Complications Thyroid Biopsy

Clinical Complications Following Thyroid Fine-needle Biopsy: A Systematic Review
Stergios A. Polyzos; Athanasios D. Anastasilakis

Clin Endocrinol. 2009;71(2):157-165.
Summary and Introduction
Summary
Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive and generally safe diagnostic
procedure in the management of thyroid nodules. Post-FNB local pain and minor haematomas are
the most common complications, while serious complications seem to be rare. Given that use of
FNB minimizes unnecessary surgery and subsequent operative morbidity and mortality as well as
the fact that the majority of FNB complications resolve spontaneously, the overall safety of FNB is
not questioned. However, awareness of the potential complications and careful estimation of the
risk-benefit ratio in an individual basis may further decrease the low morbidity of FNB. In this
systematic review we tried to collect and summarize all reported clinical complications following
diagnostic thyroid FNB, aiming to make physicians aware of possible complications and to provide
preventive measures to avoid them.
Introduction
Several procedures have been developed to obtain groups of cells or tissue from thyroid nodules.
The most commonly used procedure is fine-needle biopsy (FNB), which is considered the most
accurate and cost-effective tool in the preoperative investigation of thyroid nodules and has been
proposed as the procedure of choice.[1,2] The cytological results following FNB are divided in benign,
malignant, indeterminate and nondiagnostic[1,2] and a final result can be obtained within 24 h.[3] The
use of FNB has almost halved the percentage of patients undergoing thyroidectomy and has
doubled the yield of malignancy in patients who finally undergo surgery, thereby reducing the cost
of medical care.[4] Technically, FNB can be performed with aspiration using a syringe [fine-needle
aspiration (FNA)] or without aspiration [fine-needle capillary (FNC)] and can be guided only by
palpation [palpation-guided FNB (P-FNB)] or by ultrasound [ultrasound-guided FNB (US-FNB)].[5]
Although FNB is an invasive method, it is simple, reliable, safe and well-accepted by the patients.
Post-FNB local pain or discomfort and minor haematomas are the most common
complications.[1,3,6-9] Serious adverse events seem to be rare, but a systematic record of these does
not exist in the literature. In this review we tried to collect and summarize all reported adverse
events following diagnostic thyroid FNB. Our aim was to present the spectrum of clinical adverse
events of this procedure, not to discourage physicians, but to make them aware of the potential,
albeit rare, complications and provide useful preventive measures.
Literature Search
Computerized advanced search for primary evidence was performed in the PubMed
(Public/Publisher MEDLINE) electronic database. The search was not limited by publication time
and not restricted to English literature. First, relevant journal articles were selected. The Medical
Subject Headings (MeSH) database was used as a terminological search filter. From the
combination of terminological (MeSH terms) and methodological search filters ('PubMed clinical
queries'), journal articles relevant to our specific issue were retrieved. [10] Afterwards, the
bibliographic search was extended to the 'Related Articles' link next to each selected article in
PubMed and its references. Finally, automatic alerts were activated in PubMed ('My NCBI') to add
relevant articles published after the initial search. Articles reporting post-FNB histological (infarction,
necrosis, linear fibrosis, vascular thrombosis, vascular proliferation, capsular pseudoinvasion,
nuclear atypia, metaplasia, etc.) or biochemical changes (impact on thyroglobulin and antibodies)
were excluded. Most articles found were of level 3 of evidence, leading to grade C
recommendations,[11] since they were case reports, case series or observational studies.
A search for a relevant systematic review or meta-analysis in both the PubMed and the Cochrane
Library retrieved no result.
Series of five or more cases of complications of FNB found in this systematic search are
summarized in . Suggested preventive measures are presented in . The likelihood and a grading of
the severity of each complication are also presented in .
Table 1. Series of clinical complications following thyroid FNB according to the literature*
References
per
Study type/level of Case(s)/number Technique/needle's
complication evidence
of patients
gauge (G)
Additional
information
Pain/Discomfort
(Ramacciotti Retrospective,
et al., 1984)[12] observational/3
13/221
P-FNA/na
Overall
complication rate
86% / persistent
pain or discomfort
up to several days
(Silverman
Retrospective,
[13]
et al., 1986)
observational/3
1/309
P-FNA/22
Overall
(Gursoy et Randomized
45/49
[14]
al., 2007)
double-blinded,
placebo-controlled/2
complication rate
19% / persistent
pain (for 24 h) in 1
patient
US-FNA/25
Indirect evidence
from
placebo
group: 16, 14 and
15
patients
reported
mild,
moderate
and
severe
pain
respectively and
only 4 no pain
46/52
[15]
al., 2007)
double-blinded,
US-FNA/25
Indirect evidence
from
placebo
group: 17, 14 and
15
patients
reported
mild,
moderate
and
severe
pain
respectively and
only 6 no pain
Haemorrhage/Haematomas
(Ramacciotti (see pain/discomfort 5/221
et al., 1984)[12] section)
P-FNA/na
Moderate
to
severe
local
swelling
(3
patients) / small
subcutaneous
haematomas (2
patients)
/
spontaneous
resolution
(Silverman
(see pain/discomfort 1/309
[13]
et al., 1986)
section)
P-FNA/22
(Newkirk et Retrospective,
al., 2000)[16]
observational/3
US-FNA/22-25
15/234
Overall
complication rate
85% / higher
complication rate
for nodules 15
cm
(Braga et al., Prospective,

2001)[17]
cohort/2
11/42
US-FNA/23 or 25
Nodules after fluid

aspiration/
intranodular
haemorrhage
(Khoo et al., Retrospective, case 3/311 (FNA) vs. US-FNA/na

vs. Overall
2008)[18]
control/3
8/320
US-FNA+US-CNB/na complication rate
(FNA+CNB)
1% (FNA) vs.
31% (FNA+CNB)
Recurrent laryngeal nerve palsy
(Tomoda et Retrospective,
al., 2006)[19]
observational/3
4/10,974
P-FNA/23
All benign nodules

/
spontaneous
recovery
P-FNA/22
Transient
bradycardia
Vasovagal
reactions
(Silverman
[13]
et al., 1986)
section)
and
faintness / quick
response
symptomatic
to
therapy
P-FNA/na
(Newkirk et al., (see haemorrhage / 3/234

2000)[16]
haematomas
section)
US-FNA/22-25
Duration less than

10 min / no
therapy
(Khoo et al., (see haemorrhage / 2/311 (FNA) vs. US-FNA/na

vs. Dizziness,
2008)[18]
haematomas
2/320
US-FNA+US-CNB/na bradycardia,
section)
(FNA+CNB)
presyncope
Needle track seeding of papillary carcinoma

(Block et al., Retrospective,
1980)
(Ito
[20]
observational/3
et
al., Retrospective,
observational/3
2005)[21]
1/54
10/4912
P-FNA
and/or 1
Cutaneous
CNB/na
seeding 6 months
post-FNA/ surgery
(surgical series)
US-FNA/22
All seedings
linear
in
arrangement from
the skin to the
nodule / between
2 months and 11
years post-FNA /
6 cases were
poorly
differentiated
carcinomas / 5
cases with nodal
metastasis / 7
cases
with
extrathyroid
extension
/
surgery
Nodule volume alterations
(Gordon et Prospective,
al., 1999)[22]
cohort/2
6/17**
US-FNA/22
No
statistical
difference
in
mean volume /
marked individual
bi-directional
variation
(Guney
et Prospective,
[23]
al., 2003)
cohort/2
6/46**
US-FNA/na
No
statistical
difference
in
mean volume /
marked individual
bi-directional
variation
Post-aspiration thyrotoxicosis
(Kobayashi Retrospective,
et al., 1992)[24] observational
5/500
part (retrospective)
P-FNA/18-23 (cystic Affected patients

nodules) and 22-23 had high serum
followed
by and
1/115 (solid nodules)
prospective part/3
(prospective)
free T4, T3 and

CRP, supressed
TSH,
negative
anti-microsomal
antibodies,
low
I123 uptake at 24
h / 2-20 days
post-FNA
*Case reports and series of less than five cases were not included in the Table. References are
presented in publication date order, when there is more than one reference in the same category.
According to the definitions of the American Association of Clinical Endocrinologists.[11] The total
number of patients of the study, if the study was not a case report. There were 7 cases among
4912 patients retrospectively reviewed (014%) and 3 more cases from other institutes described
together. **The number of cases, whose nodule volume changed 50% compared with the
baseline volume. CNB, cutting needle biopsy; FNA, fine needle aspiration; na, not available; P-FNA,
palpation-guided FNA; TSH, thyroid stimulating hormone; US-CNB, ultrasound-guided CNB;
US-FNA, ultrasound-guided FNA; US-FNC, ultrasound-guided fine-needle capillary.
Table 2. Likelihood, severity and preventive measures per FNB complication according to
the literature
Complication (Likelihood*, Severity)
Preventive measures
Pain/discomfort (up to 92%/1)
Small needle size

Local anaesthesia, if necessary (Table 3)
US guidance (avoidance of neck muscles and
adjacent structures)[25]
Slight stretching of the skin above the nodule
(by fixing the nodule between two fingers of
the non-dominant hand or by using the
'two-man technique') (immobilization resulting
in reduction of adjacent tissue damage)[9]

Haemorrhage/haematomas (small haematomas: Medical history for haemorrhaging risk factors,
03-26%/1; massive haematomas: 2/3; neuritis
following haematoma: 1/3; pseudoaneurysm: 1/2;
carotid haematoma: 1/1; secondary haemangioma:
1/1)
including drugs (aspirin, other anti-platelet

drugs, NSAID, anticoagulants) and diseases
affecting coagulation (i.e. cirrhosis and
end-stage renal disease before FNB
PT or INR measurement in patients taking
acenocoumarol or warfarin; Low molecular
weight heparin stop at least 8 hour before
FNB;[26] Anti-platelet drugs stop (i.e.
clopidogrel bisulfate) 3-5 days before
FNB[26,27]
Small needle size (25-27G) especially for
markedly
hypervascular
nodules
or
re-aspiration[28,29]
FNC instead of FNA in nodules close to large
vessels[30]
US guidance, especially in nodules close to
large vessels[5,30]
Slight stretching of the skin above the nodule[9]
Firm pressure to the biopsy site with a sterile
gauze pad for 2-3 min after FNB (longer in
bleeding diathesis)[1,3,8,28]
In case of an increasing haematoma that
cannot be stopped by pressure, patients
should be advised to report to the emergency
department (massive haematomas may occur
hours after FNB)[8]
In cases of hyperthyroidism or thyroiditis De
Quervain's FNB should be delayed until
euthyroidism restoration[31,32]
In cases of complex nodules, direct biopsy
(US-FNB) of the solid part without previous
evacuation of the fluid[17]
Avoidance of repeat FNB shortly after the
initial one[33,34]
Acute transient swelling(1/1)
Delayed transient swelling(1/1)

Infection (2/3)
Alcohol cleansing and iodine skin prep at

biopsy site before FNB[28]
Adequate sterile conditions during FNB[35,36]
Antibiotics in immunosuppressed patients
after FNB (prophylactically)[37]
Sterile gel in US-FNB
Recurrent laryngeal nerve palsy (0036-09%/2)
Small needle size[38]

Not penetrating the dorsal site of the nodule[19]
Vasovagal reaction (05-13%/1)
Pain prevention
Keep the patient calm
Tracheal puncture (03%/1)
US guidance
Dysphagia (1/1)
Needle track seeding (papillary carcinoma: Small needle size (23-G or smaller)[3,28,39-43]
014%/3; follicular carcinoma: 1/3; anaplastic
carcinoma: 1/3; other thyroid malignancies: no
evidence)
Suction release before needle withdrawal or
use
of
non-aspiration
technique
[3,17,28,39-43]
(FNC)
Avoidance an excessive piston-like motion of
the needle[21]
Avoidance of multiple passes and repeat FNB,
if possible[3,28]
Needle track sinus (1/2)
Small needle size (23-G or smaller)[44]

Avoidance of serial FNB, if possible[44]
Nodule volume alterations(13-35%/1)

Post-aspiration thyrotoxicosis(1%/2)
*Likelihood is presented in percentage (%), if epidemiologic data exists in the literature, or in
numerical scale as follows: 1, extremely rare (< 5 reported cases); 2, rare ( 5 or 10 reported
cases). Severity was assessed: 1, negligible morbidity; 2, moderate morbidity; 3, severe morbidity.
Complications that are intrinsic of FNB; thereby no preventive measures are suggested for them.
The percentage of cases, whose nodule volume changed 50% compared with the baseline
volume. FNA, fine-needle aspiration; FNB, fine needle biopsy; FNC, fine-needle capillary; INR,
international normalized ratio; NSAID, non-steroid anti-inflammatory drugs; PT, prothrombin time;
US, ultrasound; US-FNB, ultrasound-guided biopsy.

the literature
Preventive measures
Small needle size

Haemorrhage/haematomas (small haematomas:

1/1)
Medical history for haemorrhaging risk factors,

FNB[26,27]
markedly
hypervascular
nodules
or
[28,29]
re-aspiration
vessels[30]
large vessels[5,30]

hours after FNB)[8]
initial one[33,34]
Infection (2/3)


Pain prevention
US guidance
Dysphagia (1/1)
evidence)
use
of
non-aspiration
technique
[3,17,28,39-43]
(FNC)
the needle[21]
if possible[3,28]


Literature Limitations
Thyroid post-FNB complications are rarely recorded systematically. In large thyroid FNB series,
including paediatric ones, complications were either not reported or mentioned to be limited in
temporary pain and small haematomas. Such results could reflect problematic definitions of
complications or under reporting of minor complications. Despite their rarity, under reporting of
major complications may also exist, since the physician or the team performing an FNB with
undesirable consequences may be unwilling to publish it. Moreover, no study was designed to
record thyroid FNB complications as its primary aim. The rarity of major complications makes their
evaluation problematic, since it requires the recruitment of a great number of patients subjected to
FNB, possibly on a multicentred basis, to lead to secure conclusions. Finally, case reports or case
series of minor or already reported complications are hardly accepted for publication. All the above
leads to underestimation of the risk of complications, because of definition, record, selection and
publication bias.
Pain and Discomfort
There are limited epidemiological data regarding local pain and/or discomfort during or after FNB.
Although they are regarded as minor, transient and well-tolerated by the patient,[3,7] pain and
discomfort are undesirable consequences of FNB and may contribute to an inadequate cytological
result.[45] However, discontinuation of the procedure due to pain is uncommon. In a series of 215
patients, FNB was discontinued in only one patient because of pain.[16]
There are not sufficient data about the pain type (i.e. kind, intensity, duration) and its relation to
parameters like needle size, number of passes, physician's expertise, technique used (P- vs.
US-FNB or FNA vs. FNC). It is rational that the pain increases with increasing needle size, but there
is not enough evidence. It seems that puncturing adjacent structures, such as blood vessels,
recurrent laryngeal nerve or sternocleidomastoid muscle produces more intense or persistent pain
than puncturing the nodule itself. Lack of expertise and vigorous handling of the needle may also
increase the possibility and severity of pain. Moreover, in our experience, repetition of FNB within 1
month may be more painful (and more haemorrhagic) than the initial one.
The placebo groups of two recent studies, designed to assess the efficacy of EMLA (Eutectic
Mixture of Local Anaesthetics) cream[14] and of needle-free subcutaneous delivery of lidocaine[15] in
post-FNB pain, provide indirect epidemiological data (). Pain appeared to be more common when
FNB was performed on deep-seated nodules or when vigorous aspiration was required.
Interestingly, women were more susceptible to the perception of pain compared with men. [14]
References
per
of patients
gauge (G)
Additional
information
Pain/Discomfort
13/221
(Silverman
Retrospective,
1/309
P-FNA/na
Overall
complication rate
86% / persistent
pain or discomfort
up to several days
P-FNA/22
Overall
complication rate
19% / persistent
patient
45/49
[14]
al., 2007)
double-blinded,
US-FNA/25
Indirect evidence
from
placebo
group: 16, 14 and
15
patients
reported
mild,
moderate
and
severe
pain
respectively and
only 4 no pain
46/52
[15]
al., 2007)
double-blinded,
US-FNA/25
Indirect evidence
from
placebo
group: 17, 14 and
15
patients
reported
mild,
moderate
and
severe
pain
respectively and
only 6 no pain

P-FNA/na
Moderate
severe
to
local
swelling
(3
patients) / small
subcutaneous
haematomas (2
patients)
/
spontaneous
resolution
(Silverman
[13]
et al., 1986)
section)
P-FNA/22
al., 2000)[16]
observational/3
15/234
US-FNA/22-25
Overall
complication rate
85% / higher
complication rate
for nodules 15
cm

2001)[17]
cohort/2
11/42
US-FNA/23 or 25
Nodules after fluid

aspiration/
intranodular
haemorrhage

vs. Overall
[18]
2008)
control/3
8/320
(FNA+CNB)
1% (FNA) vs.
31% (FNA+CNB)
al., 2006)[19]
observational/3
4/10,974
P-FNA/23
All benign nodules

/
spontaneous
recovery
(Silverman
[13]
et al., 1986)
section)
P-FNA/22
Transient
bradycardia and
faintness / quick
response
to
symptomatic
therapy
P-FNA/na
Duration less than
Vasovagal
reactions
10 min
therapy

2000)[16]
haematomas
section)
no
US-FNA/22-25

vs. Dizziness,
[18]
2008)
haematomas
2/320
section)
(FNA+CNB)
presyncope
1980)[20]
observational/3
1/54
P-FNA
CNB/na
and/or 1
Cutaneous
seeding 6 months
post-FNA/ surgery
(surgical series)
(Ito
2005)
et
al., Retrospective,
[21]
10/4912
US-FNA/22
observational/3
All
seedings
in
linear
arrangement from
the skin to the
nodule / between
2 months and 11
years post-FNA /
6 cases were
poorly
differentiated
carcinomas / 5
cases with nodal
metastasis / 7
cases
with
extrathyroid
extension
/
surgery

al., 1999)[22]
cohort/2
(Guney
et Prospective,
[23]
al., 2003)
cohort/2
6/17**
US-FNA/22
No
statistical
difference
in
mean volume /
marked individual
bi-directional
variation
6/46**
US-FNA/na
No
statistical
difference
in
mean volume /
marked individual
bi-directional
variation
part
followed
by
prospective part/3
5/500
(retrospective)
and
free T4, T3 and
(prospective)
CRP, supressed
TSH,
negative
anti-microsomal
antibodies,
low
I123 uptake at 24
h / 2-20 days
post-FNA
According to the definitions of the American Association of Clinical Endocrinologists. [11] The total
Local anaesthesia is not routinely recommended for pain prevention. [1,7,25] Its indications, methods
and disadvantages are summarized in . No form of local anaesthesia provides complete analgesia
in all patients.[14,15] Significant pain during FNB, despite local anaesthesia, may be indicative of
subacute thyroiditis, intrathyroidal haemorrhage, infarction or cyst leakage. [28]
Table 3. The role of local anaesthesia in thyroid FNB
Indications
Anxious, uncooperative, pain-phobic or needle-phobic patients[14,15,29]
Deep-seated, non-palpable nodules, which require more time and probing to be reached [28]
Children 7 years old[9]
Methods
Cutaneous administration of 05-15 ml lidocaine (1-2%) with or without epinephrine (1 : 100 000)
using an ultra thin 30-32-gauge needle[13,18,28,29]
Cutaneous application of EMLA (a combination of lidocaine 25% and prilocaine 25%) cream[14]
Needle-free subcutaneous delivery of lidocaine[15]
Application of an ice pack on the neck before FNB[28]

Disadvantages
Occasionally more pain than the FNB itself[28]
Obscure the anatomic detail, making the nodule more difficult to palpate [28]
Degeneration and loss of cellular morphology[28]
Occasionally more complications, usually haematomas, because it allows more vigorous
handling of the needle (authors' experience)
EMLA, Eutectic Mixture of Local Anesthetics; FNB, fine needle biopsy.
Post-FNB local pain can be relieved by applying an ice pack at the biopsy site. Readily accessible
ice packs that produce cold temperature with crushing can be used. Paracetamol (acetaminophen)
is also recommended.[28] Aspirin or nonsteroidal anti-inflammatory drugs (NSAID) for pain relief
should be avoided, although there is no direct evidence against them.
Haemorrhage and Haematomas
Similarly to pain, there are limited epidemiological data regarding incidence of haemorrhage and/or
haematomas during or after FNB. Haemorrhage during FNB may result in early discontinuation of
the procedure and contribute to inadequate cytological result, because of abundant blood on the
specimens.[46]
There is inconsistency in the reported incidence of haematomas during or after FNB in different
studies,[12,13,16,18] possibly due to definition or record biases. Intranodular haemorrhage within the
cystic part of a complex nodule after fluid aspiration is reported to be even more frequent. [17]
However, another study reported no intranodular haemorrhage after fluid aspiration. [47]
Haemorrhage is caused by venous extravasation into or around nodules. Factors that contribute to
the susceptibility to haemorrhage after FNB are: (i) the rich blood supply of the thyroid gland (even
richer in cases of goitre); (ii) the abnormally thin-walled veins of the thyroid nodules and (iii) the
intranodular arteriovenous shunts, which divert blood under high pressure to these weakened veins.
Straining during the procedure raises the central venous pressure contributing to haemorrhage.
Systemic arterial hypertension may also play a role in affected individuals.[27,48] An additional
mechanism for haemorrhaging soon after fluid aspiration in cystic/complex nodules is the sudden
reduction in intranodular pressure because of fluid evacuation.[17]
Severe bleeding diathesis is a relative contraindication to thyroid FNB.[26] Despite the absence of
direct evidence, FNB may be performed on a patient taking standard doses of aspirin or
anticoagulants ().[1,26]
the literature
Preventive measures
Small needle size

Haemorrhage/haematomas (small haematomas:
1/1)
Medical history for haemorrhaging risk factors,

FNB[26,27]
markedly
hypervascular
nodules
or
[28,29]
re-aspiration
vessels[30]
large vessels[5,30]
hours after FNB)[8]

initial one[33,34]
Infection (2/3)


Pain prevention
US guidance
Dysphagia (1/1)
evidence)
use
of
non-aspiration
technique
[3,17,28,39-43]
(FNC)
the needle[21]
if possible[3,28]


Small to moderate-sized haematomas do not require hospitalization,[18] are successfully managed
with cold compresses[16] and almost always spontaneously resolve in days.[3,5,8,28]
Massive Haematomas - Airway Obstruction
Only a few cases of uncontrolled haemorrhage and massive haematomas, requiring hospital
admission and more active intervention are reported in the literature.[8,27,31,48-50] A massive
haematoma may result in tracheal deviation and/or compression and may be fatal, if acute upper
airway obstruction develops rapidly. Clinical manifestations include increasing pain, swelling and
ecchymosis of the neck, dyspnoea, dysphonia and dysphagia. In severe cases, intubation and
decompression surgery (haematoma evacuation, ligation and/or thyroidectomy) may be required.
Neuritis Following Haematoma
One case of cervical neuritis following a post-FNB haematoma has been described.[32] Despite the
absence of cutaneous bruising or swelling, a large haematoma of the right thyroid lobe was
revealed on magnetic resonance imaging. The patient received paracetamol and was
symptom-free 5 months later. The proposed pathogenic mechanisms included chemical neuritis to
blood, allergic neuritis to anaesthetic or neuritis due to pressure from the large haematoma.
Pseudoaneurysm
Pseudoaneurysm is a haematoma in communication with the arterial lumen and appears as a
pulsatile mass in the neck. Although pseudoaneurysm is a well-known complication of vascular
injury, there is only one case report of post-US-FNB pseudoaneurysm (puncturing of the superior
thyroid artery).[51] Application of pressure was not sufficient to resolve it. Because of its rarity, no
standard treatment is proposed. Reduced activity is advisable. Although the pseudoaneurysm
healed spontaneously, selective embolization should be considered in cases of deterioration. [51]
Carotid Haematoma
A subendothelial carotid haematoma after US-FNB, with acute pain as the only symptom, has been
reported.[30] Pressure at the biopsy site spread the haematoma along the carotid wall. Reduced
activity in a head up position was advised. The haematoma was absorbed spontaneously within a
week. The authors suggested that acute, persistent pain during FNB may be indicative of carotid
puncture and that an US should follow to exclude haematoma formation.
Secondary Haemangioma
Although a post-FNB haematoma usually resolves completely with minimal scarring, it can rarely
give rise to unusual vascular and fibroblastic proliferation resembling to cavernous
haemangioma.[33,34,52]
Occasionally,
some
features
of
a
Masson's
intravascular
haemangioendothelioma (benign, reactive papillary hyperplasia), which mimics angiosarcoma may
be found.[33,34] In such a case, differential diagnosis is necessary to avoid radical surgery and
chemotherapy.[33,34,52]
Thyroid haemangioma should be suspected when repeated FNB yield only blood in unusual
quantity. Technetium-99 m-labelled erythrocyte scan should be considered, before invasive

diagnostic arteriography or surgery is performed.
Acute Transient Swelling
There are three case reports of acute transient swelling of the entire thyroid gland during[53,54] or
just after FNB.[55] Although FNB was performed on one lobe, swelling of both lobes and acute pain
without neck ecchymosis or airway obstruction were observed. Repeat FNB a week later in one
case did not reproduce the complication.[53]
The hyperacute swelling and its quick reversibility were indicative of vasodilation and capillary leak,
thereby excluding haemorrhage.[53,55] This was verified sonographically in one case.[54] All three
patients were subjected to thyroidectomy. In one case, medullary carcinoma positive for calcitonin
gene-related peptide could explain vasodilation and capillary leakage. [54] However, it is not a
sufficient explanation in the case of follicular carcinoma[53] and benign adenoma.[55] In the last
case,[55] local anaesthesia might have played a role.
Contrary to massive haemorrhage,[8,27,48-50] acute onset, quick recovery and absence of airway
obstruction or other local symptoms were observed in acute transient swelling. Acute swelling may
sound frightening, but, since it is self-limiting and transient, awareness helps avoiding unnecessary
interventions.
Delayed Transient Swelling
There is one case of painless swelling of prethyroid tissue, 24 h post-FNB.[56] No anaesthesia was
used. US showed oedematous infiltration of prethyroid tissue without haematoma. Corticosteroid
administration led to disappearance of the swelling 2 days later. [56] No comment is made by the
authors for the pathogenesis of this case, but a foreign body reaction cannot be excluded.
Infection
Thyroid infection is very rare, even in immunocompromised patients,[3] because of protective
mechanisms including rich blood supply, rich lymphatic drainage, high content of iodine and the
protective capsule surrounding the gland.[57] Direct seeding of pathogenic organisms has been
recognized as a possible, albeit rare, complication of FNB. [18,35-37,58,59] Opportunistic thyroid
infections post-FNB usually occur in patients with local (i.e. atopic dermatitis) or generalized
immunologic defects,[58,59] but have also been described in thyroid carcinoma[35] or healthy
individuals.[36] They are usually manifested as acute suppurative thyroiditis with high fever, chills,
painful neck swelling and even dysphagia and hoarseness a few days after FNB.[35,37,58,59] However,
milder manifestations have also been described.[36] If untreated, progressive respiratory distress or
odynophagia may arise.[37] Thyrotoxicosis as a result of a post-FNB infection has also been
reported.[59] The diagnosis is confirmed by FNB (usually yielding pus) and culture of the
aspirate.[36,59]
Prompt recognition favours the prognosis of acute suppurative thyroiditis. Treatment of choice is
drainage of pus followed by antibiotics.[58,59] Although the pus may soon disappear, symptoms and
signs may insist, because of local inflammation with fibrosis; in this case, thyroid resection is
advised.[37,59]
Recurrent Laryngeal Nerve Palsy
There are few cases of post-FNB recurrent laryngeal nerve injury resulting in unilateral transient
vocal cord palsy.[16,19,38] Usual symptoms are pain and swelling at the biopsy site immediately after
FNB followed by voice change and/or hoarseness. Spontaneous recovery is expected within 6
months,[19] but fear of malignancy may lead to unnecessary radical thyroidectomy.[38]
Proposed mechanisms include: stretching of the nerve over a thyroid haematoma and/or pressure
against the trachea; posthaemorrhaging inflammation and fibrosis around the nerve; thrombosis of
the minute artery during the acute phase; direct injury by the needle. A 23-G needle may cause only
partially nerve injury allowing faster recovery of vocal cord.[19,38]
Vasovagal Reaction
Post-FNB vasovagal reactions are not adequately studied; only a few cases have been
reported.[12,13,16,18,32] Post-FNB severe pain may play a role in their pathogenesis.
The symptoms usually last only 2-3 min, but they may be quite scary for the patient. Calming of the
patient and symptomatic treatment are advised.[28]
Tracheal Puncture
Although puncture of the trachea is a rational post-FNB complication given its anatomic location,
direct evidence for this complication is minimal with only one reported case.[13] Tracheal puncture is
clinically manifested with cough and/or haemoptysis, according to indirect data (CNB). Tracheal or
larynx puncture can be assumed in cases that cartilage fragments are seen in FNB specimens. [60]
Laryngoscopy could help to the differential diagnosis.
Dysphagia
One case of mild, transient dysphagia after a combination of US-FNB and US-CNB possibly due to
oesophageal puncture has been reported.[18] Since dyphagia is mainly a symptom of malignant
neck tumours, if it persists, it could lead to unnecessary thyroidectomy.
Needle Track Seeding (Tumour Implantation)
Despite the alarming in vitro observations, needle track seeding is very rare in vivo. Tumour cells
released into the surrounding tissues or circulation are probably destroyed by the host immune
response or other mechanisms before giving rise to clinically apparent metastases. The incidence
of tumour dissemination following FNB of thyroid carcinomas is estimated to be smaller than that of
abdominal carcinomas.[21] Additional protective mechanisms for the thyroid include: the use of
smaller needles; low malignant potential of well-differentiated thyroid carcinomas; adjuvant iodine
treatment; suppressive T4 therapy.[61] Implantation may be facilitated in cases of immunodeficiency
or untreated carcinomas.[61] Post-FNB cutaneous or muscular implantation have been described in
papillary,[20,21,39-41,62] follicular[42,61,63] and anaplastic carcinoma,[43] but not in medullary carcinoma,
thyroid lymphoma, other primary thyroid malignancy or metastatic carcinoma. Interestingly, in all
the above cases, a 23-G or larger needle was used.
In cases with a short interval between FNB and implantation, high cellular proliferative activity has
been reported.[21] It seems that tumour size and aggressiveness increase the risk of needle track
seeding.[21,42] Moreover, the implanted tumour may be more aggressive than the primary one. [21,63]
Although spontaneous cutaneous or muscular metastasis of thyroid carcinomas cannot be
excluded, implantation is more likely. Indications of needle track seeding rather than metastasis
are: (i) recurrence at the site of FNB (described in all the above cases); (ii) linear arrangement of
the skin and/or muscular seeding(s) and thyroid nodule; [21,40-42,62] (iii) implanted tumour location
away from the surgical incision;[41,42,62] (iv) absence of capsular or vascular invasion or
nodal/distant metastasis;[39,42,62,63] (v) existence of scar tissue surrounding the implant; [39] (vi)
absence of lymphoid or neurovascular tissue (which rules out the possibility of lymphatic
metastasis or perineural invasion); and [21,62] (vii) a central haemorrhagic papule on the implanted
lesion, suggestive of a previous needle injury.[43]
There is no evidence that needle track seeding affects long-term survival in patients with thyroid
carcinoma. Since survival is not affected in patients with more aggressive tumours, such as breast
and renal adenocarcinoma, the same could be assumed for thyroid carcinoma. [3,62] In any case, the
fear of this complication should not deter thyroid FNB application, since implanted tumours are very
rare and they can be surgically removed without recurrence.[21,63]
Needle Track Sinus
Two cases of post-FNB persistent discharging sinus at the needle insertion site have been
described.[20,44] The pathogenesis is unknown, although it was previously attributed to foreign body
reaction.[20]
Nodule Volume Alterations
In two prospective studies, no significant change in mean nodule volume was observed by US up to
6 months after FNB.[22,23] However, there was marked individual variation in the changes
(bi-directionally) which tended to cancel out any result for mean nodule volume. Changes
immediately after FNB were attributed to oedema, haemorrhage, necrosis or infarction. Changes
one or more months after the FNB were attributed to haemorrhage, necrosis, infarction or
fibrosis.[22,23] These changes could interfere with the interpretation of the effectiveness of
suppressive l-T4 therapy.[22,23]
Post-aspiration Thyrotoxicosis
There are two case reports with destructive thyrotoxicosis after FNB.[59,64] In a study with both
retrospective and prospective parts, post-aspiration thyrotoxicosis was identified in approximately
1% (n = 6) of the patients.[24] Thyroid hormone values in the cystic fluid in patients who developed
post-aspiration thyrotoxicosis were higher compared with patients who did not. The affected
patients experienced pain and/or cyst recurrence. One patient experienced sweating and
palpitations, whereas the remaining five were asymptomatic. Interestingly, thyrotoxicosis occurred
only in patients who had a cystic component in the nodule.[24,59,64]
The mechanism of post-aspiration thyrotoxicosis is unknown. The combination of some form of
thyroiditis and leakage of the thyroid content into the cyst might trigger the release of thyroid
hormone into the circulation.[24]
Repeat FNB in case of cyst recurrence and administration of NSAID or prednisone may help to
decrease serum thyroid hormone levels in post-aspiration thyrotoxicosis. However, most patients
will be improved without any specific treatment.[24]
Comparison between FNA and FNC
It has been proposed that FNC reduces trauma to cells and tissues, resulting in less pain, less
haemorrhage and specimens of higher quality;[29] however, this was not proved in all studies.
Similarly, some authors found higher,[29] while others comparable adequacy rates[65] between FNA
and FNC. In a meta-analysis, no method was found superior to the other. [66] No study has directly
compared the complication rate between FNA and FNC.
Comparison between P-FNB and US-FNB
US guidance enhances the diagnostic accuracy of FNB, as it helps the physician to direct the
needle tip to the desirable site.[67] It also helps to avoid adjacent structures, that is vessels in close
vicinity to the nodule or areas of central necrosis, which often yield nondiagnostic specimens. [25,29]
However, no study has to date compared P-FNB vs. US-FNB on the same nodules. US-FNB is
usually performed on smaller nodules than P-FNB, which results in selection bias in most published
studies.[68]
Routine use of US-FNB is not recommended due to cost considerations.[1,2,26] When US-FNB is
performed, care should be taken to avoid contamination of the specimens with US gel. Although
US-FNB is expected to further diminish the already limited FNB complications, there is not
sufficient direct evidence from the comparative studies of P-FNB vs. US-FNB. Anyway, even US
guidance does not nullify the post-FNB complications ().
References
per
of patients
gauge (G)
Additional
information
Pain/Discomfort
13/221
P-FNA/na
Overall
complication rate
86% / persistent
pain or discomfort
up to several days
(Silverman
Retrospective,
[13]
et al., 1986)
observational/3
1/309
P-FNA/22
Overall
45/49
[14]
al., 2007)
double-blinded,
complication rate
19% / persistent
patient
US-FNA/25
Indirect evidence
from
placebo
group: 16, 14 and
15
patients
reported
mild,
moderate
and
severe
pain
respectively and
only 4 no pain
46/52
[15]
al., 2007)
double-blinded,
US-FNA/25
Indirect evidence
from
placebo
group: 17, 14 and
15
patients
reported
mild,
moderate
and
severe
pain
respectively and
only 6 no pain
P-FNA/na
Moderate
to
severe
local
swelling
(3
patients) / small
subcutaneous
haematomas (2
patients)
/
spontaneous
resolution
(Silverman
[13]
et al., 1986)
section)
P-FNA/22
al., 2000)[16]
observational/3
US-FNA/22-25
15/234
Overall
complication rate
85% / higher
complication rate
for nodules 15
cm

2001)[17]
cohort/2
11/42
US-FNA/23 or 25
Nodules after fluid

aspiration/
intranodular
haemorrhage

vs. Overall
2008)[18]
control/3
8/320
(FNA+CNB)
1% (FNA) vs.
31% (FNA+CNB)
al., 2006)[19]
observational/3
4/10,974
P-FNA/23
All benign nodules

/
spontaneous
recovery
P-FNA/22
Transient
bradycardia
Vasovagal
reactions
(Silverman
[13]
et al., 1986)
section)
and
faintness / quick
response
symptomatic
to
therapy
P-FNA/na

2000)[16]
haematomas
section)
US-FNA/22-25
Duration less than

10 min / no
therapy

vs. Dizziness,
2008)[18]
haematomas
2/320
section)
(FNA+CNB)
presyncope

1980)
(Ito
[20]
observational/3
et
al., Retrospective,
observational/3
2005)[21]
1/54
10/4912
P-FNA
and/or 1
Cutaneous
CNB/na
seeding 6 months
post-FNA/ surgery
(surgical series)
US-FNA/22
All seedings
linear
in
arrangement from
the skin to the
nodule / between
2 months and 11
years post-FNA /
6 cases were
poorly
differentiated
carcinomas / 5
cases with nodal
metastasis / 7
cases
with
extrathyroid
extension
/
surgery
al., 1999)[22]
cohort/2
6/17**
US-FNA/22
No
statistical
difference
in
mean volume /
marked individual
bi-directional
variation
(Guney
et Prospective,
[23]
al., 2003)
cohort/2
6/46**
US-FNA/na
No
statistical
difference
in
mean volume /
marked individual
bi-directional
variation
5/500
part (retrospective)

followed
by and
prospective part/3
(prospective)
free T4, T3 and

CRP, supressed
TSH,
negative
anti-microsomal
antibodies,
low
I123 uptake at 24
h / 2-20 days
post-FNA
According to the definitions of the American Association of Clinical Endocrinologists. [11] The total
General Conditions for Best Outcome - A Synopsis
Clinical assessment before FNB is essential to select patients at greater risk for complications (i.e.
immunocompromised or patients with history or signs of bleeding diathesis) and choose the best
technique (i.e. US-FNC in nodules non-palpable or in close vicinity to carotid or trachea). It is
suggested that the physician should previously describe the procedure and its potential
complications to the patient and reassure him for the simplicity of the procedure and the rarity of
serious complications.[1,26]
If rapid cytological evaluation during the procedure is not feasible, multiple passes should be
performed.[46] There are not enough data to assess the role of the number of passes on diagnostic
accuracy and safety. However, no more than 5 passes are recently recommended, because of the
small increase in adequacy rate and the potential increase in morbidity and trauma with additional
passes.[28] Since increasing diameter of the needle increases the incidence of complications, [3,7]
without affecting adequacy rate,[29] the use of a 25-G needle with or without aspiration is
recommended for solid nodules. FNC may be a better choice for complex nodules. A 23-G needle
should be used in cystic nodules, to evacuate as much of the fluid as possible. [46]
Observation during FNB could early detect a complication and stop the procedure before a more
extensive trauma occurs.[3] After FNB, the biopsy site should be compressed against the trachea
with a bandage for about 2-3 min and then a small bandage should be applied. [28] Restriction on
activity is not necessary for most patients.[28] An empirical 30-min observation period post-FNB to
detect progressive swelling or ecchymosis is suggested.[3,7,28] After discharging home, the patient
should receive instructions to seek medical care, if sudden swelling or unrelenting pain occurs. An
information sheet with post-procedural guidelines and an emergency number is recommended. [28]
Expertise in any level of the procedure is critical for good results. In medical centres with
long-standing experience diagnostic accuracy is increased.[7,68,69] Not only may lack of expertise be
accompanied by a high complication rate, but may also lead to a high failure rate, which in turn
increases surgery rate and associated complications and morbidity.[8]
Conclusion
Most complications following fine-needle biopsy (mainly pain and small haematomas) have low
morbidity and are self-limited. Serious complications, such as massive haematomas, infections and
tumour dissemination, are very rare and can be sufficiently managed, if both the physician is aware
and the patient is informed. Given that fine-needle biopsy has halved the percentage of patients
subjected to thyroidectomy and the large number of fine-needle biopsies performed worldwide
everyday, the overall safety of the procedure is not questioned. In any case, physicians should
always weigh the risk-benefit ratio on an individual basis before the procedure.
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Correspondence
Stergios Polyzos, Endocrinologist, 13 Simou Lianidi str., 55134 Thessaloniki, Greece.Tel.: +30
2310 424710; Fax: +30 2310 424710; E-mail: stergios@endo.gr
Clin Endocrinol. 2009;71(2):157-165. 2009 Blackwell Publishing

Complications Thyroid Biopsy

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Complications Thyroid Biopsy

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Clinical Complications Following Thyroid Fine-needle Biopsy: A Systematic Review

Stergios A. Polyzos; Athanasios D. Anastasilakis

(Braga et al., Prospective,

Nodules after fluid

(Khoo et al., Retrospective, case 3/311 (FNA) vs. US-FNA/na

All benign nodules

(Newkirk et al., (see haemorrhage / 3/234

Duration less than

(Khoo et al., (see haemorrhage / 2/311 (FNA) vs. US-FNA/na

Needle track seeding of papillary carcinoma

P-FNA/18-23 (cystic Affected patients

free T4, T3 and

Pain/discomfort (up to 92%/1)

Small needle size

in reduction of adjacent tissue damage)[9]

including drugs (aspirin, other anti-platelet

Acute transient swelling(1/1)

Delayed transient swelling(1/1)

Alcohol cleansing and iodine skin prep at

Recurrent laryngeal nerve palsy (0036-09%/2)

Small needle size[38]

Vasovagal reaction (05-13%/1)

Tracheal puncture (03%/1)

Small needle size (23-G or smaller)[44]

Nodule volume alterations(13-35%/1)

US, ultrasound; US-FNB, ultrasound-guided biopsy.

Pain/discomfort (up to 92%/1)

Small needle size

Haemorrhage/haematomas (small haematomas:

Medical history for haemorrhaging risk factors,

should be advised to report to the emergency

Alcohol cleansing and iodine skin prep at

Recurrent laryngeal nerve palsy (0036-09%/2)

Small needle size[38]

Vasovagal reaction (05-13%/1)

Tracheal puncture (03%/1)

Small needle size (23-G or smaller)[44]

Nodule volume alterations(13-35%/1)

(Ramacciotti (see pain/discomfort 5/221

(Braga et al., Prospective,

Nodules after fluid

(Khoo et al., Retrospective, case 3/311 (FNA) vs. US-FNA/na

All benign nodules

(Ramacciotti (see pain/discomfort 1/221

Duration less than

et al., 1984)[12] section)

(Newkirk et al., (see haemorrhage / 3/234

(Khoo et al., (see haemorrhage / 2/311 (FNA) vs. US-FNA/na

Nodule volume alterations

Application of an ice pack on the neck before FNB[28]

Pain/discomfort (up to 92%/1)

Small needle size

Medical history for haemorrhaging risk factors,

evacuation of the fluid[17]

Alcohol cleansing and iodine skin prep at

Recurrent laryngeal nerve palsy (0036-09%/2)

Small needle size[38]

Vasovagal reaction (05-13%/1)

Tracheal puncture (03%/1)

Small needle size (23-G or smaller)[44]

Nodule volume alterations(13-35%/1)

quantity. Technetium-99 m-labelled erythrocyte scan should be considered, before invasive

(Braga et al., Prospective,

Nodules after fluid