Rare coexistence of invasive papillary carcinoma with infiltrating ductal carcinoma in male breast: report of a case

Invasive papillary breast carcinoma is a subtype of breast cancer that is more frequent in males. An intraductal carcinoma can coexist with it but association of an infiltrating carcinoma has not been described. This report presents a rare case of a 35-year-old man with dual malignancy in the same breast. The patient had two separate nodules, one with the morphology of invasive papillary carcinoma and the other having features of an infiltrating ductal carcinoma. To the best of our knowledge this is the first case report describing the coexistence of these two entities.     

Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges

Tang F, Wei B, Tian Z, Gilcrease M Z, Huo L, Albarracin C T, Resetkova E, Zhang H, Sahin A, Chen J, Bu H, Abraham S & Wu Y
(2011) Histopathology 59 , 106–115 Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges Aims: The aim of this study was to review the histomorphological features of primary neuroendocrine carcinomas (NEC) of the breast, in order to identify features useful in recognition of this entity for appropriate classification. Methods and results: 2003 World Health Organization (WHO) classification of tumors of the breast and female genital organs defined NEC of the breast as a subtype of invasive mammary carcinoma in which >50% of the tumor cells express neuroendocrine markers. Seventy‐four cases that fulfilled the WHO diagnostic criteria for NEC of the breast, excluding small cell carcinoma and low‐grade solid papillary carcinoma with a predominant in‐situ component, were identified between 1984 and 2008 from MD Anderson Cancer Center, and were included in the study. NECs of the breast had variable histomorphological features. The most common histologic patterns were papillary (80%) and nested (64%). Mixed growth patterns were common (59%), including admixed ductal component. The tumor cells could be polygonal, round, plasmacytoid, spindled, or with signet ring cell features. The cytoplasm could be granular, eosinophilic, clear, or finely vacuolated. These tumors frequently mimicked invasive or in situ ductal carcinoma, or invasive lobular carcinoma. Conclusions: NEC of the breast is underrecognized. Careful attention to cytologic and architectural features can help to identify cases that require further immunophenotypic confirmation for correct tumor classification.     

Fine-needle aspiration biopsy of invasive micropapillary carcinoma of the breast: a report of five cases

Invasive micropapillary carcinoma of the breast is an uncommon variant of infiltrating ductal carcinoma. Observing its distinctive cytologic appearance and aggressive behavior is important for early diagnosis by fine-needle aspiration cytology (FNAC). There are only a few reported cases in the literature. Five women presented with breast masses. FNAC showed malignant epithelial tumors, and mastectomy materials showed invasive micropapillary carcinoma for all of them. Three patients had axillary lymph node metastases. Invasive micropapillary carcinoma, with its angulated papillary clusters lacking a fibrovascular core, and irregular crowded nuclei, has a distinctive cytologic appearance which correlates with its histological features. A differential diagnosis from other primary or metastatic papillary lesions of the breast may be possible using immunohistochemistry and some cytologic features. The limited experience with invasive micropapillary carcinoma should not discourage others from undertaking further studies.     

Scatter factor protein levels in human breast cancers: clinicopathological and biological correlations.

Scatter factor (SF) is an invasogenic and angiogenic cytokine the cellular receptor of which is encoded by a proto-oncogene (c-met). We measured the immunoreactive SF content (nanograms of SF per milligram of protein) in tissue extracts from 166 breast cancers and correlated the values with various known prognostic parameters. Invasive cancers had nearly four times greater SF content than did ductal carcinoma in situ, and the difference was statistically significant (P < 0.02, two-tailed t-test). However, there were no significant differences in SF content among different histological types of invasive cancer. Invasive cancers that had spread to axillary lymph nodes exhibited higher SF content than did invasive cancers without regional spread (P < 0.02), but the difference in SF content between node-positive and node-negative tumors was not as great as that between invasive and ductal carcinoma in situ tumors. There was a trend toward increased SF content in larger primary tumors as compared with smaller tumors, but statistical comparison revealed borderline significance (0.05 < P < 1.0). There was no significant correlation between SF content and other parameters, including estrogen receptor, progesterone receptor, DNA ploidy, S phase, or Scarff-Bloom-Richardson score. We also measured the content of von Willebrand factor (a marker of blood vessels) and interleukin-1 beta (a pro-inflammatory cytokine) in the same tumor extracts. SF content showed a strong positive correlation with von Willebrand factor content (P < 0.001) but did not appear to be correlated with interleukin-1 beta. These findings suggest that SF is correlated with several other clinicopathological indicators of aggressive tumor behavior, consistent with the hypothesis that SF is a biological factor that may play a role in breast cancer pathogenesis.     

Prognostic significance of tumor grading and staging in mammary carcinomas with neuroendocrine differentiation

Invasive mammary carcinoma with neuroendocrine differentiation has been controversial in terms of its definition and clinical outcome. In 2003, the World Health Organization histologic classification of tumors designated this entity as neuroendocrine carcinoma of the breast and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. It is an uncommon neoplasm. Our recent study showed that it is a unique clinicopathologic entity and has a poor clinical outcome compared with invasive mammary carcinoma with similar pathologic stage. Other investigators have also demonstrated a different molecular profile in this type of tumor from that of invasive ductal carcinoma. It is unknown whether the current prognostic markers for invasive mammary carcinoma are also applicable for neuroendocrine carcinoma of the breast. In the current study, we reviewed the clinicopathologic features and outcome data in 74 cases of mammary neuroendocrine carcinoma from the surgical pathology files at The University of Texas, MD Anderson Cancer Center, to identify relevant prognostic markers for this tumor type. As shown previously by univariate analysis, large tumor size, high nuclear grade, and presence of regional lymph node metastasis are adverse prognostic factors for overall survival and distant recurrence-free survival. In the current study, multivariate analysis revealed that overall survival was predicted by tumor size, lymph node status, and proliferation rate as judged by Ki-67 immunohistochemistry. Only nodal status proved to be a significant independent prognostic factor for distant recurrence-free survival. Neither mitosis score nor histologic grade predicted survival in mammary neuroendocrine carcinoma. Our data suggest that routine evaluation of Ki-67 proliferation index in these unusual tumors may provide more valuable information than mitotic count alone.     

New prognostic histological parameter of invasive ductal carcinoma of the breast: clinicopathological significance of fibrotic focus

Immunohistochemistry, DNA ploidy analysis and molecular genetics have made it possible to predict the outcome of breast cancer more precisely than routine histological examination alone. However, in routine practice, it is difficult to incorporate these methodologies in all cases. If certain histological parameters can accurately predict the outcome of patients with breast cancer, they would be more practical for routine use. We showed that the presence of fibrotic focus (FF) in invasive ductal carcinoma (IDC) is closely associated with c-erbB-2 or p53 protein expression, high proliferative activity, and high angiogenesis of the tumors. Furthermore, multivariate analyses with well-known prognostic parameters for IDC demonstrated that the presence of FF is the most useful independent parameter to predict IDC patient outcome. In addition, our data suggested that the interaction between tumor cells and stromal fibroblasts may play an important role in the formation of FF in IDC based on growth factor and growth factor receptor protein expression in the tumor cells and fibroblasts forming FF. Based on the results of our clinicopathological studies, we propose a new prognostic classification scheme for the prediction of IDC patient outcome, which consists of FF, nuclear atypia, and fat invasion. This classification has superior predicting power to existing prognostic classifications.     

Invasive Mammakarzinome: Die aktuelle WHO-Klassifikation

The World Health Organization (WHO) classification of tumors of the breast defines the international standards for tumor categorization and nomenclature. The fourth edition, published in 2012, provides an update on the current knowledge concerning the classification, immunohistology profile, differential diagnosis and genetics of these lesions. Compared to the previous edition, some terms have been modified, some entities were reclassified and some current molecular data have been added. This article focuses on invasive carcinomas. Definitions for histological diagnosis are supplemented by clinical, macroscopic and molecular characteristics as well as prognostic and predictive features.     

Histological subtypes in triple negative breast cancer are associated with specific information on survival

Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC.A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed.Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18–3.03; p = 0.008; OS HR 1.94; 95% CI 1.28–2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes.In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.     

The 2012 ISUP Vancouver and 2016 WHO classification of adult renal tumors: changes for common renal tumors

In the past decade, the histological classification of renal neoplasia has undergone significant changes. Many new entities with distinct clinical, pathological and genetic features have been identified. In addition, common and established tumor entities have been further refined with regard to their pathological and genetic features. These changes have been incorporated in the 2012 International Society of Urological Pathology Vancouver classification and also in the 2016 World Health Organization classification. This article will focus on the new discoveries of clinical, pathological and molecular characteristics of the common renal tumors, including clear cell renal cell carcinoma, multilocular cystic renal neoplasm of low malignant potential, papillary renal cell carcinoma, chromophobe renal cell carcinoma, mucinous tubular and spindle cell renal cell carcinoma, collecting duct carcinoma, renal medullary carcinoma, papillary adenoma, oncocytoma, metanephric tumors, angiomyolipoma, and mixed epithelial and stromal tumor.     

Infiltrating lobular carcinoma of the breast with histiocytoid features: three cases

Histiocytoid carcinoma of the breast, a cellular variant of invasive breast cancer, is mainly found among infiltrating lobular carcinomas (ILC). It can be easily confused with benign conditions or other mammary tumors also composed of cells with a pink granular to foamy cytoplasm and an eccentric nucleus. We report 3 cases of histiocytoid ILC. Our aim is to discuss recent immunocytochemical data that could suggest a special type of apocrine differentiation of tumor cells, including a diffuse immunoreactivity for GCDFP-15 (Gross Cystic Disease Fluid Protein 15) and a predominant expression of androgen receptor, and to describe the features useful for the differential diagnosis.     

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

Oncotype DX is an RT-PCR-based 21-gene assay validated to provide prognostic and predictive information in the form of a Recurrence Score in patients with estrogen receptor-positive, lymph node-negative breast cancer. Although the Recurrence Score was shown to correlate with several histopathological tumor features, there is a significant proportion of cases showing an apparent discrepancy between Recurrence Score and risk estimates based on the traditional clinicopathological tumor features. In this study, we tested whether a proliferating, cellular stroma and/or admixed inflammatory cells may result in an artificially increased Recurrence Score in low-grade invasive breast cancers. We analyzed the histopathological features in 141 low-grade invasive breast carcinomas, including 41 special type (tubular, cribriform and mucinous) carcinomas, with available Recurrence Score. The tumor stroma was evaluated for increased cellularity and presence of inflammatory cells. Double immunohistochemical stains for pancytokeratin and Ki-67 was performed to assess the cell proliferation in tumor vs stromal/inflammatory cells. The clinicopathological features of tumors with Recurrence Score <18 (low risk) were compared with those with Recurrence Score ≥18 (intermediate/high risk). Carcinomas associated with Recurrence Score ≥18 showed lower progesterone receptor immunoreactivity, increased stromal cellularity and presence of inflammatory cells associated with the tumor. Double immunohistochemical stains showed significantly increased proliferation in stromal/inflammatory cells compared with carcinoma cells in cases associated with Recurrence Score ≥18. A Ki-67-positive stromal/tumor cells ratio of >1 predicted Recurrence Score ≥18 with an area under the curve of 0.8967 on receiver operator curve analysis (P<0.0001). Our results suggest that the presence of increased stromal cellularity and/or associated inflammatory cells in low-grade invasive breast carcinomas may contribute to an apparently increased risk of recurrence according to Oncotype DX Recurrence Score. Careful assessment and correlation with histopathological features in such cases may help in determining the appropriate patient management.     

Molecular classification of breast cancer

Breast cancer is a complex, multifaceted disease encompassing a great variety of entities that show considerable variation in clinical, morphological and molecular attributes. Traditional classifications including histological assessment and clinical staging are used to guide patient management. In recent years, there has been exponential progress in molecular analysis with profound implications for our understanding of breast cancer biology and, hence, classification. There are now genome-based frameworks for the molecular categorisation of breast cancer including the development of prognostic and predictive signatures that potentially allow individualisation of treatment. Here we review the current state of the molecular classifications of in situ and invasive breast cancer including special subtypes. Future perspectives are also provided.     

Invasive ductal carcinoma: correlation of apparent diffusion coefficient value with pathological prognostic factors

The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of invasive ductal carcinoma with pathological prognostic factors. A prospective study was conducted on 59 untreated female patients (mean age 46 years) with invasive ductal carcinoma. All patients were examined at 1.5 Tesla using dedicated bilateral breast coil. They underwent diffusion weighted MR imaging of the breast using a single shot echo planar imaging with a b‐factor of 200 and 400 sec/mm2. Apparent diffusion coefficient (ADC) maps were reconstructed. The ADC value of the breast cancer was calculated and correlated with the pathologic prognostic factors (tumor size, grade and lymph nodes). The mean ADC values of invasive ductal carcinoma were significantly lower in patients with high grade, large breast cancer as well as those with axillary lymph nodes metastasis in a statistically significant way (p = 0.001 for the three factors). The mean ADC value of invasive ductal carcinoma was correlated with histologic grade (r = ?0.675, p = 0.001), tumor size (r = 0.504, p = 0.001) and showed lower ADC values with positive lymph node metastasis. Apparent diffusion coefficient value is correlated with pathological parameters of invasive ductal carcinoma. The lower ADC values are associated with higher histological grade, larger tumor size and presence of axillary lymph nodes. So, the ADC value can be considered as a promising prognostic parameter that may identify highly aggressive breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.     

Breast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical management

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over‐ or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision‐making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low‐grade adenosquamous carcinoma, low‐grade fibromatosis‐like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed.     

Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features.

Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph node metastasis. The distinct patterns of P- and E-cadherin expression observed in this study strongly suggest a differential role for these cadherins in human breast carcinogenesis.     

Morphological heterogeneity of the simultaneous ipsilateral invasive tumor foci in breast carcinoma: A retrospective study of 418 cases of carcinomas

The aim of this paper was to assess whether the morphological appearance (i.e. histological tumor type and histological grade) of simultaneous invasive breast carcinoma foci is heterogeneous, since it is known that adjuvant therapy is established according to these parameters. Patients with simultaneous breast tumors in which only the features of the largest neoplastic focus are reported could thus be undertreated.