PD-L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) have limited treatment options, and immune profiling may help select patients for immunotherapy. The prevalence and relevance of programmed death-1 ligand (PD-L1) expression and the presence of immune cells in ATC and PDTC has not yet been well established. The present study investigated PD-L1 expression (clone 22C3) and cells in the tumor microenvironment (TME), including tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and dendritic cells, in whole tissue sections of 15 cases of ATC and 13 cases of PDTC. Immunohistochemical PD-L1 expression using a tumor proportion score (TPS) with a 1% cut-off was detected in 9/15 (60%) of ATC cases and 1/13 (7.7%) of PDTC cases (P=0.006). PD-L1 expression in TILs was limited to the ATC group (73.3 vs. 0% in ATC and PDTC, respectively). In the ATC group, the TPS for tumor positive PD-L1 expression revealed a non-significant trend towards worse survival, but no difference was observed when investigating PD-L1 expression in TILs and TAMs. In addition to increased PD-L1 expression, all ATC cases exhibited significantly increased CD3⁺ and CD8⁺ T cells, CD68⁺ and CD163⁺ macrophages, and S100⁺ dendritic cells compared with the PDTC cases. Loss of mutL homolog 1 and PMS1 homolog 2 expression was observed in one ATC case with the highest PD-L1 expression, as well as in the only PDTC case positive for PD-L1. Notably, the latter was the only PDTC case exhibiting positivity for p53 and a cellular microenvironment similar to ATC. The current results indicated that PD-L1 expression was frequent in ATC, but rare in PDTC. In addition to PD-L1, the present study suggested that microsatellite instability may serve a role in both the TME and the identification of immunotherapy candidates among patients with PDTC.     

Characteristics of the development of highly differentiated thyroid gland tumors

Under study was the kinetics of morphological changes of high-differentiated carcinomas of the thyroid after repeat operative interventions, the interval between those was 2--15 years. It is suggested that during the development of high differentiated thyroid tumors the morphological structure of the tumor is remained and shows no tendency to transformation into anaplastic forms. Tumors showing both papillary and anaplastic structures (papillary polymorphous cancers) are considered to be the result of irregular tumor progression under which separate zones of neoplastic cells proved to be in different stages of differentiation.     

Cytomorphologic features of poorly differentiated thyroid carcinoma

BACKGROUND:

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon and aggressive malignancy. Despite the significant clinical implications of a diagnosis of PDTC, its cytomorphologic features have not been well defined. Statistical analysis was applied to a series of 40 PDTCs to identify a specific set of cytomorphologic features that characterized these tumors on fine‐needle aspiration biopsy (FNAB).

METHODS:

In total, 40 thyroid FNABs that were highly diagnosed histologically as PDTC (19 insular carcinomas and 21 noninsular carcinomas) comprised the study group. A control group of 40 well differentiated thyroid neoplasms were selected for comparison. All FNABs were reviewed and scored for a series of 32 cytomorphologic features. The results were evaluated using univariate and stepwise logistic regression (SLR) analyses.

RESULTS:

In univariate analysis, 17 cytomorphologic features were identified that characterized the 40 PDTCs: insular, solid, or trabecular cytoarchitecture (P < .001); high cellularity (P = .007); necrosis (P = .025) or background debris (P = .025); plasmacytoid appearance (P = .0007); single cells (P < .0001); high nuclear/cytoplasmic ratio (P < .0001); scant cytoplasm (P = .03); nuclear atypia (P < .0001), including nuclear pleomorphism (P = .0052) and anisokaryosis (P < .0001); granular/coarse chromatin (P = .026); naked nuclei (P = .01); mitotic activity (P = .0001) and apoptosis (P < .0001); endothelial wrapping (P = .0053); and severe crowding (P < .0001). In logistic regression analysis, severe crowding (P = .0008) and cytoarchitecture (P < .0001) were identified as the most significant cytomorphologic features of PDTCs, and the combination of cytoarchitecture, severe crowding, single cells, and high nuclear/cytoplasmic ratio was the most predictive of PDTC.

CONCLUSIONS:

PDTCs have characteristic cytomorphologic features. By using logistic regression analysis, the features that were identified as the most predictive of PDTC were severe crowding, insular/solid/trabecular morphology, single cells, and high nuclear/cytoplasmic ratio. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Repeated surgical operations for differentiated tumors of the thyroid gland]

An analysis of 145 case histories of high-grade thyroid cancer has shown that 61 (31%) patients were reoperated on for recurrence several months to 25 years after primary surgery. Among indications for reoperative thyroid surgery were regional or implantation metastases and relapse. Errors involved in primary intervention caused most of repeat operations.     

Evaluation of galectin-8 expression in thyroid tumors

The expression of galectin-8 (gal-8) has been shown to be altered during neoplastic transformation of certain cell types. This is the first study aimed to analyze the expression of this protein in normal and pathological human thyroid tissue. A total of 41 archival thyroid tissue samples (5 follicular adenomas, 31 papillary carcinomas, 5 follicular carcinomas) together with 36 adjacent hyperplastic or normal thyroid tissues were analyzed by immunohistochemistry. Galectin-8 was expressed in the majority of papillary carcinomas (27/31; 87%). Positive but weaker staining was also found in some of the follicular thyroid carcinomas (2/5; 40%) and adenomas (2/5; 40%). This protein was not detectable in five normal thyroid tissue samples, whereas hyperplastic areas adjacent to tumor were weakly positive in 9 out of 31cases (29%). High gal-8 immunostaining in papillary thyroid carcinoma indicates that gal-8 may potentially serve as a marker of papillary thyroid carcinoma. However, it does not seem to be helpful in the differential diagnostics of follicular carcinoma and adenoma. Further studies are required to determine biological functions and molecular mechanisms underlying the increased expression of gal-8 protein in thyroid lesions, particularly, in papillary thyroid carcinoma.     

Suppression of galectin-4 attenuates peritoneal metastasis of poorly differentiated gastric cancer cells

Gastric Cancer - Peritoneal dissemination, most often seen in metastatic and/or recurrent gastric cancer, is an inoperable condition that lacks effective treatment. The use of molecular targeted...     

超声对低分化和未分化甲状腺癌的诊断价值

目的 探讨超声对低分化甲状腺癌(PDTC)和未分化(间变性)甲状腺癌(UTC)的诊断价值.方法 应用彩色多普勒超声对22例PDTC和UTC的甲状腺形态、大小、回声、边界、内部砂粒、血流分布等声像图表现及其内部血流状况进行观察,并与手术、活组织病理检查病理结果对照;扫查颈部及气管食管沟区淋巴结.根据甲状腺双叶或单叶弥漫性病变及局部淋巴结的超声表现,结合临床表现,判断甲状腺病变的性质.结果 术前或活组织病理检查前超声检出甲状腺单叶肿物16例,左甲9例,右甲7例.双叶肿物6例.超声提示UTC 2例,甲状旁腺癌1例,慢性淋巴细胞性甲状腺炎1例,其余提示甲状腺恶性肿瘤.结论 超声检查可提高PDTC和UTC的检出率和诊断率.     

Postoperative recurrence and death rates of poorly differentiated carcinoma of the thyroid

Postoperative recurrence and death rates of 54 cases of poorly differentiated thyroid carcinoma were analyzed. The rates of recurrence of 18 widely resected cases during 1979 and 1981 and 36 patients undergoing conventional surgery during 1965 and 1978 were 22.2% and 50%, respectively. The difference between the figures was statistically significant (p less than 0.05). The death rates of the two groups were 5.6% and 41.7%, respectively. These results indicate that wide resection is appropriate in the surgical treatment of the thyroid.     

调强放疗在局部晚期及复发甲状腺低分化癌中的应用

背景与目的：甲状腺低分化癌（poorly differentiated thyroid carcinoma,PDTC）是一种罕见恶性肿瘤,易发生侵袭及转移,目前尚缺乏有效的治疗方法。本研究旨在分析调强放疗对局部晚期及复发PDTC的疗效及安全性。方法：纳入2011年2月—2014年9月在复旦大学附属肿瘤医院接受调强放疗的8例局部晚期及复发PDTC患者（均经病理及影像学确诊为T_4a-b期PDTC）。1例术后无残留病灶但包膜侵犯的患者接受处方剂量60 Gy/30次的单纯放疗,其余患者甲状腺原发灶及淋巴结转移灶的处方剂量为66 Gy/33次,并接受顺铂为基础的联合化疗。结果：患者在放疗±化疗后,2例局部区域病灶完全缓解（complete response,CR）,1例部分缓解（partial response,PR）,5例保持疾病稳定（stable disease,SD）。截止末次随访或患者死亡时,局部区域控制率为87.5%（5例CR+1例PR+1例SD）。随访期间共有4例（50%）患者死亡,死亡原因分别为原发病灶进展（12.5%）和肺转移（37.5%）。大部分治疗相关不良反应为1~2级。结论：对于局部晚期及复发PDTC,调强放疗为基础的综合治疗能控制局部区域病灶,延长生存时间,不良反应可控,是一种有效且安全的治疗手段。     

Ubiquitous expression of galectin-3 mRNA in benign and malignant thyroid tumors

We measured the relative expression levels of galectin-3 mRNA to beta-actin mRNA in normal thyroid tissues, thyroid tumor tissues and thyroid-derived fibroblasts. Galectin-3 mRNA was expressed ubiquitously in both benign and malignant thyroid tumors. Although a significant increase in its expression was observed in papillary carcinomas, no significant difference was observed between follicular carcinomas and adenomas. In contrast to the previous optimistic reports using immunohistochemical analysis of the galectin-3 protein expression, these results demonstrate that galectin-3 mRNA may not be a suitable target for molecular-based diagnosis of thyroid carcinomas.     

Galectin-3在分化型甲状腺癌细胞中的表达及其临床意义

背景与目的:在诊治甲状腺结节时,首要问题是定性诊断。虽细针穿刺细胞学检查是术前定性诊断的重要方法,但其自身的局限性影响了诊断的正确率,本研究试图寻找可用于鉴别甲状腺良、恶性结节的分子生物学指标。方法:收集30例分化型甲状腺癌、10例甲状腺腺瘤、10例结节性甲状腺肿患者的细胞涂片标本及临床病理资料。利用免疫细胞化学技术检测galectin-3在甲状腺针吸涂片和印片细胞中的表达。以术后常规组织病理的诊断结果为金标准。结果:印片免疫细胞化学筛查方法的灵敏度96.66%,特异度100.00%,阳性预测值100.00%,阴性预测值95.23%,正确率98.00%。印片常规细胞学筛查方法的灵敏度86.66%,特异度100.00%,阳性预测值100.00%,阴性预测值83.33%,正确率92.00%。针吸细胞免疫细胞化学筛查方法的灵敏度86.66%,特异度100.00%,阳性预测值100.00%,阴性预测值83.33%,正确率92.00%。针吸常规细胞学筛查方法的灵敏度76.66%,特异度100.00%,阳性预测值100.00%,阴性预测值74.07%,正确率86.00%。galectin-3在分化型甲状腺癌的细胞中高表达,而在甲状腺腺瘤、结节性甲状腺肿的细胞中不表达,表达的差异具显著性(P<0.05)。结论:galectin-3在分化型甲状腺癌中高表达,在甲状腺腺瘤、结节性甲状腺肿中不表达。galectin-3的免疫细胞化学检测对分化型甲状腺癌和甲状腺腺瘤、结节性甲状腺肿的鉴别有参考价值。     

Differential expression of galectin-1 and galectin-3 in benign and malignant salivary gland neoplasms

Galectins are a family of non-integrin beta-galactosidase-binding lectins. Altered expression of galectins has been associated with neoplastic transformation and progression in several human tumors. In this study, we examined the distribution patterns of galectin-1 and galectin-3 in normal (n=45), benign (n=16), and malignant (n=49) salivary gland specimens using immunohistochemistry to determine their diagnostic and/or biological implications in salivary gland tumorigenesis. In normal salivary glands, galectin-3 expression was limited to ductal cells, and galectin-1 was usually faintly detected in ductal cells and strongly positive in myoepithelial cells. In benign tumors, galectin-3 maintained the ductal localization, but galectin-1 showed variable expression in ductal and myoepithelial cells. In malignant tumors, most of the polymorphous low-grade adenocarcinomas and carcinoma ex-pleomorphic adenomas expressed both galectins, whereas adenoid cystic and acinic cell carcinomas showed dramatically reduced galectin-3 expression and heterogeneous galactin-1 staining. Our data demonstrated altered localization and expression of galectin-3, and to lesser extent, galectin-1 in salivary gland carcinomas. These findings may assist in the differential diagnosis of some salivary gland malignancies, especially when using small and limited fine-needle aspiration materials.     

p53、CyclinD1、Ki-67在甲状腺Hurthle细胞肿瘤组织中的表达及意义

目的:探讨p53、CyclinD1、Ki-67在甲状腺Hurthle细胞肿瘤组织中的表达及意义。方法:收集石蜡包埋Hurthle细胞肿瘤组织标本73例,免疫组化EnVision二步法检测CyclinD1、p53、Ki-67的表达并对患者进行随访。结果:依据是否有浸润及肿瘤直径,将Hurthle细胞肿瘤分为4组:1级27例（<2 cm,未见浸润）,2级18例（2~3.9 cm,未见浸润）,3级21例（≥4 cm,未见浸润）,4级7例（见有浸润,不论直径）。各组肿瘤中,p53阳性率为29.6%、55.6%、90.5%、100.0%;CyclinD1阳性率为7.4%、22.2%、52.4%、100.0%;Ki-67阳性率为0.0%、5.6%、9.5%、28.6%;p53及CyclinD1阳性率与肿瘤分级呈正相关。有效随访49例,其中2例复发,均表现为p53（+）/CyclinD1（+）,其中1例Ki-67>5%。结论:p53、CyclinD1、Ki-67在浸润性Hurthle细胞肿瘤中表达升高,检测p53、CyclinD1及Ki-67可能有助于Hurthle细胞肿瘤危险性评估。