THYROIDVolume 16, Number 10, 2006© Mary Ann Liebert, Inc.

Needle Tract Implantation of Follicular Neoplasm AfterFine-Needle Aspiration Biopsy: Report of a Case

Yasuhiro Ito,1 Shuji Asahi,1 Fumio Matsuzuka,1 Yasushi Nakamura,2 Nobuyuki Amino,1 and Akira Miyauchi1

We herein report a 28-year-old woman with a follicular neoplasm showing subcutaneous needle tract implan-tation. One month after fine-needle aspiration biopsy (FNAB) for a tumor measuring 2.5 cm, the patient be-came aware of a subcutaneous nodule measuring about 1 cm at the needle insertion site. FNAB smear of thisnodule showed poorly cohesive clusters of follicular cells with nuclear crowding, overlapping and resettingwith some microfollicular architecture. Total thyroidectomy and resection of the subcutaneous nodule wereperformed. Although there was no capsular or vascular invasion of the nodule, the lesion was diagnosed asfollicular carcinoma because of the subcutaneous seeding. Ki-67 labeling indices of the thyroid nodule and im-planted tumor were higher than 5%. Furthermore, although galectin-3 was completely negative in the thyroidnodule, it was heterogeneously positive in the implanted tumor. It is therefore suggested that high cell prolif-erating activity as a characteristic of the original nodule and the subsequently obtained invasive characteristicof the implanted tumor contributed to this event. To date, there has not been any recurrence of the implantedlesion. Because implanted follicular carcinoma can be surgically removed, this complication should not impairthe usefulness of FNAB.

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Introduction

FINE NEEDLE ASPIRATION BIOPSY (FNAB) is an important andreliable technique for the diagnosis of thyroid nodules.

Although this technique is generally safe, some complica-tions may occasionally occur. Needle tract implantation ofcarcinoma cells is one such complication. Case reports de-scribing this complication have been published in 1951 and1990, and both cases were papillary carcinoma (1,2). Our hos-pital encountered seven cases of needle tract implantationby FNAB of the thyroid between 1990 and 2002 (3). All caseswere papillary carcinoma. Because 4912 patients with papil-lary carcinoma underwent FNAB at this period, we can cal-culate the incidence of this complication as 0.14%, which was10 times lower than that for hepatocellular carcinoma or pan-creatic adenocarcinoma (4). In 2005, we experienced one caseof needle tract implantation of FNAB for follicular neoplasm,which is described in this case report.

Case Report

The patient was a 22-year-old Japanese woman who wasreferred to our hospital for a thyroid nodule measuring about2.5 cm in maximal diameter in December 1999. Laboratorydata indicated euthyroid, and thyroglobulin measurementwas in the normal range. Anti-thyroid microsomal and thy-

roglobulin antibodies were both negative. Ultrasonographicfindings showed a solid nodule, and she was diagnosed ashaving follicular neoplasm by FNAB with a 22-gauge nee-dle attached to a 10-mL syringe. Thereafter, she has under-gone FNAB almost yearly. After the fifth FNAB in Novem-ber 2004, she experienced persistent pain in the neck. Onemonth later, the patient became aware of a subcutaneousnodule at the needle insertion site. However, she ignored thenodule until the next hospital follow-up in August 2005, be-cause the nodule did not show any detectable enlargementafter its initial appearance.

The size of the thyroid nodule did not enlarge after the firstexamination, but as shown in Figure 1, an elastic hard sub-cutaneous nodule measuring about 1 cm was detected. Thesubcutaneous nodule was located at the site identical to thepuncture site, which was confirmed by the physician who per-formed FNAB and by the patient herself. The FNAB smear ofthis nodule showed poorly cohesive clusters of follicular cellsshowing nuclear crowding, overlapping and some resetting,and the smear also demonstrated a lesion with microfollicu-lar architecture (Fig. 2). Thyroglobulin measurement using thewashout from the FNAB needles was high, indicating that thesubcutaneous nodule had originated from the thyroid (5).These findings indicated that the subcutaneous nodule wasdue to implantation from the thyroid nodule during FNAB.

1Kuma Hospital, Kobe City, Japan.2Department of Pathology, Wakayama Medical University, Wakayama, Japan.

Her preoperative thyroglobulin level was 26.0 ng/mL, andthere were no lung metastasis on computed tomography scan.We performed total thyroidectomy and resection of the im-planted tumor in October 2005 when the patient was 28 yearsold. Thyroid nodule did not show any extrathyroidal exten-sion. There was no detectable nodal metastasis on preopera-tive ultrasonographic examination or intraoperative palpa-tion. After surgery, her thyroglobulin level decreased below0.5 ng/mL. Figure 3 shows hematoxylin & eosin (H&E) stain-ing of the thyroid nodule and subcutaneous nodule. Althoughthere was no apparent capsular or vascular invasion of thethyroid nodule on pathological examination, it was diagnosedas follicular carcinoma because of the subcutaneous seeding.H&E findings of the subcutaneous nodule were similar tothose of the thyroid nodule. Cells formed follicular structures,and the border between the tumorous lesion and the stromawas clear. Immunostaining of thyroglobulin was diffuselypositive for the thyroid nodule and subcutaneous tumor. Fig-ures 4 and 5 show immunostaining for Ki-67 and galectin-3,respectively. A monoclonal antibody against Ki-67 (clone

MIB-1) was purchased from Dako (Glustrup, Denmark) andthat against galectin-3 was generously provided by Dr. H. In-ohara (Department of Otolaryngology and Sensory OrganSurgery, Osaka University Graduate School of Medicine). Ki-67 (MIB-1) labeling indices of thyroid nodule and implantedtumor were both higher than 5% (Fig. 4a and b). Althoughgalectin-3 was completely negative in the thyroid nodule (Fig.5a), it was heterogeneously positive in the implanted tumor(Fig. 5b). Radioiodine treatment has not been performed be-cause her thyroglobulin continues to be low and, as indicatedabove, lung metastasis could not be detected by preoperativecomputed tomography.

Discussion

All 10 cases of needle tract implantation previously en-countered in our hospital were papillary carcinomas; seven

ITO ET AL.1060

FIG. 1. Subcutaneous nodule of the patient.

FIG. 2. FNAB of the subcutaneous nodule. Original mag-nification �200.

A

B

FIG. 3. A: H&E staining of the thyroid nodule. B: H&Estaining of the implanted nodule. Original magnification�40.

patients had undergone FNAB at our hospital, and the re-maining three at other hospitals (3). Six cases were poorlydifferentiated (6), five showed clinically apparent nodal me-tastasis, and seven had extrathyroid extension, indicatingthat this complication is more likely to involve tumors withaggressive characteristics. Another important characteristicis the high cell proliferating activity of the implanted tumorin cases showing implantation within a short interval afterthe procedure.

In this report, we demonstrated a case showing needletract implantation after FNAB for follicular neoplasm. Thisis our first experience with needle tract implantation from athyroid nodule other than papillary carcinoma. Panunzi etal. reported a 76-year-old woman, who presented with a sub-cutaneous nodule within 8 months after FNAB of a thyroidnodule that had been diagnosed as follicular neoplasia by

FNAB (7). In their case, although the subcutaneous nodulewas surgically removed, surgical treatment was not per-formed for the thyroid nodule because the patient was inpoor condition after chemotherapy for multiple myeloma.When she died of multiple myeloma only 1 month after re-moval of subcutaneous tumor, autopsy was not performed.Therefore, pathological details of the thyroid nodule remainunknown. The authors hypothesized that immunodeficiencydue to multiple myeloma and/or therapy-related immuno-suppression contributed to the development of a subcuta-neous nodule.

However, our patient was a young and otherwise healthywoman, indicating that immune system deficiency was notrelated to the event in this case. Furthermore, in contrast tothe case reported by Panunzi et al., we pathologically eval-uated the nodule in the thyroid after surgical treatment. Un-like most papillary carcinomas showing needle tract im-

NEEDLE TRACT IMPLANTATION OF FOLLICULAR NEOPLASM 1061

A A

BB

FIG. 4. A: Ki-67 immunostaining of the thyroid nodule. B:Ki-67 immunostaining of the implanted tumor. Originalmagnification �40.

FIG. 5. A: Galectin-3 was negative in the thyroid nodule.B: Galectin-3 was heterogeneously positive in the implantednodule. Original magnification �40.

plantation in our hospital, this nodule did not show any ag-gressive clinicopathological features. Preoperative ultra-sonographic examination and intraoperative findingsshowed that there were no nodes suggestive of metastasis,and extrathyroid extension of the tumor could not be de-tected. Furthermore, there was no extracapsular or vascularinvasion that could be detected by pathological examination,although we diagnosed the lesion as follicular carcinoma be-cause of the subcutaneous seeding. The only characteristicsuggestive of biological aggressiveness was the high cell pro-liferation activity in both the thyroid nodule and the im-planted tumor. We previously demonstrated that, in papil-lary carcinoma, cases showing needle tract implantationwithin a short interval after FNAB had Ki-67 (MIB-1) label-ing indices above 5% (3). The present case also fulfils the cri-terion, because the Ki-67 (MIB-1) labeling indices of thesenodules were high even for follicular carcinoma (8). Inter-estingly, galectin-3 expression was also heterogeneously ob-served in the implanted tumor, although it was completelynegative in the thyroid nodule. A previous study demon-strated that galectin-3 is a useful marker for discriminatingfollicular carcinoma from adenoma (9). We recently showedthat, although galectin-3 plays only an adjuvant role in di-agnosing follicular carcinoma, the expression level was sig-nificantly increased with the grade of vascular or capsularinvasion of follicular tumor (10). Because galectin-3 was neg-ative in around 30% of even widely invasive follicular car-cinoma (10), its negativity was not discrepant with the di-agnosis of this thyroid nodule as follicular carcinoma.However, in this case, it is likely that the implanted tumorbecame more invasive, which seems reasonable because im-planted tumors must survive in a more severe environmentthan a nodule within the thyroid.

When and why the tumor became aggressive remains un-clear. However, the onset of malignant transformation or theacquisition of more aggressive characteristics may have beena recent event, because it is not likely that a tumor with sucha high proliferating activity would not have grown over the5 preceding years. In this case, FNAB had been performedalmost yearly at the discretion of the attending physician,who suspected the tumor to be malignant. It is not clearwhether frequent punctures by FNAB needle directly con-tributed to the malignant transformation or acquisition of ag-gressive characteristics in this nodule, but we cannot denythe possibility that repeated FNAB triggered a change in thetumor characteristics. Indeed, it is difficult to diagnose fol-licular carcinoma by FNAB and, because there was no ap-parent tumor enlargement or elevation of thyroglobulin levelin this case, such frequent FNAB procedures might not havebeen necessary in retrospect. Furthermore, because there arecertain other complications for FNAB such as bleeding, per-sistent pain, and recurrent nerve palsy, the frequency of theprocedure should be minimized.

In summary, we experienced FNAB needle tract implan-tation of follicular tumor, possibly follicular carcinoma.However, our findings do not imply that FNAB promotes acomplication affecting tumor progression, because we couldsuccessfully remove all implanted tumors, including that inthis case, with no focal recurrence. Although unnecessarily

frequent FNAB procedures should be avoided, we shouldrecognize FNAB as the most useful technique for diagnos-ing thyroid nodules.

References

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2. Hales MS, Hsu FSF 1990 Needle tract implantation of pap-illary carcinoma of the thyroid following aspiration biopsy.Acta Cytol 34:801–804.

3. Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, KobayashiK, Matsuzuka F, Kuma K, Miyauchi A 2005 Needle tract im-plantation of papillary thyroid carcinoma after fine-needleaspiration biopsy. World J Surg 29:1544–1549.

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5. Uruno T, Miyauchi A, Shimizu K, Tomoda C, Takamura Y,Ito Y, Miya A, Kobayashi K, Matsuzuka F, Amino N, KumaK 2005 Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervicallymph node metastasis in patients with papillary thyroidcancer. World J Surg 29:493–485.

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7. Panunzi C, Paliotta DS, Papani E, Petrucci L, Rinaldi R,Nardi F 1994 Cutaneous seeding of a follicular thyroid can-cer after fine-needle aspiration biopsy? Diag Cytopathol10:156–158.

8. Rickert D, Mittermayer C, Lindenfelser R, Biesterfeld S 2000MIB-1 immunohistometry of follicular adenoma and follic-ular carcinoma of the thyroid gland. Anal Quant Cytol His-tol 22:229–234.

9. Bartolazzi A, Gasbarri A, Papoti M, Bussolati G, Lucante T,Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, Vec-chione A, Tecce R, Larsson O; Thyroid Cancer Study Group2001 Application of an immunodiagnostic method for im-proving preoperative diagnosis of nodular thyroid lesions.Lancet 357:1644–1650.

10. Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Mat-suzuka F, Yasuoka H, Kakudo K, Inohara H, Kuma K,Miyauchi A 2005 Galectin-3 expression in follicular tumours:an immunohistochemical study of its use as a marker of fol-licular carcinoma. Pathology 37:296–298.

Address reprint requests to:Yasuhiro Ito, M.D., Ph.D.

Department of SurgeryKuma Hospital

8-2-35, Shimoyamate-Dori, Chuo-kuKobe City, 650-0011

Japan

E-mail: ito01@kuma-h.or.jp

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