Papillary Thyroid Carcinoma Manifested Solely as Microcalcifications on Sonography

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1 Sonography of Papillary Thyroid Carcinoma Head and Neck Imaging Clinical Observations Jin Young Kwak 1 Eun-Kyung Kim 1 Eun Ju Son 1 Min Jung Kim 1 Ki Keun Oh 1 Ji Young Kim 2 Kwang Il Kim 2 Kwak JY, Kim EK, Son EJ, et al. Keywords: cancer, fine-needle aspiration biopsy, thyroid gland, sonography DOI: /JR Received June 5, 2006; accepted after revision February 12, Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-gu, Seoul , Korea. ddress correspondence to E. K. Kim (ekkim@yumc.yonsei.ac.kr). 2 Department of Pathology, Pochon CH University College of Medicine, Gyeonggi-do, Korea. JR 2007; 189: X/07/ merican Roentgen Ray Society Papillary Thyroid Carcinoma Manifested Solely as Microcalcifications on Sonography OJECTIVE. The purpose of this study is to assess the utility of sonographic detection and the role of sonography-guided fine-needle aspiration biopsy (FN) in thyroid carcinomas that appear only as microcalcifications without an associated mass. CONCLUSION. This study covers 11 cases in which the only abnormal finding suggesting thyroid cancer was microcalcifications detected at sonography. ll cases described were diagnosed as thyroid papillary carcinoma after surgery. Hence, it is shown that real-time highresolution sonography is effective in the detection of thyroid carcinomas that appear as microcalcifications without an associated mass. The results of sonography-guided FN were satisfactory to diagnose these microcalcifications as thyroid carcinomas. Therefore, we believe that thyroid sonography combined with sonography-guided FN is a useful approach for diagnosing thyroid microcalcifications. any studies have suggested that M sonography can be considerably effective for predicting various thyroid malignancies such as microcalcifications, an absent halo sign, marked hypoechogenicity, extraglandular extensions, irregular or microlobulated margins, heterogeneous echotexture, and taller-than-wide shapes [1 3]. mong these sonography features, microcalcifications within the thyroid mass serve as a reliable diagnostic criterion [1, 4]. Our evaluation of the thyroid gland using high-frequency sonography revealed that some papillary thyroid carcinomas appeared only as microcalcifications without an associated mass. To our knowledge, there have been few reports of thyroid malignancy that appear solely as microcalcifications on sonography [5]. Therefore, we reviewed cases in which thyroid malignancy appeared only as microcalcifications on sonography. Materials and Methods etween January 2001 and December 2005, 2,158 patients in our hospital were diagnosed with thyroid carcinoma based on surgical pathology. During the same period, 22,842 neck sonography examinations were performed. Retrospectively, we reviewed either the sonography images (n = 1,850) or reports made after sonography (n =308) in all patients diagnosed with thyroid carcinoma. s a result, we identified 11 cases in which microcalcifications detected on sonography were the only abnormal finding suggesting the presence of thyroid carcinoma. ll of the patients were female, with ages ranging from 15 to 68 years (mean age, 38 years). mong them, seven patients (age range, years; mean age, 38.9 years) were diagnosed with usual papillary carcinoma. However, the remaining four patients (age range, years; mean age, 37.5 years) were diagnosed with a diffuse sclerosing variant of papillary carcinoma. Each patient underwent sonography-guided fine-needle aspiration biopsy (FN) and subsequent thyroidectomy. In this study, we defined sonography findings of microcalcifications as hyperechoic punctate foci that did not show posterior acoustic shadowing. We excluded both dense calcifications and precipitated colloid materials that exhibited comet-tail artifacts. The sonography images were obtained using either a SONOLINE ntares (Siemens Medical Solutions) with a 5 13-MHz linear-array probe or an HDI 3000 or 5000 (Philips Medical Systems) with a linear 7 12-MHz probe. ll sonography-guided FNs were performed by either of two of the authors, who are radiologists experienced with the procedure, using a 23-gauge needle and a 20-mL disposable plastic syringe with an aspirator. Each target lesion was aspirated at least twice, and the region that appeared to be the densely populated area of microcalcifications was targeted. The aspirated material was smeared on four slides per lesion, then immediately fixed in 95% JR:189, July

2 ethanol and stained by the Papanicolaou technique. lso, the syringe used for FN was rinsed in CytoLyt Solution (Cytyc Corporation) and additional cell-block or ThinPrep (Cytyc Corporation) preparations were created. We did not have a cytopathologist on site during FN to determine the adequacy of the obtained samples. Hence, the FN specimens of the patients included in this study were retrospectively reviewed by two experienced cytopathologists. We then compared the results of FN with the pathology obtained from surgical specimens during subsequent thyroidectomy. C Fig year-old woman with Graves disease and diffuse sclerosing variant of papillary carcinoma. and, Transverse and longitudinal sonograms of right thyroid gland reveal scattered microcalcifications (arrows) and underlying heterogeneous hypoechogenicity. C, Scattered follicular cell clusters show enlarged vesicular nuclei with intranuclear inclusion (arrow). (ThinPrep [Cytyc Corporation], Papanicolaou stain, 400) D, Photomicrograph shows that few psammoma bodies are scattered in diffuse sclerosing variant of papillary carcinoma. (H and E, 200) Sonograms of the 11 patients were analyzed retrospectively by two dedicated thyroid radiologists. The clinical history, the results of FN and surgery were also reviewed for each patient. Results Five of 11 patients complained of a palpable neck mass. One patient was diagnosed clinically with Graves disease. mong the remaining four patients, thyroid carcinomas were discovered incidentally on neck sonography. The original purpose of sonography for three cases was to rule out thyroid disease and that of one case was a health examination. ll 11 patients denied having a family history of thyroid carcinoma or previous histories of radiation to the head and the neck. Sonography showed microcalcifications of the thyroid gland on the right side in seven patients, on the left side in three patients, and on both sides in one patient. Focally distributed microcalcifications were present in less than one third of the area of the lobe in five patients and in greater than one third of the area of the lobe in six patients. The presence of metastatic lymph nodes was suspected in four pa- D 228 JR:189, July 2007

3 Sonography of Papillary Thyroid Carcinoma tients: two at level IV, one at level II, and one at level VI. We considered a lymph node to be metastatic in origin if any of the following sonography findings were revealed: the absence of a structure identifiable as fatty hilum, increased echogenicity, cystic change, or internal microcalcifications. The underlying sonogram in nine patients showed heterogeneous hypoechogenicity. The remaining two patients showed normal echogenicity. ll patients underwent sonography-guided FN of thyroid microcalcifications. Three patients also underwent sonography-guided FN of suspicious lymph nodes. Ten patients showed papillary carcinoma of thyroid microcalcifications on FN. One patient s FN was found to be negative for malignancy in the thyroid microcalcification; however, a neck lymph node was found to be metastatic. ll cases were confirmed with the initial diagnosis of thyroid papillary carcinoma via pathology obtained from subsequent thyroidectomy. Four of the patients were diagnosed with a diffuse sclerosing variant of papillary carcinoma (Fig. 1). Four patients with suspicious neck lymph nodes on sonography were diagnosed with metastatic thyroid papillary carcinoma (Fig. 2). n additional two patients with no suspicious neck lymph nodes on sonography were also diagnosed on pathology with metastatic lymph nodes. Five of nine patients showed heterogeneous hypoechogenicity on sonography and underlying lymphocytic thyroiditis on pathology (Fig. 3). However, three Fig year-old woman with thyroid papillary carcinoma and ipsilateral neck node metastasis. Lesion suspected to be thyroid carcinoma was incidentally discovered during sonography intended for evaluation of palpated cervical nodules, which were proven to be benign lymph nodes., Longitudinal sonogram of left thyroid gland reveals multiple microcalcifications (arrows) at low pole and underlying heterogeneous hypoechogenicity., Transverse sonogram reveals lymph node located at left level IV, measuring 0.7 cm in length, without identifiable structure, indicating fatty hilum (arrows). of nine patients who showed heterogeneous hypoechogenicity on sonography were diagnosed with the diffuse sclerosing variant of papillary carcinoma. Discussion Thyroid calcifications within a mass are an important sonographic finding, and a malignant nodule may show both coarse calcifications and microcalcifications [6]. Calcifications within a solitary mass can be considered an indicator of malignancy [7]. Recently, a panel discussion held by the Society of Radiologists in Ultrasound concluded that microcalcifications within a nodule on thyroid sonography raised the likelihood of malignancy [8]. lthough coarse dystrophic calcifications are considered to be of no diagnostic value, some articles have suggested that this type of calcification seems to have an association with carcinoma [6, 9]. Histopathologically, thyroid calcifications are divided into psammoma bodies and dystrophic calcifications. Psammoma bodies are laminated, basophilic, spherical concretions and are a characteristic finding of papillary carcinoma [10]. Most microcalcifications on sonography represent psammoma bodies, suggesting malignancy [6]. lthough many reports address thyroid calcifications within a mass, there are few published studies regarding thyroid carcinoma as microcalcifications on sonography without an associated mass [5]. Our review, which covers a period of approximately 5 years, revealed 11 thyroid carcinomas appearing only as thyroid microcalcifications on sonography. Interestingly, nine of 11 patients in our study showed underlying heterogeneous hypoechogenicity on sonography. This finding could make the detection of microcalcification relatively easier compared with a normal hyperechoic thyroid gland. The high prevalence of hypoechogenicity in our patients may suggest an inflammatory process as a potential contributor in this disease category. mong the nine patients showing underlying diffuse heterogeneous hypoechogenicity on sonography, six patients revealed underlying diffuse lymphocytic thyroiditis or diffuse hyperplasia on pathology. The remaining three, who had diffuse heterogeneous hypoechogenicity on sonography but no diffuse thyroid disease on pathology, were diagnosed with a diffuse sclerosing variant of papillary carcinoma. This diffuse sclerosing variant of papillary carcinoma is represented histologically by diffuse involvement of both thyroid lobes with dense fibrosis, extensive squamous metaplasia with morphologically benign nuclei, patchy lymphoid infiltration with germinal centers, psammoma bodies, and an area of conventional papillary carcinoma [11]. Scattered microcalcifications and heterogeneous hypoechogenicity seen on sonography in the diffuse sclerosing variant of papillary carcinoma seem to reflect lesions such as psammoma bodies, extensive fibrosis, and lympho- JR:189, July

4 cytic infiltration. Corresponding lesions were identified during histopathologic review of the obtained specimens. The diffuse sclerosing variant of papillary carcinoma appears to have a tendency toward younger age distribution and a higher incidence of cervical lymph node metastases compared with papillary thyroid carcinoma [12]. However, there was no difference in age distribution between papillary carcinoma and the diffuse sclerosing variant of papillary carcinoma in this study. Metastatic lymph nodes were confirmed in six of 11 patients and, interestingly, three of four patients diagnosed with the diffuse sclerosing variant of papillary C Fig year-old woman with thyroid papillary carcinoma incidentally found on thyroid sonography during health examination. and, Transverse and longitudinal sonograms of right thyroid gland reveal clustered linear microcalcifications (arrows) and underlying heterogeneous hypoechogenicity. C, Sheet of papillary carcinoma shows slightly irregular nuclei with vesicular chromatin and occasional nuclear grooves (arrow). (ThinPrep [Cytyc Corporation], Papanicolaou stain, 1,000) D, Photomicrograph shows a few psammoma bodies scattered in papillary carcinoma. (H and E, 200) carcinoma showed multiple neck lymph node metastases. This result suggests that the diffuse sclerosing variant of papillary carcinoma might have a higher incidence of cervical nodal metastases [12]. We performed sonography-guided FN in all cases because of its simplicity, safety, and high sensitivity. Ten patients had malignant cytologic results from the thyroid microcalcifications. The remaining patient had a malignant cytologic result for a lymph node suspected to be metastatic in nature based on sonography findings. Thus, we conclude that sonography-guided FN can be satisfactory for diagnosis of thyroid carcinomas without a mass that manifest as microcalcifications on sonography. The limitation of this study is the small sample size. prospective study covering a larger population will be necessary to estimate the rate of malignancy and the role of FN for both benign and malignant lesions presenting solely as microcalcifications on sonography. In conclusion, real-time high-resolution sonography allows good visualization of thyroid carcinomas appearing only as microcalcifications without an associated mass. In this study, underlying hypoechogenicity helped in the detection of echogenic microcalcifications of the thyroid gland. Furthermore, to evaluate D 230 JR:189, July 2007

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