Complications Thyroid Biopsy

7/25/2019 Complications Thyroid Biopsy

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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 costof 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


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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

complication

Study type/level of

evidence

Case(s)/number

of patients

Technique/needle's

gauge (G)

Additional

information

Pain/Discomfort

(Ramacciotti

et al., 1984)[12]

Retrospective,

observational/3

13/221 P-FNA/na Overall

complication rate

86% / persistent

pain or discomfort

up to several days

(Silverman

et al., 1986)[13]

Retrospective,

observational/3

1/309 P-FNA/22 Overall

complication rate

19% / persistent

pain (for 24 h) in 1

patient

(Gursoy et

al., 2007)[14]

Randomized

double-blinded,

placebo-controlled/2

45/49 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

(Gursoy et

al., 2007)[15]

Randomized

double-blinded,



from placebo

group: 17, 14 and

15 patients

reported mild,

moderate and


3/30

severe pain

respectively and

only 6 no pain

Haemorrhage/Haematomas

(Ramacciotti

et al., 1984)[12]

(see pain/discomfort

section)

5/221 P-FNA/na Moderate to

severe local

swelling (3

patients) / small

subcutaneous

haematomas (2

patients) /

spontaneous

resolution

(Silverman

et al., 1986)[13]


section)

1/309 P-FNA/22

(Newkirk et

al., 2000)[16]

Retrospective,

observational/3

15/234 US-FNA/22-25 Overall

complication rate

85% / higher

complication rate

for nodules 15

cm

(Braga et al.,

2001)[17]

Prospective,

cohort/2

11/42 US-FNA/23 or 25 Nodules after fluid

aspiration/

intranodular

haemorrhage

(Khoo et al.,

2008)[18]

Retrospective, case

control/3

3/311 (FNA) vs.

8/320

(FNA+CNB)

US-FNA/na vs.

US-FNA+US-CNB/na

Overall

complication rate

1% (FNA) vs.

31% (FNA+CNB)

Recurrent laryngeal nerve palsy

(Tomoda et

al., 2006)[19]

Retrospective,

observational/3

4/10,974 P-FNA/23 All benign nodules

/ spontaneous

recovery

Vasovagal

reactions

(Silverman

et al., 1986)[13]


section)

2/309 P-FNA/22 Transient

bradycardia and

faintness / quick


4/30

response to

symptomatic

therapy

(Ramacciotti

et al., 1984)[12]


section)

1/221 P-FNA/na Duration less than

10 min / no

therapy

(Newkirk et al.,

2000)[16]

(see haemorrhage /

haematomas

section)

3/234 US-FNA/22-25

(Khoo et al.,

2008)[18]

(see haemorrhage /

haematomas

section)

2/311 (FNA) vs.

2/320

(FNA+CNB)

US-FNA/na vs.

US-FNA+US-CNB/na

Dizziness,

bradycardia,

presyncope

Needle track seeding of papillary carcinoma

(Block et al.,

1980)[20]

Retrospective,

observational/3

1/54 P-FNA and/or

CNB/na

1 Cutaneous

seeding 6 months

post-FNA/ surgery

(surgical series)

(Ito et al.,

2005)[21]

Retrospective,

observational/3

10/4912 US-FNA/22 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 nodalmetastasis / 7

cases with

extrathyroid

extension /

surgery

Nodule volume alterations

(Gordon et

al., 1999)[22]

Prospective,

cohort/2

6/17** US-FNA/22 No statistical

difference in

mean volume /

marked individual


5/30

bi-directional

variation

(Guney et

al., 2003)[23]

Prospective,

cohort/2

6/46** US-FNA/na No statistical

difference in

mean volume /

marked individualbi-directional

variation

Post-aspiration thyrotoxicosis

(Kobayashi

et al., 1992)[24]

Retrospective,

observational part

followed by

prospective part/3

5/500

(retrospective)

and 1/115

(prospective)

P-FNA/18-23 (cystic

nodules) and 22-23

(solid nodules)

Affected patients

had high serum

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


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in reduction of adjacent tissue damage)[9]

Haemorrhage/haematomas (small haematomas:

03-26%/1; massive haematomas: 2/3; neuritis

following haematoma: 1/3; pseudoaneurysm: 1/2;

carotid haematoma: 1/1; secondary haemangioma:

1/1)

Medical history for haemorrhaging risk factors,

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)


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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:

014%/3; follicular carcinoma: 1/3; anaplastic

carcinoma: 1/3; other thyroid malignancies: no

evidence)

Small needle size (23-G or smaller)[3,28,39-43]

Suction release before needle withdrawal or

use of non-aspiration technique

(FNC)[3,17,28,39-43]

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;


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


the literature










in reduction of adjacent tissue damage)

[9]





1/1)











FNB[26,27]




FNC instead of FNA in nodules close to largevessels[30]


large vessels[5,30]




bleeding diathesis)[1,3,8,28]




9/30



hours after FNB)[8]








initial one[33,34]














Dysphagia (1/1)




evidence)




(FNC)[3,17,28,39-43]

Avoidance an excessive piston-like motion of

the needle[21]



10/30

if possible[3,28]





(1%/2)






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


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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

complication

Study type/level of

evidence

Case(s)/number

of patients

Technique/needle's

gauge (G)

Additional

information

Pain/Discomfort

(Ramacciotti

et al., 1984)[12]

Retrospective,

observational/3


complication rate

86% / persistent

pain or discomfortup to several days

(Silverman

et al., 1986)[13]

Retrospective,

observational/3


complication rate

19% / persistent


patient

(Gursoy et

al., 2007)[14]

Randomized

double-blinded,



from placebo

group: 16, 14 and

15 patients

reported mild,

moderate and

severe pain

respectively and

only 4 no pain

(Gursoy et

al., 2007)[15]

Randomized

double-blinded,



from placebo

group: 17, 14 and

15 patients

reported mild,

moderate and

severe pain

respectively and

only 6 no pain



12/30

(Ramacciotti

et al., 1984)[12]


section)


severe local

swelling (3

patients) / small

subcutaneous

haematomas (2

patients) /

spontaneous

resolution

(Silverman

et al., 1986)[13]


section)

1/309 P-FNA/22

(Newkirk et

al., 2000)[16]

Retrospective,

observational/3


complication rate

85% / highercomplication rate

for nodules 15

cm

(Braga et al.,

2001)[17]

Prospective,

cohort/2


aspiration/

intranodular

haemorrhage

(Khoo et al.,

2008)[18]

Retrospective, case

control/3

3/311 (FNA) vs.

8/320

(FNA+CNB)

US-FNA/na vs.

US-FNA+US-CNB/na

Overall

complication rate

1% (FNA) vs.

31% (FNA+CNB)


(Tomoda et

al., 2006)[19]

Retrospective,

observational/3


/ spontaneous

recovery

Vasovagal

reactions

(Silverman

et al., 1986)[13]


section)


bradycardia and

faintness / quick

response to

symptomatic

therapy

(Ramacciotti (see pain/discomfort 1/221 P-FNA/na Duration less than


13/30

et al., 1984)[12] section) 10 min / no

therapy

(Newkirk et al.,

2000)[16]

(see haemorrhage /

haematomas

section)

3/234 US-FNA/22-25

(Khoo et al.,

2008)[18]

(see haemorrhage /

haematomas

section)

2/311 (FNA) vs.

2/320

(FNA+CNB)

US-FNA/na vs.

US-FNA+US-CNB/na

Dizziness,

bradycardia,

presyncope


(Block et al.,

1980)[20]

Retrospective,

observational/3

1/54 P-FNA and/or

CNB/na

1 Cutaneous

seeding 6 months

post-FNA/ surgery

(surgical series)

(Ito et al.,

2005)[21]

Retrospective,

observational/3


linear

arrangement from

the skin to the

nodule / between

2 months and 11

years post-FNA /

6 cases werepoorly

differentiated

carcinomas / 5

cases with nodal

metastasis / 7

cases with

extrathyroid

extension /

surgery


(Gordon et

al., 1999)[22]

Prospective,

cohort/2


difference in

mean volume /

marked individual

bi-directional

variation

(Guney et

al., 2003)[23]

Prospective,

cohort/2


difference in


14/30

mean volume /

marked individual

bi-directional

variation


(Kobayashi

et al., 1992)[24]

Retrospective,

observational part

followed by

prospective part/3

5/500

(retrospective)

and 1/115

(prospective)

P-FNA/18-23 (cystic

nodules) and 22-23

(solid nodules)

Affected patients

had high serum

free T4, T3 and

CRP, supressed

TSH, negative

anti-microsomal

antibodies, low

I123 uptake at 24

h / 2-20 dayspost-FNA






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;


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]


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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






16/30






in reduction of adjacent tissue damage)[9]





1/1)











FNB[26,27]




FNC instead of FNA in nodules close to largevessels[30]


large vessels[5,30]




bleeding diathesis)

[1,3,8,28]





hours after FNB)[8]







17/30



initial one[33,34]














Dysphagia (1/1)




evidence)




(FNC)[3,17,28,39-43]

Avoidance an excessive piston-like motion ofthe needle[21]


if possible[3,28]




Post-aspiration thyrotoxicosis(1%/2)




18/30




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

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 apulsatile 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


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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 maysound 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.

InfectionThyroid 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


20/30

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 orlarynx 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 vitroobservations, needle track seeding is very rare in vivo. Tumour cellsreleased 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)


21/30

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 approximately1% (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


22/30

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

complication

Study type/level of

evidence

Case(s)/number

of patients

Technique/needle's

gauge (G)

Additional

information

Pain/Discomfort

(Ramacciotti

et al., 1984)[12]

Retrospective,

observational/3


complication rate

86% / persistent

pain or discomfort

up to several days

(Silverman

et al., 1986)[13]

Retrospective,

observational/3


complication rate

19% / persistent


patient

(Gursoy et

al., 2007)[14]

Randomized

double-blinded,



from placebo

group: 16, 14 and

15 patients

reported mild,

moderate and

severe pain

respectively and

only 4 no pain

(Gursoy et

al., 2007)[15]

Randomized

double-blinded,



from placebo

group: 17, 14 and

15 patients

reported mild,

moderate and


23/30

severe pain

respectively and

only 6 no pain


(Ramacciotti

et al., 1984)[12]


section)


severe local

swelling (3

patients) / small

subcutaneous

haematomas (2

patients) /

spontaneous

resolution

(Silverman

et al., 1986)[13]


section)

1/309 P-FNA/22

(Newkirk et

al., 2000)[16]

Retrospective,

observational/3


complication rate

85% / higher

complication rate

for nodules 15

cm

(Braga et al.,

2001)[17]

Prospective,

cohort/2


aspiration/

intranodular

haemorrhage

(Khoo et al.,

2008)[18]

Retrospective, case

control/3

3/311 (FNA) vs.

8/320

(FNA+CNB)

US-FNA/na vs.

US-FNA+US-CNB/na

Overall

complication rate

1% (FNA) vs.

31% (FNA+CNB)


(Tomoda et

al., 2006)[19]

Retrospective,

observational/3


/ spontaneous

recovery

Vasovagal

reactions

(Silverman

et al., 1986)[13]


section)


bradycardia and

faintness / quick


24/30

response to

symptomatic

therapy

(Ramacciotti

et al., 1984)[12]


section)

1/221 P-FNA/na Duration less than

10 min / no

therapy

(Newkirk et al.,

2000)[16]

(see haemorrhage /

haematomas

section)

3/234 US-FNA/22-25

(Khoo et al.,

2008)[18]

(see haemorrhage /

haematomas

section)

2/311 (FNA) vs.

2/320

(FNA+CNB)

US-FNA/na vs.

US-FNA+US-CNB/na

Dizziness,

bradycardia,

presyncope


(Block et al.,

1980)[20]

Retrospective,

observational/3

1/54 P-FNA and/or

CNB/na

1 Cutaneous

seeding 6 months

post-FNA/ surgery

(surgical series)

(Ito et al.,

2005)[21]

Retrospective,

observational/3


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 nodalmetastasis / 7

cases with

extrathyroid

extension /

surgery


(Gordon et

al., 1999)[22]

Prospective,

cohort/2


difference in

mean volume /

marked individual


25/30

bi-directional

variation

(Guney et

al., 2003)[23]

Prospective,

cohort/2


difference in

mean volume /

marked individualbi-directional

variation


(Kobayashi

et al., 1992)[24]

Retrospective,

observational part

followed by

prospective part/3

5/500

(retrospective)

and 1/115

(prospective)

P-FNA/18-23 (cystic

nodules) and 22-23

(solid nodules)

Affected patients

had high serum

free T4, T3 and

CRP, supressed

TSH, negative

anti-microsomal

antibodies, low

I123 uptake at 24

h / 2-20 days

post-FNA






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;


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 thesmall 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


26/30

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 lowmorbidity 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:[email protected]

Clin Endocrinol. 2009;71(2):157-165. 2009 Blackwell Publishing
mailto:[email protected]:[email protected]:[email protected]:[email protected]

Complications Thyroid Biopsy

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