occurrence of cystic form located lesions are aspirated, 30-minute
of thyroid carcinoma [18, 20]. observation is recommended).
SoR: G2; QoE: PolCon 62/62 SoR: G2; QoE: PolCon 62/62
17.4. The risk of false positive result is 1%. 19.1.2. Pain and oedema (prevention — ice
SoR: G2; QoE: + / PolCon 62/62 compress, paracetamol).
18. Contraindications to FNAB [28]. SoR: G2; QoE: PolCon 62/62
18.1. Absolute. 19.1.3. Syncope.
18.1.1. Serious haemorrhagic diathesis. SoR: G2; QoE: PolCon 62/62
PODYPLOMOWE
18.1.2. Purulent skin lesions. 19.1.4. Infection (rare even in patients with
SZKOLENIE
18.1.3. Lack of patient’s cooperation. immune deficiency), increased risk in
SoR: G1; QoE: PolCon 62/62 patients infected with HIV or with diag-
18.2. The use of anticoagulant drugs. nosis of diabetes mellitus, tuberculosis,
18.2.1. Acenocoumarol and Warfarin. atopic dermatitis.
The authors of these recommendations 19.1.4.1. Staphylococcal infection. If skin
believe, after consultation with special- hygiene is poor, skin should be
ists, that the use of acenocoumarol and thoroughly disinfected.
warfarin does not constitute an absolute SoR: G2; QoE: PolCon 62/62
contraindication to FNAB, especially 19.2. Serious — extremely rare.
when a 0.4-mm diameter needle is used 19.2.1. Needle tract implantation from thyroid
and INR ranges between 2.5–3. Replace- carcinoma has never been reported with
ment by a low molecular weight heparin reference to 23-gauge or smaller needle.
may be considered. These complications concerned mostly
SoR: G2; QoE: +++ / PolCon 62/62 core biopsy.
SoR: G2; QoE: PolCon 62/62
44Endokrynologia Polska 2018; 69 (1)
19.2.2. Recurrent laryngeal nerve palsy (the 21.2. Solid nodule.
total risk is 0.036%) — dysphonia and A solid nodule, clinically benign with a non-
dysphasia typically develop on the diagnostic FNAB result requires a clinical and/
second day after FNAB, and recovery or sonography follow-up and repeated FNAB,
takes up to four months. usually within 3–12 months, depending on
SoR: G2; QoE: PolCon 62/62 clinical and sonography risk (see par. 3).
19.2.3. Haemorrhage or haematoma requiring SoR: G2; QoE: PolCon 61/62
surgery. 21.3. Solid nodule with cystic degeneration.
SoR: G2; QoE: PolCon 62/62 In the case of the first FNAB being non-diag-
20. Immunocytochemistry. nostic, repeated FNAB is indicated within 3–12
Immunocytochemistry in FNAB aspirate may months. The solid part should be biopsied [5, 9]
provide some information, crucial for the diagno- ATA consider surgical treatment in the case of
sis. “Cell block” technique is a preferable method non-diagnostic FNAB. The authors of these
mainly due to the possibility to perform a few recommendations propose that in such a case
reactions at the same time and simultaneously the clinical and sonography risk factors of
to evaluate some features of cell architecture malignancy (see par. 3) should be relied upon.
like papillary or tubular structures. The Tg and SoR: G1; QoE: PolCon 61/62; ATA GL R10
Ct expression should be evaluated to confirm 22. Interval between non-diagnostic and second FNAB.
thyroid origin of the neoplasm. It is characterised 22.1. This interval should not be shorter than three
by a high specificity. However, it is difficult for months, unless clinical features strongly sug-
interpretation, particularly in smears (membrane gest a very high risk of malignancy (suspicion
and cytoplasmic reaction) and due to diffusion- of poorly differentiated or anaplastic thyroid
related artefacts. The evaluation of TTF-1 and carcinoma or lymphoma), or an incorrect
PAX 8 is characterised by a high sensitivity but FNAB procedure is highly probable.
low specificity. Therefore, if their expression has SoR: G2; QoE: PolCon 62/62
been demonstrated, it requires an additional 22.2. In the vast majority of cases, where the clini-
evaluation of Tg expression. To establish the cal risk is not high, repeated FNAB may be
origin of metastatic thyroid tumour, consider- performed 6–12 months later [19].
ing the frequency of occurrence and similarity SoR: G2; QoE: PolCon 62/62
in cytological pictures, one should exclude: 23. Two non-diagnostic FNABs:
• renal cancer (RCC+, PAX2+, CD10+) [29]; 23.1. Two non-diagnostic FNABs in a cyst. If two
• lung adenocarcinoma (napsin A+, PAX 8+, TTF-1+, FNABs in a pure cyst are non-diagnostic, it
Tg-), squamous cell carcinoma (p63+) [30]; should be taken into consideration that cancer
• head and neck squamous cell carcinoma (p63, risk is very small (1%); however, it cannot be
CK 5,6) [31]; definitely excluded [5, 8, 9].
• breast cancer (GATTA3+) [32]; SoR: G2; QoE: PolCon 62/62
• malignant melanoma (SOX10+, HMB45) [33]; 23.2. Two non-diagnostic FNABs in a solid lesion [5]
• colon adenocarcinoma (CDX2+); 23.2.1. Due to the lack of cancer exclusion and
• if there is a suspicion of parathyroid tumour, the possible higher probability of its detec-
assessment of PTH concentration in FNAB wash- tion, surgery should be considered PODYPLOMOWE
SZKOLENIE
out is helpful; depending on clinical and sonography
• diagnosis of anaplastic thyroid carcinoma (ATC) risk factors [8, 9].
may be confirmed by PAX8 expression (TTF-1 and SoR: G2; QoE: PolCon 62/62
Tg may be negative), p54 and a high mitotic activ- 23.2.2. In the case of two non-diagnostic FNABs
ity of cancer cells in smear (Ki-67 > 30%). in a nodule subjected for further follow-
SoR: G1; QoE: PolCon 62/62 up, subsequent FNAB performed in
21. Further follow-up after non-diagnostic FNAB [5]. another centre, should be considered.
21.1. Cyst. SoR: G2; QoE: PolCon 62/62
In the case of a pure sonographic cyst without 23.2.3. In the case of a significant lesion growth,
any solid part and failure of the first FNAB surgery should be considered unless
in obtaining diagnostic material, a repeated the clinical context explains the lack of
FNAB may be considered within 6–18 months. adequate FNAB material [5], see also
The risk of cancer is low, but not excluded [34] par. 13.
SoR: G2; QoE: PolCon 61/62 SoR: G2; QoE: PolCon 62/62
45Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma 2018 Update Barbara Jarząb et al.
23.2.4. If neither nodule growth nor sonog- 24.2.3.2. If the aggravation of sonogra-
raphy risk factors are present, surgical phy risk features is significant,
treatment may be considered with refer- particularly if signs of nodule
ence to the clinical context and a deci- invasiveness are present (par.
sion is made together with the patient. 3.2), FNAB may be repeated ear-
SoR: G2; QoE: PolCon lier — no later than 3–6 months
23.2.4.1. In a lesion < 1 cm in any di- after [9].
ameter, which does not show SoR: G1; QoE: ++ / PolCon 62/62
significant growth and clinical 24.2.3.3. In other lesions with risk fea-
risk factors and sonography tures of malignancy, the time of
features of invasiveness, sur- repeated FNAB depends on the
gery is not indicated. magnitude of clinical risk [9].
SoR: G2; QoE: PolCon 62/62 SoR: G2; QoE: PolCon 62/62
24. Further follow-up after the diagnosis of a benign 24.2.4. Indications for a repeated FNAB within
nodule on FNAB. 6–12 months may be related to nodule
24.1. Benign FNAB result does not unequivocally growth, the presence of clinical risk
negate surgery. factors, or the lower reliability of the
SoR: G1; QoE: + / PolCon 62/62 first FNAB — due to the very small le-
24.2. Follow-up of a solid nodule, with a benign sion diameter or nodule location in the
FNAB result. dorsal part of the thyroid lobe, leading
If clinical indications and the results of other to an increased risk of missing the lesion
examinations together with patient’s prefer- during FNAB.
ence do not indicate surgery, further follow-up SoR: G2; QoE: PolCon 62/62
should consider that the risk of malignancy 24.2.4.1. An increase of the nodule size is
in a nodule which has undergone FNAB is not a sufficient criterion of its ma-
significantly lower than that in a nodule that lignancy [34], but it constitutes an
had not been biopsied [35]. indication for a repeated FNAB
SoR: G1; QoE: ++ / PolCon 62/62 (if its enlargement by 20% in
24.2.1. A solid nodule, benign on FNAB, every diameter within one year
requires clinical follow-up (physical is observed).
examination or ultrasound) every 6–18 SoR: G2; QoE: PolCon 62/62
months. 24.2.4.2. The occurrence of new sonog-
SoR: G1; QoE: +++ / PolCon 62/62 raphy high-risk features of
24.2.2. Repeated FNAB is not required if no malignancy in a benign nodule
clinical doubt exists and the quality of the on the previous FNAB indicates
first FNAB is good. The frequency of the the need for a repeated FNAB.
detection of thyroid cancer in histopathol- SoR: G1; QoE: +++ / PolCon
ogy examination in patients with a benign 62/62
FNAB result, subjected to surgery without 24.3. The recommendations given in par. 24.1–2 also
PODYPLOMOWE
a repeated FNAB in Poland, is 3.6% [19]. concern solid-cystic nodules. Repeated FNAB
SZKOLENIE
SoR: G1; QoE: ++ / PolCon 62/62 is indicated if the solid part of the nodule grows
24.2.3. Repeated FNAB in a lesion demon- significantly.
strating sonography risk features of SoR: G2; QoE: PolCon 62/62
malignancy with a benign FNAB result, 24.4. Further follow-up is acceptable, even if signifi-
makes the diagnosis more reliable and cant nodule growth is observed, if the repeated
diminishes the risk of cancer omission. FNAB gives a benign result [34].
SoR: G1; QoE: PolCon 62/62 SoR: G2; QoE: PolCon 62/62
24.2.3.1. If no clinical risk factors exist, 25. Further follow-up after diagnosis of a follicular le-
no tumour growth is observed, sion of undetermined significance.
and no new sonography risk 25.1. The risk of cancer in such lesions is probably no
features have occurred, a re- higher than 5%. According to the Polish data,
peated FNAB is usually indi- it ranges between 2.4% and 5.2%.
cated no earlier than after 6–12 SoR: G2; QoE: ++ / PolCon 62/62
months. 25.2. Follow-up (repeated sonography every six
SoR: G1; QoE: PolCon 62/62 months), and repeated FNAB in 6–12 months
46Endokrynologia Polska 2018; 69 (1)
(no sooner than after three months, due to a particular centre has also to be con-
the risk of the presence of repair changes), are sidered.
recommended. SoR: G2; QoE: PolCon 62/62
SoR: G2; QoE: PolCon 62/62 26.2.2. Surgery constitutes the optimal way
25.3. If sonographic risk factors of malignancy are to establish the final diagnosis in the
present (see par. 3.2) or the FNAB reports nodule classified as Bethesda class IV.
disturbances in cell architecture suggesting SoR: G1; QoE: +++
malignancy, a repeated FNAB is recommended 26.2.3. In small lesions (up to 1 cm), if clinical
after a 3–6-month interval, depending on the and sonography risk features are absent,
clinical risk. If a similar result is obtained, sur- resignation from surgery and follow-up
gery has to be considered, particularly if strong are acceptable only under strict sonog-
sonography risk factors or features of lesion raphy and clinical monitoring.
invasiveness (see par. 3.2) are present or the SoR: G2; QoE: PolCon 62/62
FNAB report suggests malignancy. 26.2.4. If the FNAB result is suspicious for
SoR: G2; QoE: PolCon 62/62 Hurthle-cell neoplasm, surgery is rec-
25.4. Surgery is recommended in nodules > 4 cm, in ommended due to the risk of cancer of
smaller lesions if a significant nodule growth at least 15%.
is present or if the second FNAB indicates SoR: G2; QoE: PolCon 62/62
a higher cancer risk. 26.2.5. Intraoperative nodule examination does
SoR: G2; QoE: ++ / PolCon 62/62 not usually contribute any important
25.5. If a nodule with this diagnosis has an au- information.
tonomous appearance in scintigraphy, further SoR: G1; QoE: PolCon 62/62
follow-up may be recommended, together 26.3. If the decision is to resign from surgery and
with 131I treatment, because the risk of cancer the nodule is to be further followed, a repeated
does not exceed ≤ 2% [9]. FNAB may be performed no earlier than after
SoR: G2; QoE: ++ / PolCon 62/62 three months, usually after six months.
26. Further follow-up after the diagnosis of a lesion SoR: G2; QoE: PolCon 62/62
“suspicious for a follicular neoplasm”. 27. Further management after the diagnosis of a suspi-
26.1. It has to be re-emphasised that this diagno- cion for a malignant neoplasm on FNAB.
sis should be stated only in cases where the 27.1. Suspicion for malignancy (category V accord-
necessity of surgical treatment is anticipated ing to the Bethesda classification) [35].
— to obtain material and to perform the final 27.1.1. Surgery is recommended regardless of
histopathological examination [20]. the presence of sonographic risk factors.
SoR: G1; QoE: +++ SoR: G1; QoE: PolCon 62/62
26.1.1. The diagnosis has to be confirmed by 27.1.2. Confirmation of FNAB diagnosis by
another pathologist prior to surgery. a second pathologist is necessary.
SoR: G2; QoE: PolCon 62/62 SoR: G2; QoE: PolCon 62/62
26.1.2. If such confirmation has been achieved, 27.1.3. In the case of suspicion for malignancy,
repeated FNAB provides no further intraoperative histopathological exami-
essential information, especially if per- nation may be considered. PODYPLOMOWE
SZKOLENIE
formed soon after the first biopsy. SoR: G2; QoE: ++
SoR: G1; QoE: PolCon 62/62 28. Malignant neoplasm (category VI according to the
26.1.3. If there is no possibility to consult the Bethesda classification) [27].
FNAB result, surgery is acceptable in 28.1.1. Surgery is necessary.
the case of urgent clinical indications. SoR: G1; QoE: +++; ATA GL R12
SoR: G2; QoE: PolCon 62/62 28.1.2. Confirmation of FNAB diagnosis by
26.2. Indications for surgery if a lesion suspicious for a second pathologist is necessary.
a follicular neoplasm is diagnosed. SoR: G2; QoE: PolCon 62/62
26.2.1. If the FNAB result is Bethesda IV, sur- 28.1.3. In the case of preoperative diagnosis of
gery should be considered in order to anaplastic thyroid cancer, thyroid lym-
resolve diagnostic doubts, particularly if phoma, or metastases from other cancer,
clinical or sonography risk features are it is necessary to evaluate whether the
present. The risk of malignancy related tumour is amendable to surgery, and to
to this Bethesda category, observed in establish further management. In the
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