Synchronous papillary thyroid carcinoma and follicular thyroid carcinoma: case report and review of literature

Collision tumor is a term denoting two histologically distinct tumor types occuring at the same anatomic site, which is a rare clinical entity. In the thyroid gland, collision tumors are rare. Here we report a case of the synchronous occurrence of follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC). The current case report describes a 40-year-old woman with synchronous FTC and PTC. Pathologists and surgeons should be aware of collision tumors to avoid possible misdiagnosis.     

Macrofollicular variant of papillary thyroid carcinoma

A rare case of a macrofollicular variant of papillary thyroid carcinoma occurring in an 18-years-old male is described. The extirpated tumor, 5.5 × 5.5 × 3.5 cm In size, was well demarcated and multinodular, and histopathologically showed a predominantly macrofolllcular structure reminiscent of adenomatous goiter or macrofollicular adenoma. In the tumor tissue, however, there were several small foci of microfollicular or paplllary structure with the nuclei charae teristic of papillary carcinoma. Parts of the macrofollicular areas also showed similar nuclear characteristics with a transition to microfollicular or papillary areas. Incomplete capsular invasion and minimal vascular invasion were also present. Additional resected specimens contained small metastatic nodules in the residual left lobe and lymph nodes. Immunohistochemistry showed a small number of p53-positive tumor cells in the microfollicular or papillary areas. It is suggested that this tumor is a well-differentiated variant which should be distinguished from benign thyroid lesions, although there have been some cases of metastases which appear related to capsular and/or vascular invasion.     

甲状腺乳头状癌的组织病理学和神经内分泌标记物的表达

目的：研究甲状腺乳头状癌的神经内分泌标记物的表达。方法：用免疫组化方法观察ＣｇＡ、５－ＨＴ、ＣＴ、ＡＣＴＨ、Ｓｙｎ、Ｐ物质在甲状腺乳头状癌的表达。结果：ＣｇＡ阳性１２例,Ｓｙｎ阳性８例,Ｐ物质阳性５例,ＣｇＡ、ＳＳ、５－ＨＴ同时阳性２例。ＣＴ,ＡＣＴＨ阳性各５例和３例。阳性细胞多为毛玻璃样核细胞。神经内分泌物质在甲状腺乳头状癌中可能发挥重要作用,毛玻璃样核细胞可能与神经内分泌细胞有关。     

甲状腺乳头状癌中EphA7和ANXA1的表达及其意义

目的探讨受体酪氨酸激酶A7(Ephrin A7,Eph A7)和重组人膜联蛋白A1(Annexin A1,ANXA1)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中的表达及其相关性。方法应用免疫组化En Vision两步法检测65例PTC、19例结节性甲状腺肿、19例癌旁甲状腺组织中Eph A7和ANXA1蛋白的表达,并分析二者与PTC临床病理特征的关系。结果 Eph A7和ANXA1在PTC组中的阳性率(64.6%、61.5%)高于结节性甲状腺肿组(26.3%、21.1%)以及癌旁甲状腺组(31.6%、26.3%,P均0.05)。Eph A7蛋白和ANXA1蛋白在PTC伴淋巴结转移组中的表达高于不伴淋巴结转移组(P0.05)。PTC组中ANXA1蛋白表达与患者淋巴结转移和临床分期相关(P均0.05),ANXA1蛋白与患者性别、年龄、部位、肿瘤大小、TG-Ab值和TPO-Ab值无关(P均0.05)。Eph A7蛋白表达与PTC淋巴结转移、临床分期、TG-Ab值和TPO-Ab值相关,与患者性别、年龄、肿瘤大小和部位无关(P均0.05)。Eph A7与ANXA1表达呈正相关(P0.01)。结论 Eph A7与ANXA1可能参与PTC的发生、发展,促进肿瘤淋巴结转移。     

Pitfalls in the surgical pathologic diagnosis of papillary thyroid carcinoma

While the surgical pathology examination of the thyroid gland for papillary carcinoma may seem, on its surface, to be relatively straightforward, in reality it is fraught with diagnostic traps. Avoidance of these pitfalls is necessary for guiding the surgeon and endocrinologist to the appropriate treatment and follow up. This review will detail a selected group of some of the more commonly encountered challenges in making the diagnosis of papillary thyroid carcinoma from a busy head and neck pathology consultation practice.     

Expression of D2-40 in adjunct diagnosis of papillary thyroid carcinoma

The clinical pathologic criteria for nuclear features of papillary thyroid carcinoma are subjective and sometimes cannot distinguish carcinoma from adenomatous goiter and follicular neoplasms. No single antibody has demonstrated high sensitivity or specificity in making these distinctions. Using quantitative analysis of immunohistochemical staining with D2-40, a recently available monoclonal antibody used as a lymphatic endothelial marker, we examined 72 cases of papillary carcinoma. Controls included 36 follicular adenomas, 36 follicular carcinomas, and 20 adenomatous goiters with papillary hyperplasia. Cytoplasmic D2-40 immunoreactivity was present in 60 of 72 papillary carcinomas, 2 cases of follicular adenoma and 2 cases of follicular carcinoma, whereas no adenomatous goiter or normal thyroid glands contained positive epithelial cells. Overexpression of D2-40 in papillary thyroid carcinomas thus has potential diagnostic utility in differentiating these tumors from their potential histologic mimics.     

High expression of GPER1, EGFR and CXCR1 is associated with lymph node metastasis in papillary thyroid carcinoma

Clinical and epidemiological studies have shown that estrogen may be involved in the development and progression of papillary thyroid carcinoma (PTC). G protein-coupled estrogen receptor 1 (GPER1) is a novel seven-transmembrane estrogen receptor that functions alongside traditional nuclear estrogen receptors (ERs) to regulate the cellular responses to estrogen. The purpose of this study was to examine GPER1, EGFR and CXCR1 expression in PTC and to assess the association of their expression with clinicopathological indicators. GPER1, EGFR and CXCR1 protein expression in 129 PTCs, 61 nodular hyperplasia and 118 normal thyroid tissue specimens were analyzed using immunohistochemistry. The protein expression levels of these three molecules were up-regulated in PTCs. High protein expression of GPER1, EGFR and CXCR1 was significantly correlated with lymph node metastasis (LNM) (P ≤ 0.001). Furthermore, GPER1, EGFR and CXCR1 protein expression were correlated with one another. Concomitant high expression of these molecules had stronger correlation with LNM than did each alone (P = 0.002 for GPER1/EGFR, P = 0.013 for GPER1/CXCR1, P = 0.018 for EGFR/CXCR1 and P < 0.001 for GPER1/EGFR/CXCR1). Additionally, GPER1, EGFR and CXCR1 mRNA expression was assessed in 30 PTCs, 10 nodular hyperplasia and 10 normal thyroid tissue specimens using real-time RT-PCR. GPER1, EGFR and CXCR1 mRNA expression levels were up-regulated in PTCs, and high mRNA expression of GPER1, EGFR and CXCR1 was significantly correlated with LNM (P < 0.001 for all these three molecules). These results demonstrated that the evaluation of GPER1, EGFR and CXCR1 expression in PTC may be useful in predicting the risk of LNM.     

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin-fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.     

Coexistence of primary squamous cell carcinoma of thyroid with classic papillary thyroid carcinoma

Primary squamous cell carcinoma of the thyroid gland is very rare and its histogenesis is poorly defined so far. Although there have been some cases of squamous cell carcinoma with variant types of papillary thyroid carcinoma (PTC), the present case is the first primary squamous cell carcinoma with classic PTC to be reported. A 43‐year‐old woman presented with a 20 year history of neck mass. Neck ultrasound indicated a 6 × 4 × 3 cm large mass. The patient underwent total thyroidectomy. Histopathology indicated a well‐differentiated squamous cell carcinoma and squamous metaplasia in conjunction with classic PTC. On immunohistochemistry cytokeratin 7 was positive in papillary carcinoma and squamous metaplasia, thyroglobulin was positive only in papillary carcinoma, and p63 was positive in squamous metaplasia and squamous cell carcinoma. Postoperatively, the patient received 59.4 Gy adjuvant radiotherapy, hormonal therapy and radioactive iodine therapy. At 8 months after surgery the patient remained disease free.     

Distinguishing tall cell variant of papillary thyroid carcinoma from usual variant of papillary thyroid carcinoma in cytologic specimens

Tall cell variant (TCV) is an aggressive form of papillary thyroid carcinoma (PTC), usually associated with higher local recurrence and distant metastasis. Some authors have suggested that TCV can be effectively diagnosed on thyroid fine-needle aspiration (FNA); this diagnosis may help clinicians plan a more effective treatment regimen. The objective of this study was to compare the FNA specimens of TCV with those of usual variant of PTC (UV-PTC) and to define a set of distinguishing cytologic features. Thirty FNA specimens of histologically proven TCV were compared with 32 FNA specimens of histologically proven UV-PTC. All specimens were evaluated for the following features: papillary groups (PG), elongated/tall cells (EL/TC), oncocytic cytoplasm (OC), distinct cell borders (DCB), prominent central nucleoli (PCN), intranuclear grooves (NG), and intranuclear inclusions (NI). These features were semiquantitatively measured on a sliding scale of 0-4 in both air-dried Diff-Quik-stained and ethanol-fixed Papanicolaou-stained preparations. TCV showed distinctive cytologic features, which can distinguish them from UV-PTC. These included EL/TC, OC, and DCB and were also found to be statistically significant (P < 0.0001). No significant differences were noted for PG and NG. The NIs in TCV cases were qualitatively different than those in UV-PTC. In TCV there were multiple inclusions within the same nucleus imparting a "soap bubble appearance" to the nucleus. This feature was seen in almost all cases of TCV and was rarely seen in usual PTC. On the basis of the above-mentioned cytologic features, TCV can be distinguished from usual PTC in FNA specimens.     

The fine structure of papillary carcinoma of the thyroid

Eight human thyroid cancers (four papillary, and four lymph node metastases of papillary cancers) were studied at the ultrastructural level. The most characteristic anomalies affect the nucleus: 'ground glass nuclei', highly indented nuclear membrane with formation of nuclear pseudoinclusions, nuclear bodies probably of nucleolar origin, fractionation of the periphery of the nucleus into multiple lobes joined by thin bridges of nuclear substance. Other abnormalities related to the mitochondria with decrease of size and number of cristae, the rough endoplasmic reticulum which was segregated in parallel saccules and the basal lamina was often reduplicated. The significance of these anomalies is discussed.     

Encapsulated cystic papillary variant of medullary carcinoma of thyroid gland

Papillary variant of medullary carcinoma of the thyroid (MCT) is an unusual histologic pattern with some diagnostic difficulties. A case of encapsulated papillary variant of MCT with extensive cystic appearance is reported. A euthyroid, 43-yr-old woman with bone pain was incidentally found to have a 4.0-cm solitary, cold nodule on her left thyroid lobe. Histopathologic examination revealed an encapsulated tumor composed of a large cystic cavity with small papillary projections. The papillae were lined by multiple layers of neoplastic cells with small and regular nuclei containing condensed chromatin and lacking the characteristic “ground glass” appearance of the papillary carcinoma of the thyroid gland. Immunohistochemical studies revealed specific cytoplasmic staining of the tumor cells for calcitonin, chromogranin A, neuron-specific enolase, carcinoembryogenic antigen, and cytokeratin. Specific staining for thyroglobulin was not observed in any neoplastic cell. Staining with Congo red disclosed amyloid deposits within the stroma. The case was diagnosed as papillary variant of MCT. Medullary thyroid carcinomas may show a papillary pattern with a totally cystic gross appearance. Thyroid carcinomas should be classified according to their major immunoreactivity pattern rather than their morphologic pattern. Immunohistochemical and/or histochemical studies should be performed in all thyroid tumors that show unusual histologic features.     

microRNA在甲状腺乳头状癌中作用机制的研究进展

microRNA(miRNA)是一类长约22个核苷酸的非编码单链RNA分子。miRNA通过结合mRNA 3'非编码区(3'-UTR)调节基因的表达,抑制蛋白质的翻译。甲状腺癌是常见的内分泌系统恶性肿瘤,甲状腺乳头状癌是甲状腺癌中最常见的类型,它的发病率逐年上升。近年来,大量研究表明miRNA在甲状腺乳头状癌中发挥重要的作用,对癌的发生、发展及预后评估等方面具有重要意义。     

甲状腺乳头状癌CD151和CK19mRNA表达及意义

目的探讨甲状腺乳头状癌中CD151和CK19 mRNA表达及其意义。方法采用RT—PCR方法检测54例甲状腺的良恶性病变组织中CD151和CK19 mRNA的表达,并与临床及病理资料进行分析比较。结果CD151和CK19 mRNA在甲状腺乳头状癌组中的表达与滤泡性腺瘤组、结节性甲状腺肿组以及正常甲状腺组比较均差异具有显著性（P〈0．01）;CK19 mRNA表达与甲状腺癌淋巴结转移有关（P〈0．05）;在甲状腺乳头状癌中,CD151和CK19基因mRNA的表达呈正相关（P〈0．01）。结论CD151和CK19基因共同参与甲状腺癌的发生、发展,并对淋巴结转移的判断有意义。     

PRSS3-mRNA与长链非编码RNA-PRSS3P2在甲状腺乳头状癌组织中的表达及其临床意义

目的:检测PRSS3-mRNA及lncRNA-PRSS3P2在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)及癌旁甲状腺组织中的表达特点,探讨二者在PTC中表达的临床病理意义.方法:收集2016年7至10月本院55例PTC及癌旁甲状腺组织的新鲜手术标本,应用荧光实时定量PCR检测PRSS3-mRNA及lncRNA-PRSS3P2在PTC和癌旁组织中表达情况,并分析其与临床病理特征的相关性.结果:PRSS3-mRNA及lncRNA-PRSS3P2在PTC组织中表达均明显高于非肿瘤组织;PRSS3P2的表达与患者的年龄相关(P＜0.05),而PRSS3与各种临床病理特征无明显相关性.结论:在PTC组织中,PRSS3-mRNA和lncRNA-PRSS3P2的表达均明显升高,这提示二者可能参与了PTC的发病过程;PRSS3-mRNA和lncRNA-PRSS3P2可以作为PTC的诊断标志物进行进一步研究.     

甲状腺乳头状癌BRAF基因突变的检测及临床意义

目的 了解甲状腺乳头状癌(papillary thyroid carcinoma,PTC)BRAF基因T1799A点突变的情况与临床病理学特征的关系.方法 应用聚合酶链反应及DNA直接测序法对43例PTC患者,20例非PTC甲状腺病变患者及40份正常甲状腺组织对照的新鲜标本进行BRAF基因检测.分析BRAF基因突变与性别、发病年龄、原发灶大小、甲状腺包膜外浸润、颈淋巴结转移及远处转移等临床病理学特征的关系.结果 43例PTC中1 7例检出BRAF基因T1799A点突变.检出率为39.5%,而在非PTC甲状腺病变患者和40份正常甲状腺组织未发现T1799A点突变.BRAF基因突变与PTC甲状腺包膜外浸润及颈淋巴结转移密切相关(P<0.05及P<0.05),与性别、发病年龄、原发灶大小及远处转移无关.结论 BRAF基因突变与颈淋巴结转移和甲状腺包膜外浸润密切相关,突变可能增加PTC的侵袭性并影响预后.     

HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma

The cytologic diagnosis of papillary thyroid carcinoma is straightforward in most instances. However, there are some mimics including goitrous nodules and Hurthle cell neoplasms. Many studies have shown the combination of HBME-1 and CK19 expression to be useful in reaching a correct histologic diagnosis on tissue sections. We aim to assess the value of these markers in the setting of cell blocks prepared from needle aspiration specimens. We performed immunohistochemical staining of HBME-1 and CK19 on cell block material from 22 thyroid nodules that also had follow-up histology. Both CK19 and HBME-1 were strongly positive in all nine cases of papillary thyroid carcinoma, the latter showing distinct luminal accentuation. In the non-papillary carcinomas, none showed positivity for both HBME-1 and CK19. Two of six Hurthle cell neoplasms were positive for CK19, however all were negative for HBME-1. One of nine goitrous nodules was strongly positive for HBME-1 with luminal/membranous staining, but this were negative for CK19. The sensitivity, specificity and positive predictive value of HBME-1 in distinguishing between papillary thyroid carcinoma and goitrous nodules/Hurthle cell neoplasms were found to be 100%, 92.9% and 0.9, respectively; and that of HBME-1 and CK19 combination was 100%, 100% and 1. We thus conclude that the combination of positive HBME-1 (luminal/membranous) and CK 19 (cytoplasmic) staining on cell blocks of thyroid cytologic specimens is highly discriminatory in the diagnostic workup for papillary thyroid carcinoma.     

A case of multiple endocrine neoplasia type 1 combined with papillary thyroid carcinoma

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN1) in Korea. MEN1 is a hereditary disease comprising neoplastic disorders such as pituitary, parathyroid and pancreatic neuroendocrine tumor, such as gastrinoma. But papillary thyroid cancer was never regarded as its component before in Korea. Herein we present a 39-year-old woman who manifested typical features of MEN1 with a coincidental papillary thyroid carcinoma. Although the family history of MEN1 was definite, her genetic analysis of DNA had revealed no germline mutation in MEN1 gene locus. Unidentified culprit gene unable us further genetic study to find LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN1. As we have first experienced a case of MEN1 combined with papillary thyroid carcinoma in Korea, we report it with the review of literature.