Immunohistochemistry analysis of micrometastasis in pretreatment lymph nodes from patients with esophageal cancer

BACKGROUND: With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. METHODS: Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. RESULTS: 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. CONCLUSIONS: Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.     

非小细胞肺癌淋巴结微转移的临床病理研究

目的 探讨免疫组化染色检测非小细胞肺癌淋巴结微转移的可行性。方法 将25例肺癌患者术中获取的淋巴结标本进行石蜡包埋,然后连续切片,6～10张不等,切片厚为5μm。选择第1和倒数第2张切片进行苏木精伊红染色,剩余切片用于免疫组化染色。免疫组化所选抗体为鼠抗人细胞角蛋白19单克隆抗体。结果 195枚淋巴结接受了苏木精伊红染色检查。9例患者共30枚淋巴结中发现有显性转移,无一例患者的淋巴结中检测出微转移。135枚苏木精伊红染色阴性的淋巴结又进行了免疫组化染色检查,有31枚淋巴结病理切片中显现出了癌微转移。16例常规病理PN0期患者中,5例患者肺门淋巴结出现了微转移;另9例常规病理PN1期患者中,4例出现了纵隔淋巴结的微转移,差异有统计学意义（x^2=52．900,P=0．0193）。结论 普通苏木精伊红染色能准确地检测出非小细胞肺癌淋巴结中的显性转移灶,而不易发现隐匿性微转移灶。免疫组化染色能提高非小细胞肺癌淋巴结微转移的检出率,并可对部分Ⅰ、Ⅱ期患者重新进行TNN分期。     

Detection of Micrometastatic Tumor Cells in pN0 Lymph Nodes of Patients With Completely Resected Nonsmall Cell Lung Cancer: Impact on Recurrence and Survival

OBJECTIVE: To detect occult micrometastatic tumor cells in pN0 lymph nodes of nonsmall cell lung cancer (NSCLC) by a combination of cytokeratin and p53 immunohistochemistry staining, and to evaluate the relation between the micrometastasis in pN0 lymph nodes and the prognosis of patients with completely resected stage 1 NSCLC. SUMMARY BACKGROUND DATA: The average 5-year survival rate for patients with completely resected stage 1 NSCLC is only about 70%; thus, about 30% of these patients have recurrent disease. This suggests that occult micrometastasis may exist at the time of surgery; the rate is clearly underestimated by current clinical staging examinations and conventional histopathologic methods. METHODS: A total of 474 hilar and mediastinal lymph nodes were removed during surgery from 49 patients with completely resected stage 1 NSCLC. The lymph nodes analyzed for micrometastasis using immunohistochemical staining with the biclonal anticytokeratin antibody, AE1/AE3. Of these 474 lymph nodes from 49 patients, 263 lymph nodes from 25 patients, whose primary tumors were positive for the p53 protein, were subjected to immunohistochemical staining with the monoclonal anti-p53 protein antibody DO-1. RESULTS: Cells positive for cytokeratin and p53 protein were found in 35 (7.4%) of 474 and 20 (7.6%) of 263 lymph nodes, respectively; 17 (34.7%) of 49 patients had cytokeratin-positive cells and 10 (40.0%) of 25 patients had p53-positive cells in their pN0 lymph nodes. By a combination of cytokeratin and p53 protein immunohistochemical staining, micrometastatic tumor cells were identified in pN0 lymph nodes in 22 (44.9%) of 49 patients. The patients with lymph node micrometastasis identified by a combination of cytokeratin and p53 protein immunohistochemical staining had a poorer prognosis than those without micrometastasis on both univariate and multivariate analyses (overall survival, P =.0003 and 0.013, respectively). CONCLUSIONS: The detection of lymph nodal micrometastasis by cytokeratin and p53 protein immunohistochemical staining will be helpful to predict the recurrence and prognosis of patients with completely resected stage 1 NSCLC.     

Sentinel Node Biopsy in Ductal Carcinoma In Situ Patients

Background: Sentinel lymph node (SLN) mapping is an effective and accurate method of evaluating the regional lymph nodes in breast cancer patients. The SLN is the first node that receives lymphatic drainage from the primary tumor. Patients with micrometastatic disease, previously undetected by routine hematoxylin and eosin (H&E) stains, are now being detected with the new technology of SLN biopsy, followed by a more detailed examination of the SLN that includes serial sectioning and cytokeratin immunohistochemical (CK IHC) staining of the nodes.Methods: At Moffitt Cancer Center, 87 patients with newly diagnosed pure ductal carcinoma in situ (DCIS) lesions were evaluated by using CK IHC staining of the SLN. Patients with any focus of microinvasive disease, detected on diagnostic breast biopsy by routine H&E, were excluded from this study. DCIS patients, with biopsy-proven in situ tumor by routine H&E stains, underwent intraoperative lymphatic mapping, using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. All SLNs that had only CK-positive cells were subsequently confirmed malignant by a more detailed histological examination of the nodes.Results: CK IHC staining was performed on 177 SLNs in 87 DCIS breast cancer patients. Five of the 87 DCIS patients (6%) had positive SLNs. Three of these patients were only CK positive and two were both H&E and CK positive. Therefore, routine H&E staining missed microinvasive disease in three of five DCIS patients with positive SLNs. In addition, DCIS patients with occult micrometastatic disease to the SLN underwent a complete axillary lymph node dissection, and the SLNs were the only nodes found to have metastatic disease. Of interest, four of the five nodepositive patients had comedo carcinoma associated with the DCIS lesion, and one patient had a large 9.5-cm low grade cribriform and micropapillary type of DCIS.Conclusions: This study confirms that lymphatic mapping in breast cancer patients with DCIS lesions is a technically feasible and a highly accurate method of staging patients with undetected micrometastatic disease to the regional lymphatic basin. This procedure can be performed with minimal morbidity, because only one or two SLNs, which are at highest risk for containing metastatic disease, are removed. This allows the pathologist to examine the one or two lymph nodes with greater detail by using serial sectioning and CK IHC staining of the SLNs. Because most patients with DCIS lesions detected by routine H&E stains do not have regional lymph node metastases, these patients can safely avoid the complications associated with a complete axillary lymph node dissection and systemic chemotherapy. However, DCIS patients with occult micrometastases of the regional lymphatic basin can be staged with higher accuracy and treated in a more selective fashion.Presented at the 52nd Annual Meeting of Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma

BACKGROUND: The aims of this study were to assess the incidence of micrometastases of lymph nodes in patients with early gastric cancer invading the submucosal layer and to investigate the correlation between nodal micrometastases and malignancy potential to determine whether micrometastases of lymph nodes have prognostic significance, by use of an anticytokeratin immunohistochemical technique. METHODS: A total of 2272 lymph nodes taken from 88 patients (25.8 per case) were assessed by immunohistochemical technique by use of monoclonal anti-human cytokeratin 8 antibodies. Clinicopathologic parameters and prognosis were compared between patients with and without micrometastases. RESULTS: The incidence of nodal involvement by tumor cells in 88 patients with submucosal gastric cancer increased from 19.3% (17 patients) by hematoxylin-eosin (H&E) staining to 31.8% (28 patients) by cytokeratin immunostaining. The rate of positive node in this study increased from 1.0% (23 of 2272 nodes) by H&E staining to 2.5% (57 of 2272 nodes) by immunostaining (P = .0002). No correlation was observed between the incidence of lymph node micrometastases and various clinicopathologic parameters, including tumor site and size, histological differentiation, Lauren classification, gross tumor type, vascular and lymphatic invasion, and perineural invasion. There was no difference in disease-free survival, estimated by the Kaplan-Meier life-table method, between the micrometastasis-negative and -positive groups (95% and 92.9%, respectively). Multivariate analyses showed that tumor size and diffuse subtype by the Lauren classification were significant factors for survival time (P = .0042 and .014, respectively). CONCLUSIONS: Immunohistochemical staining with an anticytokeratin antibody seems to be of little prognostic value in patients with submucosal gastric carcinoma. Thus, this immunostaining technique does not offer a significant benefit of different strategies for additional therapy or follow-up over conventional pathologic staging with H&E staining.     

IHC和RT-PCR法对检测胃癌区域淋巴结微转移的价值及其意义

目的 探讨免疫组织化学方法(IHC)和逆转录聚合酶链反应(RT-PCR)两种方法对检测胃癌区域淋巴结微转移的临床价值及意义.方法 对85例胃癌根治性手术切除的淋巴结转移患者的临床资料进行了回顾性分析.共切取淋巴结1835枚,每例平均切除21.7枚.采用IHC和RT-PCR法检测细胞角蛋白20(CK20)的表达,研究淋巴结微转移与临床病理参数和预后的关系.结果 患者的淋巴结转移率经IHC法和RT-PCR法检测从HE染色的75.3%分别上升为83.5%和90.6%.经IHC和RT-PCR法检测重新分期率分别为18.8%和37.6%.淋巴结微转移的发生与肿瘤大小、部位无关·与肿瘤Lauren分型和浸润深度密切相关.82例完成随访,平均随访时间为21.2个月.微转移与预后无明显关系.结论 IHC和RT-PCR法是检测胃癌淋巴结微转移的有效手段,能准确判断临未分期,可为制定治疗方案提供依据.     

One hundred consecutive cases of sentinel lymph node mapping in early colorectal carcinoma: Detection of missed micrometastases

Almost one third of patients with "node-negative" colorectal carcinoma (CRC) develop systemic disease. This implies that these patients have occult disease that is inadequately treated by surgery alone. We have coupled sentinel lymph node mapping and a focused pathologic examination to detect occult nodal micrometastases in CRC. Since 1996, sentinel lymph node mapping has been performed in 100 consecutive patients undergoing colectomy for CRC. Peritumoral injection of 0.5 to 1.0 ml of isosulfan blue dye was performed to demonstrate the sentinel node(s). All lymph nodes in the resection specimen were examined by routine hematoxylin and eosin staining. In addition, a focused examination of multiple sections of the sentinel nodes was performed using both hematoxylin and eosin and cytokeratin immunohistochemical analysis (CK-IHC). Overall, lymphatic mapping successfully demonstrated one to four sentinel lymph nodes in 97 (97%) of 100 patients. These sentinel nodes accurately reflected the status of the nodal basin in 92 (95%) of 97 patients. All five of the false negative cases occurred in T3/T4 tumors, and three of the five occurred during the first 30 cases in the experience. Unexpected lymphatic drainage was encountered in eight patients (8%) and altered the operative approach. Twenty-six patients were node positive by routine hematoxylin and eosin staining. Of the remaining 74 patients with hematoxylin and eosin-negative nodes, an additional 18 patients (24%) were upstaged by identification of occult nodal micrometastases that were missed on routine hematoxylin and eosin staining but detected on multiple sections (n = 5) or by CK-IHC (n = 13). The sentinel lymph nodes were the only positive nodes in 19 cases. Sentinel lymph node mapping may be performed in CRC with a high degree of success and accuracy. A focused pathologic examination of the sentinel node detects micrometastatic disease that is missed by conventional techniques in a significant proportion of patients with early CRC. Further studies are necessary to elucidate the clinical relevance of these micrometastases. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001 (oral presentation). Supported in part by grant T32 CA 09689 and 090848 from the National Cancer Institute and by funding from the Rogovin-Davidow Foundation, Los Angeles, California and the Rod Fasone Memorial Cancer Fund, Indianapolis, Indiana.     

Reappraisal of metastatic lymph node topography in head and neck squamous cell carcinomas.

OBJECTIVE: To analyze the lymphatic distribution of metastatic carcinomatous cells in cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN AND SETTING: We retrospectively reviewed 119 patients treated in our hospital for HNSCC (1999-2004). Topography of the neck dissection specimens was prospectively classified according to the classification of Robbins. The 4000 lymph nodes were analyzed by optical microscopy using hematoxylin-eosin-safran (HES) staining. In cases of negative results in level II, cytokeratin (AE1/AE3) immunodetection was performed. RESULTS: Metastases were visualized using HES in 6.4% of lymph nodes for oral cavity, and 4.7% of oropharyngeal, 4.4% of hypopharyngeal, and 1.3% of endolaryngeal cancers. The highest incidence of nodal metastasis was observed in level IIa (P < 0.01). In eight patients (6.7%) with lymph node metastases, level II was spared. In these patients, all 134 nodes histologically negative on HES were confirmed to be negative by IHC. CONCLUSIONS: Level IIa is the main level involved in regional metastases of HNSCC, regardless of the primary site of cancer. However, in eight (6.7%) patients, level II was spared, as confirmed by IHC. In these cases, level II did not represent the first step of drainage from the tumor. The sentinel lymph node technique in HNSCC is discussed in light of these results.     

Breast cancer pseudometastasis in a sentinel lymph node with cytokeratin-positive debris

We report extensive pseudometastasis detected by immunohistochemical (IHC) staining within a sentinel lymph node. An 83-year-old woman underwent simple mastectomy and sentinel lymph node biopsy (SLNB) for infiltrating ductal carcinoma. Intraoperative frozen section of the SLNB specimen appeared histologically negative for metastasis. IHC staining for cytokeratin in permanent sections, however, showed what was reported as micrometastasis in the subcapsular sinus. Since these cells did not resemble the primary tumor cells morphologically, and had actually been called histiocytes in the frozen section, further IHC staining was done. The subcapsular cells were negative for epithelial membrane antigen (EMA) staining, but they were positive for CD68, a macrophage marker. Thus the cytokeratin-positive cells were not metastatic breast tumor cells, but rather were histiocytes with phagocytized cytokeratin debris. This case report illustrates that IHC staining for cytokeratin in SLNB specimens for breast cancer must be supported by morphologic assessment and further appropriate staining before it can become the basis for treatment decisions.     

Focused examination of sentinel lymph nodes upstages early colorectal carcinoma

Approximately 30 per cent of patients with early colorectal carcinoma (CRC) develop systemic disease. A subgroup of these patients may harbor occult micrometastatic disease and might benefit from adjuvant chemotherapy. We investigated sentinel lymph node (SLN) mapping and focused pathologic examination of the SLN as a means of detecting nodal micrometastases. Between 1996 and 2000 SLN mapping was performed in 50 consecutive patients undergoing colectomy for CRC. All lymph nodes in the resection specimen were examined via routine hematoxylin and eosin (H&E) staining. In addition multiple sections of each SLN were examined via both H&E and cytokeratin immunohistochemistry. At least one SLN was identified in 47 patients (94%). In seven patients (14%) SLN mapping identified aberrant drainage that altered the planned resection. The SLN(s) correctly predicted nodal basin status in 44 of 47 (94%) cases; there were three falsely negative SLNs. Sixteen cases had positive SLNs by conventional H&E staining. An additional 10 (20%) cases were upstaged by a focused examination of the SLNs. Micrometastases were identified in three cases by H&E staining of multiple sections of the SLN and in seven only by cytokeratin immunohistochemistry. In nine cases the SLN was the only node containing tumor cells. In this study, SLN mapping demonstrated aberrant nodal drainage patterns that altered the surgical resection in patients with CRC. Focused examination of SLNs may detect micrometastases missed by conventional techniques and thereby identify patients who might benefit from adjuvant therapy.     

Rapid immunohistochemical detection of lymph node micrometastasis during operation for upper gastrointestinal carcinoma

BACKGROUND: The intraoperative diagnosis of lymph node micrometastasis (LNM) may help guide the area of appropriate lymph node dissection. This study aimed to evaluate the rapid immunohistochemical detection of LNMs using frozen sections during operation for gastro-oesophageal cancer. METHODS: Rapid immunostaining with anticytokeratin (AE1/AE3) antibody was compared with conventional immunostaining. A total of 210 lymph nodes obtained from 47 patients with oesophageal squamous cell carcinoma and from 32 with gastric adenocarcinoma were examined during operation. Lymph nodes were frozen, sectioned, and examined by histological and immunohistochemical methods. RESULTS: It took 30 min to complete the rapid immunostaining procedure; the expression of cytokeratin by rapid immunostaining was similar to that by conventional immunostaining. The incidence of lymph node metastasis detected by histological and immunohistochemical examination was 17 and 23 per cent respectively. LNM was solely detected in 12 lymph nodes by immunostaining: three micrometastases and nine with tumour cell microinvolvement. CONCLUSION:: Intraoperative rapid immunostaining is a simple and useful technique for detecting LNMs. Further study should investigate the role of rapid immunostaining during cancer surgery to select appropriate areas for lymphadenectomy.     

Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers

BACKGROUND: Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. MATERIALS AND METHODS: Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining. RESULTS: CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860). CONCLUSIONS: Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.     

CK19表达及其在结肠癌淋巴结微转移诊断中的应用

目的：研究用免疫组化方法检测CK19及其在结肠癌淋巴结微转移诊断中的应用与临床病理意义。方法：取材于50例结肠癌病人肿瘤组织及癌周淋巴结255枚,同时进行HE染色组织学检查和抗角蛋白19抗体的免疫组化检测。结果：50例结肠癌组织中CK19表达均为阳性。255枚淋巴结用HE染色检查阳性者56枚(22．0％),皆同时表达CK19阳性;另20枚淋巴结HE染色阴性,而CK19表达阳性。50例中有12例淋巴结中发现微转移,其中6例常规组织学检查属淋巴结转移阴性而免疫组化染色诊断表现为转移阳性。占常规病理检查淋巴结转移阴性者的21．4％(6／28)。随着肿瘤分期增加,淋巴结CK19表达阳性率亦增加。CK19表达阳性者预后较阴性者为差。结论：CK19免疫组化法是检测结肠癌淋巴结微转移的敏感而便捷的方法,而检测结肠癌微转移有助于判断肿瘤进展程度与预后。特别对在筛选组织学检查淋巴结阴性但存在微转移的病人有实用价值。     

Impact of Lymph Node Micrometastasis in Patients with Pancreatic Head Cancer

Purpose The purpose of this study was to investigate the clinical significance of nodal micrometastasis in patients who underwent a curative operation for pancreatic cancer. Experimental Design Fifty-eight patients underwent a macroscopically curative resection with extended lymph node dissection for pancreatic cancer. The total number of resected lymph nodes was 1,058, and 944 histologically negative lymph nodes were subjected to immunohistochemical staining to detect occult micrometastases. Results Nodal micrometastases were detected immunohistochemically in 147 out of 944 resected histologically negative lymph nodes (15.6%). Forty-four of all 58 patients (75.9%) and 13 of the 23 histologically node-negative patients (56.5%) had nodal micrometastases. Nodal micrometastases existed in the N1 lymph node area most frequently, followed by the N2 and N3 lymph node areas. The distribution was similar to that of histologically metastatic lymph nodes. Ten out of 16 patients (62.5%) with histological N1, and 5 out of 16 patients (31.3%) with histological N2 had nodal micrometastases beyond the histological lymph node status. Three and 5-year survival rates of pN0 patients without lymph node nodal micrometastases were both 60.0%, while those with nodal micrometastases were 19.2% and 0%, respectively. There was statistically significant difference between the both groups (P = 0.041). Conclusions Nodal micrometastasis in pancreatic cancer existed in wider and more distant areas than histological lymph node status, and it was an unfavorable predictive factor, even in N0 patients.     

直肠癌淋巴结微转移标志物的比较研究

目的：评价直肠癌淋巴结CK20、CK19、CEA诊断微转移的敏感性、特异性，探讨微转移的临床病理意义。方法：采用免疫组织化学染色方法，以CK20、CK19、CEA为指标，检测36例直肠癌患者手术区域252枚淋巴结的微转移，对照组为淋巴结反应性增生的标本15例。结果：常规HE检测淋巴结转移阳性率7．94％，CK19、CK20、CEA阳性率分别为20．63％、23．02％、17.46％，均高于HE检测结果（P〈0．01）。三种抗体在淋巴结微转移阳性率存在统计学差异。19枚对照组淋巴结CK19阳性率47.37％，CEA阳性率10．53％．CK20表达阴性。CK20、CK19、CEA淋巴结微转移阳性率与3年复发率无统计学差异（P〉0.05）。结论：对常规病理检测未发现区域淋巴结转移的直肠癌，有必要辅以免疫组化方法检测其微转移，CK20是首先标志物。     

The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer.

BACKGROUND: Controversy exists regarding the routine use of cytokeratin immunohistochemistry (IHC) in the histopathologic examination of breast cancer sentinel lymph nodes (SLN) because the clinical significance of micrometastases detected by IHC is unclear. This analysis was performed to determine the frequency of IHC-detected micrometastases. METHODS: All patients underwent SLN biopsy, followed by completion axillary dissection. This analysis included patients who had SLN evaluated by IHC. SLN were examined by hematoxylin and eosin (H&E) stain at 2-mm intervals, with IHC in 2 sections. The axillary dissection specimen was evaluated by routine H&E staining. RESULTS: IHC was performed in SLNs from 973 patients. Of the 869 patients with negative nodes by H&E, 58 (6.7%) were "upstaged" by IHC. In 6 of 58 patients (10.3%) who had IHC-only positive SLN, nodal metastases were found in the axillary dissection specimen. CONCLUSIONS: IHC resulted in upstaging of 6.7% of patients who had negative SLN on H&E staining. These patients had a 10.3% risk of residual axillary nodal metastases. However, the clinical significance of IHC-only positive SLN requires further study.     

The usefulness of cytokeratin immunohistochemistry in detection of lymph node micrometastasis in neck dissection specimens.

OBJECTIVE: Our study was designed to find out the rate and the characteristics of micrometastasis in cervical lymph nodes using immunohistochemical staining. STUDY DESIGN AND SETTING: From 69 patients, 1710 lymph nodes negative for metastasis on hematoxylin-eosin stain, were examined. Immunohistochemical stain was performed using pan-cytokeratin AE1/AE3 antibody. RESULTS: In 13 cases, occult lymph node metastasis was detected by immunohistochemical method. On retrospective review of the hematoxylin-eosin stain by the pathologist, lymph node metastasis was detected in 4 of 13 patients. CONCLUSIONS: Because the immunohistochemical method enhanced the detection rate of occult micrometastasis in cervical lymph nodes of head and neck squamous cell carcinoma patients, it may be recommended for routine diagnostic use in patient with negative for a lymph node metastasis on routine hematoxylin-eosin stain.