Impact of clinicopathologic factors on subclinical central lymph node metastasis in papillary thyroid microcarcinoma

Purpose: We evaluated whether the clinicopathological factors of papillary thyroid microcarcinoma (PTMC), especially tumoe size, are associated with subcinical central lymph node metastasis. Materials and Methods: A total of 160 patients diagnosed with PTMC who underwent total thyroidectomy with bilateral central lymph node dissection were enrolled in this study. All patients were clinically lymph node negative PTMC. Patients were divided into 2 groups according to the size of tumor (≤5 mm vs. >5 mm). Clinicopathologic risk factors for subclinical central lymph node metastasis were analyzed. Results: Subclinical central lymph node metastasis was detected in 61 (38.1%). Patients with tumors ≤5 mm had a lower frequency of extrathyroidal extension, multifocality and subclinical central lymph node metastasis. On multivariate analysis, only male and tumor size >5 mm were independent predictors of subclinical central lymph node metastasis; age, multifocality, bilaterality, extrathyroidal extension, lymphvascular invasion and lymphocytic thyroiditis were not. Conclusion: In this study, male and tumor size >5 mm were two independent predictive factors for subclinical central lymph node metastasis in PTMC. These are easier factors to assess before surgery than other factors when planning the central lymph node dissection. However, further long-term follow-up studies are needed to confirm the prognostic significance of subclinical central lymph node metastasis in PTMC.     

Risk factors for predicting central lymph node metastasis in papillary thyroid microcarcinoma

Objectives: We aimed to determine the predictive factors for central compartment lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC). The outcome of the current study could assist greatly in decision-making regarding further treatment. Methods: Retrospective analysis of PTMC treated at the First Affiliated Hospital of Harbin Medical University. The predictive risk factors for central lymph node metastases (CLNM) were analyzed with respect to age, sex, tumor size, multifocal and capsular affection. Results: CLNM are common in thyroid microcarcinoma patients. The factors correlated with neoplasm size greater than 5 mm (odds ratio, 0.520; P = 0.001), tumor bilateral (odds ratio, 0.342; P = 0.020), and capsule invasion (odds ratio, 2.539; P = 0.000) were independently predictive of CLNM. In patients with a solitary primary tumor, tumor location in the lower third of the thyroid lobe was associated with a higher risk of CLNM. Conclusions: The risk factors such as male gender, tumor size > 5 mm, bilateral, multifocal location, lower third of the thyroid lobe and capsule invasion that can be identified preoperatively or intraoperatively, be considered for determination of prophylactic CLND in patients with PTMC.     

甲状腺微小乳头状癌中央区淋巴结转移的临床特点及清扫价值

目的探讨甲状腺微小乳头状癌(PTMC)中央区淋巴结转移(CLNM)的相关危险因素及中央区淋巴结清扫术(CLND)的应用价值。方法选取251例经病理活检确诊的甲状腺微小乳头状癌患者为研究对象,根据其淋巴结转移情况分成转移组(n=42)和非转移组(n=209)。回顾性分析2组患者一般资料,对单因素分析后存在显著性差异的指标行非条件Logistic回归分析。淋巴结转移患者予以中央区淋巴结清扫术后,随访1~3年,记录其术后相关并发症发生率及复发率。结果 2组患者在肿瘤位置、合并腺瘤、桥本甲状腺炎、结节性甲状腺肿、甲亢等因素对比差异无统计学意义(P0.05)。转移组患者中年龄小于45岁者及男性比例均显著高于非转移组,差异具有统计学意义(P0.05)。转移组患者中肿瘤直径为5~10 mm者25例(59.5%),多灶12例(28.6%),突破被膜22例(52.4%),未转移组相应的数据为70例(33.5%)、23例(11.0%)和67例(32.1%),均显著低于转移组,差异具有统计学意义(P0.05)。转移组患者术后嘶哑1例(2.3%),局部麻木6例(14.3%),神经侵犯1例(2.3%),脉管侵犯2例(4.8%),无咳呛报告;随访1~3年中,仅2例复发,复发率为4.8%。非转移组术后则无以上并发症,也无复发。结论甲状腺微小乳头状癌患者发生中央区淋巴结转移多为年龄小于45岁的男性,存在肿瘤直径超过5 mm、多灶性病变、伴有被膜突破症状等特点,临床需将满足上述条件者列为重点关注对象并予以相关防预措施,以降低中央区淋巴结转移发生风险。对甲状腺微小乳头状癌患者予以中央区淋巴结清扫术治疗,疗效确切,可有效改善其预后质量。     

S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid

The detection of papillary microcarcinomas of the thyroid is increasing due to frequent use of ultrasound and fine-needle aspiration biopsy. Although most of the papillary microcarcinomas remain quiescent and follow an indolent clinical course, some behave aggressively and metastasize early, giving rise to clinically significant disease. There have been few studies concerning factors predictive of lymph node metastasis in papillary microcarcinomas. We analyzed the expression of S100A4, cyclin D1, p27 and MUC1, the presence of the BRAF V600E mutation and the clinicopathological features of the tumors, including patient age, tumor size (>or=5 vs <5 mm), extrathyroidal extension, multifocality, histological subtype, sclerosis and encapsulation, in a series of 198 papillary microcarcinomas in relation to lymph node metastasis to determine the predictive factors of lymph node metastasis. On univariate analysis, tumor size of 5 mm or more, extrathyroidal extension, multifocality, sclerosis and the expression of S100A4 and cyclin D1 predicted lymph node metastasis, whereas patient age, expression of p27 and MUC1 and the BRAF V600E mutation did not. Moreover, tumor size 5 mm or more, multifocality and expression of S100A4, especially its strong expression in the invasive fronts, were significantly associated with macrometastasis and lateral node metastasis. On multivariate analysis, multifocality and expression of S100A4 were found to be common independent predictive factors of lymph node metastasis, macrometastases, and lateral node metastasis. In conclusion, S100A4 expression in papillary microcarcinomas may indicate the presence of nodal metastasis. Thus, S100A4 immunohistochemistry may be valuable for predicting metastatic potential in papillary microcarcinomas.     

Risk factors for central lymph node metastasis of patients with papillary thyroid microcarcinoma: a meta-analysis

Objective: To evaluate the risk factors of central lymph node metastasis of papillary thyroid microcarcinoma. Method: Published articles about papillary thyroid microcarcinoma were searched in PubMed, MEDLINE and EMBASE until October 2013 to examine the risky factors of central lymph node metastasis. Software RevMan 5.0 was used for meta-analysis. Results: Within the patients suffering papillary thyroid microcarcinoma underwent thyroidectomy plus prophylactic central lymph node dissection, tumor size, multifocality and capsular invasion have statistically relevant association with central lymph node metastasis, but no relation was observed associated with sex and age. Conclusion: The papillary thyroid microcarcinoma should be considered central lymph node metastasis when tumor size ≥0.5 cm, multifocality and have capsular invasion.     

Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases

A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castleman's disease) and is associated with significant morbidity and mortality.     

Microsatellite instability status does not predict total lymph node or negative lymph node retrieval in stage III colon cancer

The relationship between higher total lymph node resection number in colorectal cancer resection specimens and improved overall survival is well known. Recent studies describe an association between a high rate of microsatellite instability and a high total lymph node count in colorectal cancer. Higher lymph node retrieval may potentially explain the improved survival seen in cancers with microsatellite instability. We investigate whether these associations can be validated in a cohort of American Joint Committee on Cancer stage III colon cancers. Medical records from 200 cases of stage III colon cancer resection specimens were reviewed, and sufficient tissue was available for 168. Expression of DNA mismatch repair proteins was determined by immunohistochemistry, and microsatellite status, by polymerase chain reaction. The mean total lymph node count in cases with microsatellite instability versus microsatellite stable tumors (15.9 versus 16.9; P = .664) and the mean number of negative lymph nodes in each respective category (12.2 versus 13.6; P = .522) were not significantly different. There was no difference between microsatellite stable cases and cases with microsatellite instability when total lymph node counts (P = .953) or negative lymph node counts (P = .381) were analyzed with respect to percentage of cases above and below the medians. This cohort of stage III colon cancers does not support a significant relationship between microsatellite status and a higher retrieval of total or negative lymph nodes. Although microsatellite instability is associated with improved overall survival in our cohort (P = .026), the reason for this does not appear to be related to higher numbers of retrieved lymph nodes.     

三阴性乳腺癌临床病理特征及预后与淋巴结转移的相关性

目的 分析三阴性乳腺癌(triple-negative breast cancer,TNBC)临床病理特征及预后与淋巴结转移的相关性.方法 将382例可手术乳腺癌患者根据淋巴结转移情况分组,有淋巴结转移的为阳性组,无转移的为阴性组;利用免疫组织化学方法对ER、PR、Her-2蛋白表达进行检测,根据其结果分别将淋巴结阳性组和阴性组再分为两组,一组为TNBC,另一组为非三阴性乳腺癌(non-triple-negative breast cancer,non-TNBC),比较TNBC和non-TNBC的临床病理特征,Kaplan-Meier法分析乳腺癌的5年无瘤生存率.结果 21.5%(82/382)的病例为TNBC,淋巴结阳性者为163例(42.7%),其中TNBC占43例,淋巴结阴性者为219例(57.3%),其中TNBC为39例.TNBC的淋巴结阳性率(52.4%)高于non-TNBC(40.0%),两者差异有统计学意义(P=0.044).在淋巴结阳性组中,TNBC较non-TNBC肿瘤直径大(P=0.014),在淋巴结阴性组中,TNBC中有乳癌家族史的比例要高(P=0.030),其它临床病理特征差异无显著性(P>0.05).淋巴结阳性组5年无瘤生存率TNBC组为60.5%,non-TNBC组为76.7%,差异有统计学意义(P=0.041);淋巴结阴性组5年无瘤生存率TNBC组为74.4%,non-TNBC组为88.3%,差异有统计学意义(P=0.023).结论 无论淋巴结转移情况,TNBC比non-TNBC易发生复发和转移,临床预后差.     

Overall architecture and pattern of lymph flow in the rat lymph node

The immunogenic content of the afferent lymph stimulates structures in the lymph node. Thus, a better knowledge of the processes of lymph flow and filtration in the organ should help us better understand various aspects of the node's function. To gain this understanding, we analyzed the distribution of flow in rat node draining areas locally injected with a small dose of China ink. Because the lymph-flow pattern is likely related to the overall architecture of the node, we simultaneously studied its morphology. Indeed, while the different structures of the node are known, some aspects of its overall architecture need to be resolved. The present work aimed to accomplish this by an analysis of semiserial sections of nodes from various anatomical locations in normal rats; the sections were stained by the Dominici technique or silver-impregnated. With respect to their architecture, the nodes could be distinguished into those with either a discontinuous or a continuous subcapsular sinus and peripheral cortex. These are referred to here, respectively, as segmented and nonsegmented nodes. In the segmented nodes, the subcapsular sinus with the peripheral cortex is separated by “gaps,” in which medullary sinuses reached the capsule. Further, a node appears to be divided into one or more “physiological compartments,” each one representing a nodal area related to an opening of an afferent lymphatic. The findings on China-ink distribution indicate that the lymph-flow pattern varies in different nodes and is determined by the particular architecture of a node, i.e., the lymph flow in a given node aligns itself along the pattern of segmentation of the organ. The findings suggest that the lymph content is first held by the endothelium lining the inner wall of a restricted area of the subcapsular sinus in a concentration which decreases with the distance from the related afferent lymphatic opening. Part of the content, possibly its nonimmunogenic fraction, would later be released to flow further along the sinus. It would then be phagocytosed by the macrophage accumulation located in the portions of medullary sinuses into which the lymph enters from the subcapsular sinus. The lymph thus filtered then flows along the medullary sinuses and leaves the organ. The latter findings also indicate that a node is divided into physiological compartments, each one being stimulated by the lymph from a given afferent lymphatic opening. As the immunogenic content of the lymph can differ from one lymphatic to another, this explains the frequent variations in similar structures located in different areas of a given node. Hence, the pattern of distribution of the openings of the afferent lymphatics of a node can account for the particularities of its overall architecture and its division into physiological compartments.     

原发淋巴结套细胞淋巴瘤临床病理分析

目的：探讨原发淋巴结套细胞淋巴瘤（MCL）的临床病理与免疫组化特点。方法：收集6例淋巴结MCL,免疫组化ABC法确定肿瘤细胞特征,使用的抗体有CD45、CD20、CD79、CD45RO、CD30、CD68、TdT、CD43、CD5、cyclinD1、c-myc,IgD,IgM等。结果：光镜可将MCL分为4种亚型：套区型1例,结节型1例,弥漫型2例,母细胞化型2例。肿瘤细胞表达全B细胞标记,IgD CD43 ,cyclinD1(5/6),CD5(4/6) 。结论：MCL是一种具有特殊免疫表型的B细胞淋巴瘤,不同的组织学构型其预后可能不同,临床应与其它类型B细胞淋巴瘤鉴别,如淋巴结边缘区B细胞淋巴瘤（MZL）,滤泡性淋巴瘤（FL）及CLL／SLL等鉴别。     

HPV and histological status of pelvic lymph node metastases in cervical cancer: a prospective study

AIMS: The purpose of this prospective study was to describe the incidence and distribution pattern of human papillomavirus (HPV) DNA in intraoperative dissected lymph nodes and to relate this to the pathological confirmation of metastasis. METHODS: Samples of primary cervical cancer lesions and dissected lymph nodes were obtained from women undergoing surgical treatment. The presence of HPV DNA was detected by the polymerase chain reaction. RESULTS: Tissue from 79 tumours and 365 lymph nodes was analysed. Metastasis to the lymph nodes was found in 19 cases. Metastasis correlated with the volume of the primary lesion, the depth of cervical and vaginal invasion, and with invasion of the corpus. HPV DNA was found in 60 of the primary lesions and 31 of the lymph nodes. The presence of HPV DNA in the lymph nodes correlated with the volume of the primary lesion and vaginal invasion. CONCLUSIONS: The incidence of HPV DNA in lymph nodes is twice as high as that of histopathologically confirmed metastases. The risk of the presence of HPV DNA and histopathologically confirmed metastases in lymph nodes is related to certain features of the primary tumour.     

Clinical and pathologic predictors of lymph node metastasis in papillary thyroid microcarcinomas

Papillary thyroid microcarcinoma (PTMC) has the highest incidence among all thyroid carcinomas. Although surgery is the primary treatment for PTMC, it inevitably leads to trauma and some complications. To formulate an optimal treatment strategy, we aim to clarify the risk factors for lymph node metastasis (LNM) in PTMC patients. This study retrospectively analyzed patients who underwent thyroidectomy during 1995–2015, and grouped them according to lymph node metastasis. Age, gender, tumor size, thyroid functions, Hashimoto's thyroiditis, multifocal tumor, extrathyroidal extensions, capsular invasion were analyzed. Of the 2434 PTMC subjects, proportion of patients with no LNM (NLNM), LNM, central LNM (CLNM), lateral LNM (LLNM), CLNM + LLNM were 82.9%, 17.1%, 7.0%, 7.6% and 2.5%. Patients with NLNM were older and had a lower proportion of males compared to patients with CLNM, LLNM and CLNM + LLNM (p < 0.05). The NLNM group also had a smaller size of ultrasound tumor, lower proportion of multifocal tumor and extrathyroidal extension compared to CLNM, LLNM and CLNM + LLNM groups (p < 0.05). On univariate analyses, male gender, age <45 years, tumor size of pathology (˃0.75 cm), multifocality, and extrathyroidal extension were significantly associated with LNM. Multivariate analyses revealed that male gender, age <45 years, multifocality were risk factors for LNM. In conclusion, PTMC patients with male gender, age <45 years and multifocality should be evaluated carefully for possible LNM.     

Temporal differences of onset between primary skin lesions and regional lymph node lesions for tularemia in Japan: a clinicopathologic and immunohistochemical study of 19 skin cases and 54 lymph node cases

For tularemia, a zoonosis caused by the gram-negative coccobacillus Francisella tularensis, research of the relation between skin lesions and lymph node lesions has not been reported in the literature. This report describes skin lesions and lymph node lesions and their mutual relation over time for tularemia in Japan. Around the second day after infection (DAI), a subcutaneous abscess was observed (abscess form). Hand and finger skin ulcers formed during the second to the fourth week. Subcutaneous and dermal granulomas were observed with adjacent monocytoid B lymphocytes (MBLs) (abscess-granulomatous form). From the sixth week, large granulomas with central homogeneous lesions emerged diffusely (granulomatous form). On 2-14 DAI, F. tularensis antigen in skin lesions was detected in abscesses. During 7-12 DAI, abscesses with adjacent MBLs appeared without epithelioid granuloma (abscess form) in regional lymph nodes. During the second to fifth week, granulomas appeared with necrosis (abscess-granulomatous form). After the sixth week, large granulomas with a central homogeneous lesion (granulomatous form) appeared. F. tularensis antigen in lymph node lesions was observed in the abscess on 7-92 DAI. Apparently, F. tularensis penetrates the finger skin immediately after contact with infected hares. Subsequently, the primary lesion gradually transfers from skin to regional lymph nodes. The regional lymph node lesions induced by skin lesion are designated as dermatopathic lymphadenopathy. This study revealed temporal differences of onset among the skin and lymph node lesions.     

Stromal expression of vascular endothelial growth factor C is relevant to predict sentinel lymph node status in melanomas

The dissemination of tumour cells to the lymph nodes is a complex process involving the formation of new lymph vessels, or lymphangiogenesis, produced by the tumour itself. The main growth factor involved in lymphangiogenesis is vascular endothelial growth factor C (VEGF-C), which is secreted by several different malignant tumours, including melanoma. Not only has VEGF-C expression been found in tumour cells, it has also been detected in tumour stromal cells like macrophages and fibroblasts. This study aimed to determine whether the expression of VEGF-C in tumour and stromal cells in cutaneous melanoma determines lymphangiogenesis and neoplastic dissemination to lymph nodes. We examined cases from 50 patients with melanoma who underwent selective biopsy of the sentinel lymph node. Immunohistochemical study was done with D2-40 to label lymph vessels, and the expression of VEGF-C was evaluated in tumour and stromal cells. Lymph vessel density was greater in sentinel lymph node-positive than in sentinel lymph node-negative cases, though the difference was not significant (P = 0.075). A significant correlation was seen between lymph vessel density and tumour thickness and the presence of ulceration. The main finding was that the expression of VEGF-C in fibroblasts was highly associated with the presence of metastasis in the sentinel node and with the Clark level. However, VEGF-C expression showed no relation in either tumour cells or macrophages with node status or other prognostic factors, such as the Breslow index or Clark level. Our results highlight the relevance of the stroma in tumour progression in cutaneous melanoma and its role in the spread to lymph nodes.     

Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

Avian lymph node: Light and electron microscopic study

We have observed by light and transmission electron microscopy lymphoid accumulations (LA) in the chicken located along the posterior tibial-popliteal and lower femoral veins. Three types of LA were characterized: (1) LA on the wall of the lymphatic, (2) LA with germinal center, and (3) well-developed LA possessing germinal centers and an intricate lymphatic sinus system. The latter will be termed a lymph node and is perhaps the structure responding to foot-pad injection of antigen and/or phytohemagglutinin (PHA). After the injection of PHA into the foot-pad, the lymph node enlarged and revealed the intermingling of two distinct groups of cells consisting of either small lymphocytes or medium lymphocytes and lymphoblasts. Because our earlier immunological paper proved the presence of T and B cells in the node, the two histologically distinct groups of cells appearing after PHA injection could reflect compartmentalization of T and B cells in the avian lymph node. Lymphoid and adipose tissues are in the same compartment. After PHA or antigen injection into the foot pad, the lymphoid tissue proliferates and the amount of the adipose tissue rapidly decreases. This suggests that lymphoid and adipose tissue form a special complex which is separated from the surrounding tissue by delicate connective tissue capsule. The relationship of the lymphoid and adipose tissue is comparable with that of myeloid and adipose tissue in the bone marrow. The majority of the sinuses shows smooth endothelial lining while others contain “hairy” macrophages attached to the endothelium. The germinal centers are located at the periphery of the node, but a few occur inside. The cellular content of the germinal centers is not unusual except for the presence of plasma cells.