MEDICINE
REVIEW ARTICLE
Fine Needle Aspiration in the Investigation of Thyroid Nodules Indications, Procedures and Interpretation Joachim Feldkamp, Dagmar Führer, Markus Luster, Thomas J. Musholt, Christine Spitzweg, Matthias Schott
SUMMARY Background: Thyroid nodules are a common finding in Germany. Most are benign; thyroid cancer is very rare. The challenge for the physician is to diagnose malignant tumors early. Fine needle aspiration is an important tool for this purpose. Method: This review is based on pertinent articles (1980–2014) retrieved by a selective search in PubMed and on the current recommendations of guidelines issued by the specialty societies in Germany and abroad. Results: Clinical, ultrasonographic, and scintigraphic criteria are used to identify high-risk nodules, which are then further studied by fine needle aspiration. Important ultrasonographic criteria for malignancy are low echodensity (positive predictive value [PPV]: 1.85), microcalcifications (PPV: 3.65), irregular borders (PPV: 3.76), and intense vascularization. Fine needle aspiration of the thyroid gland is an inexpensive and technically straightforward diagnostic procedure that causes little discomfort for the patient. It helps prevent unnecessary thyroid surgery and is used to determine the proper surgical strategy if malignancy is suspected. The cytological study of fine needle aspirates enables highly precise diagnosis of many tumor entities, but follicular neoplasia can only be diagnosed histologically. In the near future, molecular genetic methods will probably extend the diagnostic range of fine needle aspiration beyond what is currently achievable with classic cytology. Conclusion: Fine needle aspiration biopsy of the thyroid gland in experienced hands is an easily performed diagnostic procedure with very little associated risk. It should be performed on ultrasonographically suspect nodules for treatment stratification and before any operation for an unclear nodular change in the thyroid gland. ►Cite this as: Feldkamp J, Führer D, Luster M, Musholt TJ, Spitzweg C, Schott M: Fine needle aspiration in the investigation of thyroid nodules—indications, procedures and interpretation. Dtsch Arztebl Int 2016; 113: 353–9. DOI: 10.3238/arztebl.2016.0353
Clinic for General Internal Medicine, Endocrinology, Diabetology, Pneumology, and Infectiology; Bielefeld Clinical Centre, Germany: PD Dr. med. Feldkamp Department of Endocrinology and Metabolic Disorders, Essen University Hospital, Germany: Prof. Dr. Dr. med. Führer Department of Nuclear Medicine, Philipps University Marburg, Germany: Prof. Dr. med. Luster Department of General, Abdominal and Transplantation Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany: Prof. Dr. med. Musholt Department of Internal Medicine II, Hospital of the University of Munich, Germany: Prof. Dr. med. Spitzweg Division of Special Endocrinology, University Hospital of Düsseldorf: Prof. Dr. med. Schott
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2016; 113: 353–9
enign thyroid nodules are common in Germany (1–3). One contributing factor is iodine deficiency, which was prevalent in the country until the beginning of the millennium, but has now been mitigated by the increased use of iodized table salt in private homes, the food industry and animal production. Thyroid cancer is rare and accounts for less than 1% of all space-occupying lesions of the thyroid (e1). Fine needle aspiration (FNA) biopsy is considered the gold standard diagnostic tool for thyroid nodules. Benign FNA results help to prevent unnecessary thyroid surgery. If malignant cells are detected, the FNA result is a decisive factor in determining the surgical strategy (hemithyroidectomy vs. total thyroidectomy, extent of lymph node dissection). The indication, significance, limitations, and potential risks of FNA are discussed below in detail.
B
Methods The article is based on a review of pertinent articles (1980–2014) that were retrieved by a selective search in the PubMed database employing the search terms “thyroid nodules” and “biopsy“. In addition, the reference sections in the identified original articles and reviews were analyzed. Furthermore, current recommendations of national and international professional societies (European Thyroid Association, British Thyroid Association, and American Thyroid Association) were taken into consideration (4–8).
Criteria for malignancy Thyroid cancer can already be suspected based on a patient’s clinical history and certain physical examination findings, such as a firm, rapidly growing cervical mass or, less frequently, symptoms of a space-occupying lesion. If this is the case, ultrasonography is indicated for immediate diagnostic evaluation. Should the results be conspicuous, FNA is indicated and, where required, scintigraphy. A history of neck radiation is associated with an increased risk of thyroid cancer. An analysis of pooled data calculated an excess relative risk per Gray radiation dose of 7.7, with an almost linear increase (9). While well-differentiated thyroid carcinoma is rarely hereditary, approximately 25% of medullary thyroid cancer has a genetic cause (e2). Newly developed hoarseness as well as firm palpable lymph nodes may be a sign of thyroid malignancy (e3, e4).
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MEDICINE
TABLE 1a Sonographic patterns, estimated risk of malignancy, and fine needle aspiration guidance for thyroid nodules* Sonographic pattern
Ultrasound features
Estimated risk of malignancy, %
FNA size cutoff (largest dimension)
High suspicion
Solid hypoechoid nodule or solid hypoechoic component of a partially cystic nodule with one or more of the following features: irregular margins (infiltrative, microlobulated), microcalcifications, taller than wide shape, rim calcifications with small extrusive soft tissue component, evidence of ETE.
>70–90*1
Recommend FNA at ≥ 1 cm
Intermediate suspicion
Hypoechoic solid nodule with smooth margins without microcalcifications, ETE, or taller than wide shape .
10–20
Recommend FNA at ≥ 1 cm
Low suspicion
Isoechoic or hyperechoid solid nodule, or partially cystic nodule with eccentric solid areas, without microcalcification, irregular margin or ETE, or taller than wide shape.
5–10
Recommend FNA at ≥ 1,5 cm
Very low suspicion
Spongiform or partially cystic nodules without any of the sonographic features described in low, intermediate, or high suspicion patterns.
1 cm with at least two ultrasound criteria for malignancy ● Nodules of any size with extracapsular extension or indeterminate cervical lymph nodes ● Nodules of any size in patients with a history of neck radiation ● History of well-differentiated thyroid carcinoma in more than two first-degree relatives ● Medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) type 2 ● Increased calcitonin levels. Smoking, proton-pump inhibitors, renal failure, and chronic alcohol consumption may lead to a mild to moderate increase in calcitonin levels (check abstinence levels, where appropriate). Fine needle aspiration biopsy should explicitly not be performed if the nodule represents an area of focal autonomy on thyroid scintigraphy and/or has no ultrasound features suspicious of malignancy. Needle biopsy of simple cysts is not advisable. Complications The range of complications associated with FNA biopsy is very small. Pain: Data on pain associated with FNA are scarce. A mild pain was reported by 8.9% of patients who underwent FNA biopsy (e10). Bleeding: Easily comparable epidemiological data on the occurrence of bleeding events during or after thyroid FNA biopsy are not available because of the retrospective design of the majority of studies and the
356
use of different techniques and needle sizes. The published bleeding rates range between 0.3% and 2.3% (e11, e12). Metastatic spread: In patients with thyroid cancer, metastasis along the needle canal is extremely rare and only few individual case reports have been published (19). This is because well-differentiated thyroid carcinoma, the most common form of thyroid malignancy, is treated with radioiodine therapy which would also eliminate any cancer cells spread during the FNA. The risk of local tumor cell spread is almost always limited to the highly malignant anaplastic carcinoma. Needle biopsy in patients with anticoagulation therapy Needle biopsy in patients taking acetylsalicylic acid (ASA, aspirin) can be performed without an increased risk up to a dose of 100 mg ASA (20). Patients receiving higher doses of ASA should pause treatment for 10 days prior to the intervention. In patients taking phenprocoumon/coumadin, it is recommended to hold anticoagulation therapy until the INR (International Normalized Ratio) is
REVIEW ARTICLE
Fine Needle Aspiration in the Investigation of Thyroid Nodules Indications, Procedures and Interpretation Joachim Feldkamp, Dagmar Führer, Markus Luster, Thomas J. Musholt, Christine Spitzweg, Matthias Schott
SUMMARY Background: Thyroid nodules are a common finding in Germany. Most are benign; thyroid cancer is very rare. The challenge for the physician is to diagnose malignant tumors early. Fine needle aspiration is an important tool for this purpose. Method: This review is based on pertinent articles (1980–2014) retrieved by a selective search in PubMed and on the current recommendations of guidelines issued by the specialty societies in Germany and abroad. Results: Clinical, ultrasonographic, and scintigraphic criteria are used to identify high-risk nodules, which are then further studied by fine needle aspiration. Important ultrasonographic criteria for malignancy are low echodensity (positive predictive value [PPV]: 1.85), microcalcifications (PPV: 3.65), irregular borders (PPV: 3.76), and intense vascularization. Fine needle aspiration of the thyroid gland is an inexpensive and technically straightforward diagnostic procedure that causes little discomfort for the patient. It helps prevent unnecessary thyroid surgery and is used to determine the proper surgical strategy if malignancy is suspected. The cytological study of fine needle aspirates enables highly precise diagnosis of many tumor entities, but follicular neoplasia can only be diagnosed histologically. In the near future, molecular genetic methods will probably extend the diagnostic range of fine needle aspiration beyond what is currently achievable with classic cytology. Conclusion: Fine needle aspiration biopsy of the thyroid gland in experienced hands is an easily performed diagnostic procedure with very little associated risk. It should be performed on ultrasonographically suspect nodules for treatment stratification and before any operation for an unclear nodular change in the thyroid gland. ►Cite this as: Feldkamp J, Führer D, Luster M, Musholt TJ, Spitzweg C, Schott M: Fine needle aspiration in the investigation of thyroid nodules—indications, procedures and interpretation. Dtsch Arztebl Int 2016; 113: 353–9. DOI: 10.3238/arztebl.2016.0353
Clinic for General Internal Medicine, Endocrinology, Diabetology, Pneumology, and Infectiology; Bielefeld Clinical Centre, Germany: PD Dr. med. Feldkamp Department of Endocrinology and Metabolic Disorders, Essen University Hospital, Germany: Prof. Dr. Dr. med. Führer Department of Nuclear Medicine, Philipps University Marburg, Germany: Prof. Dr. med. Luster Department of General, Abdominal and Transplantation Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany: Prof. Dr. med. Musholt Department of Internal Medicine II, Hospital of the University of Munich, Germany: Prof. Dr. med. Spitzweg Division of Special Endocrinology, University Hospital of Düsseldorf: Prof. Dr. med. Schott
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2016; 113: 353–9
enign thyroid nodules are common in Germany (1–3). One contributing factor is iodine deficiency, which was prevalent in the country until the beginning of the millennium, but has now been mitigated by the increased use of iodized table salt in private homes, the food industry and animal production. Thyroid cancer is rare and accounts for less than 1% of all space-occupying lesions of the thyroid (e1). Fine needle aspiration (FNA) biopsy is considered the gold standard diagnostic tool for thyroid nodules. Benign FNA results help to prevent unnecessary thyroid surgery. If malignant cells are detected, the FNA result is a decisive factor in determining the surgical strategy (hemithyroidectomy vs. total thyroidectomy, extent of lymph node dissection). The indication, significance, limitations, and potential risks of FNA are discussed below in detail.
B
Methods The article is based on a review of pertinent articles (1980–2014) that were retrieved by a selective search in the PubMed database employing the search terms “thyroid nodules” and “biopsy“. In addition, the reference sections in the identified original articles and reviews were analyzed. Furthermore, current recommendations of national and international professional societies (European Thyroid Association, British Thyroid Association, and American Thyroid Association) were taken into consideration (4–8).
Criteria for malignancy Thyroid cancer can already be suspected based on a patient’s clinical history and certain physical examination findings, such as a firm, rapidly growing cervical mass or, less frequently, symptoms of a space-occupying lesion. If this is the case, ultrasonography is indicated for immediate diagnostic evaluation. Should the results be conspicuous, FNA is indicated and, where required, scintigraphy. A history of neck radiation is associated with an increased risk of thyroid cancer. An analysis of pooled data calculated an excess relative risk per Gray radiation dose of 7.7, with an almost linear increase (9). While well-differentiated thyroid carcinoma is rarely hereditary, approximately 25% of medullary thyroid cancer has a genetic cause (e2). Newly developed hoarseness as well as firm palpable lymph nodes may be a sign of thyroid malignancy (e3, e4).
353
MEDICINE
TABLE 1a Sonographic patterns, estimated risk of malignancy, and fine needle aspiration guidance for thyroid nodules* Sonographic pattern
Ultrasound features
Estimated risk of malignancy, %
FNA size cutoff (largest dimension)
High suspicion
Solid hypoechoid nodule or solid hypoechoic component of a partially cystic nodule with one or more of the following features: irregular margins (infiltrative, microlobulated), microcalcifications, taller than wide shape, rim calcifications with small extrusive soft tissue component, evidence of ETE.
>70–90*1
Recommend FNA at ≥ 1 cm
Intermediate suspicion
Hypoechoic solid nodule with smooth margins without microcalcifications, ETE, or taller than wide shape .
10–20
Recommend FNA at ≥ 1 cm
Low suspicion
Isoechoic or hyperechoid solid nodule, or partially cystic nodule with eccentric solid areas, without microcalcification, irregular margin or ETE, or taller than wide shape.
5–10
Recommend FNA at ≥ 1,5 cm
Very low suspicion
Spongiform or partially cystic nodules without any of the sonographic features described in low, intermediate, or high suspicion patterns.
1 cm with at least two ultrasound criteria for malignancy ● Nodules of any size with extracapsular extension or indeterminate cervical lymph nodes ● Nodules of any size in patients with a history of neck radiation ● History of well-differentiated thyroid carcinoma in more than two first-degree relatives ● Medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) type 2 ● Increased calcitonin levels. Smoking, proton-pump inhibitors, renal failure, and chronic alcohol consumption may lead to a mild to moderate increase in calcitonin levels (check abstinence levels, where appropriate). Fine needle aspiration biopsy should explicitly not be performed if the nodule represents an area of focal autonomy on thyroid scintigraphy and/or has no ultrasound features suspicious of malignancy. Needle biopsy of simple cysts is not advisable. Complications The range of complications associated with FNA biopsy is very small. Pain: Data on pain associated with FNA are scarce. A mild pain was reported by 8.9% of patients who underwent FNA biopsy (e10). Bleeding: Easily comparable epidemiological data on the occurrence of bleeding events during or after thyroid FNA biopsy are not available because of the retrospective design of the majority of studies and the
356
use of different techniques and needle sizes. The published bleeding rates range between 0.3% and 2.3% (e11, e12). Metastatic spread: In patients with thyroid cancer, metastasis along the needle canal is extremely rare and only few individual case reports have been published (19). This is because well-differentiated thyroid carcinoma, the most common form of thyroid malignancy, is treated with radioiodine therapy which would also eliminate any cancer cells spread during the FNA. The risk of local tumor cell spread is almost always limited to the highly malignant anaplastic carcinoma. Needle biopsy in patients with anticoagulation therapy Needle biopsy in patients taking acetylsalicylic acid (ASA, aspirin) can be performed without an increased risk up to a dose of 100 mg ASA (20). Patients receiving higher doses of ASA should pause treatment for 10 days prior to the intervention. In patients taking phenprocoumon/coumadin, it is recommended to hold anticoagulation therapy until the INR (International Normalized Ratio) is
