A case of apocrine carcinoma of the breast presenting as two cysts

A case of apocrine carcinoma of the breast presenting as two cysts is reported. A 60-year-old woman had two soft, mobile, well-defined masses measuring 4 X 2.5 cm and 1.5 X 2.5 cm in diameter in the lower-inner quadrant of the right breast. Tumor markers such as CEA, CA153, BCA225 and NCC-ST-439 were within normal limits. Mammography showed two oval radioopaque masses with microcalcification in the smaller one. Ultrasonography disclosed two cysts and papillary projection in the larger one. Fine needle aspiration cytology revealed apocrine carcinoma of the breast. Excisional biopsy confirmed the diagnosis of apocrine carcinoma with focal invasion. Modified radical mastectomy was performed. Pathological study showed that the tumor mainly proliferated in the cysts and the two cysts communicated with each other through an involved duct. There was no apocrine metaplasia in adjacent mammary gland. There were no metastatic lymph nodes. This case may be regarded as intraductal apocrine carcinoma developing two cysts with focal invasion.     

Bilateral synchronous spindle cell, apocrine and scirrhous carcinoma breast cancer in a case or malignant lymphoma

An unusual case of synchronous bilateral breast cancer occurring during combination chemotherapy and radiation to the outside of the breast for malignant lymphoma is reported. Two histologically rare carcinomas, spindle cell carcinoma and apocrine carcinoma, were observed in this case. A 77-year-old woman, who had been treated for stage IIIA non-Hodgkin's lymphoma, developed bilateral breast tumors. Aspiration biopsy cytology findings of the tumor in the left breast showed several clusters of adenocarcinoma cells and some large atypical spindle shaped cells, which suggested spindle cell carcinoma. The cytologic findings of the right breast tumor were highly suggestive of scirrhous carcinoma. A modified radical mastectomy was performed on both breasts. Pathological examination disclosed two separate cancer lesions in the left breast. The lesion which had been detected before the operation, was a spindle cell carcinoma. Another lesion, detected for the first time by pathological examination, was an apocrine carcinoma. The lesion in the right breast was a scirrhous carcinoma. Since non-invasive foci were detected in these three cancer lesions, each lesion was thought to be a primary cancer. All dissected bilateral axillary lymph nodes showed malignant lymphoma. Immuno-histochemistry of the spindle cell carcinoma revealed positive immunoreactivity for cytokeratin, which suggested the epithelial as well as mesenchymal nature of this tumor. Synchronous existence of malignant lymphoma and three independent breast cancers including spindle cell carcinoma and apocrine carcinoma is very rare.     

Apocrine carcinoma of the breast: Clinicopathological analysis and histological subclassification of 12 cases

Background  Apocrine carcinoma is rare and most of its clinicopathological features are still unknown. The purpose of this study was to identify the clinicopathological characteristics of apocrine carcinoma. Methods  We clinicopathologically analyzed apocrine breast carcinomas resected from 12 Japanese women and subclassified them histopathologically. Results  The average age of the patients at diagnosis was 60.1 years (range: 38-78). Tumor diameters ranged from 0.5 to 4.5 cm (median 2.4). Mammography revealed tumor shadows without microcalcifications in all patients. Two (17%) of the 12 patients were lymph node metastasis-positive, and lymphatic permeation by tumor cells was observed in 3 (25%). Apocrine carcinoma in this study could be classified into three subtypes according to predominant histopathological growth pattern: type I, intraductal spreading type (4 patients); type II, adenosis-associated type (3 patients); and type III, infiltrating type (5 patients). Types I and II showed no lymph node metastasis and had an excellent prognosis, whereas the infiltrating type was associated with lymph node metastasis and death from cancer. Estrogen receptors and progesterone receptors were positive in 17% (1/6) and 60% (3/5), respectively, of the tumors tested. Conclusions  In the present study, apocrine carcinoma of the breast was characterized by higher patient age and tumor shadows without microcalcifications on mammography. However, the tumors were heterogenous with regard to pattern of local spread.     

Molecular characterization of apocrine carcinoma of the breast: Validation of an apocrine protein signature in a well‐defined cohort

Invasive apocrine carcinomas (IACs), as defined by morphological features, correspond to 0.3–4% of all invasive ductal carcinomas (IDC), and despite the fact that they are histologically distinct from other breast lesions there are currently no standard molecular criteria available for their diagnosis and no unequivocal information as to their prognosis. In an effort to address these concerns we have been using protein expression profiling technologies in combination with mass spectrometry and immunohistochemistry (IHC) to discover specific biomarkers that could allow us to molecularly characterize these lesions as well as to dissect some of the steps in the processes underlying breast apocrine metaplasia and development of precancerous apocrine lesions. Establishing these apocrine‐specific markers as best practice for the routine pathology evaluation of breast cancer, however, will require their validation in large cohorts of patients. Towards this goal we have composed a panel of antibodies against components of an apocrine protein signature that includes probes against the apocrine‐specific markers 15‐prostaglandin dehydrogenase (15‐PGDH), and acyl‐CoA synthetase medium‐chain family member 1 (ACSM1), in addition to a set of categorizing markers that are consistently expressed (AR, CD24) or not expressed (ERα, PgR, Bcl‐2, and GATA‐3) by apocrine metaplasia in benign breast lesions and apocrine sweat glands. This panel was used to analyze a well‐defined cohort consisting of 14 apocrine ductal carcinoma in situ (ADCIS), and 33 IACs diagnosed at the Cancer Institute Hospital, Tokyo between 1997 and 2001. Samples were originally classified on the basis of cellular morphology with all cases having more than 90% of the tumour cells exhibiting cytological features typical of apocrine cells. Using the expression of 15‐PGDH and/or ACSM1 as the main criterion, but taking into account the expression of other markers, we were able to identify unambiguously 13 out of 14 ADCIS (92.9%) and 20 out of 33 (60.6%) IAC samples, respectively, as being of apocrine origin. Our results demonstrate that IACs correspond to a distinct, even if heterogeneous, molecular subgroup of breast carcinomas that can be readily identified in an unbiased way using a combination of markers that recapitulate the phenotype of apocrine sweat glands (15‐PGDH+, ACSM1+, AR+, CD24+, ERα−, PgR−, Bcl‐2−, and GATA‐3−). These results pave the way for addressing issues such as prognosis of IACs, patient stratification for targeted therapeutics, as well as research strategies for identifying novel therapeutic targets for developing new cancer therapies.     

Locally recurrent penile apocrine carcinoma initially diagnosed as metastatic adenocarcinoma of colon

Apocrine carcinoma is a rare malignant adnexal neoplasm. The differential diagnosis between apocrine carcinoma and cutaneous metastasis is often difficult. Here, we report a case of locally recurrent penile apocrine carcinoma initially diagnosed as metastatic adenocarcinoma of the colon. A 75-year-old man with a history of surgical resection due to sigmoid colon cancer and penile metastasis two years prior to this study presented with a nodule at the left penile base. He underwent a wide local resection of the penile mass under a suggested preoperative diagnosis of extra-mammary Paget＇s disease （EMPD） associated with previous sigmoid colon cancer. However, the previously and currently resected penile masses were identified as primary apocrine carcinoma upon hematoxylin and eosin （H＆E） staining and immunohistochemical staining. Although the incidence is extremely rare, both clinicians and pathologists should be alert to the possibility of synchronous double primary apocrine carcinoma in cancer patients with malignant cutaneous lesions.     

S100 protein positive human breast carcinomas: An immunohistochemical study

An immunohistochemical study for S100 protein was performed on 95 human breast carcinomas. S100 protein positive carcinoma cells were recognized in 54 cases (57%). The S100 protein positive and negative carcinomas were then compared in terms of stage, histologic type, nuclear grade, appearance of minute calcification, immunoreactivity for estrogen receptor (ER), tumor recurrent pattern, and prognosis. The S100 protein positive cases had a tendency to show a low nuclear grade (P < 0.01). They were also more often seen in the ER positive group. For further analysis of the nature of S100 protein positive carcinoma cells, immunoreactivity for neuron-specific enolase (NSE) and actin was investigated. The positive staining for NSE and actin was seen in 46 cases (48%) and 3 cases (3%), respectively. There was, however, no specific correlation among the S100 protein, NSE, or actin staining. The nature of S100 protein positive carcinoma cells still remains unclear. The S100 protein positive carcinomas, however, exhibit relatively better characteristics. © Wiley-Liss, Inc.     

Serum and immunohistochemical studies of NCC-ST-439 in breast cancer

It has been thought that NCC-ST-439 antigen (ST-439) is a tumor-related carbohydrate antigen. The authors conducted serum and immunohistochemical studies to investigate the clinical significance of ST-439 in breast cancer. The level of serum ST-439 was elevated in advanced and recurrent breast cancers. In comparison with CEA and CA15–3, ST-439 was superior in sensitivity but inferior in specificity to these markers. The level of serum ST-439 showed no correlation with the levels of CEA or CA15–3. In the combination assay of these three markers, 80.6% of recurrent cases and 33.8% of primary cases were positive. Immunohistochemically, the expression of ST-439 was observed in 28.1% of noncancerous mammary duct epithelium and in 38.1% of the cancerous portion. From the above, we concluded that ST-439 was a tumor-related antigen and could be a tumor marker with high sensitivity in breast cancer. © 1993 Wiley-Liss, Inc.     

Semi-quantitative immunohistochemical analysis of aromatase expression in ductal carcinoma in situ of the breast

Although estrogens whose production is catalyzed by aromatase are considered to play a role in human breast carcinogenesis, it remains unclear whether aromatase expression occurs in ductal carcinoma in situ (DCIS) of the breast. Aromatase expression in 61 cases of pure DCIS and 101 cases of invasive ductal carcinoma (IDC) was investigated by immunohistochemical analysis using a polyclonal anti-aromatase antibody. The level of aromatase expression was semiquantified by the H-score which was estimated by the percentage of positive-staining cells and the intensity of staining. The levels of aromatase expression were compared between the DCIS and IDC samples, and were also compared among the tumor cells and stromal cells in the DCIS and IDC samples. Positive cytoplasmic staining for aromatase expression was found not only in stromal cells but also in tumor cells. The levels of aromatase expression in the tumor cells and stromal cells from the DCIS samples were significantly higher than those in the respective cells from the IDC samples. Among the DCIS samples, those specimens from patients of ages 50 years or over showed higher levels of aromatase expression in stromal cells, than those from patients below 50 years. The finding that significantly higher aromatase expression levels were found in DCIS than in IDC indicates that it may be possible to treat DCIS patients with aromatase inhibitors, especially as an adjuvant hormonal therapy for postmenopausal patients.     

Ultrasound characteristics of histologically proven grade 3 invasive ductal breast carcinoma

High‐grade invasive ductal carcinoma (IDC) may paradoxically display features similar to benign breast masses. This study analysed the ultrasound features of histologically proven cases of grade 3 IDC. At North Western BreastScreen Victoria, from 4 February 1993 to 30 September 2002, 181 cases of grade 3 IDC that had ultrasound evaluation were available for retrospective analysis. For each tumour, four features were assessed: margin, attenuation characteristics, echotexture and depth versus width ratio. Eighty‐seven per cent of tumours had an aggressive margin with an echogenic rind, microlobulation or angular margins. However, 11% had a well‐defined smooth margin. The classic sonographic malignant feature of posterior shadowing was present in only 30%, whereas the tissues posterior to the lesion remained isoechoic in 48% and showed posterior enhancement in 11%. Six per cent of the tumours were isoechoic and difficult to appreciate on ultrasound. The best feature to characterize lesions as malignant was the margin of the lesion. To ensure that malignant lesions are correctly categorized, it is important that interfaces between the tumour and adjacent breast parenchyma are meticulously evaluated in a real‐time fashion rather than viewed as a single still image.     

乳腺腺病及乳腺癌的核形态图像分析

应用图像分析手段，对乳腺癌、乳腺腺病和正常乳腺组织进行了７项核形态参数测定。除形状因子外，其余６项均显示正常乳腺与Ⅰ级腺病间无差异（Ｐ＞０．０５）。Ⅰ、Ⅱ级腺病及乳癌间均存在显著性差异（Ｐ＜０．０１）。经逐步判别分析对７项核形态参数进行综合评定，选出三项较优指标，建立判别函数，对Ⅱ级腺病及乳癌的判定回代符合率分别为９３．５５％和８７．８％。结果表明：利用图像分析，结合有效的统计学方法，有可能对具有癌变可能的Ⅱ级腺病及癌的判定，提供客观可靠的手段。     

乳腺浸润性微乳头状癌临床病理分析

目的:探讨乳腺浸润性微乳头状癌(IMPC)的临床病理特征、诊断、鉴别诊断及预后。方法:回顾性分析7例乳腺IMPC患者的临床表现、组织病理特点、免疫组化结果,同时进行文献复习。结果:7例乳腺IMPC患者无特殊临床症状和体征。组织病理特点:IMPC肿瘤细胞团排列形成不含纤维血管轴心的微小乳头状或假腺管状结构,其外侧缘呈锯齿或毛刺状;每个肿瘤细胞团与周边的间质之间存在大小不等的腔隙,其内缺乏内容物。免疫组化染色EMA阳性部位在癌细胞巢团的外缘。结论:乳腺IMPC是一种特殊类型的乳腺浸润性癌,比较少见,但因其具有高淋巴血管侵犯、高淋巴结转移等恶性生物学行为,预后较差,应引起病理及临床医生的足够重视。     

Validation of an immunohistochemical signature predictive of 8-year outcome for patients with breast carcinoma

We recently reported that standardized quantitative immunohistochemical (IHC) assays allowed prediction of an adverse outcome among 572 node negative (N-) patients with breast carcinoma (BrCa). To further validate our prior findings, we repeated the IHC stains including a second series of BrCa diagnosed at Yale University. Tissue microarrays (TMAs) of two cohorts of patients with BrCa (418 Marseille University and 303 Yale University) were respectively investigated for IHC expression of 15 markers (HIF-1α, PI3K, pAKT, pmTOR, moesin, P21, 4(E) BP-1, P27, Ker5-6, pMAPKAPK-2, SHARP2, claudin-1, ALDH, AF6 and CD24). Quantitative measurements of immunoprecipitates densitometry assessed with an image analyzer were correlated with 8-year patients' outcome and compared in the two cohorts. The best predictive signature consisted of a combination of five markers that included HIF-1α, PI3K, claudin-1, AF6 and pAKT in N- BrCa. This combination permitted an accurate prediction of outcome in 92.34% (386/418) of N- patients in the first set (Marseille) and 89.8% (158/176) in the second set (Yale). The close results in both cohorts confirmed the validity of this original IHC signature predictive of prognosis in node negative BrCa. This validation suggests that in clinical practice, it would be possible with standardized kits (i) to identify patients with poor prognosis at diagnosis time, particularly in the N- BrCa subset, who would require more aggressive adjuvant therapy and (ii) to avoid useless expensive therapies and their side effects in N- patients with favorable prognosis.     

Bilateral nonpalpable breast carcinomas in a patient withbrca2 germ line mutation and past history of osteosarcoma

A 34-year-old premenopausal woman developed asynchronous bilateral nonpalpable breast cancers at the age of 32 and 34 years. She had undergone amputation of her left lower leg because of osteosarcoma at the age of 16. Her mother had been diagnosed with breast cancer at the age of 45. The clinicopathological features of the two breast tumors in this patient closely resembled each other; both were nonpalpable, and detectable only by helical CT scan. Histologically, they consisted mainly of an intraductal component with small grade 3 invasive foci. In addition, both tumors estrogen receptor (ER) status was negative, and both were positive for c-erbB-2 protein on immunohistochemical staining. A missense germ line mutation ofBRCA2 (exon 25 codon 3118; Met31 1 8Thr) was detected in this patient. These data may provide useful information on the carcinogenesis and biological behavior of breast cancers which develop in patients withBRCA2 germ line mutations.     

乳腺包裹性乳头状癌临床病理分析

目的:探讨14例乳腺包裹性乳头状癌(encapsulated papillary carcinoma,EPC)的临床病理学特点.方法:对14例乳腺EPC患者进行回顾性分析,观察其组织病理学形态、免疫表型、诊断及预后,并复习相关文献.结果:14例患者中,年龄39~87岁,平均年龄65岁,女性13例,男性1例.肿瘤大体呈囊实性,肿瘤最大直径为2.0~7.5cm.镜检显示肿瘤由纤维囊壁包裹,与周围乳腺组织分界清楚,囊内肿瘤细胞呈乳头状结构.免疫组化染色显示囊内乳头状成分肌上皮完全缺失,11例肿瘤周围肌上皮完全缺失,3例肿瘤周围肌上皮呈不连续表达,ER和PR弥漫强阳性,Her-2阴性,Ki-67增殖指数为1%~20%.13例经肿瘤完全切除确诊,1例经粗针穿刺(core needle biopsy,CNB)确诊,所有病例术后无复发.结论:乳腺EPC是一种预后良好的惰性浸润性癌,主要发生于老年妇女,病理诊断依赖于肿瘤大体切除标本,处理方式与乳腺导管原位癌(ductal carcinoma in situ,DCIS)相同.     

乳腺髓样癌19例诊治分析

目的：探讨乳腺髓样癌临床特征、治疗和预后。方法：回顾性分析我科2004年3月至2007年12月收治的19例乳腺髓样癌临床资料。结果：19例中腋淋巴结阳性率21.1%（4/19）,免疫组化检测雌激素受体阳性率（ER＋）、孕激素受体阳性率（PR＋）和HER-2的表达率分别为26.3%、21.1%和31.6%。全组进行手术和辅助化疗,其中9例服用三苯氧胺,2例腋窝淋巴结阳性〉3者行局部放疗。Ⅱa期13例,Ⅱb期3例,Ⅰ期、Ⅲa期和Ⅲc期各1例。随访2-5.5年,除1例Ⅲc期患者在手术后3年发生肺和肝转移而死亡,1例Ⅲa期患者手术后3年发生骨转移外,其余患者术后定期复查未见复发和转移。结论：乳腺髓样癌属低度恶性肿瘤,预后较好,手术加辅助性化疗是治疗的主要手段。而腋窝淋巴结阳性〉3者有远处转移的可能,治疗上应更积极。     

Clinicopathological feature and long-term prognosis of apocrine carcinoma of the breast in Japanese women

Because of the rarity of apocrine carcinoma and lack of standardized criteria for the diagnosis, the definitive conclusions of clinicopathologic features and the prognosis has not been determined. We retrospectively examined data on 2091 curatively treated Japanese patients with primary breast carcinoma. Among them, 33 (1.6%) who had been diagnosed of apocrine carcinoma were reviewed. Compared with non-apocrine carcinoma, apocrine carcinoma was characterized by less positive rates of ER and PR, and by frequent rates of unilateral multicentric breast carcinoma with significant difference. The clinicopathological factors influencing 12-year survival rate were lymph node metastasis, lymphatic involvement and vascular involvement. There was no difference in survival rates at 10 years after operation between apocrine carcinoma and non-apocrine carcinoma. Our result shows unique hormone response and unilateral multicentricity are only typical clinicopathological features of apocrine carcinoma.     

Grade of recurrent in situ and invasive carcinoma following treatment of pure ductal carcinoma in situ of the breast

The grade of recurrent in situ and invasive carcinoma occurring after treatment of pure ductal carcinoma in situ (DCIS) has been compared with the grade of the original DCIS in 122 patients from four different centres (The Royal Marsden Hospitals, London and Sutton, 57 patients; Guy's Hospital, London, 19 patients; Nottingham City Hospital, 31 patients and The Royal Liverpool Hospital, 15 patients). The recurrent carcinoma was pure DCIS in 70 women (57%) and in 52 women (43%) invasive carcinoma was present, which was associated with an in situ element in 43. In all, 19 patients developed a second recurrence (pure DCIS in 11 and invasive with or without an in situ element in eight). The majority of invasive carcinomas followed high-grade DCIS. There was strong agreement between the grade of the original DCIS and that of the recurrent DCIS (kappa=0.679), which was the same in 95 of 113 patients (84%). The grade of the original DCIS showed only fair agreement with the grade of recurrent invasive carcinoma (kappa=0.241), although agreement was stronger with the pleomorphism score of the recurrent carcinoma (kappa=0.396). There was moderate agreement, in recurrent invasive lesions, between the grade of the DCIS and that of the associated invasive element (kappa=0.515). Other features that showed moderate or strong agreement between the original and recurrent DCIS were necrosis and periductal inflammation. The similarity between the histological findings of the original and subsequent DCIS is consistent with the concept that recurrent lesions represent regrowth of residual carcinoma. In addition, although agreement between the grade of the original DCIS and that of any subsequent invasive carcinoma was only fair, there is no suggestion that low-grade DCIS lesions progress to higher grade lesions or to the development of higher grade invasive carcinoma. This is in agreement with immunohistochemical and molecular data indicating that low-grade and high-grade mammary carcinomas are quite different lesions.     

乳腺黏液癌7例临床病理分析

目的：探讨乳腺黏液癌的临床及病理特征,对其诊断、病理分型和鉴别诊断进行讨论。方法：对7例乳腺黏液癌患者进行回顾性分析,同时复习相关文献。结果：本组黏液腺癌占同期乳腺癌的4.73%,中位年龄42岁,绝经前患者占71.43%,病灶大小1.0-6.5cm。单纯型黏液癌均无腋窝淋巴结转移,混合型转移率为33.33%。结论：国内30-50岁女性,临床诊断为良性纤维瘤的乳房肿块,需警惕为乳腺黏液癌。乳腺黏液癌生长缓慢,预后较好。