Prognostic factors for aggressiveness in subcentimeter papillary thyroid carcinoma: impact of tumor size and lymph node metastases

Kayhan, Yusuf; Azizova, Leyla; Yılmaz, Merve; Bakış, Muhsine; Kefeli, Mehmet; Kan, Elif Kılıç; Atmaca, Ayşegül; Çolak, Ramis

doi:10.20945/2359-4292-2023-0422

Brasil

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Original Article • Arch. Endocrinol. Metab. 68 • 2024 • https://doi.org/10.20945/2359-4292-2023-0422 linkcopy

Prognostic factors for aggressiveness in subcentimeter papillary thyroid carcinoma: impact of tumor size and lymph node metastases

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective Subcentimeter papillary thyroid carcinoma (sPTC), also known as papillary thyroid microcarcinoma, is associated with a good prognosis and low mortality risk. However, some sPTCs exhibit biologically aggressive characteristics. The aim of this study was to identify factors affecting the prognosis and aggressiveness of sPTC by considering the demographic characteristics of patients with sPTC and the pathologic characteristics of the tumors.

Subjects and methods The study included 255 patients aged ≥ 18 years who were operated on at Ondokuz Mayis University, Faculty of Medicine (Samsun, Turkey) between June 2008 and December 2021. All patients had histopathologic confirmation of sPTC (≤10 mm) and underwent regular follow-up for at least 36 months.

Results The tumors had a mean size of 5 mm (0.1-10 mm) and were multifocal in 53.7% of patients. Capsular invasion was observed in 9% of patients. Vascular invasion, lymphatic invasion, and extrathyroidal invasion were present in 2%, 5.5%, and 0.8% of patients, respectively. Metastatic cervical lymph nodes were observed in 9.4% of patients. On multivariate logistic regression analysis, tumor size (odds ratio [OR] 1.380, 95% confidence interval [CI] 1.106-1.722, p = 0.004) and sex (OR 4.233, 95% CI 1.355-13.226, p = 0.013) were the main predictive factors influencing lymph node metastasis. Tumors > 5 mm, compared with tumors ≤ 5 mm, had higher rates of multifocality (p = 0.009), parenchymal invasion (p = 0.008), calcifications (p = 0.001), microscopic lymphatic invasion (p = 0.002), and presence of metastatic lymph nodes (p < 0.001).

Conclusion The findings of this study highlight important factors to consider in making decisions about prophylactic central compartment neck dissection in patients with sPTCs, particularly those with clinically node-negative tumors.

Subcentimeter papillary thyroid carcinoma; papillary thyroid microcarcinoma; tumor size; prognosis; lymph node metastasis; surgical pathology

Focality n – (%)		Tumor size – average (mm)	5 (0.1-10)
Unifocal	118 (46.3)
Multifocal	137 (53.7)
Histopathologic subtypes – n (%)		Calcification – n (%)
Classic	99 (38.8)	Yes	32 (12.5)
Tall cell	30 (11.8)	No	222 (87.1)
Solid	1 (0.4)	Not mentioned	1 (0.4)
Hobnail	2 (0.8)
Follicular	109 (42.7)
Clear cell	11 (4.3)
Unspecified	3 (1.2)
Vascular invasion – n (%)		Lymphatic invasion – n (%)
Yes	5 (2)	Yes	14 (5.5)
No	249 (97.6)	No	240 (94.1)
Not mentioned	1 (0.4)	Not mentioned	1 (0.4)
Capsular invasion – n (%)		Perineural invasion – n (%)
Yes	23 (9)	Yes	2 (0.8)
No	231 (90.6)	No	252 (98.8)
Not mentioned	1 (0.4)	Not mentioned	1 (0.4)
Parenchymal invasion – n (%)		Extrathyroidal extension – n (%)
No	61 (23.9)	Yes	2 (0.8)
Yes	193 (75.7)	No	251 (98.4)
Not mentioned	1 (0.4)	Not mentioned	2 (0.8)
Necrosis – n (%)		Surgical margin – n (%)
No	254 (99.6)	Intact	228 (89.4)
Not mentioned	1 (0.4)	Positive	24 (9.4)
		Not mentioned	3 (1.2)
Mitosis – n (%)		Metastatic lymph nodes – n (%)
Yes	6 (2.4)	Yes
No	248 (97.3)	No	24 (9.4)
Not mentioned	1 (0.4)		231 (90.6)

	Lymph node metastasis		P values

	Present (n = 24)	Absent (n = 231)
Age at diagnosis – years (mean ± SD)	42.96 ± 11.07	49.09 ± 10.82	0.009
Age groups – n (%)
<55 years	21 (11.6)	159 (88.3)	0.094
≥55 years	3 (4.1)	72 (96)
Sex – n (%)
Female	15 (7.2)	194 (92.8)	0.021
Male	9 (19.6)	37 (80.4)
Type of surgery – n (%)
Lobectomy	0 (0)	19 (100)	0.387
Total thyroidectomy	23 (10.1)	204 (89.9)
Subtotal thyroidectomy	1 (11.1)	8 (88.9)
RAI treatment – n (%)
Yes	23 (25.8)	66 (74.2)	< 0.001
No	1 (0.6)	165 (99.4)
Recurrence – n (%)
Yes	2 (50)	2 (50)	0.045
No	22 (8.8)	229 (91.2)
Distant metastases – n (%) Pulmonary None
Yes	0 (0)	1 (100)	1
No	24 (9.4)	230 (90.6)
Death – n (%)
Yes	0 (0)	4 (100)	1
No	24 (9.6)	227 (90.4)
Suppressive therapy duration – years (mean ± SD)	2 (0-6)	2 (0-9)	0.271
Follow-up duration – years (mean ± SD)	3 (3-8)	4 (3-12)	0.165

	Lymph node metastases

	Present (n = 24)		Absent (n = 231)
Histopathologic subtypes – n (%)
Classic	9 (9.1)	90 (90.9)	<0.001
Tall cell	9 (30)	21 (70)
Solid	0 (0)	1 (100)
Hobnail	2 (100)	0 (0)
Follicular	3 (2.8)	106 (97.2)
Clear cell	1 (9.1)	10 (90.9)
Unspecified	0 (0)	3 (100)
Focality – n (%)
Unifocal	8 (6.8)	110 (93.2)	0.262
Multifocal	16 (11.7)	121 (88.3)
Tumor size – mm	8 (2-10)	5 (0.1-10)	<0.001
Capsular invasion – n (%)
Yes	3 (13)	20 (87)	0.515
No	21 (9.1)	210 (90.9)
Not mentioned	0 (0)	1 (100)
Parenchymal invasion – n (%)			0.134
No	10 (16.4)	51 (83.6)
Yes	14 (7.3)	179 (92.7)
Not mentioned	0 (0)	1 (100)
Necrosis – n (%)
No	24 (9.4)	230 (90.6)	1
Not mentioned	0 (0)	1 (100)
Mitosis – n (%)
Yes	1 (16.7)	5 (83.3)	0.504
No	23 (9.3)	225 (90.7)
Not mentioned	0 (0)	1 (100)
Calcification – n (%)
Yes	9 (28.1)	23 (71.9)	0.001
No	15 (6.8)	207 (93.2)
Not mentioned	0 (0)	1 (100)
Vascular invasion – n (%)
Yes	2 (40)	3 (60)	0.159
No	22 (8.8)	227 (91.2)
Not mentioned	0 (0)0	1 (100)
Lymphatic invasion – n (%)
Yes	8 (57.1)	6 (42.9)	<0.001
No	16 (6.7)	224 (93.3)
Not mentioned	0 (0)	1 (100)
Perineural invasion – n (%)
Yes	0 (0)	2 (100)	1
No	24 (9.5)	228 (90.5)
Not mentioned	0 (0)	1 (100)
Extrathyroidal extension – n (%)
Yes	0 (0)	2 (100)	1
No	24 (9.6)	227 (90.4)
Not mentioned	0 (0)	2 (100)
Surgical margin – n (%)
Intact	19 (8.3)	209 (91.7)	0.129
Positive	5 (20.8)	19 (79.2)
Not mentioned	0 (0)	3 (100)

	B	Sig	Exp(B)	95% CI for Exp(B)

				Lower	Upper
Age at diagnosis	-.047	.071	.954	.907	1.004
Tumor size	.322	.004	1.380	1.106	1.722
Male sex	1.443	.013	4.233	1.355	13.226
Histopathologic subtype		.344
Tall cell	1.213	.052	3.363	.989	11.436
Solid	-21.363	1.000	.000	.000	.
Hobnail	22.102	.999	396.4	.000	.
Follicular	-.768	.295	.464	.110	1.951
Clear cell	.209	.858	1.233	.124	12.218
Unspecified	-18.667	.999	.000	.000	.
Calcification		.806
No calcification	.503	.511	1.654	.368	7.428
Not mentioned	-18.555	1.000	.000	.000	.
Lymphatic invasion		.054
No lymphatic invasion	-1.668	.054	.189	.035	1.026
Constant	-1.586	.281	.205

Histopathologic subtypes	Tumor size group – n (%)		P value

	≤5 mm	>5 mm
Classic	53 (55.2%)	43 (44.8%)	0.049
Tall cell	10 (33.3%)	20 (66.7%)
Solid	0 (0%)	1 (100%)
Hobnail	0 (0%)	2 (100%)
Follicular	63 (59.4%)	43 (40.6%)
Clear cell	5 (45.5%)	6 (54.5%)

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[TFN1] Abbreviation: n, number.