Breast cancer in young women: clinicopathologic correlation.

It has been suggested that early-onset breast carcinomas may be different from those that occur in older women. The clinicopathologic characteristics of 191 young female patients (under 40 years of age) diagnosed with breast carcinoma (BC) were studied. Clinical history, staging, treatment and outcome were reviewed. Histology was assessed for tumor subtypes, invasive and in situ components, nuclear and histologic grades and lymph node status. Adjacent nontumoral breast tissue was evaluated. Clinically, 11 patients were stage 0, 21 stage I, 94 stage II, 38 stage III, 6 stage IV, and in 21 no information was obtained. Sixty five percent of patients had positive lymph nodes at diagnosis; 102 patients (54%) relapsed at a median of 29 months after diagnosis. Histologically, 180 cases were infiltrating BC, 150 ductal (83%), 19 lobular (11%) and 11 of special types (6%); 11 cases were ductal carcinoma in situ. We found no cases of medullary carcinoma. High nuclear grade and vascular invasions were frequent (68% and 67%, respectively) even in patients who remained disease-free at least 5 years after diagnosis (61% and 60%, respectively). Our study demonstrates that the histologic types of early-onset breast cancer are not different from other BC. However, BC in young women is often associated with histologic features of high-grade malignancy even in patients with better survival. Our results suggest that BCs in young women are different from those that occur in older women.     

Sarcomatoid carcinoma of the urinary bladder. A clinicopathologic analysis of 12 cases and review of the literature

Twelve carcinomas of the urinary bladder with a prominent component of spindle-shaped cells (sarcomatoid carcinomas) that arose in patients from 60 to 83 (average, 71.5 years) years of age are reported. The seven male and five female patients typically complained of hematuria. Seven tumors were sessile and five were polypoid. On microscopic examination, the malignant spindle cells merged with in situ transitional cell carcinoma or various forms of invasive carcinoma, including transitional cell carcinoma (11 cases), adenocarcinoma (2 cases), squamous cell carcinoma (2 cases), and small cell undifferentiated carcinoma (2 cases). Immunocytochemical stains were performed in 11 cases; the spindle cells stained for cytokeratin, epithelial membrane antigen, and vimentin. Limited follow-up in this series does not allow for conclusions concerning differences in behavior between sarcomatoid carcinoma and conventional transitional cell carcinoma of similar grade and stage. However, the typically deep invasion of the former tumors and their histologic features indicate that they are highly aggressive neoplasms.     

Metaplastic breast carcinoma: a retrospective study of 26 cases

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.     

Oncocytic carcinoma of the breast: frequency, morphology and follow-up

Oncocytic breast carcinomas are tumors composed of no fewer than 70% of oncocytic cells (World Health Organization). The purpose of this study was to determine the frequency, morphologic, immunohistochemical, and clinical features of invasive oncocytic carcinoma in a large series. Twenty-eight cases of putative oncocytic breast carcinoma (selected cases group) and 76 consecutive cases of invasive breast carcinoma (consecutive cases group) were analyzed. Immunohistochemistry for mitochondria, gross cystic disease fluid protein 15, chromogranin, estrogen receptor, progesterone receptor, androgen receptor, HER2/Neu, cytokeratin 7, cytokeratin 14, epithelial membrane antigen, and differentiation cluster 68 was performed. Score for mitochondria was based on intensity and percentage of immunopositive cells. Classes were as follows: (1) oncocytic carcinoma: at least 70%, 3+; (2) mitochondrion-rich carcinoma: 50% to 70%, 3+, or more than 50%, 2+; and (3) all the other cases were referred to as invasive breast carcinoma. Ultrastructural examination was available for 6 cases of oncocytic carcinoma. Morphologic and immunohistochemical features of the 3 groups were compared using Fisher exact test (P < .05). For overall survival analysis, Kaplan-Maier curves were compared using log-rank and Wilcoxon tests (P < .05). Our results suggest that oncocytic breast carcinoma is a morphologic entity with distinctive histologic and ultrastructural features. Mitochondrion-rich carcinomas are histologically similar to oncocytic carcinomas and constitute 19.7% of all invasive carcinomas, indicating that cytoplasmic eosinophilia in breast cancer cells is often due to accumulation of mitochondria. Oncocytic carcinomas and mitochondrion-rich carcinomas are more often grade III tumors and show human epidermal growth factor receptor 2 overexpression. Clinical features and overall survival of oncocytic carcinomas are not distinctive because they are similar to those of the other cases when matched for grade and stage.     

Pathology and behavior of small breast carcinomas.

Mammographic screening and increased public awareness have changed the clinical spectrum of breast carcinoma with important implications for therapy. Small invasive breast carcinomas T1a,b, defined as 1.0 cm or less in maximum diameter, now comprise 22% of invasive carcinomas in our institution, enabling comparison of 273 T1a,b with 563 T1c (1.1 to 2.0 cm), 447 T2 (2.1 to 5.0 cm), and 40 T3 (>5 cm) carcinomas. Nuclear measurements were made with calibrated ocular grids. Hormone receptors were measured in cytosol or immunohistochemically. S-phase fraction (SPF) was measured prospectively on all carcinomas by counting cells in histologic preparations after vitro labeling with tritiated thymidine or 5-bromo-2'deoxyuridine. T1a (0.2 to 0.5 cm) carcinomas were similar to T1b (0.6 to 1.0 cm) in histologic and biologic features, but T1b carcinomas had higher detection rates of axillary metastasis (0% v 10%). The latter may reflect longer duration of metastases, permitting growth to detectable size. Low-grade carcinoma types (mucinous, tubular, cribriform) became less frequent as T stage increased, with the major decrease occurring at T1b (0.6 to 1.0 cm)/T1c (1.1 to 2.0 cm) boundary. T1a,b carcinomas preponderantly had low-grade histologic and biochemical characteristics and low SPF. SPF increased significantly with increasing tumor size from T1b through T2 but not beyond T2. Increases in proportion of patients with axillary metastases occurred over each T transition. Estrogen and progesterone receptor (ER, PgR) positivity decreased with increasing stage. Larger tumors were significantly associated with younger patient age. While this may reflect ease of diagnosing small carcinomas after the menopause, young age was also associated with predictors of aggressive tumor behavior (high SPF, negative assays for ER, PgR). T1a,b patients with mid or high SPF or axillary metastases were more likely than others to have received cytotoxic adjuvant therapy. Conclusions are: (1) Development of cell lines that have metastatic capability appears to occur near the T1b/T1c interface, but they exist very early in some carcinomas. (2) T1a carcinomas may be managed without axillary dissection. When T1b patients are candidates for adjuvant therapy, we advocate sentinel node biopsy with intensive study for micrometastases. (3) Accurate determination of size is very important in prognosis of small breast carcinomas. (4) Prognostic efficacy of proliferation and other prognostic markers in retrospective studies, but not in our patients who often received adjuvant therapy, suggest that micrometastases from small breast carcinomas are highly responsive to adjuvant chemo/hormonal therapy.     

脾脏转移癌的临床病理特点

目的探讨脾脏转移癌的临床病理特点及其转移规律。方法总结16例脾脏转移癌病例,复习临床、外检、尸检记录资料,对其性别、年龄、临床症状、原发部位、组织学类型、脾脏的大体特点、脾脏内肿瘤的生长方式进行了分析。结果16例脾脏转移癌中,男性12例,女性4例;男性显著多于女性;年龄范围从48岁到90岁,其中位年龄为66．5岁;临床症状主要表现为左上腹不适,疼痛,消瘦乏力,食欲不振等,有些病例可扪及脾肿大,CT可发现脾内占位。肺是脾脏转移癌的最主要的原发部位,占总例数的43．8％（7／16）;男性最常见的原发部位是肺,占50．0％（6／12）,而女性最多见的是卵巢（2／4）。组织学类型中,肺未分化癌是最多见的类型,占25．0％（4／16）,其中小细胞未分化癌3例,大细胞未分化癌1例;其他依次为：肺细支气管肺泡癌2例;结肠腺癌2例;卵巢浆液性乳头状囊腺癌2例;前列腺腺癌2例。男性最多见的类型是肺未分化癌,而女性为卵巢浆液性乳头状囊腺癌。脾脏转移癌的生长方式分为单结节性、弥漫性和多结节性3种类型,多数肿瘤表现为单结节性的生长方式,少数高转移潜能的肿瘤（5／16）表现为弥漫性和多结节的生长方式,包括肺小细胞未分化癌（3／3）,肺腺癌（1／1）和前列腺腺癌（1／2）。结论脾脏转移癌少见,掌握其临床病理形态特点对于病理诊断和临床处理有指导意义。     

Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.     

HER2/neu amplification in breast cancer: stratification by tumor type and grade

The presence of HER2/neu gene amplification is prognostically and therapeutically significant for patients with breast cancer. We sought to determine whether a relationship exists between HER2/neu gene amplification and the histologic type and grade of tumor. The histologic features and corresponding HER2/neu amplification results of 401 cases of invasive breast carcinoma were reviewed. Lobular carcinomas were less likely than ductal carcinomas to have HER2/neu amplification. Amplification was less frequent in Scarff-Bloom-Richardson grade I ductal carcinomas than in grades 2 and 3. Metastatic carcinomas frequently displayed HER2/neu amplification (6/20 [30%]). Our results support a correlation between HER2/neu amplification and the histologic type and grade of breast cancer. We suggest reexamination of tumors diagnosed as Scarff-Bloom-Richardson grade I invasive ductal carcinomas or lobular carcinomas if the lesion displays HER2/neu amplification to assure the exclusion of a higher grade of lesion or of missed ductal components.     

Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast. Are WT1, CA125, and GCDFP-15 useful in differential diagnosis?

Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast have close histologic similarities. Thus, when these cancers occur synchronously or metachronously in the same patient, it is difficult to determine the primary site. We examined 23 serous papillary adenocarcinomas (16 ovarian, 5 endometrial, and 2 peritoneal) and 37 invasive micropapillary carcinomas of the breast (12 pure and 25 mixed types) on immunohistochemical expression of Wilm's tumor antigen-1 (WT1), CA125, and gross cystic disease fluid protein-15 (GCDFP-15), which have been reported to be useful in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary. The positive rates of WT1, CA125, and GCDFP-15 in serous papillary adenocarcinomas were 78%, 78%, and 0%, respectively, and the corresponding rates in invasive micropapillary carcinomas were 3%, 40%, and 38%. The CA125-positive rate of invasive micropapillary carcinoma was higher than the rate reported for other types of breast carcinomas. We consider CA125 to be not always useful in the differential diagnosis of serous papillary adenocarcinoma and invasive micropapillary carcinoma. Although the positive rate of WT1 was significantly higher in serous papillary adenocarcinoma than in invasive micropapillary carcinoma, WT1 expression in endometrial serous papillary adenocarcinoma was infrequent (20%). WT1 and GCDFP-15 could be useful markers for the differential diagnosis of ovarian and peritoneal serous papillary adenocarcinoma versus breast invasive micropapillary adenocarcinoma. However, the availability of GCDFP-15 is limited because of the low positive rate of GCDFP-15 in invasive micropapillary carcinomas.     

Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma.

Breast carcinoma with a high histologic grade is highly invasive and metastatic. One reason for its irregular morphology is the formation of excessive protrusions due to assemblages of branched actin filament networks. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein2 (WAVE2), a member of the WASP protein family. In this study, the localization Arp2 and WAVE2 in breast carcinoma was investigated to clarify whether coexpression of the two proteins is associated with histologic grade or patient outcome. Immunohistochemical staining of Arp2 and WAVE2 was performed on mirror specimens of 197 breast carcinomas, and the association between coexpression of the two proteins and clinicopathologic factors was examined. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of Arp2 and WAVE2 coexpression in breast carcinoma. Coexpression of Arp2 and WAVE2 was detected in 64 (36%) of 179 invasive ductal carcinomas and in 2 (11%) of 18 ductal carcinomas in situ, but was not detected in any adjacent non-cancerous tissue. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with high histologic grade (P<0.0001), and cases with lymph node metastasis (P=0.0150). The patients whose cancer cells showed such coexpression had shorter disease-free (P=0.0002) and overall survival (P=0.0122) than patients whose cancer cells expressed only one or none of Arp2 and WAVE2. Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent factor for both tumor recurrence (P=0.0308) and death (P=0.0455). These results indicate that coexpression of Arp2 and WAVE2 is a significant prognostic factor that is closely associated with aggressive morphology of invasive ductal carcinoma of the breast.     

Breast carcinoma with micropapillary features: clinicopathologic study and long-term follow-up of 100 cases

To study the clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma of breast (IMPC), 100 cases of invasive breast carcinoma with an IMPC component were reviewed. Compared with invasive ductal carcinoma, not otherwise specified, with similar histologic grades, carcinomas with IMPC were larger sized, had a higher lymph node metastasis rate with more nodes involved per case, and exhibited increased lymphovascular invasion. The presence of IMPC strongly correlated with the more aggressive behavior. No significant association was established between the proportion of the IMPC component and overall tumor size, histologic grade, lymph node metastasis rate, and distant metastasis, but a trend was noted. Long-term follow-up demonstrated a poorer 5-year and 10-year survival rate for patients with breast carcinoma containing an IMPC component. Breast carcinomas with micropapillary features are more aggressive tumors with a poorer prognosis. This specific structure should be carefully evaluated in the surgical pathology examination of breast carcinoma specimens.     

Invasive lobular carcinoma: to grade or not to grade.

Grading of invasive ductal carcinoma of no special type using the Nottingham combined histologic grading system provides independent prognostic information. The prognostic utility of grading invasive lobular carcinomas, however, has not been fully elucidated. In addition, the relationship between grade in invasive lobular carcinomas and expression of predictive biomarkers is less certain. The purpose of this study was to correlate histologic grade in invasive lobular carcinoma with known prognostic and predictive markers. All primary resections for invasive mammary carcinomas diagnosed in Mount Sinai Hospital, Toronto, between the years 1996 and 2002 were reviewed (n=1053). Of these cases, 50 were pure invasive lobular carcinoma (incidence 4.7%). The median age at diagnosis was 64 years. These tumors were graded using the Nottingham combined histologic grading system and analyzed for estrogen receptor, progesterone receptor, HER2/neu and E-cadherin expression. Tumor grade was correlated with tumor size (P=0.03), and the American Joint Committee on Cancer nodal status (P=0.05). Assessment of the individual components of grade showed that the mitotic score was highly correlated with tumor size (P=0.02), lymph node positivity (P=0.02) and overall American Joint Committee on Cancer stage (P=0.01). Estrogen receptor and progesterone receptor were highly expressed irrespective of the grade of tumor. HER2/neu protein overexpression and E-cadherin protein expression was absent in all invasive lobular carcinomas studied. We conclude that pure invasive lobular carcinoma is uncommon and occurs predominantly in postmenopausal women. Increasing tumor grade is correlated with median tumor size and the American Joint Committee on Cancer nodal stage, but not correlated with the expression of estrogen receptor, progesterone receptor, E-cadherin or HER2/neu protein overexpression.     

Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma

Rsf-1 protein is a member of a chromatin-remodeling complex that plays an important role in regulating gene expression and cell proliferation. Our previous study showed that Rsf-1 was an amplified gene that participated in the development of ovarian serous carcinoma. To further elucidate the role of Rsf-1 in ovarian cancer, we studied Rsf-1 immunoreactivity in 294 ovarian tumors of various histologic types. Because the Rsf-1 amplicon overlaps an amplified region reported in breast cancer, we included 782 neoplastic and normal breast tissues for comparison. Immunohistochemistry was performed on tissue microarrays using a 4-tiered scoring system. Overexpression of Rsf-1 was defined as a nuclear immunointensity of 3+ to 4+ because of a strong correlation between 3+ and 4+ immunointensity and Rsf-1 gene amplification, based on our previous fluorescence in situ hybridization analysis. Rsf-1 overexpression was observed in 25% of high-grade ovarian serous carcinomas and in only rare cases (<7%) of low-grade ovarian serous, ovarian endometrioid, and invasive breast carcinomas but not in any ovarian serous borderline tumors, ovarian clear cell carcinomas, ovarian mucinous carcinomas, intraductal carcinomas of the breast, and normal ovaries and breast tissues. Thus, overexpression of Rsf-1 was significantly associated with high-grade ovarian serous carcinoma (P < .05), as compared with other types of ovarian tumors and breast carcinomas. Our results provide evidence that Rsf-1 expression is primarily confined to high-grade serous carcinoma, the most aggressive ovarian cancer. Because Rsf-1 overexpression occurs in only a small number of breast carcinomas, it is unlikely that Rsf-1 is a critical gene in the development of breast carcinoma.     

Carcinoma Arising in Microglandular Adenosis: An Immunohistochemical Analysis of 20 Intraepithelial and Invasive Neoplasms

Microglandular adenosis (MGA) of the breast is an uncommon, benign lesion that may mimic invasive carcinoma and has recently been recognized as having significant premalignant potential. When carcinomas arise in MGA, there is often a transition from ordinary MGA to atypical MGA (AMGA) to carcinoma. Nineteen cases of carcinoma arising in MGA are reported: 7 invasive carcinomas, 7 intraductal carcinomas (DCIS), and 5 with both invasive and intraductal carcinoma. A single case of AMGA without carcinoma is also reported. The 20 patients ranged in age from 36 to 81 years (mean 52). The most common clinical presentation was either a palpable mass (13 patients) or a mammographic abnormality (4 patients). All 20 cases contained AMGA, and in some cases AMGA was the predominant lesion. In 18 of the 19 cases with carcinoma, there was a clear transition from AMGA to the carcinoma. Twelve cases contained ordinary MGA, but in only 2 cases was MGA a prominent component of the lesion. In contrast to ordinary MGA, the glands of AMGA were more irregularly shaped, closely packed, and cytologically atypical and tended to lack secretions. A solid, occlusive proliferation of cells in the tubules was seen in 10 cases. All 12 examples of in situ carcinoma were either grade 2 or 3 and typically showed a solid proliferation of severely atypical cells within the glands; a cribrifrom pattern was also present in 1 case. The invasive carcinomas were morphologically diverse and included 2 with a basaloid morphology and 2 metaplastic carcinomas. Various immunostains were performed, and each lesion (AMGA, in situ, and invasive carcinoma) was separately assessed for immunoreactivity. As expected, S-100 was positive in the vast majority of AMGA and in situ carcinomas and in all 12 invasive carcinomas. S-100beta was also positive in the majority of cases although the staining was weaker. Laminin and type IV collagen highlighted the basement membrane around the AMGA and in situ carcinoma and are useful stains in difficult cases. Except for a single case, ER and PR were negative in all lesions. Cytokeratin 7 (CK 7) was positive, while cytokeratin 20 (CK 20) was negative in all cases. Immunostains for CK903 showed no reactivity in any of the invasive carcinomas, in situ carcinomas, or atypical MGA but was focally present in the associated MGA in 2 of the 8 cases studied. Immunostains for MIB-1 and p53 were semiquantitatively assessed and both were positive in AMGA but tended to show a more intense staining in the carcinomas. Five cases were also studied for immunoexpression of alpha-1 antitrypsin (AAT), alpha-1 antichymotrypsin (ACTP), lysozyme, and salivary gland amylase. All 5 invasive carcinomas were positive for ACTP, though the staining was very focal in about 10% of the cells in a basaloid carcinoma. The in situ carcinoma as well as the AMGA in 4 of the 5 cases were positive for ACTP. Three of the 5 invasive carcinomas were positive for AAT in 10% to 40% of the cells. The most intense positivity for AAT and ACTP was in cells with coarsely granular apocrine appearance evident in 2 of the 5 cases. Four of the 5 invasive carcinomas were positive for lysozyme in 10% to 50% of the cancer cells; the in situ carcinoma and the associated AMGA showed similar immunoreaction in each case. None of the 5 cases showed convincing positivity for salivary gland amylase. The MGA in all 5 cases was negative for AAT and ACTP; the MGA in 1 of the 5 cases was positive for lysozyme. This study confirms the potential of MGA to develop into an invasive carcinoma, more clearly defines the features of AMGA, highlights the importance of AMGA in the evolution of carcinoma from MGA, and expands our knowledge of the immunophenotype of AMGA and the carcinomas arising from it. The diagnostic criteria briefly noted previously for diagnosis of AMGA and carcinoma arising in MGA are expanded and formally proposed. Int J Surg Pathol 8(4):303-315, 2000     

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.     

E-cadherin status in breast cancer correlates with histologic type but does not correlate with established prognostic parameters

Our objective was to assess the loss of E-cadherin (EC) as a diagnostic marker or a predictor of prognosis. We stained 276 breast carcinomas with monoclonal antibodies to EC (invasive lobular carcinomas [ILC] and variants, 59; invasive ductal carcinoma and ductal special types [IDC], 204; tubulolobular carcinoma [TLC], 4; and invasive carcinoma [IC], uncertain whether lobular or ductal type, 9). The results were as follows: EC+IDCs, 99.5%; EC-ILCs, 90%; EC+ILCs, 10%; EC+pleomorphic ILCs, 20%; EC-ICs, 44%. All 4 TLCs showed positive tubules while cords were negative. Statistically a correlation of EC loss with a positive diagnosis of ILC was found but there was no correlation with any prognostic tumor variables. A negative EC stain confirms the diagnosis of ILC (specificity, 97.7%; negative predictive value, 96.8%; sensitivity, 88.1%; positive predictive value, 91.2%). EC is helpful in classifying cases with indeterminate histologic features. EC loss is uncommon in nonlobular carcinomas with no correlation to currently established prognostic variables.     

c-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma.

AIMS: To assess c-erbB-2 immunostaining in relation to morphological type of in situ and invasive breast carcinoma. METHODS: Formalin fixed, wax embedded archival tissue was used. Invasive carcinomas comprised 50 infiltrating ductal (NOS); seven medullary, 10 tubular, 15 mucinous and 24 classic invasive lobular. In situ carcinomas comprised 48 ductal (DCIS) and 10 cases of lobular (LCIS). The antibodies used were pAB1 (polyclonal) which stains cell lines that over express the c-erbB-2 oncogene, and ICR 12 (monoclonal) which stains sections of breast carcinoma known to show c-erbB-2 amplification. RESULTS: Immunostaining consistent with c-erbB-2 overexpression was found in 10 out of 50 cases of infiltrating ductal carcinoma (NOS), one of 24 infiltrating lobular carcinomas and one of seven medullary carcinomas only. Seventy per cent of ICR 12 positive cases of infiltrating ductal carcinoma also had extratumoral DCIS. Forty six per cent of pure DCIS lesions also showed strong membrane staining for c-erbB-2 protein, confined to large cell types. CONCLUSIONS: Immunostaining for c-erb B-2 oncoprotein occurs mainly in large cell DCIS and infiltrating ductal carcinoma NOS, especially those with an extratumoral DCIS component. There is a low incidence in other types of breast cancer, including those associated with a better prognosis. Different biological mechanisms may be responsible for histologically distinct types of breast carcinoma.     

Mucinous breast carcinomas lack PIK3CA and AKT1 mutations

Activating point mutations in the phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) are among the most common molecular defects in invasive breast cancer. Point mutations in the downstream kinase AKT1 are seen in a minority of carcinomas. These mutations are found preferentially in estrogen receptor-positive and Her2-positive breast carcinomas; however, special morphologic types of breast cancer have not been well studied. Twenty-nine cases of pure invasive mucinous carcinoma and 9 cases of ductal carcinoma with mucinous differentiation were screened for a panel of point mutations (>321 mutations in 30 genes) using a multiplex polymerase chain reaction panel with mass spectroscopy readout. In addition, associated ductal carcinoma in situ, hyperplasia, or columnar cell lesions were separately tested where available (25 lesions). In 3 invasive cases and 15 ductal carcinoma in situ/proliferative lesions, PIK3CA hotspot mutations were, instead, tested by direct sequencing. No point mutations were identified in invasive mucinous breast carcinoma. This contrasts with the 35% frequency of PIK3CA mutations in a comparative group of invasive ductal carcinomas of no special type. Interestingly, PIK3CA hotspot point mutations were identified in associated ductal carcinoma in situ (3/14) and hyperplasia (atypical ductal hyperplasia [2/3], usual ductal hyperplasia [2/3], columnar cell change [1/5]), suggesting that PIK3CA mutations may play a role in breast epithelial proliferation. This series represents the largest study, to date, of PIK3CA genotyping in mucinous carcinoma and supports the unique pathogenetics of invasive mucinous breast carcinoma.     

Breast carcinoma in patients receiving neuroleptic therapy. Morphologic and clinicopathologic features of thirteen cases.

We report 13 cases of breast carcinoma in patients treated with neuroleptics (prolactin-releasing drugs). Twelve of the patients were female and one was male. Nine patients had unicentric carcinoma, one had multicentric tumors arising synchronously, and three had bilateral tumors (synchronous in one case and metachronous in two cases). Thirteen tumors in ten patients were invasive ductal carcinomas, two tumors in one patient were mucinous carcinomas, and the two other patients had lipid-secreting carcinomas. Immunohistochemical staining showed alpha-lactalbumin (alpha-LA) in the lipid-secreting carcinomas at sites exhibiting active lipid secretion. A precise cause-effect relationship is difficult to elucidate, since the patients ranged in age from 40 to 64 years (mean: 51 years) when cancer was first diagnosed. However, the relatively high incidence of multiple tumors and the production of lipid and alpha-LA by the cancer cells were unusual features suggesting an association with neuroleptic therapy.     

Secretory breast carcinoma: a clinicopathological and immunophenotypic study of 15 cases with a review of the literature

Secretory breast carcinoma is a rare breast cancer with indolent clinical behavior. Recent research showed that secretory breast carcinoma belongs to the phenotypic spectrum of basal-like breast carcinomas. In this study, a clinicopathological and immunophenotypic analysis of secretory breast carcinomas from 15 Chinese patients was conducted. This patient group consisted of 2 males and 13 females, with ages ranging from 10 to 67 years old (median, 36 years old). All patients presented with a painless and firm mass. Tumor size ranged from 10 to 55?mm. Most tumors were located in the outer upper quadrant of the breast. Two patients (2 of 13, 15%) displayed positive axillary lymph nodes. At the microscopic level, the presence of intracellular and extracellular secretory material was the most remarkable feature. Most cases showed mild dysplasia cytologically. All cases were negative for estrogen receptor, progesterone receptor and HER2. The expression rate of the basal-like marker (CK5/6 or epidermal growth factor receptor) was 87% (13 of 15). The basal-like phenotype was identified in 13 cases (87%). Follow-up time ranged from 10 to 55 months (median, 19 months). None of the cases had evidence of recurrence and metastasis. Our study reveals that secretory breast carcinoma is a distinct subset of invasive breast carcinoma, with expression of basal-like markers. It should be noted that secretory breast carcinoma is different from conventional basal-like breast carcinomas. Future studies are required to further understand the prognostic significance of the basal-like markers expression in secretory breast carcinomas.