World J Surg DOI 10.1007/s00268-014-2460-z
Scattered Psammomatous Calcifications around Papillary Thyroid Carcinoma Yong Sang Lee • Soon Won Hong • Hang-Seok Chang Cheong Soo Park
•
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Background Although psammomatous calcification is a characteristic pathologic feature of papillary thyroid carcinoma (PTC), the clinical meaning of histologically determined scattered psammomatous calcifications around PTC is unknown. Objective The aim of this study was to evaluate the clinical significance of scattered psammomatous calcifications around PTC. Materials and methods Between January 2009 and July 2009, a total of 546 patients who underwent total thyroidectomy for PTC were enrolled. They were classified into two groups: patients with scattered psammomatous calcifications and patients without psammomatous calcifications. The clinical findings, preoperative diagnostic findings, and histopathologic features were compared between the two groups. Results Scattered psammomatous calcifications around PTC were found in 209 patients (38 %), and mostly in younger patients (p = 0.007), those with infiltrative tumor margin (p = 0.022), those with capsule invasion (p = 0.013), and those with lymph node metastasis (p \ 0.001). No statistical significance was found in
Y. S. Lee H.-S. Chang (&) C. S. Park Thyroid Cancer Center, Departments of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 135-720, Korea e-mail: [email protected] Y. S. Lee e-mail: [email protected] S. W. Hong Thyroid Cancer Center, Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 135-720, Korea
gender, tumor size, multiplicity, and coexisting lymphocytic thyroiditis. Conclusions Although further studies with large-scale, long-term follow-up will be necessary to validate the relationship between scattered psammomatous calcifications and prognosis, scattered psammomatous calcification around PTC may have correlations with the aggressiveness of the PTC.
Introduction Psammomatous calcifications, well circumscribed laminated calcifications, are found most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of the ovary [1]. In PTC, psammomatous calcifications are found within the cores of papillae or in tumor stroma, but usually not in neoplastic follicles. Although various theories have been put forth regarding the pathogenesis of psammomatous calcification, its biochemical mechanism is unclear [2]. The association between psammomatous calcification and PTC has been demonstrated by several histologic studies showing that only 0.05–1.6 % of normal or benign glands have psammomatous calcification, in contrast with 12.0–61.0 % of PTC [3]. Psammomatous calcification is one of the most important diagnostic criteria of PTC in fine-needle aspiration (FNA) cytology, and the characteristic pathologic features of PTC. However, the clinical significance of histopathologically determined scattered psammomatous calcification in PTC and that around PTC are still unknown. The aim of this study was to evaluate the clinical significance of scattered psammomatous calcification around PTC.
123
World J Surg Fig. 1 Histopathology of psammoma bodies. Group I papillary carcinoma revealed several lamellated psammoma bodies in the papillary cores (a and b), intratumoral parenchyma (c), and peritumoral normal thyroid parenchyma (d). (Hematoxylin and eosin 9 400)
Materials and methods Between January 2009 and July 2009, of the 762 patients who underwent thyroid surgery at the Thyroid Cancer Center, Gangnam Severance hospital, Yonsei University College of Medicine, 546 patients (71.6 %) who satisfied our inclusion criteria were enrolled. We excluded those patients with less-than-total thyroidectomy, benign thyroid diseases, recurrent/persistent thyroid cancer, non-papillary thyroid cancer, and the diffuse sclerosing variant of PTC. All patients underwent preoperative ultrasonography to evaluate the primary tumor. Preoperative diagnosis was made using FNA cytology, and thyroid cancer was confirmed by postoperative histopathologic examination. All patients underwent total thyroidectomy along with routine central compartment node dissection, and lateral neck dissection was performed only in cases with clinically evident node metastases. Two pathologists analyzed all histologic specimens and various histologic subtypes of PTC with the same criteria. Scattered psammomatous calcifications around PTC were defined as psammomatous calcifications scattered in the background thyroid parenchyma (Fig. 1). Patients were divided into two groups according to the presence of psammomatous calcifications determined by postoperative histopathologic findings: patients with psammomatous calcifications were classified as Group I (N = 209) (Fig. 2a, b), and patients without psammomatous calcifications as Group II (N = 337) (Fig. 2c). The classification was conducted in an ‘all or nothing’ fashion.
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All clinicopathological data were analyzed according to age at diagnosis, gender distribution, tumor size in diameter, capsular invasion, coexisting lymphocytic thyroiditis, multiplicity, and lymph node involvement. Student’s t, v2, or Fisher’s exact tests were used to compare differences between two groups. A p value B0.05 indicated significance, and a p value between 0.05 and 0.1 indicated marginal significance. Approval to conduct a retrospective review of the images and medical records of patients was obtained from the Institutional Review Board of Gangnam Severance Hospital, Yonsei University College of Medicine. The Institutional Review Board approved this retrospective observational study and required neither patient approval nor informed consent for the review of their records.
Results Scattered psammomatous calcifications were present in 38 % (209 of 546) in this series. The clinicopathologic characteristics between the two groups are listed in Table 1. The mean age for group I was slightly lower than that for group II (46.3 vs. 48.6 years) with statistical significance (p = 0.007). The gender distribution of the patients was similar between the two groups. The mean tumor size for group I was 1.03 cm, and that for group II was 0.85 cm (p = 0.174). Papillary microcarcinomas were defined as less than 1.0 cm in diameter in 91.9 % of all patients; 88.5 % in group I and 94.1 % in group II (p \ 0.001).
World J Surg
Fig. 2 Histopathology of groups I and II. Group I revealed several lamellated psammoma bodies in the intratumoral parenchyma (a) and peritumoral normal thyroid parenchyma (b). (Hematoxylin and eosin 940, arrows and insets; psammoma bodies, hematoxylin and
eosin 9400). Group II showed typical papillary carcinoma characteristics without psammoma bodies (c) (hematoxylin and eosin 940, arrow and insets; tumor giant cells, hematoxylin and eosin 9400)
Table 1 Clinicopathologic characteristics between groups I and II (N = 546)
patients (p = 0.022). Tumor multiplicity and coexisting lymphocytic thyroiditis were also prevalent in group I rather than group II, but these were not statistically significant. Lymph node metastasis was found in 60.3 % of group I patients and 31.8 % of group II patients (p \ 0.001). Mean number of metastatic central lymph nodes was 1.87 and 1.52, and mean number of metastatic lateral lymph nodes was 8.47 and 6.84 in group I and II, respectively. According to the univariate and multivariate analysis, psammomatous calcification was significantly related to central lymph node metastasis (odds ratio [OR] 2.623; 95 % confidence interval [CI] 1.842–3.733), p \ 0.001] (Table 2). However, psammomatous calcification was not significantly related to the lateral neck node metastasis (Table 3).
Variables
Group Ia (N = 209)
Group IIb (N = 337)
p value
Age at diagnosis, years
46.3 ± 12.4
48.6 ± 10.4
0.007
Gender distribution
0.145
Male
39 (18.7)
50 (14.8)
Female
170 (81.3)
287 (85.2)
Tumor size in diameter, cm
1.03 ± 0.63
0.85 ± 0.59
0.174
Microcarcinomas (\ 1.0 cm in diameter)
185 (88.5)
317 (94.1)
\0.001
Multiplicity Unilateral
28 (13.4)
35 (10.4)
Bilateral
61 (29.2)
83 (24.7)
0.209
Tumor margin
0.022
Expanding type
57 (27.3)
Infiltrative type
152 (72.7)
216 (64.1)
Capsule invasion
133 (63.6)
180 (53.6)
0.013
Coexisting lymphocytic thyroiditis
69 (33.0)
101 (30.0)
0.257
Lymph node metastasis
126 (60.3)
107 (31.8)
\0.001
118 (56.5)
99 (29.4)
\0.001
1.87 ± 1.01
1.52 ± 0.72
38 (18.2) 8.47 ± 4.56
29 (8.6) 6.84 ± 3.24
Central node metastasis Number Lateral node metastasis Number
121 (35.9)
0.001
Data are presented as N (%) or mean ± SD unless otherwise indicated SD standard deviation a
Patients with scattered psammomatous calcifications
b
Patients without psammomatous calcifications
Statistically significant differences were found in some of the pathologic characteristics. Capsule invasion, as confirmed by postoperative histopathologic examination, was found in 63.6 % of group I patients and 53.6 % of group II patients (p = 0.013). Infiltrative tumor margin type was found in 72.7 % of group I patients and 64.1 % of group II
Discussion Psammomatous calcifications are concentric lamellate calcified structures, so-called because of their resemblance to grains of sand. Psammomatous calcifications are said to represent the process of dystrophic calcification in which the deposition occurs locally in non-viable or dying tissues with normal serum levels of calcium and in the absence of derangements in calcium metabolism. In the process of dystrophic calcification, single necrotic cells constitute seed crystals that become encrusted with mineral deposits, and the progressive acquisition of outer layers may create its lamellated configurations, giving rise to psammomatous calcifications. In cytologic preparations, these calcospherites are 50–70 lm in size, round shaped with a glassy appearance, and stain dark-blue to black with Giemsa staining and brown to black in Papanicolaou staining [4]. Calcification within the thyroid gland is a common finding both on thyroid imaging and in thyroid histopathologic
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World J Surg Table 2 Logistic regression analysis of central node metastasis
CI confidence interval, OR odds ratio
Univariate p value
OR (95 % CI)
p value \0.001
Age at diagnosis
0.992 (0.989–0.996)
\0.001
0.968 (0.953–0.983)
0.844 (0.744–0.943)
0.002
0.569 (0.358–0.904)
0.017
Tumor size in diameter (cm)
1.229 (1.172–1.287)
\0.001
2.230 (1.581–3.146)
\0.001
Multiplicity
1.084 (1.005–1.162)
0.036
1.173 (0.806–1.707)
0.405
Infiltrative tumor margin
1.083 (1.005–1.161)
0.036
1.004 (0.681–1.479)
0.986
Capsular invasion
1.240 (1.168–1.311)
\0.001
2.255 (1.545–3.290)
\0.001
Psammomatous calcification
1.283 (1.210–1.356)
\0.001
2.623 (1.842–3.733)
\0.001
Univariate
Multivariate
OR (95 % CI)
p value
OR (95 % CI)
p value 0.074
Age at diagnosis
0.996 (0.994–0.998)
\0.001
0.987 (0.955–1.002)
Gender (female vs. male)
0.907 (0.842–0.971)
0.002
0.549 (0.286–1.051)
0.070
Tumor size in diameter (cm)
1.193 (1.157–1.229)
\0.001
3.481 (2.296–5.278)
\0.001
Multiplicity
1.038 (0.087–1.089)
0.144
1.067 (0.595–1.915)
0.828 0.001
Infiltrative tumor margin
1.103 (1.053–1.153)
\0.001
4.121 (1.784–9.516)
Capsular invasion
1.092 (1.045–1.140)
\0.001
1.014 (0.532–1.933)
0.967
Central node metastasis
1.191 (1.144–1.238)
\0.001
3.722 (1.933–7.166)
\0.001
Psammomatous calcification
1.114 (1.066–1.163)
\0.001
1.518 (0.843–2.734)
0.164
findings, and has been reported to be present in up to 21 % of plain radiographs of the thyroid gland and 39 % of thyroid ultrasonographies [5, 6]. The presence of calcification is strongly suggestive of malignancy in preoperative diagnosis, so psammomatous calcifications in FNA cytology are diagnostic characteristics for PTC [7–10]. In the present study, scattered psammomatous calcifications around PTC were found in 38 % of the patients, and they had strong associations with infiltrative tumor margin (p = 0.022), capsule invasion (p = 0.013), and lymph node metastasis (p \ 0.001). Although there were no significant differences in multiplicity (p = 0.209), the presence of scattered psammomatous calcifications implied more aggressive disease progression and stromal infiltration. In agreement with this concept, the presence of psammomatous calcification implied a significant relationship with lymph node metastasis. It has been reported that lymph node metastases are found in up to 70 % of PTC cases, depending on the tumor characteristics, extent of surgery, and number of lymph node sections examined by the pathologist [10]. Controversy still surrounds the prognostic relevance of lymph node metastasis in differentiated PTC. Some reports have documented that the presence of neck node metastases had no impact on recurrence or survival [11–13]. Others have reported that the presence of neck node metastases was an independent predictor of recurrence and survival in their series [14]. It is commonly
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OR (95 % CI)
Gender (female vs. male)
Table 3 Logistic regression analysis of lateral node metastasis
CI confidence interval, OR odds ratio
Multivariate
accepted that lymph node metastasis has no major impact on survival [11–13], but it has been suggested that the presence of nodal involvement was closely associated with capsule invasion and the increased rate of local recurrence and distant metastasis [15–18]. From these points of view, we can hypothesize that the presence of scattered psammomatous calcifications around PTC may have correlations with aggressiveness and prognosis for local recurrence. In conclusion, although further large-scale studies with long-term follow-up, and grading of the scattering of calcification will be necessary to validate the relationship between scattered psammomatous calcification and prognosis, scattered psammomatous calcifications around PTC may have correlations with the aggressiveness of PTC. Acknowledgment
No grant support was received for the research.
Conflict of interest interest to disclose.
No authors have any financial conflicts of
Disclosure Supported by a faculty research grant of a Yousei University College of medicine in 2008 (Grant No. 6-2008-0184).
References 1. Das DK, Mallik MK, Haji BE et al (2004) Psammoma body and its precursors in papillary thyroid carcinoma: a study by fineneedle aspiration cytology. Diagn Cytopathol 31:380–386
World J Surg 2. LiVolsi VA, Gupta PK (1992) Thyroid fine-needle aspiration: intranuclear inclusions, nuclear grooves and psammoma bodies: paraganglioma-like adenoma of the thyroid. Diagn Cytopathol 8:82–83 3. Gargangiu ML, Zampi G, Pupi A et al (1985) Papillary carcinoma of the thyroid. A clinicopathologic study of 241 cases treated at the University of Florence, Italy. Cancer 55:805–828 4. Triggiani V, Guastamacchia E, Licchelli B et al (2008) Microcalcifications and psammoma bodies in thyroid tumors. Thyroid 18:1017–1018 5. Komolafe F (1981) Radiological patterns and significance of thyroid calcification. Clin Radiol 32:571–575 6. Hayashi N, Tamaki N, Yamamoto K et al (1986) Real-time ultrasonography of thyroid nodules. Acta Radiol Diagn (Stockh) 27:403–408 7. Singer PA, Cooper DS, Daniels GH et al (1996) Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. Arch Intern Med 156:2165–2172 8. Khoo ML, Asa SL, Witterick IJ et al (2002) Thyroid calcification and its association with thyroid carcinoma. Head Neck 24:651–655 9. Kakkos SK, Scopa CD, Chalmoukis AK et al (2000) Relative risk of cancer in sonographically detected thyroid nodules with calcifications. J Clin Ultrasound 28:347–352 10. Noguchi S, Noguchi A, Murakami N (1970) Papillary carcinoma of the thyroid. I. Developing pattern of metastasis. Cancer 26:1053–1060
11. McConahey WM, Hay ID, Woolner LB et al (1986) Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc 61:978–996 12. Shah JP, Loree TR, Dharker D et al (1992) Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164:658–661 13. Hughes CJ, Shaha AR, Shah JP et al (1996) Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis. Head Neck 18:127–132 14. Mazzaferri EL, Jhiang SM (1994) Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97:418–428 15. Coburn MC, Wanebo HJ (1992) Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. Am J Surg 164:671–676 16. Sellers M, Beenken S, Blankenship A et al (1992) Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. Am J Surg 164:578–581 17. Noguchi S, Murakami N, Yamashita H et al (1998) Papillary thyroid carcinoma: modified radical neck dissection improves prognosis. Arch Surg 133:276–280 18. Ortiz S, Rodrı´guez JM, Soria T et al (2001) Extrathyroid spread in papillary carcinoma of the thyroid: clinicopathological and prognostic study. Otolaryngol Head Neck Surg 124:261–265
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Scattered Psammomatous Calcifications around Papillary Thyroid Carcinoma Yong Sang Lee • Soon Won Hong • Hang-Seok Chang Cheong Soo Park
•
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Background Although psammomatous calcification is a characteristic pathologic feature of papillary thyroid carcinoma (PTC), the clinical meaning of histologically determined scattered psammomatous calcifications around PTC is unknown. Objective The aim of this study was to evaluate the clinical significance of scattered psammomatous calcifications around PTC. Materials and methods Between January 2009 and July 2009, a total of 546 patients who underwent total thyroidectomy for PTC were enrolled. They were classified into two groups: patients with scattered psammomatous calcifications and patients without psammomatous calcifications. The clinical findings, preoperative diagnostic findings, and histopathologic features were compared between the two groups. Results Scattered psammomatous calcifications around PTC were found in 209 patients (38 %), and mostly in younger patients (p = 0.007), those with infiltrative tumor margin (p = 0.022), those with capsule invasion (p = 0.013), and those with lymph node metastasis (p \ 0.001). No statistical significance was found in
Y. S. Lee H.-S. Chang (&) C. S. Park Thyroid Cancer Center, Departments of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 135-720, Korea e-mail: [email protected] Y. S. Lee e-mail: [email protected] S. W. Hong Thyroid Cancer Center, Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 135-720, Korea
gender, tumor size, multiplicity, and coexisting lymphocytic thyroiditis. Conclusions Although further studies with large-scale, long-term follow-up will be necessary to validate the relationship between scattered psammomatous calcifications and prognosis, scattered psammomatous calcification around PTC may have correlations with the aggressiveness of the PTC.
Introduction Psammomatous calcifications, well circumscribed laminated calcifications, are found most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of the ovary [1]. In PTC, psammomatous calcifications are found within the cores of papillae or in tumor stroma, but usually not in neoplastic follicles. Although various theories have been put forth regarding the pathogenesis of psammomatous calcification, its biochemical mechanism is unclear [2]. The association between psammomatous calcification and PTC has been demonstrated by several histologic studies showing that only 0.05–1.6 % of normal or benign glands have psammomatous calcification, in contrast with 12.0–61.0 % of PTC [3]. Psammomatous calcification is one of the most important diagnostic criteria of PTC in fine-needle aspiration (FNA) cytology, and the characteristic pathologic features of PTC. However, the clinical significance of histopathologically determined scattered psammomatous calcification in PTC and that around PTC are still unknown. The aim of this study was to evaluate the clinical significance of scattered psammomatous calcification around PTC.
123
World J Surg Fig. 1 Histopathology of psammoma bodies. Group I papillary carcinoma revealed several lamellated psammoma bodies in the papillary cores (a and b), intratumoral parenchyma (c), and peritumoral normal thyroid parenchyma (d). (Hematoxylin and eosin 9 400)
Materials and methods Between January 2009 and July 2009, of the 762 patients who underwent thyroid surgery at the Thyroid Cancer Center, Gangnam Severance hospital, Yonsei University College of Medicine, 546 patients (71.6 %) who satisfied our inclusion criteria were enrolled. We excluded those patients with less-than-total thyroidectomy, benign thyroid diseases, recurrent/persistent thyroid cancer, non-papillary thyroid cancer, and the diffuse sclerosing variant of PTC. All patients underwent preoperative ultrasonography to evaluate the primary tumor. Preoperative diagnosis was made using FNA cytology, and thyroid cancer was confirmed by postoperative histopathologic examination. All patients underwent total thyroidectomy along with routine central compartment node dissection, and lateral neck dissection was performed only in cases with clinically evident node metastases. Two pathologists analyzed all histologic specimens and various histologic subtypes of PTC with the same criteria. Scattered psammomatous calcifications around PTC were defined as psammomatous calcifications scattered in the background thyroid parenchyma (Fig. 1). Patients were divided into two groups according to the presence of psammomatous calcifications determined by postoperative histopathologic findings: patients with psammomatous calcifications were classified as Group I (N = 209) (Fig. 2a, b), and patients without psammomatous calcifications as Group II (N = 337) (Fig. 2c). The classification was conducted in an ‘all or nothing’ fashion.
123
All clinicopathological data were analyzed according to age at diagnosis, gender distribution, tumor size in diameter, capsular invasion, coexisting lymphocytic thyroiditis, multiplicity, and lymph node involvement. Student’s t, v2, or Fisher’s exact tests were used to compare differences between two groups. A p value B0.05 indicated significance, and a p value between 0.05 and 0.1 indicated marginal significance. Approval to conduct a retrospective review of the images and medical records of patients was obtained from the Institutional Review Board of Gangnam Severance Hospital, Yonsei University College of Medicine. The Institutional Review Board approved this retrospective observational study and required neither patient approval nor informed consent for the review of their records.
Results Scattered psammomatous calcifications were present in 38 % (209 of 546) in this series. The clinicopathologic characteristics between the two groups are listed in Table 1. The mean age for group I was slightly lower than that for group II (46.3 vs. 48.6 years) with statistical significance (p = 0.007). The gender distribution of the patients was similar between the two groups. The mean tumor size for group I was 1.03 cm, and that for group II was 0.85 cm (p = 0.174). Papillary microcarcinomas were defined as less than 1.0 cm in diameter in 91.9 % of all patients; 88.5 % in group I and 94.1 % in group II (p \ 0.001).
World J Surg
Fig. 2 Histopathology of groups I and II. Group I revealed several lamellated psammoma bodies in the intratumoral parenchyma (a) and peritumoral normal thyroid parenchyma (b). (Hematoxylin and eosin 940, arrows and insets; psammoma bodies, hematoxylin and
eosin 9400). Group II showed typical papillary carcinoma characteristics without psammoma bodies (c) (hematoxylin and eosin 940, arrow and insets; tumor giant cells, hematoxylin and eosin 9400)
Table 1 Clinicopathologic characteristics between groups I and II (N = 546)
patients (p = 0.022). Tumor multiplicity and coexisting lymphocytic thyroiditis were also prevalent in group I rather than group II, but these were not statistically significant. Lymph node metastasis was found in 60.3 % of group I patients and 31.8 % of group II patients (p \ 0.001). Mean number of metastatic central lymph nodes was 1.87 and 1.52, and mean number of metastatic lateral lymph nodes was 8.47 and 6.84 in group I and II, respectively. According to the univariate and multivariate analysis, psammomatous calcification was significantly related to central lymph node metastasis (odds ratio [OR] 2.623; 95 % confidence interval [CI] 1.842–3.733), p \ 0.001] (Table 2). However, psammomatous calcification was not significantly related to the lateral neck node metastasis (Table 3).
Variables
Group Ia (N = 209)
Group IIb (N = 337)
p value
Age at diagnosis, years
46.3 ± 12.4
48.6 ± 10.4
0.007
Gender distribution
0.145
Male
39 (18.7)
50 (14.8)
Female
170 (81.3)
287 (85.2)
Tumor size in diameter, cm
1.03 ± 0.63
0.85 ± 0.59
0.174
Microcarcinomas (\ 1.0 cm in diameter)
185 (88.5)
317 (94.1)
\0.001
Multiplicity Unilateral
28 (13.4)
35 (10.4)
Bilateral
61 (29.2)
83 (24.7)
0.209
Tumor margin
0.022
Expanding type
57 (27.3)
Infiltrative type
152 (72.7)
216 (64.1)
Capsule invasion
133 (63.6)
180 (53.6)
0.013
Coexisting lymphocytic thyroiditis
69 (33.0)
101 (30.0)
0.257
Lymph node metastasis
126 (60.3)
107 (31.8)
\0.001
118 (56.5)
99 (29.4)
\0.001
1.87 ± 1.01
1.52 ± 0.72
38 (18.2) 8.47 ± 4.56
29 (8.6) 6.84 ± 3.24
Central node metastasis Number Lateral node metastasis Number
121 (35.9)
0.001
Data are presented as N (%) or mean ± SD unless otherwise indicated SD standard deviation a
Patients with scattered psammomatous calcifications
b
Patients without psammomatous calcifications
Statistically significant differences were found in some of the pathologic characteristics. Capsule invasion, as confirmed by postoperative histopathologic examination, was found in 63.6 % of group I patients and 53.6 % of group II patients (p = 0.013). Infiltrative tumor margin type was found in 72.7 % of group I patients and 64.1 % of group II
Discussion Psammomatous calcifications are concentric lamellate calcified structures, so-called because of their resemblance to grains of sand. Psammomatous calcifications are said to represent the process of dystrophic calcification in which the deposition occurs locally in non-viable or dying tissues with normal serum levels of calcium and in the absence of derangements in calcium metabolism. In the process of dystrophic calcification, single necrotic cells constitute seed crystals that become encrusted with mineral deposits, and the progressive acquisition of outer layers may create its lamellated configurations, giving rise to psammomatous calcifications. In cytologic preparations, these calcospherites are 50–70 lm in size, round shaped with a glassy appearance, and stain dark-blue to black with Giemsa staining and brown to black in Papanicolaou staining [4]. Calcification within the thyroid gland is a common finding both on thyroid imaging and in thyroid histopathologic
123
World J Surg Table 2 Logistic regression analysis of central node metastasis
CI confidence interval, OR odds ratio
Univariate p value
OR (95 % CI)
p value \0.001
Age at diagnosis
0.992 (0.989–0.996)
\0.001
0.968 (0.953–0.983)
0.844 (0.744–0.943)
0.002
0.569 (0.358–0.904)
0.017
Tumor size in diameter (cm)
1.229 (1.172–1.287)
\0.001
2.230 (1.581–3.146)
\0.001
Multiplicity
1.084 (1.005–1.162)
0.036
1.173 (0.806–1.707)
0.405
Infiltrative tumor margin
1.083 (1.005–1.161)
0.036
1.004 (0.681–1.479)
0.986
Capsular invasion
1.240 (1.168–1.311)
\0.001
2.255 (1.545–3.290)
\0.001
Psammomatous calcification
1.283 (1.210–1.356)
\0.001
2.623 (1.842–3.733)
\0.001
Univariate
Multivariate
OR (95 % CI)
p value
OR (95 % CI)
p value 0.074
Age at diagnosis
0.996 (0.994–0.998)
\0.001
0.987 (0.955–1.002)
Gender (female vs. male)
0.907 (0.842–0.971)
0.002
0.549 (0.286–1.051)
0.070
Tumor size in diameter (cm)
1.193 (1.157–1.229)
\0.001
3.481 (2.296–5.278)
\0.001
Multiplicity
1.038 (0.087–1.089)
0.144
1.067 (0.595–1.915)
0.828 0.001
Infiltrative tumor margin
1.103 (1.053–1.153)
\0.001
4.121 (1.784–9.516)
Capsular invasion
1.092 (1.045–1.140)
\0.001
1.014 (0.532–1.933)
0.967
Central node metastasis
1.191 (1.144–1.238)
\0.001
3.722 (1.933–7.166)
\0.001
Psammomatous calcification
1.114 (1.066–1.163)
\0.001
1.518 (0.843–2.734)
0.164
findings, and has been reported to be present in up to 21 % of plain radiographs of the thyroid gland and 39 % of thyroid ultrasonographies [5, 6]. The presence of calcification is strongly suggestive of malignancy in preoperative diagnosis, so psammomatous calcifications in FNA cytology are diagnostic characteristics for PTC [7–10]. In the present study, scattered psammomatous calcifications around PTC were found in 38 % of the patients, and they had strong associations with infiltrative tumor margin (p = 0.022), capsule invasion (p = 0.013), and lymph node metastasis (p \ 0.001). Although there were no significant differences in multiplicity (p = 0.209), the presence of scattered psammomatous calcifications implied more aggressive disease progression and stromal infiltration. In agreement with this concept, the presence of psammomatous calcification implied a significant relationship with lymph node metastasis. It has been reported that lymph node metastases are found in up to 70 % of PTC cases, depending on the tumor characteristics, extent of surgery, and number of lymph node sections examined by the pathologist [10]. Controversy still surrounds the prognostic relevance of lymph node metastasis in differentiated PTC. Some reports have documented that the presence of neck node metastases had no impact on recurrence or survival [11–13]. Others have reported that the presence of neck node metastases was an independent predictor of recurrence and survival in their series [14]. It is commonly
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OR (95 % CI)
Gender (female vs. male)
Table 3 Logistic regression analysis of lateral node metastasis
CI confidence interval, OR odds ratio
Multivariate
accepted that lymph node metastasis has no major impact on survival [11–13], but it has been suggested that the presence of nodal involvement was closely associated with capsule invasion and the increased rate of local recurrence and distant metastasis [15–18]. From these points of view, we can hypothesize that the presence of scattered psammomatous calcifications around PTC may have correlations with aggressiveness and prognosis for local recurrence. In conclusion, although further large-scale studies with long-term follow-up, and grading of the scattering of calcification will be necessary to validate the relationship between scattered psammomatous calcification and prognosis, scattered psammomatous calcifications around PTC may have correlations with the aggressiveness of PTC. Acknowledgment
No grant support was received for the research.
Conflict of interest interest to disclose.
No authors have any financial conflicts of
Disclosure Supported by a faculty research grant of a Yousei University College of medicine in 2008 (Grant No. 6-2008-0184).
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