Diagnostic significance of clay-like materials aspirated from thyroid nodules

INTRODUCTION

Fine-needle aspiration cytology (FNAC) has been established as a reliable modality for the pre-operative diagnosis of thyroid nodules. The diagnostic accuracy depends on the methods and techniques of aspiration, smearing, fixation, and staining, as well as the diagnostic skills and experience of cytopathologists. The key factor is obtaining representative samples from targeted thyroid lesions. To reduce the incidence of non-diagnostic samples, several methods, including aspiration with ultrasound guidance,^[1,2] rapid on-site evaluation (ROSE),^[3,4] and liquid-based cytology (LBC),^[5,6] have been performed.

The simplest way to determine the adequacy of aspirated materials is on-site gross visual assessment for aspirated materials.^[7-14] A speculative diagnosis is occasionally possible. Honey-like, abscess-like, and watery-clear fluid materials indicate benign thyroid nodules,^[15] acute suppurative thyroiditis^[16] or anaplastic thyroid carcinoma,^[17] and parathyroid cysts,^[18] respectively. When aspirates from regional lymph nodes are liquid, metastatic papillary thyroid carcinoma is a possible diagnosis.^[19] Ren et al. described that toothpaste-like materials were aspirated from the early stage degenerating thyroid nodules.^[20] The materials are reddish-brown in color, three-dimensional, and sticky, giving them the appearance of clay. No detailed study of the aspirate showing its characteristic gross findings had been found. This study aimed to clarify the diagnostic significance of clay-like materials aspirated from thyroid nodules.

MATERIAL AND METHODS

Ethical approval was obtained from the Ethics Committee of our hospital. The study protocol was reviewed and approved by the Institutional Review Board (20200709-1). We reviewed the cytology report database of 69,848 thyroid nodules that underwent FNAC performed by a single pathologist (MHir) at Kuma Hospital from January 2007 to August 2021. Clinical and cytological data were obtained from the medical records of patients at Kuma Hospital. All findings and test results in the electronic medical records (HOPE Cloud Chart, Fujitsu, Tokyo, Japan) and pathology reporting system (CNA-Net, Sakura Finetek Japan Co., Tokyo, Japan) were stored in a data warehouse. We extracted relevant data using a keyword search from the database. Ultrasonography was performed using the APLIO 80 SSA-770A (Toshiba Medical Systems Co., Ltd., Otawara, Japan) or APLIO 500 TUS-A500 (Toshiba) ultrasound machine with PLT-805AT (8 MHz, Toshiba) or PLT-1005BT (10 MHz, Toshiba) probes. Ultrasound-guided Fine-needle aspiration (FNA) was performed using a 22-gauge needle without local anesthesia. The needle was inserted in a plane perpendicular to the scanning plane (perpendicular positioning).^[21] Smears were prepared using the press and release method and subsequently stained with Papanicolaou stain. Clay-like materials were defined as reddish brown, sticky, and three-dimensional [Figure 1]. Among the 69,848 nodules, 355 (0.5%) nodules had aspirates described as clay-like materials in the medical records and were retrospectively examined. Ultrasound reports were categorized based on the American Thyroid Association guidelines.^[22] The sonographic patterns were classified into high suspicion, intermediate suspicion, low suspicion, very low suspicion, and benign. FNAC results were categorized based on the Japanese System for Reporting Thyroid Cytopathology.^[23-26] The diagnostic categories were classified into unsatisfactory, cyst fluid, benign, undetermined significance, follicular neoplasm, suspicious for malignancy, and malignant. The follow-up period ranged from 1 to 14 years (mean 11.2 years).

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Figure 1:

Macroscopic finding of clay-like material. It is reddish-brown and looks like clay.

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RESULTS

Pathological findings

Among 355 thyroid nodules, 33 and 321 were surgically resected and followed up, respectively. The findings of the remaining 7 nodules were unknown because the patients were transferred to another hospital. Table 4 shows the pathological diagnoses of the resected nodules. Nineteen (57.6%) and 14 (42.4%) nodules were benign and malignant, respectively. Among the 19 benign lesions, 15 (78.9%) were cystic follicular nodular disease, and the clay-like materials accounted for the cystic contents [Figure 2] and/or blood clots [Figure 3]. Nine (64.3%) of the 14 malignant tumors were papillary thyroid carcinomas. Clay-like materials aspirated from three of nine papillary thyroid carcinomas and two of three follicular thyroid carcinomas [Figures 4 and 5] were necrotic cells derived from the infarcted areas. Those in medullary thyroid carcinoma and anaplastic thyroid carcinoma were consistent with amyloid deposition and abscess-like areas, respectively.

Table 4: Pathological diagnoses of 33 thyroid nodules with clay-like materials.

Lesion type	Pathological diagnosis	Cases
Benign lesions (19)	Follicular nodular disease, cystic	15
	Burned out tumor	2
	Lymphoepithelial cyst	1
	Follicular adenoma	1
Malignant tumors (14)	Papillary thyroid carcinoma	9
	Follicular thyroid carcinoma	3
	Medullary thyroid carcinoma	1
	Anaplastic thyroid carcinoma	1

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Figure 2:

Cystic follicular nodular disease. (a) Papillary thyroid carcinoma-suspected hypoechoic mass (white arrow) (Ultrasound B mode). (b) Cholesterol crystal and proteinaceous materials (Papanicolaou stain, x400). (c) Unilocular cystic lesion (white arrow). (d) Cholesterol crystal and proteinaceous materials (Hematoxylin and Eosin stain, x200).

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Figure 3:

Hemorrhagic follicular nodular disease. (a) Degenerative red blood cells (Papanicolaou stain, x400). (b) Cystic nodule containing blood clot. (c) Red blood cells (Hematoxylin and Eosin stain, x100).

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Figure 4:

Infarcted papillary thyroid carcinoma. (a) Necrotic cells (Papanicolaou stain, x400). (b) Solid tumor with focal necrotic area. (c) Coagulative necrosis of papillary thyroid carcinoma with papillary growth pattern. (Hematoxylin and Eosin stain, x200).

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Figure 5:

Infarcted follicular thyroid carcinoma. (a) Necrotic cells and hematoidin (Papanicolaou stain, x400). (b) Encapsulated solid tumor with capsular invasio n and necrosis. (c) Necrotic carcinoma cells and hematoidin (Hematoxylin and Eosin stain, x200).

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DISCUSSION

Implementation of rapid on-site evaluation reduced the non-diagnostic rate and improved the overall adequacy,^[3,4,27,28] but the method is not widely available . On-site gross visual assessment is simple, fast, free of charge, and feasible for all patients, and can predict the adequacy of the samples.^[7,10,11] Meena et al. prospectively demonstrated that the presence of defined as gooey white material on FNA aspirates correlated strongly with adequacy.^[8] Granular materials on the preparation are likely to be diagnostic.^[10,11] Williams et al. graded the macroscopic sample appearances on a five-point scale from 1 (blood with no particulate material) to 5 (solid tissue pieces); the positivity rate increased stepwise from 50% to 100% from grade 1 to grade 5 samples.^[12] Neither granular materials nor solid tissue pieces have been observed in clay-like materials in the present study. However, cytological assessment of the clay-like materials was adequate in all nodules. Our study confirmed that clay-like materials are equivalent to grade 5, although they lacked solid tissue pieces. Therefore, the recognition contributes to avoiding unnecessary second punctures.

In the present study, most nodules with clay-like materials were cyst fluid or benign in FNA. These materials are mainly composed of non-epithelial components, including colloid or proteinaceous materials, foamy histiocytes, and degenerative red blood cells. Thus, the clay-like materials are likely derived from the contents of blood clots from benign cystic lesions. Similarly, Ren et al. described that hemorrhage appears as a reddish toothpaste-like muddy material in the early stage and brown bread-like material in the second stage of hemorrhage regression.^[20] However, although rare, papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma aspiration materials can also contain clay-like materials. Moreover, the first two are observed when an infarction has occurred, and the latter when it contains abundant amyloid. The properties of clay-like materials must differ for benign and malignant lesions. If they were grossly subclassified based on their gross characteristics, our report would have been more worthwhile. However, it was not possible to subclassify them due to the retrospective nature of the study.

The American Thyroid Association management guidelines present the risk of malignancy according to each sonographic pattern. According to the guidelines,^[22] the estimated risks of malignancy of high suspicion, intermediate suspicion, low suspicion, very low suspicion, and benign were 70–90%, 10–20%, 5–10%, <3%, and <1%, respectively. In comparison, the risk of malignancy (37.5%) of high suspicion in nodules with clay-like materials was considerably lower. We found that nodules with clay-like materials tended to be overestimated on ultrasonography. Concerning FNA, the risk of malignancy (37.5%) for undetermined significance in nodules with clay-like materials was considerably higher (16%) than that described in the Bethesda System,^[29] whereas for malignancy, it was lower (57.1 vs. 94%). These findings demonstrate that FNA tends to be underestimated for thyroid nodules with clay-like materials.

SUMMARY

We investigated the diagnostic significance of clay-like materials aspirated from thyroid nodules. As the materials were considered sufficient specimens, the recognition contributes to avoiding unnecessary second punctures. Most of these are derived from the contents or blood clots of benign cystic lesions. The risk of malignancy was 3.9%, and the tumor could be a necrotic carcinoma due to infarction. Ultrasound examination tended to overestimate nodules with clay-like materials, whereas FNAC diagnosis tended to be more conservative. We should reaffirm that on-site gross visual assessment is a fast and reasonably accurate predictor of on-site adequacy of samples.