Recurrence following treatment of ductal carcinoma in situ with skin-sparing mastectomy and immediate breast reconstruction

Skin-sparing mastectomy with immediate breast reconstruction can provide an excellent cosmetic result. Despite its increasing popularity, few studies have assessed the risk of recurrence when the procedure is used for the treatment of ductal carcinoma in situ. To evaluate the oncologic safety of skin-sparing mastectomy used for the treatment of ductal carcinoma in situ, the recurrence rate was analyzed. Patients with ductal carcinoma in situ or invasive carcinoma or both who underwent skin-sparing mastectomy with immediate breast reconstruction between 1985 and 1994 and had a follow-up period of at least 6 years were included in this retrospective analysis. The recurrence rates were determined for invasive carcinoma (with or without foci of ductal carcinoma in situ) and ductal carcinoma in situ alone. A total of 221 patients were included, 177 patients with invasive carcinoma and 44 patients with ductal carcinoma in situ alone. The immediate breast reconstructions were performed with transverse rectus abdominis muscle (TRAM) flaps in 62 percent of patients, implants in 34 percent of patients, and latissimus dorsi myocutaneous flaps (with or without implants) in 4 percent of patients. The local recurrence rate was zero of 44 for patients with ductal carcinoma in situ and 5.6 percent (10 of 177) for patients with invasive carcinoma during a mean follow-up period of 9.8 years. There was a 6.8 percent (12 of 177) metastatic recurrence rate in the invasive carcinoma group. All recurrences were invasive ductal carcinoma. Of the patients with ductal carcinoma in situ alone, none developed metastatic disease. The combined metastatic and local recurrence rates for the invasive carcinoma group (n = 177) with each type of reconstruction were 13 percent (14 of 110), 12 percent (seven of 60), and 14 percent (one of seven) for TRAM flaps, implants, and latissimus dorsi flaps, respectively. The risk of recurrence following skin-sparing mastectomy and immediate breast reconstruction for ductal carcinoma in situ is low during this follow-up period. Therefore, skin-sparing mastectomy with immediate breast reconstruction seems to be a safe oncologic treatment option for ductal carcinoma in situ; however, a longer follow-up period is important to determine the long-term risk of recurrence.     

Cytologic characteristics of endocrine ductal carcinoma in situ of the breast. A case report

BACKGROUND: Endocrine ductal carcinoma in situ is a rare form of ductal carcinoma in situ. It is regarded as a distinct subgroup of mammary carcinoma. However, the cytologic features of endocrine ductal carcinoma in situ have not been previously reported. CASE: A case of endocrine ductal carcinoma in situ exhibited characteristic cytologic findings on a specimen obtained by the scrape method (stained with hematoxylin and eosin and Diff-Quik). CONCLUSION: The cytologic criteria for endocrine ductal carcinoma in situ are sufficiently distinct and are useful for making the diagnosis on fine needle aspiration.     

CD44及CD24在乳腺癌组织中的表达及与临床病理特征的关系研究

目的:探讨肿瘤标志因子CD44及CD24在乳腺癌组织中的表达及与临床病理特征的关系。方法:选择从2015年1月到2017年1月在我院接受手术治疗的乳腺癌患者80例纳入本次研究,另选同期在我院治疗的导管原位癌患者30例,小叶增生患者20例及导管单纯增生患者20例的组织提取标本进行对照,分析CD44及CD24在乳腺癌组织和不同病变类型中的表达,并分析CD44~+/CD24~-细胞在癌症免疫分型中的表达以及CD44~+/CD24~-细胞与乳腺浸润导管癌相关病理特征的关系。结果:乳腺癌组织内的CD44阳性率为52.50%,CD24的阳性率为57.50%,均显著高于癌旁组织的11.25%和15.00%,差异均有统计学意义(均P0.05)。CD44及CD24在导管原位癌及乳腺浸润导管癌中的阳性率高于小叶增生和导管单纯增生,导管原位癌的阳性率高于乳腺浸润导管癌,差异均有统计学意义(均P0.05),且CD44在乳腺浸润导管癌不同分化类型中的阳性率差异有统计学意义(P0.05)。CD24在乳腺浸润导管癌不同分化类型中的阳性率差异不显著(P0.05)。CD44~+/CD24~-细胞在不同癌症免疫分型以及不同分化中的阳性率比较差异均有统计学意义(P0.05)。CD44~+/CD24~-细胞与乳腺浸润导管癌患者的年龄、月经状态、肿瘤直径、淋巴结转移以及远处转移之间均无明显关系(均P0.05)。结论:CD44及CD24在乳腺癌组织内存在较高的阳性率,且CD44~+/CD24~-在乳腺原位癌及低分化的乳腺癌组织内具有更高的阳性率,临床上可尝试通过监测CD44~+/CD24~-的阳性表达情况评价患者的病情及预后。     

凋亡相关基因p53、bcl-2在乳腺导管非典型增生中表达的研究

为观察凋亡相关基因-p53,bcl-2在乳腺导管非典型增生及乳腺癌中的表达,探讨其与乳腺癌组织发生的关系。本实验应用原位杂交方法检测凋亡相关基因p53,bcl-2mRNA,应用免疫组织化学方法检测p53蛋白在44例乳腺导管非典型增生组织中的表达,并与6例乳腺导管单纯性增生及26例乳腺癌对比分析,实验结果为,p53mRNA在乳腺导管单纯性增生组织中呈较强表达（66.7%),在乳腺导自欺欺人这非典型增生组织中阳性表达为40%（轻度;55.6%,中度：41.7%,重度;26.1%)。在癌组织中的表达率为19.2%(导管内癌：21.4%,浸润性导管癌：16.7%),p53蛋白在导管单纯性增生组无表达,在导管非典型增生组阳性表达为24%（轻度：11.1%,中度;25%,重度;34.8%)。在癌组织中的阳性表达为38.4%(导管内癌：35.7%,浸润性导管癌：41.7%),bcl-2mRNA在单纯性增生组无表达,在非典型增生组中阳性表达为轻度：11.1%,中度：16.7%,重度：39.1%,在乳腺癌组织中阳性表达为导管内癌;78.6%,浸润性导管癌83.3%。实验结果表明,在乳腺导管重度非典型增生组织中可检测到p53基因有较高的表达缺失,突变及bcl-2mRNA过表达。     

The cytopathology of ductal carcinoma in situ of the breast. A detailed analysis of fine needle aspiration cytology of 58 cases compared with 101 invasive ductal carcinomas

Bonzanini M., Gilioli E., Brancato B., Cristofori A., Bricolo D., Natale N., Valentini A., and Dalla Palma P. (2001)Cytopathology 12, 107-119. The cytopathology of ductal carcinoma in situ of the breast. A detailed analysis of fine needle aspiration cytology of 58 cases compared with 101 invasive ductal carcinomas. The existence of cytological findings that discriminate ductal carcinoma in situ (DCIS) of the breast from invasive ductal carcinoma (IDC) has not been unanimously accepted and the role of fine needle aspiration cytology (FNAC) remains controversial. We report the cytological findings of a large series of FNAC from histologically proven DCIS compared with those of ductal carcinomas having a different extent of the invasive component. The association of high cohesiveness of atypical cells and absence of tubular aggregates showed good sensitivity (SE) and specificity (SP) for the diagnosis of DCIS vs IDC. The simultaneous presence of necrotic background, atypical cells with abundant eosinophilic cytoplasm and a low percentage of single malignant cells resulted in low sensitivity but high specificity and positive predictive value (PPV) for differential cytological diagnosis of DCIS vs IDC.     

Benign mucocele-like lesion of the breast: how to differentiate from mucinous carcinoma before surgery.

The aim of the study was to improve the pre-operative diagnosis of mammary mucinous lesions. All mucinous lesions detected by fine needle aspiration (FNA) and confirmed by histological examination were reviewed by cytological findings, mammographic appearances and sonographic findings. Twenty aspirates had corresponding pathology, including 12 mucinous carcinomas, two mucocele-like lesions (MLL) with atypical ductal hyperplasia, three MLL with ductal hyperplasia and three simple MLL. Simple MLL and mucocele-like with ductal hyperplasia showed scant cellularity, no or rare intact single tumour cells, monolayered arrangement and absence of nuclear atypia. In contrast, most mucinous carcinomas showed higher cellularity, more single tumour cells, three-dimensional clusters, and mild to marked nuclear atypia. However, MLL with atypical ductal hyperplasia showed cytological features overlapping with mucinous carcinoma. MLL had a non-specific mammographic appearance and showed a cystic lesion on sonography. Mucinous carcinoma appeared as a solid mass on sonography and as a distinct nodule on mammography. Based on the combination of FNA cytology and image findings, benign MLL can be correctly distinguished from mucinous carcinoma before surgery.     

Mammary mucinous carcinoma with marked cytoplasmic hyalinization. A report of 2 cases with emphasis on fine needle aspiration cytologic findings

BACKGROUND: Cytoplasmic eosinophilia in breast tumors is due mainly to abundance of secretory granules, lysosomes and/or mitochondria. Diffuse cytoplasmic hyalinization caused by intermediate filaments has not been described before. CASES: Two cases of pure mammary mucinous carcinoma occurred with marked cytoplasmic hyalinization among 556 wide excision/mastectomy specimens of mammary ductal carcinoma, either in situ or invasive, encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the period from 1994 to the end of 2001. Preoperative fine needle aspiration cytology was available in 1 case, showing cohesive clusters and micropapillae of tumor cells in abundant background mucin. The tumor cells had low mitotic activity and possessed round to oval nuclei, solitary macronucleoli; ample, eosinophilic cytoplasm and discrete cell borders. Cytoplasmic granularity, intracytoplasmic vacuoles or "cometlike" cells were not found. Histologic examination of the surgical specimens in both cases revealed pure mucinous carcinoma with diffuse and marked cytoplasmic hyalinization. There was no evidence of peritumoral lymphovascular permeation or regional lymph node metastasis. Ultrastructural examination showed minimal secretory activity, with abundant, loose aggregates of intermediate filaments in the cytoplasm. There was a relative paucity of other organelles. CONCLUSION: Diffuse cytoplasmic hyalinization is a peculiar morphologic change in mammary ductal carcinoma and apparently unique to pure mucinous carcinoma. Recognition of this phenomenon may help to avoid misdiagnosis of other types of ductal carcinoma with cytoplasmic eosinophilia, such as apocrine carcinoma and ductal carcinoma with neuroendocrine differentiation, which sometimes are also associated with pools of extracellular mucin.     

A morphologic and morphometric study of cells from colloid carcinoma of the breast obtained by fine needle aspiration. Distinction from other breast lesions

Morphologic and morphometric studies were carried out on eight cases of pure and mixed colloid carcinoma of the breast initially diagnosed by fine needle aspiration (FNA). Key morphologic features included (1) cellular smears, (2) single cells, loose aggregates and cohesive groups of cells bathed in a mucinous background, (3) single cells displaying nuclear eccentricity and (4) little variation in nuclear size or shape, with bland-to-accentuated chromatin and rare nucleoli. These morphologic features are compared with those observed in pregnancy adenoma, lobular carcinoma, fibroadenoma, ductal carcinoma and medullary carcinoma. A morphometric study employing the major and minor axes of the nucleus, its axis product and axis ratio was also performed. Statistical treatment confirmed that the nuclear axis product (a size factor) distinguished colloid carcinoma from the other breast lesions, except the small-cell type of ductal carcinoma. Furthermore, the nuclear axis ratio (a shape factor) discriminates pregnancy adenoma and small-cell ductal carcinoma from the other breast lesions studied. By combining morphologic and morphometric criteria, one can specifically separate colloid carcinoma from the other breast lesions when examining smears obtained by FNA. Since colloid carcinoma is usually composed of cells with a relatively benign-appearing cytomorphology, the importance of recognizing this entity in fine needle aspirates is emphasized.     

E-cadherin和Cathepsin D的表达与乳腺导管癌的侵袭和淋巴结转移的关系

目的　观察上皮性钙粘素 (E cadherin)和组织蛋白酶D (CathepsinD)在乳腺导管癌中的表达并分析其与肿瘤侵袭及腋下淋巴结转移的关系。方法　应用免疫组织化学方法检测E cadherin和CathepsinD在乳腺导管癌组织中的表达。结果　乳腺导管原位癌 (carcinomainsitu ,CIS)组织中E cadherin的表达与浸润性导管癌 (infiltratingductalcarcinoma ,IDC)相比无明显差异 (P >0 0 5 )。乳腺导管癌腋下淋巴结阴性组 (nodenegativeductalcarcinoma,NNDC)中E cadherin的表达与腋下淋巴结阳性组 (nodepositiveductalcarcinoma ,NPDC)相比差异不明显 (P >0 0 5 )。乳腺导管癌间质中CathepsinD的表达CIS与IDC相比差异显著 (P <0 0 1) ,NNDC与NPDC相比差异显著 (P <0 0 5 ) ;而在癌细胞中CathepsinD的表达在上述两组中差异均不明显 (P >0 0 5 )。结论　E cadherin在乳腺导管癌的表达与肿瘤的侵袭及淋巴结转移无相关关系。CathepsinD在乳腺导管癌间质的表达与肿瘤的侵袭及淋巴结转移密切相关 ,可作为临床判定肿瘤恶性程度的一个参考指标。     

AgNOR analysis of atypical ductal hyperplasia and intraductal carcinoma of the breast

OBJECTIVE: To determine the diagnostic and prognostic value of argyrophilic nucleolar organizer regions (AgNORs) in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and microinvasive ductal carcinoma (MDCA) of the breast. STUDY DESIGN: Image analysis of histologic sections from biopsies of 46 breast ADH and DCIS and 18 cases of MDCA. Determination of morphometric features of cell nuclei and nucleolar organizer regions by using AMBA software system. Data were compared with the estrogen receptor/progesterone receptor (ER/PR) content as well as with the growth fraction, determined immunohistochemically. RESULTS: AgNOR number and total AgNOR area increased from ADH to DCIS. The highest values were recorded in cases of DCIS with microinvasion. Differences between ADH and intraductal or microinvasive ductal carcinoma were statistically significant. Within the group of intraductal carcinomas, the lowest values were measured in the solid type and highest values in the comedo type. A correlation was found between AgNOR features and growth fraction but not between these features and ER/PR status. CONCLUSION: Selected AgNOR features are relevant for differentiation between ADH and DCIS as well as between low and high grade DCIS and microinvasive ductal carcinoma. Therefore, objective and reproducible data obtained by AgNOR analysis may allow better evaluation of the prognostic significance of these lesions.     

Case report: Metaplastic carcinoma presenting as a breast abscess

Metaplastic breast carcinoma (MBC) is a rare neoplasm containing a mixture of epithelial and mesenchymal elements. The epithelial component is usually ductal carcinoma but may include other variants of breast carcinomas including squamous carcinoma and osteogenic sarcoma. There is a relative paucity of data regarding such tumours. Metaplastic carcinoma carries a prognosis not dissimilar to that of comparable ductal carcinoma. This is the case of a 57 year old patient with MBC presenting with a breast abscess. A thorough literature search has not revealed any previous reports of MBC presenting as a breast abscess.     

Expression of matrix metalloproteinase 9 in pancreatic ductal carcinoma is associated with tumor metastasis formation

The objective of the current study was to assess the expression of matrix metalloproteinase 9 (MMP-9) in pancreatic ductal carcinoma and to examine its correlation with chosen clinico-anatomical parameters. The study group consisted of 36 patients with pancreatic ductal carcinoma. Tumors were stained using immunohistochemical method (NCL -MMP-9, Novocastra). No correlation was found between tumor MMP-9 expression and age, gender or grade of histological malignancy. However, statistical analysis revealed a relationship between tumor MMP-9 expression and histological type (adenocarcinoma mucinosum) of pancreatic carcinoma. The expression was strongly correlated with lymph node involvement and occurrence of distant metastases (p<0.00001). The results indicate a correlation between the expression of MMP-9 in pancreatic ductal carcinoma and worse prognosis (shown by lymph node involvement and distant metastases).     

Malignancy-associated changes in breast tissue detected by image cytometry.

In several tissues, nuclear differences have been described in normal-appearing cells from patients with invasive carcinomas compared to cases without invasive carcinoma, a phenomenon known as malignancy-associated changes (MACs). The aim of this study was to determine the presence of malignancy-associated changes in breast tissue. Image cytometry was performed on Feulgen stained tissue sections of patients with usual ductal hyperplasia with (n = 30) or without (n = 41) adjacent invasive breast carcinoma. Nuclear features of normal-appearing cells as well as of usual ductal hyperplastic cells were separately compared between the two groups. Many features of normal-appearing epithelial cells were significantly different between cases with and without invasive cancer. Significant differences were also found by measuring ductal hyperplastic nuclei instead of normal-appearing nuclei. Cases with or without cancer could be distinguished with a classification accuracy of 80% by discriminant analysis using 2 nuclear features derived from ductal hyperplastic cells. In conclusion, image cytometry on breast tissue sections shows that malignancy-associated changes can be found in normal as well as in usual ductal hyperplastic breast cells. This could be clinically relevant for the detection of occult breast cancer, for the prediction of risk in these lesions, and to monitor the effect of chemopreventive agents.     

Expression of the Na(+)/I(-) symporter in invasive ductal breast cancer

The function of the sodium iodide symporter (Na(+)/I(-), (NIS), a membrane protein that mediates iodide transport into cells, is the best described in the thyroid cells. NIS is also found in mammary cells during lactation and in breast carcinoma cells. The aim of this study was evaluation of incidence and grade of NIS expression in invasive ductal breast cancer. Immunohistochemistry using a panel of antibodies against NIS was carried out in surgical paraffin-embedded tissue obtained from 50 patients with invasive ductal breast carcinoma. NIS expression was found in 45 (90%) cases. The demonstration of NIS expression in breast carcinoma cells may provide a novel approach to its diagnosis and treatment.     

Actin-rich (myoepithelial) cells in ductal carcinoma-in-situ of the breast

The distribution of the myoepithelial cells in 32 cases of ductal carcinoma-in-situ (DCIS) of the breast (11 not associated, 21 associated with invasive carcinoma) was investigated with a recently developed immunoperoxidase method for actin. Actin-rich myoepithelial cells were detected at the periphery of some ducts, however, their presence was neither constant nor continuous. Large areas of DCIS were devoid of a myoepithelial cell layer and the neoplastic cells were directly in contact with the stroma. No differences related to the histological pattern of DCIS or the presence and absence of invasive carcinoma were noted. The behaviour of the myoepithelial cells in ductal carcinoma appears different from that observed in cases of lobular carcinoma (Bussolati 1980) and of cystic disease, and may thus be of diagnostic interest. The selective destruction of myoepithelial cells in cases of DCIS might result in a focal disruption of the basement membrane, thus faciliatating invasion.     

乳腺导管上皮内瘤变32例影像诊断分析

目的：探讨全数字化乳腺X线摄影与磁共振成像检查相结争对乳腺导管上皮内瘤变（DIN）的诊断价值。方法：对32例经乳腺平板数字X线摄影及磁共振检查并且病理证实为乳腺导管上皮内瘤变的病例进行回顾性分析。结果：32例DIN中,普通导管上皮增生（UDH）17例,DIN1A2例;DIN1B1例;乳腺导管原位癌（DIN1C--DIN3）12例。采用全数字化X线乳腺摄影与MRI相结合诊断乳腺增生18例,乳腺导管原位癌11例,3例未能明确诊断。结论：平板数字X线乳腺摄影及磁共振成像综合诊断,对乳腺导管原位癌的旱期发现具有重要意义．显著提高患者的生存质量。     

Pleomorphic lobular carcinoma of the breast. A case report

BACKGROUND: Pleomorphic lobular carcinoma of the breast is associated with aggressive behavior. CASE: Fine needle aspiration cytology was performed on a breast lump in a 55-year-old woman. The aspirates showed highly pleomorphic, large cells in a dyscohesive pattern, with a tendency of few cells to aggregate in small groups. A diagnosis of ductal carcinoma was made on cytology. On histology, the paraffin sections showed features of pleomorphic lobular carcinoma of the breast. CONCLUSION: The cytologic features of pleomorphic lobular carcinoma overlap with those of infiltrating ductal carcinoma. It is very difficult to make a diagnosis of pleomorphic lobular carcinoma prospectively on cytology. However, if Indian file arrangement and cytoplasmic vacuolation are present, pleomorphic lobular carcinoma must at least be suggested for the differential diagnosis as it has different clinical implications.     

Differentiation of tumours of ductal and lobular origin: I. Proteomics of invasive ductal and lobular breast carcinomas

The vast majority of invasive breast tumors are ductal and lobular breast carcinomas. Despite the many similarities, some clinical follow-up data and the patterns of metastases suggest that these histological subtypes of breast cancer are biologically distinct. Few papers, however, describe immunohistochemical markers useful for differentiation of these carcinomas. Many investigations suggest that E cadherin protein expression is lost in lobular but not in ductal carcinoma. The absence of E-CD, as a partial loss of epithelial differentiation, may account for the extended spread of lobular carcinoma in situ and the peculiar diffuse invasion mode of invasive lobular carcinoma. Some investigations report the significance of E-CD associated proteins alpha-, beta-, gamma-catenin expression, as well as the usefulness of cytokeratins 5, 6, 8, 7 and thrombospondin in differentiating histological types of breast invasive carcinomas. Several reports have suggested the possibility that invasive ductal and lobular cancers differ with respect to expression of antigens involved in proliferation and cell cycle regulation. It has been shown that vascular endothelial growth factor expression, also the expression of maspin, a tumour suppressor gene product, is higher in ductal, than in lobular carcinoma. Expression of NKX3.1, a member of the NK-class of homeodomain, is highly restricted and is found primarily in lobular carcinoma. Some histological and immunohistochemical characteristics of pleomorphic lobular carcinoma are also discussed.     

Aromatase and in situ estrogen production in DCIS (ductal carcinoma in situ) of human breast

Ductal carcinoma in situ or DCIS belongs to intraductal proliferative lesions, which are a group of cytologically and architecturally diverse ductal proliferations, typically originating from the terminal duct–lobular units. In these intraductal proliferative diseases, estrogens are considered to be involved in the progression of the disease especially from ductal non-neoplastic hyperplasia to DCIS and possibly development of invasive carcinoma from DCIS. Estrogen receptor (ER) alpha is abundantly expressed in atypical ductal hyperplasia and low grade DCIS. Suppression of estrogenic actions using tamoxifen resulted in inhibition of recurrence of DCIS and/or of progression into invasive carcinoma. Intratumoral estrogen concentration in DCIS determined by liquid chromatography/electrospray tandem mass spectrometry is significantly higher than that in non-neoplastic breast tissues with statistically not lower than that in invasive carcinoma. Aromatase mRNA expression in both stromal and parenchymal cells of DCIS determined by quantitative RT-PCR following laser capture microdissection was also much higher than that in non-neoplastic breast, although lower than that in invasive carcinoma. Immunohistochemistry of aromatase also revealed the similar patterns of immunolocalization as in invasive carcinoma. Aromatase is overexpressed in noninvasive breast malignancies including DCIS and results in elevated concentrations of intratumoral estradiol. These findings could provide the scientific rationale as to employing aromatase inhibitors in the management of ER positive DCIS patients.