Usefulness of fine needle aspiration cytology in the diagnosis of loco-regional recurrence of differentiated thyroid carcinoma

doi:10.1016/j.ejso.2004.12.012

European Journal of Surgical Oncology (EJSO)

Volume 31, Issue 3, April 2005, Pages 288-293

https://doi.org/10.1016/j.ejso.2004.12.012 Get rights and content

Abstract

Aim

The aim of our study was to define the usefulness of fine needle aspiration cytology (FNAC) in the assessment of loco-regional recurrence of differentiated thyroid carcinoma (DTC).

Methods

Among 1182 consecutive patients treated and followed for DTC from 1992 to 2001, we retrospectively analysed 65 FNAC results of patients presenting a suspicion of loco-regional recurrence. Recurrences were proved at histology in 35 cases and by cervical radioiodine uptake on post-therapeutic WBS (whole body scan) in nine cases.

Results

Among the 44 recurrences, FNAC results were malignant, benign and unsatisfactory in 33, two and nine cases, respectively. For the diagnosis of malignancy, FNAC sensitivity was 94%, specificity 100%, positive predictive value 100% and negative predictive value 87%. In the 35 cases where divergent results between diagnostic WBS (37–111 MBq ¹³¹I) and Tg level were observed, FNAC assessed the final status in 22 cases (malignant and benign in 17 and five cases, respectively). Of the 12 non-functioning and non-secreting lesions, FNAC diagnosed malignancy in four of the five malignant cases and ruled out malignancy in all seven benign lesions.

Conclusion

These results outline the interest of FNAC in the assessment of loco-regional recurrences of DTC, especially when classical follow-up tools such as WBS and/or Tg level are unable to detect the recurrences.

Introduction

Differentiated thyroid cancer (DTC) is associated with an excellent prognosis.¹ Nevertheless, local recurrences in thyroid bed or cervical lymph-nodes metastases originating from DTC occur in 5–24% of cases1, 2, 3, 4 and are associated with a shortened life expectancy.1, 3, 5

After initial treatment including surgical thyroidectomy and radioiodine ablation of the thyroid remnant tissue, the detection of such recurrences was based, until recently, on abnormal cervical uptake at whole body scan (WBS) and or elevated serum thyroglobulin (Tg) level under TSH stimulation.4, 6, 7, 8, 9

However, diagnostic WBS sensitivity has been reported to be low, reaching 75%.¹⁰ Recent studies outlined that WBS was useless in the follow-up of patients with DTC.11, 12 Moreover, some recurrences, especially poorly differentiated ones presented no radioiodine uptake and or no abnormal Tg level. Such characteristics are known to be associated with a poor prognosis.¹³

A recent study demonstrated that cervical ultrasonography (US) performed by an experienced operator is a sensitive tool for detecting neck recurrences of DTC.¹⁴ Moreover, fine needle aspiration cytology (FNAC) when associated with neck ultrasonography has been shown to be the most sensitive method to detect tumoral tissue in the thyroid bed or regional lymph nodes.15, 16, 17, 18, 19 The usefulness of FNAC in case of negative or divergent diagnostic WBS and Tg levels has never been clearly documented.

The aim of our study was to evaluate the usefulness of the FNAC in the diagnosis of lymph node metastasis or cervical local recurrence in a cohort of patients treated and followed for DTC. The impact of the FNAC on the patient management was studied, with a particular interest on cases where WBS results and/or Tg level were non-diagnostic.

Section snippets

Patients

From January 1992 to April 2001, 1182 consecutive patients were treated and followed for DTC in our department. Among the series, 73 patients were subjected to FNAC for suspected recurrence in the thyroid bed and/or cervical lymph node. The recurrence was suspected because of abnormal palpation in 29 cases, increase of Tg level in 22 cases, and neck US abnormalities in 22 cases. In 11 patients, data concerning the final diagnosis of the suspected recurrences were unavailable and such patients

Results

There were 20 suspicions of recurrences in the thyroid bed and 45 of lymph-node metastases. The masses located in the thyroid bed were palpable in nine cases, with an US volume (mean±standard deviation) of 5.8 cm³±12. The lymph nodes were palpable in 29 cases, with an US volume of 1.3 cm³±1.6. When compared with a non-parametric test, lesion size was not significantly different between these two groups (p=0.72).

FNAC results were consistent with malignancy in 33 cases, non-malignancy in 15 cases,

Discussion

In the follow-up of DTC, several authors state that loco-regional recurrences should be detected and treated early to improve the patients quality of life and survival.³ Criteria such as lack of ¹³¹I uptake and/or Tg secretion, were reported as decreasing survival.¹³ Our study emphasises the usefulness of FNAC in the diagnosis of DTC local recurrences and/or lymph-node metastases when diagnostic WBS and Tg measurement provide divergent results.

FNAC sensitivity and specificity of 94 and 100%,

Conclusion

Systematic cervical palpation associated with US and FNAC procedure in case of suspicious findings, is a useful tool for the diagnosis of DTC recurrences, with an accurate and earlier screening of lesions amenable to surgery. FNAC is especially valuable in the case of non-functioning and or non-secreting lesions and should be considered as a reliable tool to detect recurrence. Such diagnostic procedure associated with US and Tg measurement under recombinant human thyroid stimulating hormone

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Cited by (12)

The value of thyroglobulin in washout of fine needle aspirate from 16 cervical lesions in patients with thyroid cancer
2013, Endocrinologia y Nutricion
La tiroglobulina del lavado de aguja (Tg-PAAF) junto con la citología de la punción-aspiración con aguja fina (cito-PAAF) son procedimientos recomendados para el diagnóstico de metástasis ganglionares cervicales y recurrencias del cáncer diferenciado de tiroides. El objetivo de este estudio fue valorar la utilidad de estas técnicas en 16 lesiones cervicales de pacientes con cáncer de tiroides del epitelio folicular (CT).
Se incluyeron 6 pacientes con CT y adenopatías laterocervicales evaluadas antes de la cirugía tiroidea inicial y 10 pacientes en seguimiento por CT ya operado y lesiones cervicales ecográficamente sospechosas y/o persistentes. Las 16 lesiones fueron sometidas a PAAF. Los resultados de la Tg-PAAF, cito-PAAF y de la combinación de ambas se compararon con el diagnóstico definitivo asignado a cada lesión.
En 10 lesiones comprobadamente malignas tras extirpación quirúrgica (9 metástasis ganglionares y una recurrencia en lecho), la cito-PAAF, la Tg-PAAF y la combinación de ambas técnicas permitieron llegar al diagnóstico correcto en 7, 9 y 10 casos respectivamente. En 6 lesiones consideradas benignas, la cito-PAAF pudo confirmar la benignidad de la lesión en 4, resultó no diagnóstica en una y falsamente positiva en otra, mientras que la Tg-PAAF se halló por debajo del valor de corte establecido (para considerar malignidad) en todos los casos.
En pacientes con CT y lesiones cervicales sospechosas, la Tg-PAAF mejora la rentabilidad diagnóstica de la cito-PAAF aislada justificándose así su recomendación sistemática al realizar la PAAF. Quedan sin embargo por definir una estandarización universal de la técnica y unos valores de corte válidos de Tg-PAAF (de acuerdo al inmunoanálisis empleado) por encima de los cuales considerar la lesión maligna.
Thyroglobulin in the needle washout (Tg-FNA) and cytology of fine needle aspiration (cyto-FNA) are recommended for diagnosis of metastatic lymphadenopathies and recurrence of differentiated thyroid cancer. The objective of this study was to assess the value of these procedures in 16 cervical masses from patients with thyroid cancer of the follicular epithelium (TC).
The study included six patients with TC and cervical lymphadenopathies evaluated before initial thyroid surgery and 10 patients followed up after TC surgery with cervical lumps discovered. FNA was performed in all 16 masses. Results of cyto-FNA, Tg-FNA and of the combined tests were compared to the final diagnosis of each lesion.
Among 10 lesions proven to be malignant at surgery, cyto-FNA, Tg-FNA and the combination of both allowed for adequate diagnosis in 7, 9, and 10 cases respectively. Among 6 lesions considered to be benign, cyto-FNA was able to confirm diagnosis in 4, was non-diagnostic in one, and was falsely negative in the remaining case, while Tg-FNA was below the established cut-off value (to consider malignancy) in all cases.
In patients with TC and suspect cervical masses, Tg-FNA improved the diagnostic yield of cyto-FNA alone, thus warranting its routine recommendation when FNA is performed. However, universal standardization of the technique and definition of valid cut-off thyroglobulin values (depending on the immunoassay used) above which the lesion should be considered to be malignant are still pending.
Guideline on good practices for the use of cervical ultrasound and echo-guided techniques in the management of differentiated thyroid cancers of vesicular origin
2011, Annales d'Endocrinologie
Good practice guide for cervical ultrasound scan and echo-guided techniques in treating differentiated thyroid cancer of vesicular origin
2011, Annales d'Endocrinologie
Citation Excerpt :
Another major cause of “nondiagnostic cytology” is the presence of a metastatic microfocus not touched by the needle aspiration; however, the size of the lymph node does not appear to have an influence on the quality of the needle aspiration, as the effective results have been obtained from biopsies of small lymph nodes [34,80]. One particular point remains open to debate: how to insure that a lymph node FNAB is representative?
Des recommandations américaines, européennes et françaises pour la prise en charge des cancers thyroïdiens différenciés de souche vésiculaire ont été récemment publiées. L’échographie cervicale apparaît désormais comme un examen clef du suivi de ces cancers. Non invasif, facile à réaliser et à obtenir, peu coûteux, cet examen reste, cependant, opérateur dépendant. Il n’existe pas, à ce jour, de recommandations publiées rassemblant les aspects techniques, les résultats, les indications et les limites de cet examen dans le bilan initial et le suivi de ces cancers. Un groupe de travail fait d’un panel d’experts sensibilisé à la pratique de l’échographie s’est réuni en vue d’établir un guide de bonnes pratiques sur l’usage de l’échographie cervicale et des techniques écho-guidées dans la prise en charge des cancers thyroïdiens différenciés de souche vésiculaire. Les objectifs sont de : (a) standardiser la procédure et les comptes rendus, (b) définir les critères de malignité et de bénignité d’une lésion identifiée par une échographie cervicale, (c) standardiser les indications de la cytologie et du dosage des marqueurs in situ, (d) aider le médecin à sélectionner les patients qui doivent bénéficier d’une échographie cervicale et ou d’une cytologie, (e) discuter du rythme des examens en fonction du risque de récidive.
Good practice guide for cervical ultrasound scan and echo-guided techniques in treating differentiated thyroid cancer of vesicular origin. American, European and French Recommendations for the treatment of differentiated vesicular thyroid cancer were recently published. Cervical ultrasound scanning is now considered a key examination in the follow-up of these cancers. This examination is noninvasive, easy to perform and to obtain, is not costly, but remains operator-dependent. To date, there are no recommendations published that assemble all the technical aspects, results, indications and the limits of this examination in the initial medical report and the follow-up of these cancers. In order to standardise the procedure and validate the quality of the examination, a workgroup made up of a panel of experts particularly involved in carrying out ultrasound scans was set up. The aim was to draw up a good practice guide for performing cervical ultrasound scans and echo-guided techniques in treating patients with differentiated thyroid cancer of vesicular origin. The main objectives are to: (a) standardise the procedure and reports, (b) define the criteria for establishing whether lesions identified during a cervical ultrasound scan are malignant or benign, (c) standardise the indications for carrying out cytological tests and an in situ assay of markers, (d) help doctors to select the patients who ought to receive a cervical ultrasound scan and or cytological tests, (e) discuss how frequently the examinations should be carried out depending on the risk of recurrence.
Radioguided surgery using an intraoperative PET probe for tumor localization and verification of complete resection in differentiated thyroid cancer: A pilot study
2011, Surgery
The major concerns in the surgical treatment of extensive or recurrent thyroid cancer include the difficulty of precise intraoperative and real-time tumor localization, the possibility of missing small metastatic lymph nodes during the operation, the need for reoperation due to recurrence, and complications. The usefulness and feasibility of an intraoperative PET probe have been reported for many other cancers; however, a standard, radioguided, operative protocol using a PET probe in thyroid cancer has not been established. The purpose of the current study was to evaluate the feasibility of an intraoperative PET probe with respect to precise tumor localization, verification of complete resection, and a decrease in unnecessary reoperations and complications.
This was a prospective, controlled study. Inclusion criteria were thyroid cancer requiring a total thyroidectomy with a modified radical neck dissection (MRND) and recurrent thyroid cancer after thyroid surgery. The types of procedures included total thyroidectomy with MRND, selective neck dissection (SND), and excision of recurrent thyroid masses. The PET probe NodeSeeker^® is a high-energy gamma probe seeking 511 keV photons. Operative exploration was carried out between 2 and 6 h after injection of ¹⁸F-FDG. The surgeon calculated the target-to-background ratio (T/B ratio) by checking the 10-sec accumulated count using the PET probe. We performed a re-exploration if the T/B ratio was >1.3 in the operative bed.
Twelve patients underwent PET probe-guided operation. SNDs, mass excisions, total thyroidectomy with MRND, and MRND were performed on 7, 4, and 1 patient, respectively. All tumors were localized by the PET probe precisely in real time, and the lesions not observed on preoperative PET were detected by the PET probe in 7 patients. Furthermore, additional lymph nodes that were not identified on preoperative ultrasonography were detected in 1 patient. The mean T/B ratio of thyroid carcinoma was 1.51 ± 0.53 (range, 1.17–4.03) and the postoperative serum thyroglobulin off thyroid hormone was <2.0 ng/ml.
Radioguided surgery using an intraoperative PET probe in thyroid cancer appears to be a useful method for real-time tumor localization, verification of complete excision, and minimization of the possibility of residual cancer. Therefore, an intraoperative PET probe in thyroid cancer may decrease unnecessary reoperations and complications due to persistent disease.
Feasibility and benefit of fluorine 18-fluoro-2-deoxyglucose-guided surgery in the management of radioiodine-negative differentiated thyroid carcinoma metastases
2005, Surgery
Fluorine 18–fluoro-2-deoxyglucose (FDG) positron emission tomography (¹⁸F-FDG PET) can be used to visualize metastases in patients with differentiated thyroid carcinoma that does not take up radioiodine (¹³¹I). This study was aimed at evaluating the feasibility of ¹⁸F-FDG radio-guided surgery in patients with radioiodine-negative differentiated thyroid cancer.
Ten patients received a mean activity of 265 MBq of ¹⁸F-FDG 30 minutes before operation. Radioactivity uptake (counts per second [cps], with a pretime of 10 seconds) in tumor and normal tissues was measured before and after resection.
Patients with 1 to 5 foci detected by FDG-PET were included in the study. Six of these patients were injected with recombinant human thyroid-stimulating hormone (TSH) preoperatively. Abnormal findings detected by preoperative ¹⁸F-FDG PET were also detected with the gamma probe in all patients. The mean tumor activity in vivo was 3,272 cps, and tumor-to-neck and tumor-to-shoulder ratios were, respectively, 1.40 and 1.73. Tumor resection was incomplete in 3 patients. When resection was complete, mean radioactivity at the tumor site was decreased by 22%. The ex vivo mean tumor-to-normal tissue ratio was 2.4. All positive tissues detected with the probe were confirmed histologically to be differentiated thyroid cancer. The surgeon's hands were exposed to 90 to 270 μSv.
These results show the feasibility and benefit of ¹⁸F-FDG radio-guided surgery with a gamma probe in the management of differentiated thyroid cancer patients with radioiodine-negative recurrence.
3,3′-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease
2005, Biochemical and Biophysical Research Communications
Considerable epidemiological evidence exists to link thyroid disease with differing patterns of dietary consumption, in particular, cruciferous vegetables. We have been studying the anti-thyroid cancer (TCa) activity of indole-3-carbinol (I3C) found in cruciferous vegetables and its acid catalyzed dimer, 3,3′-diindolylmethane (DIM). There are no studies as yet to elucidate the effect of these compounds on the altered proliferative patterns in goiter or thyroid neoplasia. In this study, we tested the anti-proliferative effects of I3C and DIM on four different thyroid cancer cell lines representative of papillary (B-CPAP and 8505-C) and follicular carcinoma of the thyroid (CGTH-W-1 and ML-1), and primary human goiter cells. Cell survival and IC₅₀ values for I3C and DIM were calculated by the XTT assay and cell cycle distribution analysis was done by flow cytometry. DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C. The anti-proliferative activity of DIM in follicular TCa was mediated by a G1 arrest followed by induction of apoptosis. DIM also inhibited the growth of primary goiter cells by 70% compared to untreated controls. Contrary to traditional belief that cruciferous vegetables are “goitrogenic,” DIM has anti-proliferative effects in glandular thyroid proliferative disease. Our preclinical studies provide a strong rationale for the clinical exploration of DIM as an adjuvant to surgery in thyroid proliferative disease.

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Usefulness of fine needle aspiration cytology in the diagnosis of loco-regional recurrence of differentiated thyroid carcinoma

Abstract

Aim

Methods

Results

Conclusion

Introduction

Section snippets

Patients

Results

Discussion

Conclusion

Am J Med

Endocrinol Metab Clin North Am

Endocrinol Metab Clin North Am

Surgery

Eur J Radiol

Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer

J Clin Endocrinol Metab

Recurrent thyroid cancer. Role of surgery versus radioactive iodine (I131)

Ann Surg

Natural history, treatment, and course of papillary thyroid carcinoma

J Clin Endocrinol Metab

Outcome in cervical recurrences of papillary or follicular thyroid cancer

Ann Chir

Serum thyroglobulin measurements in thyroid cancer: evaluation of ‘false’ positive results

Clin Endocrinol (Oxf)

Serum thyroglobulin in thyroid carcinoma and other thyroid disorders

J Endocrinol Invest

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma

Eur J Nucl Med

Clinical evaluation of tumor characteristics predisposing serum thyroglobulin to be undetectable in patients with differentiated thyroid cancer

Cancer

Is diagnostic iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer?

J Clin Endocrinol Metab