Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study

Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent ( P  < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor ( P  < 0.05, P  < 0.01), a higher frequency of HER-2 overexpression ( P  < 0.025), and more frequent lymph node metastases ( P  < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains ( P  < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.     

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.     

Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast

Aims:  Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are implicated in tumour chemotaxis and metastasis. The aim was to examine their roles in the metastasis of invasive micropapillary carcinoma (IMPC) of the breast, a tumour with a high propensity for nodal spread.
Methods and results:  We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH). The results showed that the predominant cytoplasmic expression of both SDF-1 and CXCR4 was greater in tumour cells of the IMPC components than in those of the non-IMPC components and the control IDC cases, and was correlated significantly with the number of positive lymph nodes ( P  < 0.05). SDF-1 expression on cell membranes was less frequently identified in IMPC than IDC ( P  = 0.021). Immunohistochemical detection of SDF-1 in endothelial cells of lymphatic vessels was more common in IMPC ( P   =  0.007) and correlated significantly with lymph node status ( P  = 0.002), although SDF-1 mRNA was rarely detected by CISH.
Conclusions:  This study suggests that up-regulation of cytoplasmic expression of SDF-1/CXCR4 might be one of the molecular mechanisms facilitating lymph node metastasis of IMPC.     

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.     

Pleomorphic ductal carcinoma of the breast with predominant micropapillary features

An 83-year-old woman with long-standing chronic ischemic cardiac and obstructive pulmonary disease, presented with a painless tumor in her right breast. Microscopically the tumor consisted of micropapillary formations and loosely cohesive nests and strands of large, highly pleomorphic cells. Micropapillary formations were surrounded by peritumoral retraction clefting, and the papillae lacked a true fibrovascular core. Multinucleated giant and bizarre tumor cells were also present and numerous. Within the tumor a high-grade intraductal component with the same cell morphology and necrosis and mucin production was found. Micropapillary pattern occupied approximately 60% of the tumor mass, loosely cohesive nests and strands approximately 20% and an intraductal component was noted in approximately 20% of the tumor mass. On immunohistochemistry the tumor cells were positive for pan-cytokeratin, epithelial membrane antigen (EMA), S100 protein and E-cadherin while estrogen and progesterone receptors, HER2-neu and Bcl2 were negative. EMA staining was diffuse and observed in the outer and inner margins of neoplastic nests. The diagnosis of pleomorphic breast carcinoma with predominant micropapillary features was established. In summary, micropapillary carcinoma can be distinguished from other types of breast carcinoma with micropapillary growth pattern on the basis of reverse cell polarity, which is easily confirmed on immunohistochemistry.     

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.     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast

AIM: To determine the pathognomonic diagnostic cytological features of invasive micropapillary carcinoma of the breast which is a poor prognostic subtype of infiltrating ductal carcinoma. METHODS: A series of 20 histologically proven tumours were reviewed retrospectively to evaluate the various cytological features, including tumour morules, isolated malignant cells, staghorn epithelial structures, mucinous background and apocrine metaplasia. RESULTS: Tumour morules formation and isolated malignant cells were the two most reliable and constant cytological features, being present in 75% (15/20 cases) of cases. Staghorn epithelial structures were present in 35% (7 cases). Mucinous background (2 cases, 10%) and apocrine metaplasia (4 cases, 20%) of the tumour cells were seen in a few cases only and did not appear very helpful. CONCLUSION: Tumour morules formation, isolated malignant cells and staghorn epithelial structures are the most reliable cytological features, and the presence of these should raise suspicion of invasive micropapillary carcinoma.     

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。     

乳腺浸润性微乳头状癌临床病理因素的研究现状

目的 探讨年龄、肿瘤大小、组织学及核分级、腋淋巴结、激素受体、生长因子受体及细胞增值率等临床病理因素在乳腺浸润性微乳头状癌（IMPC）发生、发展、转移及预后的评估中的意义.方法 应用Pubmed及CNKI数据库系统以“IMPC”为关键词检索文献,筛选出相关一次文献,对文献进行分析.结果 IMPC中肿瘤大小、IMPC成分的比例、共存病灶的病理类型和组织学分级均与淋巴结转移的发生率无关;IMPC独特的形态学特征和间质淋巴细胞浸润可能是其高侵袭性的原因所在;IMPC中雌激素受体（ER）和人类表皮生长因子受体2（HER2）阳性表达比率高,其中,ER阳性表达可作为一个积极预后指标.结论 对IMPC这一特殊亚型认识还比较肤浅,随着研究的不断深入,IMPC的诊治状况将得到进一步的改观.     

Expression of vascular endothelial growth factor-C and its receptor in invasive micropapillary carcinoma of the breast

Invasion to lymphatic vessels and metastasis to lymph nodes are frequent complications in invasive micropapillary carcinoma (IMPC) of human breast cancer. Vascular endothelial growth factor-C (VEGF-C) and its receptor, VEGFR-3 have been implicated as the important factors in the formation of lymphatic vessels and recent experimental evidence strongly suggests that lymphangiogenesis in tumor promotes lymphatic metastasis. To clarify the mechanism of its occurrence, the expression of VEGF-C, VEGFR-3 and lymphatic vessel density (LVD) was examined in 40 cases of IMPC (pure and mixed type) and in 40 cases of pseudo-IMPC. Cytoplasmic expression of VEGF-C and VEGFR-3 were more frequent in tumor cells of IMPC compared to those of pseudo-IMPC. A significant positive correlation was found between the expression of VEGF-C and VEGFR-3 in both IMPC and pseudo-IMPC. The expression of VEGF-C was also significantly associated with higher peritumoral LVD, lymphatic invasion and number of lymph node metastasis in IMPC. These findings suggest that VEGF-C promotes the proliferation of peritumoral lymphatic vessels and that lymphatic invasion and metastasis to lymph nodes are frequently induced in IMPC of breast.     

乳腺浸润性微乳头状癌的病理学特征与淋巴结转移的关系

目的研究乳腺浸润性微乳头状癌(IMPC)的病理学特征与淋巴结转移的关系。方法观察51例乳腺IMPC的主要病理学特征及淋巴结转移情况,采用免疫组织化学方法(LSAB法)检测IMPC中血管内皮生长因子(VEGF)-C和VEGF受体(R)-3的表达并计数淋巴管密度,分析其与淋巴结转移的关系。结果(1)乳腺IMPC病理组织学分级Ⅱ、Ⅲ级组的淋巴结转移数平均12.5个,明显高于Ⅰ级组的4.0个;(2)间质淋巴细胞浸润(+)和(++)组的淋巴结转移率(27/28,96.4%)明显高于(-)和(±)组(14/23,60.9%),且其淋巴结转移数平均14.4个,也明显高于(-)和(±)组的4.6个;(3)IMPC肿瘤细胞的VEGF-C表达在病理组织学分级Ⅱ、Ⅲ级组显著高于Ⅰ级组(P=0.03),VEGF-C的表达与淋巴结转移呈正相关(P=0.006);淋巴管密度与VEGF-C表达(P=0.009)、淋巴结转移(P=0.007)呈正相关;(4)肿瘤组织中IMPC成分的多少与淋巴结转移无显著性关系,淋巴结转移灶为纯IMPC或以IMPC成分为主;(5)28例伴有导管原位癌的IMPC中,14例为微乳头状型导管原位癌(14/28,50%)。结论乳腺IMPC的病理组织学分级、淋巴管密度及间质淋巴细胞浸润可能是影响IMPC淋巴结转移的关键性因素。VEGF-C和VEGFR-3表达增高是促使IMPC发生淋巴结转移的重要原因。微乳头状型导管原位癌可能是IMPC的早期阶段。     

Primary invasive micropapillary carcinoma of the stomach

Reported herein is the case of a 74-year-old man with an unusual gastric carcinoma that developed at the lesser curvature of the stomach. The tumor consisted of small clusters of carcinoma cells surrounded by clear spaces, with histopathology similar to invasive micropapillary carcinoma (IMPC) of the breast. The carcinoma cells, which had downregulation of E-cadherin expression, invaded the subserous tissue and metastasized to the perigastric lymph nodes. IMPC, an unusual subtype of invasive breast carcinoma, is known to have frequent lymph node metastases, resulting in a poor clinical outcome. Although IMPC has been reported in breast, urinary bladder, ureter, lung, salivary gland and colon, to the best of the authors' knowledge this is the first report of IMPC arising in the stomach. Presented here are the clinicopathological features of primary IMPC of the stomach.     

Intracytoplasmic lumina in invasive micropapillary carcinoma of the lung

Micropapillary carcinoma of the lung is a rare neoplasm, and several reports on micropapillary carcinoma of the lung have been presented to date. We present a case of micropapillary carcinoma of the lung here. A 75-yr-old Japanese man received the medical checkup and his chest X-ray disclosed the abnormal shadow of the lower lobe of the left lung. The histological examination of resected lung and extirpated lymph node showed the finding of micropapillary carcinoma. Some neoplastic cells of primary site contained intracytoplasmic lumina positive for Alcian blue and PAS stains. Pleural effusion appeared 9-mo after the operation. The cytology of pleural effusion showed cohesive clusters of neoplastic cells consisting of 3-20 cells without fibrovascular core. Additionally, intracytoplasmic lumina were observed in some neoplastic cells. Finally, carcinoma cells with micropapillary morphology may possess the intracytoplasmic lumina in the cytoplasm of metastatic site as well as primary site.     

Overexpression of TNF-alpha and TNFRII in invasive micropapillary carcinoma of the breast: clinicopathological correlations

Aims: Angiogenesis is essential for tumour growth and metastasis and tumour necrosis factor (TNF)‐α is a potent angiogenic factor. Invasive micropapillary carcinoma of the breast (IMPC), a rare subtype of breast cancer, possesses a lymphotropic nature with a high incidence of lymph node metastasis and poor prognosis. The aim was to evaluate the role of TNF‐α and its receptor TNFRII in the vascular development and metastasis of IMPC. Methods and results: One hundred cases of IMPC and 97 cases of invasive ductal carcinoma, not otherwise specified (IDC) were studied in parallel by immunohistochemistry for TNF‐α and TNFRII, and microvessel density (MVD) of the tumours was measured. The results showed that the expression of TNF‐α and TNFRII and the MVD were higher in IMPC than in IDC (P < 0.05). In IMPC, MVD was significantly increased in those with lymph node metastasis compared with those without nodal metastasis (P = 0.001). TNF‐α expression showed a significant positive correlation with the rate of proliferation, histological grade, lymph node metastasis and MVD (P < 0.05), whereas expression of TNFRII was correlated with TNF‐α expression and the proliferation of tumour cells in IMPC (P < 0.05). Conclusions: Expression of TNF‐α and TNFRII might play an important role in the angiogenesis, tumour cell proliferation and metastasis of IMPC. These markers could represent new targets for therapeutic intervention, i.e. blocking of TNF‐α and its signal transduction could be a promising tool for treatment.     

Invasive lobular carcinoma of the breast: incidence and variants

The criteria for the separation of invasive lobular and ductal carcinomas are analysed. Lobular tumours account for 14% of invasive cancers in our material. The widely differing figures given in the literature are mainly attributable to intrinsic difficulties of classification. In addition to the classical dissociated-cell patterns with single filing, a tragetoid appearance and related features, variants with trabecular, loose alveolar and tubular features are recognized; a 'solid' variant requires further investigation. The variants either represent better differentiated forms, or in some cases, an 'earlier' phase in the production of the more traditional Indian file formations and dartboard patterns. Focal signet-ring cell differentiation is another newly-recognized feature. The theoretical and practical implications of these variants are considered. The division into invasive lobular and ductal carcinomas is not as easy as most of the literature implies. Five per cent of cases could not be so classified and, in some of these unclassified cases, both ductal and lobular differentiation may be present. In the diagnosis of problem cases, no single parameter proved reliable but a combination of several parameters enables one to make an objective diagnosis in about 95% of cases.     

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.     

乳腺小管癌与浸润性导管癌中NY-BR-1表达的对比观察

目的 探讨乳腺癌分化抗原NY-BR-1在乳腺小管癌中的表达,并与其在浸润性导管癌中表达进行对比.方法 收集29例小管癌和101例浸润性导管癌石蜡标本,采用免疫组化PV-9000通用型两步法分别进行NY-BR-1、ER、PR、Her-2、Ki-67、nm23、MDR-1及LRP的研究.结果 NY-BR-1在乳腺小管癌和浸润性导管癌中的表达率分别为51.7%、49.5%.NY-BR-1与组织学分化程度密切相关,其在浸润性导管癌组织学Ⅰ～Ⅲ级的阳性率逐渐降低分别为60%、52%、17%.NY-BR-1在小管癌中的表达明显高于浸润性乳腺癌组织学Ⅲ级的表达,差异有统计学意义(P<0.05).NY-BR-1在小管癌和Luminal A型乳腺癌中的表达无差异,在小管癌和浸润性导管癌组织学Ⅰ、Ⅱ级中的表达无差异.NY-BR-1与ER(rs=0.286,P=0.004)、PR(rs=0.252,P=0.010)的表达呈正相关.结论 作为分化抗原的一种,NY-BR-1在低分化的高级别癌中的表达率低,而在高分化的低级别癌中的表达率高.本研究结果显示NY-BR-1在小管癌和低级别浸润性导管癌中的表达率相似,提示小管癌与低级别、luminal型乳腺癌之间具有相似的组织学分化程度.     

A rare case of secretory breast carcinoma in a male adult with axillary lymph node metastasis

Secretory breast carcinoma is a rare tumor originally described in children but occurring equally in adult population, especially in women. This unusual subtype has a generally favorable prognosis, although several cases have been described in adults with increased aggressiveness and a risk of metastases even death. So far, merely ten cases of secretory breast carcinoma with metastatic axillary lymph node in male were reported. Here, we describe the eleventh case, a 24-years-old male who presented with a painless mass in the right breast was diagnosed to be “secretary breast carcinoma”, and subsequently underwent modified radical mastectomy and adjuvant chemotherapy.     

Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survival

Aims: To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node‐positive, hormone treatment‐naive patients undergoing radical prostatectomy and extended lymphadenectomy. Methods and results: The median number of nodes examined per patient was 21 (range 9–68), and the median follow‐up time was 92 months (range 12–191). ENE was observed in 71 patients (70%). They had significantly more, larger and less differentiated nodal metastases, paralleled by significantly larger primary tumours at more advanced stages and with higher Gleason scores than patients without ENE. ENE defined a subgroup with significantly decreased biochemical recurrence‐free (P = 0.038) and overall survival (P = 0.037). In multivariate analyses the diameter of the largest metastasis and Gleason score of the primary tumour were independent predictors of survival. Conclusions: ENE in prostatic cancer is an indicator lesion for advanced/aggressive tumours with poor outcome. However, the strong correlation with larger metastases suggests that ENE may result from their size, which was the only independent risk factor in the metastasizing component. Consequently, histopathological reports should specify the true indicator of poor survival in the lymphadenectomy specimens, which is the size of the largest metastasis in each patient.