乳腺浸润性微乳头状癌的研究现状与进展

乳腺浸润性微乳头状癌是乳腺癌的一种少见类型,除了其独特的组织形态学表现外,该肿瘤具有较高的浸润性和转移潜能,高度的淋巴管侵袭和淋巴结转移是其最主要的特征,并且预后不良。     

Invasive micropapillary carcinoma of breast: an under-recognized entity. a series of eight cases

Invasive micropapillary carcinoma (IMPC) of breast is a morphologically distinct and relatively uncommon variant of invasive ductal carcinoma. It is characterized by small clusters of tumor cells with surrounding clear stromal spaces; a tendency for vascular permeation and therefore, an aggressive clinical course. This morphologic pattern can be easily missed especially in a small biopsy specimen because pathologists may disregard the clear spaces as artifactual. With a tendency of presenting at a higher stage, this morphological pattern needs to be mentioned in the histopathology report whenever it is encountered, either in its pure form or admixed with conventional ductal carcinoma. We describe eight cases of IMPC of breast along with their variable clinical presentations.     

Prognosis of invasive micropapillary carcinoma compared with invasive ductal carcinoma in breast: A meta-analysis of PSM studies

BackgroundInvasive micropapillary carcinoma (IMPC) is a rare histological subtype of breast cancer. The outcome of IMPC remains controversial; we conducted a meta-analysis of propensity score matching (PSM) studies to evaluate the prognostic difference between IMPC and invasive ductal carcinoma (IDC).MethodsWe searched PubMed, EMBASE and the Cochrane library for PSM studies comparing survival data between IMPC and IDC. The summarized odds ratios (ORs) and 95% confidence interval (95% CI) are calculated by STATA software utilizing fixed-effect or random-effect models, depending on the heterogeneity of the eligible studies.ResultsEight PSM studies including 2102 IMPC patients are included in the meta-analysis. Compared with IDC, IMPC has a similar overall survival (OS) (estimated OR = 0.87, 95% CI: 0.61–1.25), but a shorter relapse free survival (RFS) (estimated OR = 1.31, 95% CI: 1.06–1.61); the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC (estimated OR = 3.60, 95% CI: 1.99–6.52). Funnel plots and Egger’s tests are used to evaluate publication bias and the p value for OS and RFS are 0.036 and 0.564 respectively.ConclusionsOur results demonstrate that compared with IDC, IMPC exhibits a similar, even favorite OS, but a shorter RFS; and the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC. These results could contribute to the individualized therapy and follow-up strategies for IMPC patients.     

Presence of a micropapillary pattern in mucinous carcinomas of the breast and its impact on the clinical behavior

Infiltrating micropapillary carcinomas (IMPC) of breast are highly angioinvasive tumors with poor prognosis. This study is based on the observation that a similar micropapillary pattern is also observed in mucinous carcinomas of breast. About 102 mucinous carcinomas were evaluated for the presence and impact of this micropapillary pattern on the clinical behavior. Of these, 68 were mucinous carcinomas with a micropapillary pattern (MUMPC), 20 had MUMPC mixed with an infiltrating duct carcinoma component, two were solid variants of papillary carcinoma with mucin (SVPCMU), five had collision of the MUMPC and SVPCMU patterns and seven were mucinous carcinomas with signet ring cells (MUS). The factors negatively affecting overall survival (OAS) and disease-free survival (DFS) included the histological type of mucinous carcinoma, nodal metastases, an irregular tumor border, <50% mucin and an IMPC type of local recurrence or metastases. In the multivariate analysis, the histologic type of mucinous carcinoma and an irregular tumor border were most significant for OAS and DFS. Thus, 86% of mucinous carcinomas in this study were mucinous variants of the angioinvasive infiltrating micropapillary carcinomas. These tumors can produce IMPC type of metastases and thus should be treated aggressively.     

Outcomes of patients with invasive mucinous and tubular carcinomas of the breast

Invasive tubular carcinoma (ITC) and invasive mucinous carcinoma (IMC) of the breast are rare histologic subtypes of breast cancer associated with favorable prognoses. The aim of our study was to investigate the outcomes for these rare subtypes using the National Cancer Database. Female patients diagnosed with ITC or IMC between 2005 and 2014 were analyzed. The primary outcome was overall survival (OS), and we analyzed its association with adjuvant therapy. 2735 patients with ITC and 5602 patients with IMC were identified. ITC presented in younger patients (57 vs. 67 years), had smaller tumors (size <1 cm, 63.1% vs. 25.4%), earlier stage, and less node-positive disease (5% vs. 8.6%), compared with IMC. Older age, government insurance, lower income, treatment in a community cancer program, large tumor size, positive nodal status, and without endocrine therapy were associated with worse OS with either subtype on multivariate analysis. No OS benefit was found for node-positive ITC that received adjuvant chemotherapy compared with those who did not. (5-year OS of 96.0% vs. 91.3%, p = 0.17).OS was improved for IMC that received adjuvant chemotherapy (10-year OS: 82.5% vs. 60.1%, p = 0.008) and endocrine therapy (10-year OS: 86.6% vs. 81.2%, p < 0.001). We concluded that ITC has favorable clinicopathological characteristics and prognosis, even with node-positive disease. ITC and IMC may need to be evaluated independently when administering adjuvant treatment plans.     

Micropapillary variant of mucinous breast carcinoma: A distinct subtype

Invasive micropapillary carcinoma of the breast is a subtype with high malignant potential characterized by lymphovascular invasion (LVI) and a predilection for axillary lymph node (AXLN) metastases. In contrast, pure mucinous breast carcinoma (MBC) is relatively indolent with low metastatic potential. Recent studies have described a histologic variant of breast cancer that displays combined mucinous and micropapillary patterns, ie, micropapillary variant of mucinous carcinoma (MpVMBC). This underrecognized variant is, as yet, incompletely characterized clinicopathologically. Extant reports suggest a more aggressive lesion than pure MBC with greater propensity for both LVI and AXLN metastases. Here we present our institution's experience with MpVMBCs including clinicopathologic and immunohistochemical (IHC) analyses. Greater awareness and recognition of this variant could positively contribute to patient care by (1) avoiding underestimation of malignant potential for individuals whose tumors may have been diagnosed as simply “MBC, not otherwise specified”, and (2) recommending a postsurgical adjuvant approach emphasizing the hormone receptor targets, even perhaps in younger women presenting with AXLN positive disease.     

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long‐term survival analysis

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl‐2 regarding prognosis. Sixty‐nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow‐up data, were collected to analyze ARID1A and bcl‐2 expressions immunohistochemically with prognosis. The median follow‐up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor‐2 (Her‐2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4‐26.6, P=.02; HR=15.9, 95% CI 3.5‐71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1‐14.9, P=.04; HR=7.2, 95% CI 2‐25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year‐OS (P=.001) and 10 year‐DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her‐2 positivity have significant adverse effect clinical outcomes of IMPC patients.     

乳腺浸润性小叶癌的诊断与治疗现状

乳腺浸润性小叶癌以癌细胞突破乳腺小叶内末梢乳管或腺泡基底膜而向小叶间质浸润性生长为主要特点。患者诊断时通常具有如下特点:年龄和肿瘤较大,腋窝淋巴结转移率较高,健侧容易发生。乳腺浸润性小叶癌通常具有较好的预后表型,低级别的组织学分级,较低的有丝分裂指数。浸润性小叶癌具有较高的侵袭性和广泛转移增殖倾向,与其它浸润性癌比较,预后较差。     

Papillotubular carcinoma with an invasive micropapillary carcinoma component of the breast,characterized by a rapid increase in size due to intra-tumoral hemorrhage: A case report

IntroductionRapidly enlarging mammary tumors, including invasive breast tumors, are clinically rare. Invasive micropapillary carcinoma (IMPC) of the breast is known to have aggressive behavior and poor clinical course compared to invasive ductal carcinoma.Case presentationAn 87-year-old woman presented with a rapidly enlarging tumor of the right breast over the course of 3 weeks. Ultrasonography and computed tomography of the chest revealed a giant tumor located on the right chest wall, with heterogeneous parenchymal components and several cystic lesions. Emergency mastectomy was performed because of rapid tumor enlargement complicated by hemorrhage. Histopathological diagnosis confirmed a papillotubular invasive ductal carcinoma with an IMPC component. Tumor cells were negative for estrogen and progesterone receptors, and the human epidermal growth factor receptor 2 score was 2+.DiscussionThere has been only one report of breast carcinoma with rapid enlargement caused by spontaneous intratumoral hemorrhage to date. IMPC is associated with a high incidence of axillary lymph node metastases, frequent local recurrence, and a poor clinical outcome. In the present case, the specific breast cancer type can be considered as potential factors responsible for hemorrhage induction within the tumor that further enhanced rapid tumor growth.ConclusionIMPC is a rare, clinically aggressive variant of invasive ductal carcinoma. Owing to its aggressive clinical behaviors, surgeons should readily recognize the morphology of IMPC.     

乳腺浸润性微乳头状癌与浸润性导管癌的临床病理对照研究

目的 探讨浸润性微乳头状癌(invasive micropapillary carcinoma,IMPC)和浸润性导管癌(invasive ductal carcinoma,IDC)的差异,分析乳腺浸润性微乳头状癌的临床病理及免疫组化特点.方法 回顾性分析2004年10月至2007年11月51例浸润性微乳头状癌患者临床病理资料.选取同期临床病理资料完整的102例浸润性导管癌患者做对照.结果 浸润性微乳头状癌和浸润性导管癌的乳头侵犯、淋巴管侵犯、淋巴结转移率、淋巴结转移水平、软组织侵犯、雌激素受体(estrogen receptor,ER)、孕激素受体(progestin receptor,PR)、三阴(ER,PR,HER2均为阴性)表达差异有统计学意义(P＜0.05).而闭经状态、发病侧别、淋巴结转移个数、人类表皮生长因子受体2(human epidermal growth factor receptor-2,HER2)表达及局部复发和远处器官转移差异无统计学意义.浸润性微乳头状癌组中位随访时间46个月(16～ 75个月),3年生存率和无病生存率分别为90.2％和84.3％.结论 浸润性微乳头状癌是一种呈现侵袭性生长方式的少见乳腺癌类型,具有嗜淋巴特性和易发结外软组织侵犯的特点.乳腺浸润性微乳头状癌高表达激素受体,三阴乳腺癌比例较少.     

Impact of neoadjuvant and adjuvant chemotherapy on invasive lobular carcinoma: A propensity score‐matched analysis of SEER data

Invasive lobular carcinoma (ILC) has a different treatment response from invasive ductal carcinoma (IDC). We assessed whether perioperative chemotherapy was associated with improved prognosis in patients with ILC. Retrospective data of women who underwent surgery for ILC were extracted from the SEER database. Subjects were divided into non‐chemotherapy and chemotherapy groups. Overall, 10 537 patients were included, and 2107 patients were stratified into each group after propensity score matching. Perioperative chemotherapy significantly improved 10‐year survival rates for ILC, particularly in patients with large tumor size and lymph node metastases. Perioperative chemotherapy is effective for ILC patients with proper selection.     

The survival benefit of postmastectomy radiotherapy for breast cancer patients with T1-2N1 disease according to molecular subtype

ObjectiveTo evaluate the significance of postmastectomy radiotherapy (PMRT) in female breast cancer patients with T1-2N1M0 disease according to molecular subtypes and other risk factors.MethodWe conducted a retrospective cohort-based study utilizing the Surveillance, Epidemiology, and End Results database. Patients who were diagnosed with T1-2N1M0 invasive breast cancer and received mastectomy between 2010 and 2014 were enrolled in our study. Overall survival (OS) was calculated with Kaplan-Meier method, and multivariant Cox hazard model was conducted to identify the impact of PMRT according to molecular subtypes and other risk factors. Propensity score matching (PSM) was applied to balance measurable confounders.ResultsOf all the 16,521 enrolled patients, 5775 (35.0%) cases received PMRT. The distribution of molecular subtype is 71.4% for Luminal A, 13.2% for Luminal B, 5.1% for HER2 enriched, and 10.3% for TNBC. The OS was significantly better for patients in PMRT group than the Non-PMRT group (P < 0.0001). Stratified by molecular subtype, PMRT significantly prolonged survival in Luminal A patients (HR: 0.759, 95% CI: 0.651–0.884, P < 0.001), Yet it brought no significant survival advantage in Luminal B, TNBC or HER2 enriched subtype (P = 0.914, P = 0.124, P = 0.103, respectively). Also, PMRT bore prognostic significance among those patients who were older than 56 years old, single, white, exempt from reconstruction and chemotherapy, and were with ductal, GradeⅡtumor (all P < 0.05). After PSM, the survival benefit of PRMT sustained in Luminal A patients with T1 tumor concomitant with one positive lymph node.ConclusionOur study demonstrates a beneficial impact for PMRT on overall survival among Luminal A subtype breast cancer patients with T1-2N1 disease. The selection of PMRT should be stratified by molecular subtype and other risk factors.     

Elevations of DNA topoisomerase I in invasive carcinoma of the breast

Abstract: DNA topoisomerase I (topo I) is the molecular target of the camptothecin group of anticancer drugs. Laboratory experiments indicate that breast cancer cell lines are sensitive to these agents and recent clinical trials have suggested that some breast cancer patients may respond to drugs targeting topo I. Since it is known that cells responding to topo I-targeted drugs have elevated levels of topo I, these results suggest that some breast cancers may have elevated expression of the enzyme. To test this we used a new topo I monoclonal antibody to immunostain 22 primary breast cancers and 5 lymph nodes with metastatic disease. Tissue was fixed in formalin and paraffin embedded. Expression of topo I was subjectively determined by noting the intensity of the immunostain. We found increased expression of topo I in 41% (9/22) of the primary tumors. We conclude that immunohistochemical staining of breast cancers for topo I can be easily performed and may help in defining the molecular parameters of those neoplasms sensitive to drugs targeting the en-zyme.     

The impact of lymph node metastases on the survival of breast cancer patients with ten or more positive lymph nodes

To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10–15 nodes, or the 11 with 16–25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%–75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with <50% or >75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.     

Bilateral breast carcinoma: clinical characteristics and its impact on survival

The higher incidence of breast cancer, the improvements in diagnosis and treatment, together with the growing life expectancy have brought about an increase in the number of patients at risk for bilateral breast carcinoma. The aim of this study is to describe the characteristics of patients suffering from bilateral breast carcinoma who underwent surgery at the Breast Pathology Service of the Buenos Aires British Hospital and to analyze impact on survival. Between January 1970 and May 2007, 4,085 cases of breast carcinoma in 3,864 patients were treated at the Breast Diseases Division of the Buenos Aires British Hospital. A retrospective study of 194 patients with bilateral breast carcinoma was carried out: 80 synchronous and 114 metachronous. In order to compare survival, a group of 2,237 patients with unilateral breast carcinoma who had undergone surgery was analyzed. The risk of developing a contralateral breast carcinoma was 0.9% per year, with an accumulated risk at 15 years of 12.75%. The 5-year survival was 85.9% for unilateral carcinomas, 94.6% for metachronous carcinoma, and 63.3% for synchronous carcinoma. The 15-year survival was 65.5% for unilateral carcinomas, 52.3% for metachronous, and 37.2% for synchronous. The incidence of bilateral carcinomas is low. Survival was worse in patients with metachronous carcinoma diagnosed within 5 years of the first malignancy. Survival in patients with metachronous carcinoma diagnosed after 5 years is similar to those with unilateral carcinoma. Synchronous carcinoma was associated to worse survival, being an independent risk factor for mortality.     

The case for the omission of axillary staging in invasive breast carcinoma that exhibits a predominant tubular growth pattern on preoperative biopsy

True invasive tubular breast carcinoma (TBC) is unlikely to metastasize to axillary nodes, yet it is routinely subjected to sentinel lymph node biopsy (SLNB), even if the diagnosis was suspected preoperatively. The positive predictive value (PPV) of core biopsy for TBC and the incidence and predictors of axillary metastasis in invasive breast carcinomas identified as tubular‐rich on core biopsy are unknown. Prospective patient and tumor data regarding postoperatively confirmed TBCs, and tubular‐rich carcinoma identified on preoperative core biopsy between January 2005 and May 2016 was analyzed retrospectively. Axillary metastasis occurred in only 4.2% (4/95) of TBCs, all of which measured >15 mm pathologically. In 11.1% (11/99) of TBCs, the initial core biopsy was either indeterminate/suspicious or ductal carcinoma in situ (DCIS); therefore, their true tubular histotype and size were ascertained following operative excision and before SLNB. Nine were ≤15 mm, and all were node‐negative. Only 63.9% (46/72) of tubular‐rich core biopsies were confirmed as TBCs; the remaining 36.1% (26/72) were well‐differentiated invasive nontubular carcinomas. None of the preoperative patient or tumor features were predictive of true TBC on multivariable analysis; 10.1% (7/69) of carcinomas identified as tubular‐rich on core biopsy (regardless of their true histotypes) were node‐positive; 23.1% (6/26) in nontubular and 2.3% (1/43) in true tubular carcinomas. Preoperative ultrasound size >15 mm was associated with axillary metastasis in 40.0% (4/10) compared to 5.7% (3/53) in those ≤15 mm (OR = 11.11, 95% CI = 1.99‐62.04; multivariable P = .010). Axillary metastasis in TBC is dependent on pathological size; therefore, a case is made for omitting SLNB in small true TBCs confirmed following excision. Preoperative tubular‐rich core biopsy is not adequately diagnostic of TBC; however, it selects carcinomas that are well‐differentiated, small, and unlikely to metastasize to the axilla, thus allowing for the selective omission of SLNB.     

浸润性乳腺癌分子分型与辅助化疗方案选择

随着基因表达谱与基因芯片技术的开展,乳腺癌在分子水平上表现出的高度异质性也逐渐受到关注。不同分子分型的乳腺癌,其流行病学危险因素、疾病自然进展过程以及对全身或局部治疗的反应性都不尽相同;对于乳腺癌的准确分型能够较为精确地反映肿瘤的生物学行为,对于判断预后、制定更具个体化的治疗策略具有深刻的意义。2011年的St.Gallen共识已针对不同的乳腺癌分子分型给出了原则性的治疗建议,标志着乳腺癌的治疗已逐步进入了在规范化多学科综合治疗模式的基础上,倡导个体化治疗的时代。     

Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: A multi-institutional investigation

Purpose

To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy.

Colonic micropapillary carcinoma,a recently recognized subtype associated with histological adverse factors: clinicopathological analysis of 15 cases

Aim Micropapillary carcinoma (MPC) is regarded as an aggressive variant of adenocarcinoma in any location. The reported proportion of a micropapillary carcinoma component in an entire tumour ranges from 5 to 95% and only one case of pure MPC has been reported. To date, approximately 130 cases of MPC in the colorectum have been reported, but it is likely that this small number is to some extent due to under‐reporting because this pattern is not well recognized by the general pathologist. All previous studies have combined colonic and rectal primary tumours and most have only analysed patients with clinical Stages I or II. Method We analysed 15 cases of MPC of the colon alone, diagnosed in our institution, and compared them with 105 conventional carcinomas of the colon. Results An MPC component was present in 10% of all colonic carcinomas. These tumours presented at a median age of 56 years, and all were of American Joint Committee on Cancer Stages III and IV. Subserosal tissue invasion was present in every case, 60% had more than four positive lymph nodes, 60% were accompanied by poorly differentiated conventional carcinoma, 40% had had an incomplete resection and a third demonstrated lymphovascular invasion. Despite these adverse prognostic factors, tumours containing MPC showed the same survival, stage by stage, as conventional adenocarcinoma in multivariate analysis, although 3‐year survival (81.7%vs 87.3%, P = 0.035) was worse on univariate analysis. Conclusion The histopathologist should be aware of the possibility of MPC. Three‐year survival is worse than in patients with conventional colonic carcinomas in Stage III.