Breast Tumor Resembling the Tall Cell Variant of Papillary Thyroid Carcinoma

Abstract:  We describe the case of a 66-year-old woman with a palpable mass in her left breast. Although the diagnosis on core biopsy was an intraductal papilloma, the surgically excised lesion showed it to be an infiltrating carcinoma which appeared to arise in a complex sclerosing lesion and is similar to the recently described breast tumor resembling the tall cell variant of papillary thyroid carcinoma.     

Papillary Thyroid Carcinoma Variants

Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but genetic susceptibility and other factors also contribute to the development of papillary thyroid carcinoma. The most common variants include conventional, follicular variant and tall cell variant. However, many other uncommon variants have been described including oncocytic, columnar cell, diffuse sclerosing and solid forms. Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites. Markers such as HBME-1 and CITED1 can assist in separating some difficult cases of follicular variants of papillary thyroid carcinomas from follicular adenomas. Molecular studies have shown that the BRAF V600E mutation is found mainly in papillary and anaplastic thyroid carcinomas. Other molecular markers such as HMGA2 and insulin-like growth factor II mRNA binding protein 3 have been used recently as molecular tests to separate papillary thyroid carcinoma and its variants from follicular adenomas and other benign thyroid nodules.     

CCR7在甲状腺乳头状微小癌中的表达及临床意义

目的探讨CCR7在甲状腺乳头状微小癌中表达情况及其与甲状腺乳头状微小癌临床病理特征的关系。方法采用免疫组织化学S-P法检测31例甲状腺乳头状微小癌,34例直径>1 cm的甲状腺乳头状癌、34例结节性甲状腺肿以及12例甲状腺乳头状微小癌对侧正常甲状腺组织中CCR7的表达情况。结果 CCR7在甲状腺乳头状微小癌及直径>1 cm甲状腺乳头状癌中的表达阳性率均为100%,其差异无统计学意义(P>0.05),而在结节性甲状腺肿和正常甲状腺组织中CCR7的表达阳性率分别为64.7%和33.3%,与甲状腺乳头状微小癌相比差异有统计学意义(P<0.05)。CCR7的表达与患者性别、年龄、侵犯甲状腺被膜及淋巴结转移均无关(P>0.05)。结论 CCR7的表达在甲状腺乳头状微小癌和直径>1 cm甲状腺乳头状癌中均呈高表达,两者可能具有相同的生物学特性,两者均易发生颈淋巴结转移,均需要进行颈淋巴结(中央区)清扫。     

Prognostic Factors in Papillary and Follicular Thyroid Carcinoma: Their Implications for Cancer Staging

Background Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are two distinct histological types of thyroid carcinoma but have often been studied and staged as a collective group, known as differentiated thyroid carcinoma (DTC). However, this may not be an optimal approach to cancer staging. Methods A total of 760 patients with DTC, comprising 589 (77.5%) with PTC and 171 with (22.5%) FTC, being managed at our institution from 1961 to 2001 were retrospectively reviewed. Their clinicopathological features, treatment modalities received, and postoperative outcome were analyzed. Both univariate and multivariate analyses were performed to identify prognostic factors related to cancer-specific survival (CSS) for PTC and FTC. Results There were statistically significant differences between PTC and FTC in terms of age ≥50 years at diagnosis (P = .040), tumor size (P < .001), lymph node metastases (P < .001), distant metastases (P < .001), extrathyroidal extension (P < .001), multifocality (P = .002), capsular invasion (P < .001), extent of thyroid resection (P < .001), radioiodine ablation (P < .001), and external-beam irradiation (P = .003). Although PTC and FTC had similar 10-year and 15-year CSS (P = .846), each possessed its own set of independent prognostic factors for CSS. Age at diagnosis and completeness of resection were independent prognostic factors in both PTC and FTC. Conclusions There were marked differences in clinicopathologic features, treatment, and prognostic factors between the two histologic types of DTC. Different staging systems should be evaluated and validated for PTC and FTC individually in the future.     

Sclerosing Papillary Carcinoma Arising in a Lingual Thyroid: Report of a Case

Ectopic lingual thyroid tissue is an uncommon congenital anomaly. Tumors with identical pathological characteristics to those arising in thyroid tissue may be present in ectopic locations, but there are very few cases of malignant ectopic thyroid tumors reported in the literature. We present a review of this phenomenon and report a case of papillary carcinoma of the base of the tongue, located in ectopic lingual thyroid tissue, in a 30-year-old woman. The patients presenting symptoms were dysphagia and oral bleeding, and we performed radical resection of the neoformation at the base of the tongue with part of the muscles of the floor of the mouth and the body of the hyoid bone, as well as total thyroidectomy. Histological examination revealed a sclerosing papillary carcinoma. The patient was treated with ¹³¹I and substitutive thyroid hormonal therapy. An ultrasonogram done 5 years later showed bilateral laterocervical lymph node recurrence, which was effectively treated with bilateral laterocervical lymphectomy.     

Anaplastic Carcinoma of the Thyroid Arising More Often from Follicular Carcinoma than Papillary Carcinoma

Background Anaplastic thyroid carcinoma (ATC), a rare and highly malignant tumor, has long been thought to arise from well-differentiated carcinoma (WDC) such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC). The purpose of this study was to test this notion by examining whether and, if so, how often ATC harbors the oncogenes that are commonly associated with WDC, such as RAS in FTC and BRAF in PTC. Methods We analyzed the mutation hotspots of BRAF (codon 600) and N-, K-, and H-RAS (codons 12, 13, and 61) in 16 ATCs. We also examined two genes, PIK3CA (exons 9 and 20) and TP53 (exons 5–9), both of which have been reported in ATCs. Results The results showed that approximately 31% (5 of 16) of ATCs harbored N-RAS mutation, 6% (1 of 16) had mutated BRAF, and approximately 56% (9 of 16) had mutated TP53. As to the three ATCs that had coexisted PTCs, mutated BRAF was detected in all PTC components but only in one ATC, while mutated PIK3CA was found in only one PTC component but not in the ATC. Conclusion A number of ATCs arise from WDCs, more often from RAS-mutant tumors than from BRAF-mutant tumors, implying that particular attention should be paid to the WDC harboring RAS mutation.     

人甲状腺乳头状癌原代细胞的体外长期培养

目的探索人甲状腺乳头状癌原代细胞的体外长期培养方法及其监测鉴定手段。方法常规分离甲状腺乳头状癌细胞,并用含10%胎牛血清、L-谷氨酰胺和20 ng/ml人重组表皮生长因子(EGF)的高糖型DMEM培养液培养,分别在不同时间观察甲状腺乳头状癌细胞生长情况,测定培养液中的甲状腺球蛋白(Tg)和甲状腺过氧化物酶(TPO)水平,用免疫细胞化学方法检测Tg的表达。结果培养约8 d甲状腺乳头状癌细胞长满约80%的培养瓶底,符合传代标准;在培养45 d内生长良好,经5~6传代后细胞逐渐老化。细胞培养液中Tg含量随培养时间延长呈抛物线形变化,培养约14 d Tg达到峰值(985.2μg/L);TPO在细胞培养液中始终未检测到。免疫荧光染色结果显示,体外培养甲状腺乳头状癌原代细胞的Tg表达阳性。结论应用本研究建立的培养条件可以使人甲状腺乳头状癌原代细胞传5~6代,细胞存活约45 d。建立了简便、系统的监测及鉴定甲状腺乳头状癌细胞生物活性手段,提示在14 d左右该细胞用于基因研究较为合适,为研究甲状腺乳头状癌发生、发展机理及其特征提供了一种合适替代工具。     

连续整块切除原则在腔镜辅助甲状腺微小乳头状癌手术中的应用

目的探讨整块与分块切除在腔镜辅助甲状腺微小乳头状癌手术中的应用效果。方法回顾性分析2013年2月~2014年2月北京安贞医院腔镜辅助手术中快速冰冻病理证实甲状腺微小乳头状癌患者62例资料,前24例先行患侧腺叶、峡部切除,继而在纳米碳示踪下行中央区淋巴结分块清扫(分块切除组),后38例将患侧腺叶、峡部、中央区淋巴脂肪组织连续整块切除一次完成(整块切除组)。对2组手术时间、术中出血量、中央区淋巴结清扫数量、术后并发症情况进行比较。结果 2组手术均顺利完成,无中转开放手术。整块切除组较分块切除组手术时间长[(86.1±10.0)min vs.(73.5±8.9)min,t=4.997,P=0.000],2组术中出血量差异无显著性(P0.05),而中央区淋巴结清扫数量整块切除组明显多于分块切除组[(8.2±1.6)枚vs.(6.1±1.5)枚,t=5.131,P=0.000]。2组均无永久性喉返神经损伤及低钙血症。术后暂时性声音嘶哑整块切除组3例,分块切除组4例,总发生率为11.3%(7/62),2组间差异无显著性(χ2=0.424,P=0.515),未予特殊处理,均于术后8周内恢复正常。术后随访5~17个月,平均10个月,均无局部种植、复发和远处转移。结论整块切除较分块切除更符合无瘤原则,在腔镜辅助甲状腺微小乳头状癌手术中可以得到安全的应用。     

A comparative evaluation of the surgical and radioiodine treatments for Graves’ disease

Radioactive iodine treatment is currently the most popular treatment modality for hyperthyroidism in many patients of the world. In Japan, however, a considerable number of patients with hyperthyroidism have undergone successful surgery. To elucidate the advantages and disadvantages of surgical and¹³¹I treatment, the thyroid function of 66 patients from each group was compared, 5 to 8 years after treatment. None of the surgically treated patients had been reoperated upon on, whereas 12 (18 per cent) of the patients treated with¹³¹I required 2 or more doses. The number of patients with normal ranges of serum T₃, T₄ and TSH values was almost identical: 33 (50 per cent) of the postoperative patients and 31 (47 per cent) of the post-irradiated patients. In the surgically treated group, there was no tendency for hypothyroidism to develop with the passage of the time. However, although the distribution of T₃ and T₄ in the normal control and postoperative groups showed a normal bell-shaped distribution, the post-irradiated group did not exhibit this distribution. The normal control group and the postoperative group showed positive correlations of T₃ and T₄ but the post-irradiated group did not (p<0.05). When the titers of antithyroglobulin and antimicrosomal antibodies prior to therapy were compared with those following therapy, they had decreased in 41 per cent and 76.8 per cent, respectively, of the postoperative cases, but in only 24.2 per cent and 45.5 per cent of the post-irradiated cases.     

甲状腺峡部乳头状癌诊治进展

甲状腺乳头状癌通常被认为具有低生物侵袭性,具有良好的整体预后.位于峡部的甲状腺乳头状癌比位于腺叶的甲状腺乳头状癌具有更高的侵袭性特征,包括更频繁的腺外浸润、淋巴结转移和多灶性等特征.手术治疗是甲状腺峡部乳头状癌的最佳治疗手段,目前术前检查无法确诊淋巴结是否转移,针对甲状腺峡部乳头状癌的手术切除范围及淋巴结清扫存在很多争...     

Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression

Peripheral localisation of papillary thyroid microcarcinoma (PTMC), in comparison with intraparenchymal PTMC (i-PTMC) is related to some clinicopathological features related with biological aggressiveness, including lymph node metastasis (LNM). The expression of PD-L1 in tumour cell has been associated with increased tumour survival, progression, and potentially an aggressive clinical course. This study evaluates the relation between clinicopathological features of PTMC, including tumour localisation, with PD-L1 immunoexpression. The study included 99 patients with the histological diagnosis of PTMC (≥ 5 mm). PD-L1 protein expression was assessed by immunohistochemistry. PTMCs were divided into the four following groups: G1– peripherally localised PTMC (p-PTMC) with PD-L1 expression; G2–p-PTMC without PD-L1 expression; G3–i-PTMC with PD-L1 expression and G4–i-PTMC without PD-L1 expression. G1 was the most frequent (n = 46; 46.5%), followed by G4 (n = 25; 25.3%) and similar distribution of G3 (n = 15; 15.2%) and G2 (n = 13; 13.1%). In comparison with other groups, G1 was significantly associated with classical morphology, invasive growth, lymphatic invasion (LI), vascular invasion (VI), psammoma bodies, intratumoral fibrosis, PD-L1 positive tumour-infiltrating lymphocytes, and multinuclear giant cells (MGCs). G4 more commonly exhibited follicular morphology, expansive/circumscribed growth, and absence of the following: intratumoural fibrosis, LI, VI, psammoma bodies, PD-L1 positive tumour-infiltrating lymphocytes, and MGCs. LNMs were significantly more frequent in G1 in comparison with the other groups (p = 0.000). In conclusion, morphology and tumour microenvironment of p-PTMC with PD-L1 expression is different from i-PTMC without PD-L1 expression. The differences between these two groups of PTMC include clinicopathological features related with biological aggressiveness such as the occurrence of LNM.     

T1-T2期单侧甲状腺乳头状癌伴同侧颈侧区淋巴结转移时甲状腺原发灶切除范围研究进展

甲状腺乳头状癌（PTC）伴侧颈淋巴结转移并不少见。对于单侧TNM T1-T2期PTC伴同侧颈侧区淋巴结转移者,如不存在淋巴结结外侵犯或转移淋巴结直径≥3 cm等危险因素,甲状腺癌原发灶切除范围的选择存在争议。对于此类病人,甲状腺癌原发灶的切除范围的选择应综合考虑到甲状腺腺体重要的内分泌功能、颈侧区淋巴结转移对预后的影响以及中危组病人为了术后碘治疗而行全甲状腺切除术的必要性。未来对于颈侧区淋巴结转移的病人,应在进行精准的危险分层之后对甲状腺原发灶的切除范围做出合理的选择。     

Expression of bcl-2 in Papillary Thyroid Cancers and its Prognostic Value

Purpose: Papillary thyroid cancer has a good prognosis. This favourable prognosis may be attributed to the apoptotic tendency of the cancer cells. This study aims to evaluate the expression of bcl-2, which is an antidote of apoptosis, and aims to evaluate the value of bcl-2 as a prognostic marker in papillary thyroid cancer. Material-Methods : Bcl-2 expression in the archival materials of 31 patients with papillary thyroid cancer was examined with immunohistochemical methods using bcl-2 and p-53 stains. The results were compared with 31 normal thyroid tissue specimens, which consisted of the contralateral lobes of these patients. The results were then analyzed in accordance with the clinical features of the patients.

Results : Thirty (96.7%) patients of the control group were positive for bcl-2 whilst one (3.3%) was negative. The staining for bcl-2 was positive in 12 (%75) patients with microcarcinomas (p < 0.05) and 13 (86.6%) with papillary cancers (p > 0.05). Two cases of the papillary cancer group were admitted to the hospital with local recurrence (6.4%) and both were positive for bcl-2 (p > 0.05). All cases (4/31), whose MACIS scores were higher than 7 were positive for bcl-2. Twenty-one of 27 cases whose MACIS scores were lower than 7 (77.7%) were positive for bcl-2 (p > 0.05). All tumours of this series were negative for p-53 immunstaining.

Conclusion : The rate of bcl-2 expression in microcarcinomas of papillary thyroid cancer decreases when compared to normal thyroid tissue. This may be an early sign of oncogenesis, and a reason for the favourable prognosis in microcarcinomas. However, bcl-2 cannot be used as a prognostic marker.     

Macrofollicular Variant of Follicular Thyroid Carcinoma (MV-FTC) with a Somatic DICER1 Gene Mutation: Case Report and Review of the Literature

Benign thyroid lesions such as multinodular goiter and adenomatoid nodules are well-circumscribed lesions displaying a macrofollicular growth pattern and lack of nuclear atypia. The highly unusual macrofollicular variant of follicular thyroid carcinoma (MV-FTC) mirrors these attributes and is thereby misclassified by cytological examination of fine-needle aspiration biopsies. The MV-FTC diagnosis is instead suggested following histological investigation, in which malignant attributes, most commonly capsular invasion, are noted. The bulk of MV-FTCs described in the literature arise in younger female patients and carry an excellent prognosis. A recent coupling to mutations in the DICER1 tumor suppressor gene has been proposed, possibly indicating aberrancies in micro-RNA (miRNA) patterns as responsible of the tumorigenic process. We describe the cytological, histological and molecular phenotype of a 35 mm large MV-FTC arising in the right thyroid lobe of a 33-year-old female with a family history of multinodular goiter. The tumor was encapsulated and strikingly inconspicuous in terms of cellularity and atypia, but nevertheless displayed multiple foci with capsular invasion. A next-generation molecular screening of tumor DNA revealed missense variants in DICER1 (p. D1709N) and MET (p. T1010I), but no established fusion gene events. After sequencing of germline DNA, the DICER1 mutation was confirmed as somatic, while the MET variant was constitutional. The patient is alive and well, currently awaiting radioiodine treatment. This MV-FTC mirrors previous publications, suggesting that these tumors carry a favorable prognosis and predominantly arise in younger females. Moreover, DICER1 mutations should be considered a common driver event in the development of MV-FTCs.     

Distinguishing classical papillary thyroid microcancers from follicular-variant microcancers

Background

Papillary thyroid microcarcinomas (mPTCs), tumors less than or equal to 1 cm, have been considered the same clinical entity as microfollicular-variant papillary thyroid microcarcinomas (mFVPTCs). The purpose of this study was to use population-level data to characterize differences between mFVPTC and mPTC.

Materials and methods

We identified adult patients diagnosed with mFVPTC or mPTC between 1998 and 2010 in the Surveillance, Epidemiology, and End Results database. Binary comparisons were made with the Student t-test and chi-squared test. Multivariate logistic regression was used to further analyze lymph node metastases and multifocality.

Results

Of the 30,926 cases, 8697 (28.1%) were mFVPTC. Multifocal tumors occurred with greater frequency in the mFVPTC group compared with the mPTC group (35.4% versus 31.7%; P < 0.01). Multivariate logistic regression indicated that patients with mFVPTC had a 26% increased risk of multifocality (odds ratio, 1.26; 95% confidence interval, 1.2–1.4; P < 0.01). In contrast, lymph node metastases were nearly twice as common in the mPTC group compared with the mFVPTC group (6.8% versus 3.6%; P < 0.01). Multivariate logistic regression confirmed that patients with mPTC had a 69% increased risk of lymph node metastases compared with patients with mFVPTC (odds ratio, 1.69; 95% confidence interval, 1.4–2.0; P < 0.01).

Conclusions

Multifocality is not unique to classical mPTC and occurs more often in mFVPTC. The risk of lymph node metastases is greater for mPTC than mFVPTC. The surgeon should be aware of these features as they may influence the treatment for these microcarcinomas.     

Papillary Thyroid Carcinoma: Factors Influencing Recurrence and Survival

Background The prognosis of patients with papillary thyroid carcinoma (PTC) is usually favorable; however, a subset of patients can develop local recurrence or distant metastases. The aim of this study was to evaluate the prognostic factors influencing the recurrence and the survival rate in 950 PTC patients. Materials and Methods From 1990 to 2005, 950 consecutive patients affected by PTC were operated on at our Department. We analyzed the prognostic role of the following parameters: gender, age at initial treatment, extent of thyroid surgery, node dissection, tumor size, node metastases, distant metastases, stage, and 131-I therapy. Results Seventy-nine patients (8.3%) developed locoregional or distant metastases after an average follow-up of 7.8 years (range 2–17 years); in particular local recurrence was observed in 25 cases and distant metastases in 54 cases. The global 10- and 15-year survival rates were 91.38% and 88.69%, respectively. At univariate analysis, all variables were significantly correlated with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2), node dissection (P = .5), and node metastases (P = .06) were not significant on 10- and 15-year survival. At multivariate analysis the age at first treatment, T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted to be significant and independent prognostic factors (P < .001). Conclusion Our data, in disagreement with other staging systems, suggest that gender does not play a significant role both in recurrence and survival. Moreover, the 131-I therapy was a statistically significant prognostic factor at univariate and multivariate analyses.     

兔甲状腺近全切除术＋131I清甲的甲状腺功能减退模型建立

目的通过对兔行甲状腺近全切除术＋131I清甲建立短期甲状腺功能减退的动物模型。方法新西兰大白兔60只,随机分成假甲状腺切除术组（ST组）、双侧甲状腺近全切除术组（NT组）和双侧甲状腺近全切除＋131I清甲组（NT＋131I组）。检测术前、术后3周和术后5周各组TSH、FT3、b3＇4及术后5周各组兔甲状腺显影结果。结果与术前比NT组和NT＋131I组在术后3周和术后5周甲状腺功能均明显降低。与sT组比较,NT组和NT＋131I组甲状腺显影明显减低,其中NT＋ 131I组甲状腺未见明显显影。结论可以通过甲状腺近全切除术＋131I清甲建立兔甲状腺功能减退模型。