Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma?

The sentinel lymph node (SLN) biopsy has become an increasingly important procedure used in the primary staging of malignant melanoma. However, micrometastases in a lymph node can be easily missed on routine H&E-stained sections. Therefore, S-100 and HMB-45 IHC stains are standardly performed on grossly negative SLNs for detection of metastatic melanoma. Each of these IHC markers, however, is not ideal. The authors investigated whether the newer IHC marker Melan-A would improve the detection of metastatic melanoma in SLN biopsies. Forty lymph nodes previously diagnosed with metastatic melanoma were retrospectively evaluated for S-100, HMB-45, and Melan-A expression. In addition, 42 SLN biopsies for metastatic melanoma detection were prospectively collected and evaluated for S-100, HMB-45, and Melan-A expression. All lymph nodes with metastatic melanoma from the retrospective study demonstrated S-100 reactivity. Five of the lymph nodes with metastatic melanoma from the retrospective study failed to express either HMB-45 or Melan-A, all of which displayed a desmoplastic morphology. One of the metastases positive for S-100 and HMB-45 failed to show reactivity with Melan-A (3%). The prospective study found 10 lymph nodes from 42 cases to be positive for metastatic melanoma, which were positive for S-100 (100%). Nine of the involved lymph nodes were positive for HMB-45(90%), and nine were positive for Melan-A (90%). Melan-A, although very specific, cannot replace the use of S-100 and HMB-45 for the detection of metastatic melanoma in SLNs. It can, however, substitute for HMB-45 with equally good results.     

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.     

Sentinel lymph node investigation in melanoma: detailed analysis of the yield from step sectioning and immunohistochemistry

AIMS: To evaluate in detail the extent to which step sectioning and immunohistochemical examination of sentinel lymph nodes (SLNs) in patients with melanoma reveal additional node positive patients, to arrive at a sensitive yet workable protocol for histopathological SLN examination. METHODS: The study comprised 29 patients with one or more positive SLN after a successful SLN procedure for clinical stage I/II melanoma. SLNs were lamellated into pieces of approximately 0.5 cm in size. One initial haematoxylin and eosin (H&E) stained central cross section was made for each block. When negative, four step ribbons were cut at intervals of 250 microm. One section from each ribbon was stained with H&E, and one was used for immunohistochemistry (IHC). RESULTS: When taking the cumulative total of detected metastases at level 5 as 100%, the percentage of SLN positive patients increased from 79%, 83%, 83%, 90% to 93% in the H&E sections through levels 1-5, and with IHC these values were 83%, 86%, 90%, 97%, and 100%, respectively. One of six patients in whom metastases were detected at levels 2-5 only had metastases in the subsequent additional lymph node dissection. CONCLUSIONS: Multiple level sectioning of SLNs (five levels at 250 microm intervals) and the use of IHC detects additional metastases up to the last level in melanoma SLNs. Although more levels of sectioning might increase the yield even further, this protocol ensures a reasonable workload for the pathologist with an acceptable sensitivity when compared with the published literature.     

乳腺癌前哨淋巴结术中分子诊断的临床实用性初探

目的 探讨GeneSearchTM乳腺淋巴结检测试剂盒(以下简称GeneSearch)在乳腺癌前哨淋巴结(SLN)术中诊断的临床实用性.方法 对复旦大学附属肿瘤医院2009年2月至6月诊治的88例乳腺癌患者行SLN活检.首先垂直长轴将所得淋巴结切成数块厚约2 mm的组织块,对各切面进行术中细胞印片后,奇数号组织块用于术后连续切片检查,偶数号组织块采用GeneSearch进行检测,应用即时荧光定量逆转录聚合酶链反应检测SLN中CK19和乳腺球蛋白表达的Ct值.将GeneSearch以术后连续切片的诊断为准,与术中细胞印片、术后连续切片的病理结果分别进行比较.结果 88例共获得225枚SLN,其中宏转移淋巴结27枚,微转移淋巴结9枚,阴性淋巴结189枚(其中5枚为孤立肿瘤细胞).从切割淋巴结开始到最终形成报告,GeneSearch耗时范围为35～45 min(平均40 min).基于淋巴结数目,GeneSearch与术后连续切片的总体符合率为95.6%(215/225),其检测敏感度为86.1%(31/36),均高于术中细胞印片[分别为94.7%(213/225)和72.2%(26/36)].SLN转移灶大小与CKl9和乳腺球蛋白的Ct值存在统计学相关性(P＜0.01).结论 GeneSearch用于SLN术中诊断时,其检测敏感度高于术中细胞印片,达到比较满意的效果,但在应用中仍存在一些问题.     

Micromorphometric features of positive sentinel lymph nodes predict involvement of nonsentinel nodes in patients with melanoma

The aim of the present study was to determine whether micromorphometric features of positive sentinel lymph nodes (SLNs) from patients with melanoma are useful for predicting further nodal involvement in completion lymph node dissection (CLND) specimens. Of 986 patients with melanoma undergoing SLN biopsy between March 1992 and February 2001, 175 (17.7%) had at least 1 positive SLN and 140 had subsequent CLND specimens available for review. Further nodal involvement in CLND specimens was present in 24 (17.1%) of 140 patients. Of 8 micromorphometric features of the SLNs that were assessed, the presence of metastases in CLND specimens was correlated significantly with a tumor penetrative depth (maximum distance of melanoma cells from the inner margin of the SLN capsule) of more than 2 mm (P < .05), a deposit size of more than 10 mm2 (P < .01), the presence of melanoma cells in perinodal lymphatic vessels (P < .01), and the effacement of nodal architecture by metastatic melanoma cells (P < .05). Our results indicate that some morphologic features of melanoma metastases in SLNs predict the likelihood of further nodal involvement in CLND specimens.     

Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer

AIM: To investigate whether multiparameter flow cytometry (MP-FCM) can be used for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast cancer. METHODS: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n = 238) from 98 patients were analysed. For each lymph node, sections for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for cytokeratin (MNF116) were cut at three levels with a distance of 500 microm. The intervening material was used for MP-FCM. Cells were immunostained with MNF116, followed by an incubation with fluorescein isothiocyanate (FITC) labelled goat antimouse immunoglobulin. DNA was stained using propidium iodide. From each lymph node 100,000 cells were analysed on the flow cytometer. RESULTS: Thirty eight of the 98 patients with breast carcinoma showed evidence of metastatic disease in the SLN by one ore more of the three methods. In 37 of 38 cases where metastatic cells were seen in the routine H&E and/or IHC, more than 1% cytokeratin positive cells were detected by MP-FCM. In 24 patients, metastatic foci were more than 2 mm (macrometastasis) and in 14 these foci were smaller than 2 mm (micrometastasis). In three of these 14 cases, MP-FCM revealed positive SLNs, although this was not seen at first glance in the H&E or IHC sections. After revision of the slides, one of these three remained negative. However, MP-FCM analysis of the cytokeratin positive cells showed an aneuploid DNA peak, which was almost identical to that of the primary breast tumour. Duplicate measurements, done in 41 cases, showed a 99% reproducibility. In five of 14 patients with micrometastasis, one or two metastatic foci were found in the non-SLN. However, in 15 of 24 macrometastases multiple non-SLNs were found to have metastatic tumour. All micrometastases except for the remaining negative one mentioned above showed only diploid tumour cells, despite the fact that their primary tumours contained both diploid and aneuploid tumour cells. In primary tumours with more than 60% aneuploid cells, predominantly aneuploid macrometastasis were found, whereas diploid primary tumours only showed diploid micrometastases or macrometastases in their SLN. Aneuploid SLN macrometastases were associated with non-SLN metastases in five of seven patients, whereas diploid cases showed additional non-SLN metastases in only seven of 16 patients. CONCLUSION: In all cases, MP-FCM was sufficient to detect micrometastatic tumour cells in a large volume of lymph node tissue from SLNs. In some cases it was superior to H&E and IHC staining. Approximately 30% of SLN micrometastases are accompanied by additional non-SLN metastases. The size of the aneuploid fraction (> 60%) in the primary tumour may influence the risk of having both SLN and non-SLN metastases.     

Sentinel lymph nodes in cutaneous melanoma: the experience in the Florence area

In the period 1997-2001, 466 sentinel lymph nodes from 342 lymphatic basins in 322 melanoma patients were examined at the Health Unit of Florence. The lymphatic mapping was performed through pre-operative lymphoscintigraphy using technetium-labelled nano-colloid, intradermal injections of vital blue dye and intra-operative gamma-probe. The examined patients were 182 females and 140 males. Sentinel lymph node was one in 65.2% of cases; two sentinel lymph nodes were detected in 27% of cases and more than 2 sentinel nodes were detected in 7.8% of cases. Melanoma metastases in one or more sentinel lymph nodes were found in 61/322 patients (18.9%). Lymphatic basins resulted to be involved by melanoma metastases were 64/342 (18.7%); sentinel lymph nodes containing metastatic melanoma deposits were 73/466 (15.6%). No metastasis was found in patients with melanoma thickness < or = 1 mm. One or more positive sentinel lymph nodes were found in 7.5% of patients with melanoma thickness > 1.00 and < or = 1.50 mm, in 27.7% of patients with melanoma > 1.50 and < or = 3.00 mm, in 38.2% of patients with melanoma > 3.00 and < or = 4.00, and in 60.7% of patients with melanoma > 4.00 mm. Frozen section analysis of sentinel lymph nodes, performed in 59/61 patients with nodal metastases, detected nodal involvement in 21 patients (35.6%). Metastases were identified by routine hematoxylin-eosin staining in 57/64 positive lymphatic basins; in 7 cases (11%) metastases were detected by immunohistochemical stainings (S100 and HMB-45). A nodal nevus was found in 3/466 sentinel lymph nodes (0.6%). Our data are analyzed and compared to previously data of the literature. The value of frozen section analysis and the major problems in the diagnosis of melanoma micrometastases in sentinel lymph nodes are discussed. The importance of the sentinel node biopsy for the detection of occult metastases and for the correct staging of melanoma patients are stressed, according to the new TNM melanoma classification.     

HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma

The diagnosis of melanoma metastatic to lymph node remains a difficult problem given its histological diversity. We examined the staining patterns of S-100, NK1/C3, HMB-45, and MART-1 (DC10) in melanoma metastases to lymph nodes. Immunohistochemical stains were performed on tissue sections of 126 formalin-fixed lymph nodes from 126 patients with an established diagnosis of metastatic melanoma. A total of 98% of cases (123 of 126) stained positive for S-100, 93% (117 of 125) stained positive for NK1/C3, 82% (103 of 126) stained positive for MART-1, and 76% (95 of 125) stained positive for HMB-45. The distribution and intensity of staining varied among these markers. A diffuse staining pattern, defined as >50% of tumor cells stained, was observed in 83% of MART-1-positive cases but in only 56% of S-100-positive cases, 48% of NK1/C3-positive cases, and 34% of HMB-45-positive cases. A maximally intense signal was almost always observed for MART-1 (83% of positive cases) but was rarely observed for NK1/C3 (20%). S-100 and HMB-45 showed maximally intense staining in 50% and 54% of cases, respectively. S-100 and NK1/C3 stained both histiocytes and melanocytes, whereas MART-1 and HMB-45 stained only melanocytes. Seventy-eight cases (63%) stained positive for all 4 markers, 17 cases (14%) stained for all markers except HMB-45, 13 cases (10%) stained for all markers except MART-1, 6 cases (5%) stained only with S-100 and NK1/C3, 4 cases (3%) stained only with S-100 and HMB-45, and 2 cases stained for all markers except S-100. One case each stained for the following: only S-100, only S-100 and HMB-45, and all markers except NK1/C3. One case exhibited absence of staining for any of these markers. We demonstrate that lymph node metastases of melanoma are heterogeneous with regard to tumor marker expression. S-100 and NK1/C3 were the most sensitive stains for detecting metastatic melanoma; however, they both also stain other nontumor cells in lymph nodes. MART-1 did not stain histiocytes and exhibited a more frequently intense and diffuse staining pattern than NK1/C3. HMB-45 was less sensitive and demonstrated less diffuse staining than MART-1.     

Rapid immunohistochemistry of sentinel lymph nodes for metastatic melanoma

Sentinel lymph node (SLN) biopsy is performed on patients with malignant melanoma (MM) to assess the need for selective complete lymphadenectomy. Melanoma metastasis to regional lymph nodes is an important prognostic indicator in patients with MM. This study assesses the sensitivity and specificity of rapid immunohistochemistry (RIHC) in intraoperative delineation of melanoma metastasis to SLN. RIHC for S-100 protein, HMB45, and a melanoma marker cocktail (melan A, HMB45, and tyrosinase) was performed on 71 SLNs obtained from 28 patients with MM. Frozen sections (6 micro thick) on plus slides were fixed for 2 to 3 minutes in cold acetone and then stored at -70 degrees C. The EnVision kit (Dako, Carpinteria, CA) for rapid immunohistochemistry (RIHC) on frozen tissue sections was used, and the staining technique took 19 minutes. Together with preparation of the frozen sections and fixation in acetone, immunostained slides were available in approximately 25 minutes. Of the 71 SNLs examined, 7 showed melanoma metastasis in permanent sections. RIHC of frozen sections detected metastatic melanoma in 6 SLNs, with a sensitivity of 86% for HMB45 and 71% for S-100 protein and the melanoma cocktail and a specificity of 97% for HMB45 and 100% for S-100 and the melanoma cocktail. We conclude that RIHC for HMB45, S-100 protein, and the melanoma cocktail may help detect melanoma metastasis in SLN intraoperatively, leading to total lymph node dissection and obviating the need for 2 surgical procedures. Section folds and background stain can make interpretation difficult. Intraoperative time constraints require a more rapid technique. A recent consensus group has discouraged frozen-section examination of SLN.     

KBA.62: a useful marker for primary and metastatic melanomas

We previously described a novel antimelanoma antibody, designated KBA.62. However, review of the literature showed that only a few studies have reported on this antibody. We report our experience in the diagnosis of melanoma using KBA.62 and its value in both primary and metastatic conditions. In addition to conventional melanomas, we included desmoplastic and spindle cell melanomas, whose diagnosis can be challenging. We also focus on identification of malignant cells in sentinel lymph node biopsies using KBA.62, by comparison with anti-S-100 protein and HMB-45 antibodies, because discrepancies in sensitivity and specificity of melanoma markers have given rise to numerous studies aiming to determine the best panel for the evaluation of sentinel lymph node from patients with melanoma. Overall, KBA.62 was positive in 93% of primary and metastatic melanomas. Interestingly, the 12 cases of desmoplastic and spindle cell melanomas had strongly positive results. In addition, the results of our study performed on a series of 215 sentinel lymph nodes showed that the sensitivity of anti-S-100 protein and KBA.62 antibodies in detecting occult metastasis was similar. Moreover, KBA.62 identified 6 patients (3%) who had confirmed sentinel lymph node metastasis but were negative for HMB-45. The resolution was higher with KBA.62 than that observed with anti-S-100 protein antibody, as the nonmelanocytic positive cells for KBA.62 in lymph nodes were only represented by endothelial cells, which therefore constituted an intrinsic positive control. We conclude that KBA.62 antibody is a useful additional marker for melanoma, specifically in desmoplastic/spindle cell cases and in the context of micrometastasis in sentinel lymph node.     

Implementation of step sectioning in the examination of sentinel lymph nodes to improve the detection of micrometastases in breast cancer patients

The object of this study was to examine whether a new protocol for examination of sentinel lymph nodes (SLNs) would lead to the detection of more metastases. Sections of 1 mm would identify most SLN macrometastases, and step sections at intervals of 200-250 μm would identify most micrometastases. A total of 111 breast cancer patients who underwent the SLN procedure at St. Olavs University Hospital in Trondheim, Norway in 2008 were included in the study group. Their SLNs were processed according to a new standardized protocol with sections of 2-3 mm being step sectioned at intervals of 200-250 μm. A total of 109 breast cancer patients undergoing the SLN procedure in 2007 were used as a reference group. Metastases were found in 29% of the cases, compared with 26% in the reference group. Step sectioning of SLNs revealed metastases in five cases initially found to be negative. The metastases of the study group were smaller, with a median value of 1.25 mm compared with 4.25 mm in the reference group. Step sectioning led to the detection of metastases in SLNs initially found to be negative. The median size of the metastases was considerably smaller in the study group than in the reference group.     

Melanoma-derived mediators can foster the premetastatic niche: crossroad to lymphatic metastasis

The natural history of advanced malignant melanoma demonstrates that, in most cases, widespread tumor dissemination is preceded by regional metastases involving tumor-draining lymph nodes [sentinel lymph nodes (SLNs)]. Under physiological conditions, LNs play a central role in immunosurveillance to non-self-antigens to which they are exposed via afferent lymph. The dysfunctional immunity in SLNs is mediated by tumor secretory factors that allow the survival of metastatic melanoma cells within the LN by creating a premetastatic niche (PMN). Recent studies outline the altered microenvironment of LNs shaped by melanoma mediators. Here, we discuss tumor secretory factors involved in subverting tumor immunity and remodeling LNs and highlight emerging therapeutic strategies to reinvigorate antitumoral immunity in SLNs.     

Pathologic examination of the axillary sentinel lymph nodes in patients with early-stage breast carcinoma: current and resolving controversies on the basis of the European Institute of Oncology experience

Several controversial aspects of sentinel lymph node biopsy (SLNB) for patients with early-stage, node-negative breast carcinoma have been dealt with and resolved in the past decade since its introduction. Unfortunately, however, there is still no consensus on how best to examine sentinel lymph nodes (SLN) histologically. As a consequence, the protocols for SLN examination are remarkably variable in different institutions, leading to a very poor reproducibility of the data stemming from investigations on series of patients whose SLNs have been evaluated according to diverse protocols. Patient outcomes, however, can be optimised only by standardization of the whole procedure of SLNB, with particular reference to the histopathologic scrutiny. Lack of a standardized histopathologic protocol likely derives also from the uncertainties about the clinical implications of minimal lymph node involvement (isolated tumour cells and micrometastases) with regard both to the risk of additional metastases to non-sentinel lymph nodes of the same basin and to the prognostic value for patients’ survival. This review aims at highlighting some of the controversial issues of the histopathologic examination of the SLNs, including the number of sections and cutting intervals, the use of immunohistochemistry and the role of molecular biology assays.     

Detection of micrometastases in bone marrow and sentinel lymph nodes of breast cancer patients

Objective: To study the sensitivity and clinical significance of HE-staining,IHC and RT-PCR in detecting breast cancer micrometastases in bone marrow and sentinel lymph nodes (SLNs). Methods:After general anesthesia, all patients underwent bone marrow puncture and sentinel lymph node biopsy (SLNB) by 1% isosulfan blue, and then HE-staining,IHC and RT-PCR were used to detect micrometastases. Results:Of 62 patients with breast cancer whose axillary lymph nodes showed negative HE-staining results, 15 cases presented with positive RT-PCR and 9 cases showed positive IHC results positive in bone marrow micrometastases detection. PT-PCR and IHC showed good uniformity(kappa=0.6945)and there was significant difference in detective rate between these two methods (χ2=4.1667,P=0.0412). In SLN samples, 13 showed positive RT-PCR results, while 7 showed positive IHC results. PT-PCR and IHC showed good uniformity (kappa=0.6483)and significant difference was also found in detective rate between these two methods (χ2=4.1667,P=0.0412). Both bone marrow and SLN samples were RT-PCR positive in 3 cases,which indicated that bone marrow micrometastases did not always accompany SLN micrometastases(χ2=0.067,P=0.796). Conclusion: Even if no axillary lymph node involvement or distant metastases are present in routine preoperative examination, micrometastases can still be detected in bone marrow or SLNs. Because the bone marrow micrometastases and axillary node micrometastses are not present simultaneously, combination test of multiple indicators will detect micrometastases more accurately.     

Minimal metastatic disease in sentinel lymph nodes in breast carcinoma: some modest proposals to refine criteria for "isolated tumor cells"

Axillary lymph node status is one of the most important prognostic factors in breast carcinoma. The weight of cumulative evidence suggests that the development of the sentinel lymph node (SLN) biopsy procedure has not only allowed for accurate lymph node-staging but has also helped avoid the morbidity of a full axillary dissection in those patients who are unlikely to have metastatic tumor in that location. The detection of metastases in SLNs is facilitated by the, now relatively routine, enhanced histopathologic examination via step-sectioning and immunohistochemistry. In clinical terms, the finding of a metastatic deposit that measures between 0.2 and 2 mm, that is, "micrometastasis" in a SLN is largely noncontroversial; however, the presence of smaller metastatic foci detected either by routine hematoxylin and eosin stain or by cytokeratin immunostain [<0.2 mm, ie, so-called "isolated tumor cells (ITCs)"] has remained problematic since the advent of the SLN biopsy. In this communication, attention is drawn to the broad morphologic range of metastatic disease in SLN that may be placed in the category of so-called ITC. To facilitate the reproducible classification of the various strata of minimal metastasis in sentinel lymph nodes, we recommend the following: (1) the term "isolated tumor cell" (note singular form) be restricted to cases that show the presence of only a single tumor cell. (2) In situations where there are multiple isolated single cells and/or cell cluster(s) present and each cluster measures<0.2 mm, the term "submicroscopic metastasis" be adopted and an actual count of tumor cells present may be given. (3) Restrict the use of the term micrometastasis to cases wherein the largest metastatic focus is larger than 0.2 mm but smaller than 2.0 mm.     

本院5年来乳腺癌前哨啉巴结活检报告

目的探讨乳腺癌前哨淋巴结活检技术的可行性和前哨淋巴结的组织学状况能否准确预告腋淋巴结的状况。方法使用美蓝染色和或^99mTc-SC同位素示踪法对我院收治的108例乳腺癌患者进行前哨淋巴结活检。结果108例患者中有95例成功确定前哨淋巴结，检出率88％，其中关蓝组为87S（S5／98），美蓝与核素联合组全部检出（100S）。40岁以下的妇女检出率明显高于40岁以上的妇女（P〈0．05），而假阴性率有显著性增高。97例浸润性癌（包括导管癌和腺癌）中假阴性率为22％，但当使用免疫组化检查法以后，假阴性率下降至14％。结论前哨淋巴结活检技术在临床是可行的，绝大多数前哨淋巴结可以比较准确地反映其余腋窝淋巴结的组织学特点。美蓝染色和／或^99mTc-SC同位素示踪法结合应用是较好的选择方法。     

影响乳腺癌前哨淋巴结数目的临床病理特征分析

目的分析影响乳腺癌前哨淋巴结数目的相关因素,探讨最佳的前哨淋巴结活检值。方法回顾性分析2007年1月-2011年12月中国医学科学院肿瘤医院乳腺癌前哨淋巴结活检病例578例。采用Logistic回归模型分析前哨淋巴结数目与临床病理特征的相关性。结果全组女性,平均年龄49.9(21～90)岁。总共获得2 222枚前哨淋巴结,平均每例3.8枚(1～15)。淋巴结转移率17.8%(103/578),转移组和无转移组淋巴结数目无差异。单因素分析显示,术式、显像方法和体质指数影响前哨淋巴结数目(P<0.05)。多因素分析中,单纯乳房切除、联合显像、BMI≤30者前哨淋巴结较多(P<0.05)。前哨淋巴结限于5枚时,转移病例检出率100%。18.7%(108/578)病例不必继续送检淋巴结,298枚淋巴结免于切除。结论乳腺癌前哨淋巴结活检数量受到显像方法、乳腺术式和体质指数的影响,5枚前哨淋巴结可能是一个比较合适的参考标准。     

Pathologic evaluation of sentinel lymph nodes in colorectal carcinoma

BACKGROUND: The identification of lymph node metastases in colorectal resection specimens is necessary for accurate tumor staging. However, routine lymph node dissection by the pathologist yields only a subset of nodes removed surgically and may not include those nodes most directly in the path of lymphatic drainage from the tumor. Intraoperative mapping of such sentinel lymph nodes (SLNs) has been reported in cases of melanoma and breast cancer. We applied a similar method to cases of colorectal carcinoma, with emphasis on the pathology of the SLNs. METHODS: Eighty-three consecutive patients with colorectal carcinoma were evaluated after intraoperative injection of 1 to 2 mL of 1% isosulfan blue dye (Lymphazurin) into the peritumoral subserosa. Blue-stained lymph nodes were suture-tagged by the surgeon within minutes of the injection for identification by the pathologist, and a standard resection was performed. Designated SLNs were sectioned at 10 levels through the block; a cytokeratin immunostain (AE1) was also obtained. To evaluate the possibility that increased detection of metastases in the SLN might be solely due to increased histologic sampling, all initially negative non-SLNs in the first 25 cases were sectioned also at 10 levels. RESULTS: Sentinel lymph nodes were identified intraoperatively in 82 (99%) of 83 patients and accounted for 152 (11.9%) of 1275 lymph nodes recovered, with an average of 1.9 SLNs per patient. A total of 99 positive lymph nodes (38 positive SLNs and 61 positive non-SLNs) were identified in 34 node-positive patients. The SLNs were the only site of metastasis in 17 patients (50%), while 14 patients (41%) had both positive SLNs and non-SLNs. Three patients (9%) had positive non-SLNs with negative SLNs, representing skip metastases. In patients with positive SLNs, 91 (19%) of 474 total lymph nodes and 53 (12%) of 436 non-SLNs were positive for metastasis. In patients with negative SLNs, 8 (1%) of 801 total lymph nodes and 8 (1.2%) of 687 non-SLNs were positive for metastasis. Multilevel sections of 330 initially negative non-SLNs in the first 25 patients yielded only 2 additional positive nodes (0. 6%). All patients with positive SLNs were correctly staged by a combination of 4 representative levels through the SLN(s) together with a single cytokeratin immunostain. CONCLUSIONS: Intraoperative mapping of SLNs in colorectal carcinoma identifies lymph nodes likely to contain metastases. Focused pathologic evaluation of the 1 to 4 SLNs so identified can improve the accuracy of pathologic staging.