甲状腺继发性肿瘤细胞病理学特征

doi:10.16150/j.1671-2870.2023.03.10

摘要/Abstract

摘要：

目的：观察经超声引导下行细针抽吸术（fine-needle aspiration, FNA）细胞学检查诊断为甲状腺继发性肿瘤（secondary thyroid neoplasm, STN）及细胞学病理特征。方法：收集2011年1月至2021年5月期间空军军医大学第一附属医院病理科经FNA细胞学检查诊断为甲状腺恶性肿瘤的病例5 023例。对其中所有STN的FNA样本制作的传统涂片、液基制片和细胞蜡块，行苏木素-伊红(hematoxylin-eosin，HE)染色、巴氏染色和细胞免疫组织化学（immunohistochemistry，IHC）染色，并以甲状腺髓样癌涂片为对照，由2位高年资细胞病理专科医师，分析STN细胞病理学特征及细胞免疫组化特征，结合临床，总结STN与甲状腺髓样癌间的细胞病理鉴别要点。结果：5 023例甲状腺恶性肿瘤病例中，STN 8例（0.16%），甲状腺髓样癌33例（0.66%），甲状腺乳头状癌4 955例（98%），淋巴瘤16例（0.32%），鳞状细胞癌7例（0.14%），间变性癌及低分化癌各2例（0.04%）。33例髓样癌细胞形态多样，呈浆细胞样、上皮样、梭形，可见少量奇异性巨细胞，且背景中可见淀粉样物。8例STN均无典型甲状腺乳头状癌的细胞核特征；1例转移性肺腺癌可见三维立体乳头状结构及腺样结构；4例转移性鳞状细胞癌可见成簇或散在分布的异型鳞状细胞，结合其各自的特征性免疫表型，可明确诊断；2例转移性乳腺癌、1例转移性肺小细胞癌则与甲状腺髓样癌间的细胞学形态特征有部分重叠，细胞均体积小、深染，需要检测免疫组化标志物雌激素受体（estrogen receptor，ER）、孕激素受体（progesterone receptor PR）、细胞角蛋白7（cytokeratin7，CK7）、GATA3、突触素（synaptophysin，Syn）、神经细胞黏附分子（neural cell adhesion molecule，CD56）、嗜铬素A（chromogranin A，CgA）、降钙素（calcitonin，CT）、甲状腺球蛋白（thyroglobulin，TG）、甲状腺转录因子-1（thyroid transcription-1，TTF-1）、配对盒基因8（paired box gene 8，PAX-8）等，并综合临床病史进行鉴别。结论：本组样本中，STN仅占甲状腺恶性肿瘤的0.16%，较少见，对于有髓样癌表现的病例，要注意乳腺癌、肺癌性STN可能，需结合免疫组化及病史进行鉴别诊断。

关键词: 甲状腺继发性肿瘤, 细胞学诊断, 鉴别诊断, 细针抽吸术

Abstract:

Objective: To observe the cytological pathological features of secondary thyroid neoplasm (STN) by ultrasound-guided fine-needle aspiration（FNA）. Methods: A total of 5023 cases of thyroid malignancy diagnosed by FNA cytology in The First Affiliated Hospital of Air Force Medical University from January 2011 to May 2021 were collected. Hematoxylin-eosin (HE) staining, Pap staining and cellular immunohistochemistry (IHC) staining were performed on traditional smears, liquid-based preparation and cell wax blocks made from FNA samples of all these STNs respectively. Using medullary thyroid carcinoma smear as a control, two senior cytopathologists analyzed the cytopathological and cellular immunohistochemical features of STN. Based on clinical practice, the key points of cytopathological differentiation between STN and medullary thyroid carcinoma were summarized. Result: Among 5023 cases of thyroid malignancy, there were 8 cases of STN (0.16%), 33 cases of medullary thyroid carcinoma (0.66%), 4955 cases of papillary thyroid carcinoma (98%), 16 cases of lymphoma (0.32%), 7 cases of squamous cell carcinoma (0.14%), and 2 cases each of anaplastic carcinoma and poorly differentiated carcinoma (0.04%). The 33 cases of medullary carcinoma tumor cells were diverse in morphology, including plasmacytoid cells, epithelioid cells, and fusiform cells, with a small number of bizarre giant cells and amyloid in the background. None of the 8 STNs showed typical nuclear features of thyroid papillary carcinoma， three-dimensional papillary and adenoid structures were seen in 1 case of metastatic lung adenocarcinoma， clusters or scattered heterotypic squamous cells were seen in 4/4 cases of metastatic squamous cell carcinoma, combined with their respective characteristic immunophenotypes, the diagnosis can be confirmed. The cytological morphological characteristics of 2 metastatic breast cancers and 1 metastatic small cell lung carcinoma overlapped with medullary thyroid carcinoma. The cells were all small and hyperchromatic nuclei, which required the detection of immunohistochemical markers including estrogen receptor (ER), Progesterone receptor（PR）, Cytokeratin7 (CK7), GATA3, Synaptophysin (Syn), Neural cell adhesion molecule (CD56), Chromogranin A (CgA), Calcitonin (CT), Thyroglobulin(TG), Thyroid transcription factor-1(TTF-1), Paired box gene 8 (PAX-8), and identification were made in the combination with medical history. Conclusions: STN accounts for 0.16% of thyroid malignancies and is relatively rare. In cases with myeloid cancer cell morphology, attention should be paid to the possibility of STN, and differential diagnosis should be made in combination with immunohistochemistry and medical history.

Key words: Secondary thyroid neoplasms, cytologic diagnosis, differential diagnosis, Fine-needle aspiration

中图分类号:

R736.1

杨巧, 付欣, 王哲, 刘坦坦. 甲状腺继发性肿瘤细胞病理学特征[J]. 诊断学理论与实践, 2023, 22(03): 270-276.

YANG Qiao, FU Xin, WANG Zhe, LIU Tantan. Cytopathologic analysis of thyroid secondary tumors[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(03): 270-276.

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	Sex	Age (years)	History disease	Ultrasound results	Follow-up (months)
1	Female	57	/	Right, mixed echo region, 1.9cm×1.5cm	1
2	Female	64	Small cell carcinoma of the left lung, 2 years and 8 months, cervical lymph node metastasis lasted 6 months	Right, low echo area, 2.4cm×1.4cm	24 (death)
3	Female	56	Breast cancer, 5 years and 6 months	Isthmus to the right, Low echo area, 1.7cm×1.2cm	29
4	Female	58	Breast cancer, eight years and ten months	Right, low echo area, 2.2cm×1.5cm	18
5	Male	56	Squamous cell carcinoma of larynx， 1 year	Right, low echo area, 0.9cm×0.8cm	24
6	Male	68	Squamous cell carcinoma of the esophagus, 3 years	Right, low echo area, 1.5cm×1.2cm	60 (death)
7	Male	75	Squamous cell carcinoma of hypopharynx, 4 years and 2 months	Right, low echo area, 3.2cm×3.7cm	81
8	Male	64	Squamous cell carcinoma of the trachea, 5 days	Right, low echo area, 2.8cm×2.6cm	48

	Number of cases	Normal follicles in the background	Arrangement mode	Cytological characteristics	Nuclear chromatin	Positive (IHC)	Negative (IHC)
Adenocarci- noma of lung	1	Occasionally	Three-dimensional adenoid structure, papillary structure	Large, abundant cytoplasm, visible mucous vacuoles	Obvious nucleolus	CK7、TTF-1、NapsinA	CA125、WT-1、TG、PAX-8
Small cell carci- noma of lung	1	Massive necrosis, apoptosis	Clustered,scattered, Mosaic-like	Uniform size, bare nucleus	Pepper salt like, fine granular	Syn、CD56、CgA	CT、TG
Breast cancer	2	Not seen	Clumps, clusters, scattered	Difference in size, The cytoplasm is medium to abundant with occasional vacuoles	Hyperchromatic nuclei, nucleolus were not obvious	ER、PR、CK7、GATA3	TTF-1、PAX-8、CT
Squamous cell carcinoma	4	More or less, Neutrophils visible	Lamellar, nestlike, scattered	Significant size difference, round or fusiform, cytoplasmic keratosis is common	Hyperchromatic nuclei, polygon, irregular nuclear membranes	P63、P40	TG
Medullary thyr- oid carcinoma	33	More or less	Single scattered, cell boundaries is unclear	Plasmacytoid, epithelioid, strange giant cell	Pepper salt like, fine granular	Syn、CD56、CgA、CT	TG