Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis

Ushiku T, Matsusaka K, Iwasaki Y, Tateishi Y, Funata N, Seto Y & Fukayama M
(2011) Histopathology  59 , 1081–1089
Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis Aims: This study aimed to characterize the clinicopathological features of invasive micropapillary carcinoma (IMPC) of the stomach. Methods and results: Seventeen cases of gastric IMPC were identified from histological reviews of 1178 consecutive cases. IMPC components occupied 10–90% of the entire tumours. Fifteen tumours showed invasion into the muscularis propria or deeper, whereas two tumours were limited to the submucosa. All 17 cases were associated with tubular or papillary adenocarcinoma. Lymphatic and venous invasion were identified more frequently in cases with IMPC components than in those without (P = 0.0023 and P = 0.0009, respectively). Nodal metastases were identified in 14 of 17 (82%) cases with IMPC components, whereas they were detected in 540 of 1161 (47%) cases with no IMPC components (P = 0.0053). Multivariate analysis demonstrated that the presence of IMPC was an independent predictor of nodal metastasis. Conclusions: Conservative treatments, such as endoscopic resection, should not be used for gastric carcinoma with IMPC components, as these cases are associated with a high propensity for lymphovascular invasion and nodal metastasis.     

Clinicopathological significance of invasive micropapillary carcinoma component in invasive breast carcinoma

Invasive micropapillary carcinoma (IMP) of the breast is a rare variant of invasive breast carcinoma and most cases of IMP are associated with nodal metastasis and lymphatic invasion. Lesions composed of an IMP component alone are rare and almost always coexist with other pathological components. However, few reports have documented IMP along with its proportion and the coexistent pathological type. We analyzed the total 486 breast cancer lesions operated in our hospital in 1998. We classified the lesions into five groups by the proportion of the IMP component in each lesion. Then we evaluated the incidence of nodal metastasis and lymphatic invasion in each group. The incidence of the invasive carcinoma containing any IMP components was 8.4%. The incidence of nodal metastasis and lymphatic invasion in lesions with an IMP component were significantly higher than that in those with no IMP. No correlation was seen between the incidence of nodal metastasis and the coexistent pathological type, shape of tumor clusters, nuclear grade and the expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and gross cystic disease fluid protein-15 in IMP components. The presence of IMP components was a significant predictive factor for nodal metastasis, even if it is detected in only a small proportion of the tumor.     

Pure invasive micropapillary carcinoma of the esophagogastric junction with lymph nodes and liver metastasis

Invasive micropapillary carcinoma (IMPC), an aggressive variant of adenocarcinoma, is associated with a poor prognosis. Although IMPC has been reported to occur in various organs, pure IMPC has only been reported in the breast, pancreas and colon. There are no reports of IMPC of the esophagogastric junction (EGJ). According to previous reports on gastric IMPC, IMPC occupied, at most, 90 % of the whole tumor. IMPC is reported to occur least frequently in the gastric cardia. We herein report a rare case of pure IMPC of the EGJ. A 71‐year‐old male patient presented with epigastric distress. Gastric endoscopy demonstrated an irregularly‐elevated lesion of 50 mm in diameter at the EGJ. The patient underwent proximal gastrectomy, resection of the regional lymph nodes and a punch biopsy of the liver. A histopathological examination revealed that almost all of the regions, including the lymph nodes and the sites of liver metastasis, contained IMPC and that a minute region (<1 % of the whole cancer) contained tubular or papillary adenocarcinoma. The further accumulation of pure IMPC cases like the present case would help to elucidate its pathogenesis.     

淋巴结转移密度与乳腺浸润性导管癌预后的关系

目的探讨淋巴结转移密度与手术治疗乳腺浸润性导管癌患者预后的关系。方法回顾性分析113例乳腺浸润性导管癌的临床资料,按淋巴结转移密度分为ND40组、ND=0组和ND≤40组,采用Kaplan-Meier法和Cox比例风险模型,比较临床病理特征及淋巴结转移密度评价手术治疗乳腺浸润性导管癌患者5年无瘤生存率和总生存率的价值。结果 ND40组、ND=0组和ND≤40组5年无瘤生存率及总生存率,差异有统计学意义(P均0.05)。在Ⅲ期乳腺癌患者中,淋巴结转移密度提供良好的分层意义,ND40组Ⅲ期乳腺癌与Ⅳ期乳腺癌预后无差异(P=0.453)。单因素分析显示,脉管癌栓、淋巴结转移密度、TNM分期、雌、孕激素受体状态及p N分期均与患者的5年无瘤生存率和总生存率有关(P均0.05)。多因素分析显示,组织学分级及淋巴结转移密度是影响患者5年无瘤生存率的独立因素(P均0.05);淋巴结转移密度是影响患者5年总生存率的独立因素(P0.05)。结论淋巴结转移密度是手术治疗乳腺浸润性导管癌患者预后的独立因素,提示其可作为乳腺癌预后的参考标准,ND40组提示预后不良。     

Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma

AIMS: Invasive micropapillary carcinoma of the breast is an aggressive and distinctive variant of breast cancer. These tumours have a characteristic histological appearance and have been associated with a high incidence of axillary lymph node metastases and a poor clinical outcome. The aims of this study were to investigate the immunohistochemical profile of invasive micropapillary carcinoma of the breast, to compare it with invasive ductal carcinoma, and to identify the morphological parameters which predict its poor outcome. METHODS AND RESULTS: Fifty-three (2.6%) invasive micropapillary carcinomas of the breast from 2022 cases of infiltrating breast carcinomas were identified by retrospective review. The patient age at presentation ranged from 33 to 78 years (mean 52.5 years). The tumour size ranged from 5 to 70 mm (mean 27 mm). Eighty-two percent (43 of 53) were of high histological grade; 69% (33 of 48) of cases with axillary lymph node dissections had positive lymph nodes; and 75.5% (40 of 53) had lymphatic invasion: 46% (22 of 48) of cases had extranodal extension. Of lymph node-positive cases, 61% had four or more metastatic lymph nodes. Of tumours with tumour size >10 mm, 77% had positive lymph nodes. The percentages of cases positive for oestrogen receptor (ER) and progesterone receptor (PR) were 68% and 61%, respectively. These values were significantly higher than the values for invasive ductal carcinomas. p53 and c-erbB-2 were detected in 48% and 54% of cases, respectively. The mean value of Ki67 was 26%. Follow-up was available in 36 patients. Eight patients had local recurrences, nine patients had distant metastases, and 10 patients died of disease within a follow-up period of 9 years. CONCLUSION: Lymphotropism and an unfavourable prognosis are the hallmarks of this distinct entity. Prognostic markers such as ER, PR, p53, and c-erbB-2 failed to provide new criteria to allow discrimination of these tumours from other breast cancers.     

Increased expression of integrin beta-4 in papillary thyroid carcinoma with gross lymph node metastasis

Although the prognosis is generally good for patients with papillary thyroid carcinoma, gross nodal metastasis of carcinoma has a poor prognosis. It is necessary to clarify how carcinoma progresses to gross nodal metastasis in order to establish a cure. The adhesion molecule integrin beta-4 is considered to be related to cell migration and metastasis in many carcinomas. In the present study, we examined integrin beta-4 expression in 65 cases of human papillary thyroid carcinoma using immunohistochemical methods. Expression of integrin beta-4 was found in all papillary carcinomas, but in few normal thyrocytes. Interestingly, integrin beta-4 expression in the carcinomas with gross (> or =3 cm) lymph node metastasis was significantly higher than that in carcinomas with small (<3 cm) or no lymph node metastasis. These results suggest that integrin beta-4 expression in thyroid carcinoma may play a role in the development of gross lymph node metastasis of papillary carcinomas.     

Nuclear expression of CXCR4 in tumor cells of non-small cell lung cancer is correlated with lymph node metastasis

The stromal-derived factor 1α (CXCL12)/chemokine receptor CXCR4 system plays an important role in the metastatic process of a variety of cancers, with CXCR4 frequently expressed by tumor cells homing to CXCL12-rich compartments. The current study evaluated a possible association of CXCR4 expression with lymph node metastasis in primary non–small cell lung cancer. CXCR4 expression levels were evaluated using immunohistology in 46 non–small cell lung cancer specimens of patients without or with lymph node involvement (N0 = 24, N1/N2/N3 = 22). Evaluation of immunostaining was performed semiquantitatively by visual assessment. Statistical analyses with multiple testing adjustments for confirmatory comparisons were performed to assess relevant parameters associated with lymph node metastases. In all samples of non–small cell lung cancer, tumor cells stained positively for cytoplasmic CXCR4. The intensity of the CXCR4 staining varied considerably between specimens: 2 (4%) tumors demonstrated weak cytoplasmic CXCR4, 22 (48%) intermediate, and 22 (48%) strong staining. Membranous staining was absent; however, nuclear staining of CXCR4 was observed in 5 non–small cell lung cancer samples. Statistical analyses of the association between presence of lymph node metastases and CXCR4 expression levels revealed that cytoplasmic CXCR4 expression was not associated with the presence of lymph node metastases. However, nuclear CXCR4 was significantly correlated with increasing lymph node stage (P = .008), linear-to-linear association. The association between aberrant expression of CXCR4 in the nucleus of non–small cell lung cancer and metastasis to lymph nodes points toward a potential tumor metastasis promoting function of nuclear CXCR4.     

Phenotypic Knockout of CXCR4 on Molt-4 with SDF-1α/54 Attached with KDEL

Objective :To investigate the mechanism of phenotypic knockout of CXCR4 on T-cell leukemia cell line Molt-4 via SDF-1α/54/KDEL intrakine technology, which the mutant SDF-1α/54, human stromal cell-derived Faceor-1 (SDF-1α) was deleted its Cterminal α-helix and attached with a endoplasimc reticulum retention signal 4-peptide-KDEL encoding gene, so that retain the newly synthesized receptor CXCR4 within the Molt-4 cells endoplasmic reticulum. Methods: The recombinant vector pEGFP-C3/SDF-1α/54/KDEL were transfected into Cos-7 cells by liposome, SDF-1α/54/KDEL fusion protein was confirmed with western blot. The recombinant plasmids were transfected transiently into Molt-4 by electroporation. Results:Western blot confirmed SDF-1α/54/KDEL expression in Cos-7. A dramatic downregulation of CXCR4 expression on Molt-4 was demonstrated by flow cytometric (FCM) analysis. Conclusion:SDF-1α/54/KDEL and SDF-1αKDEL have no significant deviation for phenotypic knockout of CXCR4. These suggest that the phenotypic knockout effects of SDF-1α/54 against CXCR4 are not influenced by deleting of SDF-1α helix in the C-terminal.     

Adenoid cystic carcinoma of the breast: a case with axillary lymph node metastasis

A breast tumour with proven lymph node metastasis is conclusively characterized as an adenoid cystic carcinoma using immunocytochemistry and electron microscopy. The majority of tumour cells showed certain of the characteristic features of myoepithetial cells while the pseudocystic spaces contained large amounts of reduplicated basal lamina. A small proportion of tumour cells, however, showed epithelial differentiation with the formation of true lumina.     

Lymphangiogenesis in breast cancer is associated with non-sentinel lymph node metastases in sentinel node positive patients

Axillary lymph node dissection (ALND) is not suggested in breast cancer patients with negative sentinel lymph node (SLN) biopsies, and SLN is the only positive node in 40-70% of the remaining cases. To distinguish a subgroup in which ALND would be omitted, we investigated the role of lymphangiogenesis in primary breast cancer as a risk factor for distal lymph node involvements in patients with positive SLNs. 86 patients were included in this study. The frequency of proliferative lymphatic endothelial cells (LECP%) was evaluated in each specimen after immunohistochemical double staining for D2-40 and Ki-67. Larger primary tumor size, increased number of positive SLNs, lymphatic vessel invasion and LECP% were significantly associated with non-SLN metastases in the univariate analysis, but only LECP% retained significance in the multivariate model. A positive correlation between LECP% and lymphatic vessel invasion was also revealed. Our study confirmed the important role of lymphangiogenesis in tumor spread, and suggested that LECP% is a promising predictor for additional axillary lymph node involvements.     

Reduced expression of the cell-cycle inhibitor p27Kip1 is associated with progression and lymph node metastasis of gastric carcinoma

AIMS: p27Kip1 (p27), a cyclin-dependent kinase inhibitor, plays an important role as inhibiting the progression of the cell cycle. Decreased expression of p27 is associated with high histological grade and aggressiveness of several human tumours. We aimed to evaluate the role of p27 in the progression and metastasis of gastric carcinoma. METHODS AND RESULTS: We analysed the expression of p27 in 67 primary gastric carcinomas and 31 lymph node metastases by immunohistochemistry. Reduced expression of p27 was found more frequently in advanced gastric cancer (40.9%) than in early gastric cancer (15.6%) (P < 0.001). Decreased p27 expression correlated with large tumour size, high histological grade, lymphatic invasion, advanced stage, deep invasion, lymph node metastasis and recurrence. The expression of p27 showed an inverse correlation with the Ki67 labelling index. There was a significant reduction of p27 expression in metastatic tumour cells in lymph nodes (mean positive cells: 3. 7%) when compared to the corresponding primary gastric carcinomas (mean positive cells: 8.1%) (P = 0.008). CONCLUSIONS: Alterations of p27 expression may play an important role in the progression and metastasis to lymph node of tumour cells in human gastric carcinoma.     

Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma

AIMS: One important step in tumour invasion is the penetration of the basement membrane. Matrix metalloproteinases (MMPs) play a key role in the migration of normal and malignant cells through the basement membrane. The aim of this study was to investigate correlations between matrix metalloproteinase 2 (MMP-2) immunoreactivity and currently used classification systems and possible relationships between lymph node metastasis and MMP-2 expression. METHODS AND RESULTS: This prospective study analysed specimens obtained from 114 gastric cancer patients (mean age 64 years; range 33-86 years) who underwent gastrectomy with extended lymphadenectomy. All specimens were categorized according to UICC classification, WHO classification, tumour differentiation, Laurén classification, Ming classification and Goseki classification. Formalin-fixed paraffin-embedded tumour specimens were stained using an avidin-biotin complex peroxidase assay. MMP-2 expression in the tumour epithelium was studied by immunohistochemistry with semiquantitative (score 0-3) evaluation. The MMP-2 staining pattern was positive (score 1-3) in 93 (81.6%) specimens and negative (score 0) in 21 (18.4%) samples. No significant correlations were found between MMP-2 expression and other variables such as age, tumour differentiation, WHO, Lauren, Goseki, and Ming classifications. In contrast, the intensity of MMP-2 staining in tumour cells correlated significantly with depth of tumour infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), and UICC stage. CONCLUSIONS: Expression of MMP-2 is strongly associated with tumour progression and lymph node metastasis in gastric cancer. Therefore MMP-2 staining may be clinically useful as predictor of tumour progression, especially for lymph node metastasis.     

超声对乳腺癌腋下淋巴结转移状态评估价值的研究进展

超声技术作为术前评估乳腺癌腋下淋巴结转移(axillary lymph node metastasis,ALNM)状态最常用的方法,可通过二维灰阶图像、血流表现、弹性成像、超声造影等手段根据淋巴结的形态、纵横比、皮质状态、淋巴门表现、血流情况等指标预测淋巴结转移与否.但超声技术受众多影响因素如腋下淋巴结的大小、位置、腋窝深度、医师经验、超声仪器分辨率不同等的限制,其检出率及准确率仍未达到令人满意的水平.因此,如何提高超声对乳腺癌ALNM的评估效能成为亟需解决的问题.     

乳腺癌中Syk、VEGF-C表达与淋巴结转移的关系

目的研究乳腺癌组织中Syk、VEGF-C的表达与淋巴结转移的关系。方法分别采用免疫组织化学EnVision两步法及SP法检测55例乳腺癌组织中Syk、NFκB(p65)及VEGF-C的表达情况。结果55例乳腺癌组织中,Syk、VEGF-C及p65阳性率分别为50.9%,56.4%,81.8%。Syk在淋巴结转移组的表达低于无淋巴结转移组(P0.05);VEGF-C在淋巴结转移组的表达高于无淋巴结转移组(P0.05);p65在两组之间的表达差异无显著性(P0.75),p65胞核移位率在淋巴结转移组高于无淋巴结转移组(P0.025)。随着Syk表达增强VEGF-C的表达减弱,二者呈负相关(r=-0.620,P=0.000);p65胞核移位与Syk的表达强度降低有关(r=0.448,P=0.002),而与VEGF-C的表达强度增高有关(r=0.310,P=0.036)。结论乳腺癌中,Syk可能通过抑制NFκB的活性而下调VEGF-C的表达,从而抑制乳腺癌的淋巴结转移。     

High expression of GPER1, EGFR and CXCR1 is associated with lymph node metastasis in papillary thyroid carcinoma

Clinical and epidemiological studies have shown that estrogen may be involved in the development and progression of papillary thyroid carcinoma (PTC). G protein-coupled estrogen receptor 1 (GPER1) is a novel seven-transmembrane estrogen receptor that functions alongside traditional nuclear estrogen receptors (ERs) to regulate the cellular responses to estrogen. The purpose of this study was to examine GPER1, EGFR and CXCR1 expression in PTC and to assess the association of their expression with clinicopathological indicators. GPER1, EGFR and CXCR1 protein expression in 129 PTCs, 61 nodular hyperplasia and 118 normal thyroid tissue specimens were analyzed using immunohistochemistry. The protein expression levels of these three molecules were up-regulated in PTCs. High protein expression of GPER1, EGFR and CXCR1 was significantly correlated with lymph node metastasis (LNM) (P ≤ 0.001). Furthermore, GPER1, EGFR and CXCR1 protein expression were correlated with one another. Concomitant high expression of these molecules had stronger correlation with LNM than did each alone (P = 0.002 for GPER1/EGFR, P = 0.013 for GPER1/CXCR1, P = 0.018 for EGFR/CXCR1 and P < 0.001 for GPER1/EGFR/CXCR1). Additionally, GPER1, EGFR and CXCR1 mRNA expression was assessed in 30 PTCs, 10 nodular hyperplasia and 10 normal thyroid tissue specimens using real-time RT-PCR. GPER1, EGFR and CXCR1 mRNA expression levels were up-regulated in PTCs, and high mRNA expression of GPER1, EGFR and CXCR1 was significantly correlated with LNM (P < 0.001 for all these three molecules). These results demonstrated that the evaluation of GPER1, EGFR and CXCR1 expression in PTC may be useful in predicting the risk of LNM.     

Increased expression of IRS-1 is associated with lymph node metastasis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China, which is with characteristics of early cervical lymph node metastasis and high incidence rate of distant metastasis. Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that is encoded by the IRS-1 gene in humans, plays an important role in the development, progression, invasion and metastasis of tumors. The aim of the present study was to investigate the association between the expression of IRS-1 protein and clinicopathological characteristics in NPC by immunohistochemistry. The results showed that the expression level of IRS-1 was significant higher in NPC than that in the control nasopharyngeal epithelia (P = 0.042). The positive percentage of IRS-1 expression in NPC with lymph node metastasis was also significantly higher than those without lymph node metastasis (P = 0.008). Positive expression of IRS-1 was proved to be the independent predicted factor for lymph node metastasis of NPC (P = 0.025) regardless of age, gender, histological type and clinical stages by multivariate logistic regression analysis. In addition, results showed higher sensitivity and agreement rate of IRS-1 for predicting lymph node metastasis of NPC patients. Taken together, high expression of IRS-1 might be closely correlated with lymph node metastasis in NPC and positive expression of IRS-1 could be used as an independent biomarker for predicting lymph node metastasis of NPC.     

Tumor size of breast invasive ductal cancer measured with contrast-enhanced ultrasound predicts regional lymph node metastasis and N stage

Purpose: This study aimed to determine the role of breast invasive ductal cancer (BIDC) size measured with Contrast-enhanced Ultrasound (CEUS) in the prediction of regional lymph node metastasis (LNM) and N stage. Methods: One hundred and six consecutive patients with breast lesions underwent ultrasound imaging within 2 weeks before mastectomy and axillary lymph node dissection. The largest transverse (width) and anteroposterior (depth) diameter were measured under CEUS by using calipers. The correlation between tumor size and regional LNM metastasis and N stage was evaluated. Results: Univariate analysis showed the diameters measured with CEUS were associated with lymph node metastasis (P < 0.05). The tumor size could distinguish grouped N stage (all P < 0.05). Tumor area (TA) might be an indicator that can differentiate No BIDC from N1-3 BIDC (cutoff = 5.37 cm²), N0-1 BIDC from N2-3 BIDC (cutoff = 6.48 cm²), and N0-2 BIDC from N3 BIDC (cutoff = 8.23 cm²) with the sensitivity of 71%, 72% and 83%, respectively, and the specificity of 79%, 68% and 84%, respectively. Conclusions: The TA of BIDC measured with CEUS may be a predictor of regional LNM and N stage.     

乳腺癌前哨淋巴结活检术中不同染色淋巴结与肿瘤转移的关系

目的探讨乳腺癌前哨淋巴结活检术(SLNB)中不同染色情况的淋巴结与肿瘤转移的关系。方法选择我院2014年1月至2018年1月行前哨淋巴结活检的乳腺癌患者92例,以亚甲蓝为示踪剂,根据92例乳腺癌患者SLNB中淋巴结染色情况的不同分为无染色组、完全染色组和染色不均组,病理检测3组患者淋巴结的肿瘤转移情况并作比较。结果92例乳腺癌SLNB共取得淋巴结256枚,平均每例患者2.8枚,无染色组(80枚)肿瘤转移率为13.8%,完全染色组(112枚)肿瘤转移率为43.8%,染色不均组(64枚)肿瘤转移率为62.5%,3组间肿瘤转移率差异有统计学意义(P<0.05)。结论乳腺癌SLNB中染色不均的淋巴结最易出现肿瘤转移,其次为完全染色的淋巴结,染色淋巴结附近看到的未染色淋巴结也有肿瘤转移的可能,宜一并切除送检,有利于降低假阴性率。     

Overexpression of cytokeratin 17 is associated with the development of papillary thyroid carcinoma and the presence of lymph node metastasis

Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, appears to play an important role in the progression of several human malignancies. Increased CK17 expression has previously described in cases of papillary thyroid carcinoma (PTC). However, no studies to date have investigated the clinical significance of CK17 expression in patients with PTC. The aim of this study was to compare the expression of CK17 in patients with PTC with that observed in normal thyroid tissue and benign thyroid lesions, and to examine the relationship between CK17 expression and clinicopathologic characteristics of patients with PTC. CK17 protein expression was evaluated by immunohistochemistry on tissue microarrays containing thyroid tissue samples from 108 PTCs, 16 nodular goiters, and 81 healthy controls. Sixty-five of the 108 (60.2%) PTC tissue samples exhibited positive CK17 expression, whereas all nodular goiters and normal thyroid tissue samples showed a complete absence of CK17 immunoreactivity. The difference in frequency of CK17 positivity between PTC (65/108, 60.2%), normal thyroid tissue (0/81, 0.0%), and benign thyroid lesions (0/16, 0.0%) was statistically significant (P<0.001). Positive CK17 expression in PTC was significantly associated with the presence of lymph node metastasis (P=0.024) and higher pN stage (P=0.028). Expression of CK17 is significantly increased in cases of PTC compared to normal tissue and benign thyroid lesions, and CK17 overexpression is associated with the presence of lymph node metastasis in patients with PTC. These findings suggest that CK17 is involved in the development and metastasis of PTC.     

Tenascin-C expression in Merkel cell carcinoma lymph node metastasis

Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20. All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate.