Breast cancer is a complex and heterogeneous disease, comprising multiple tumor entities associated with distinctive histological patterns and different biological features and clinical behaviors. Microarray-based high-throughput technologies have been employed to unravel the molecular characteristics of breast cancer, including its proclivity to disseminate to distant sites, and the molecular basis for histological grade. In addition, a breast cancer molecular taxonomy based solely on transcriptomic analysis has been proposed. Most microarray studies have focused on invasive ductal carcinomas of no special type, neglecting the important information about the biology and clinical behavior of breast cancers conveyed by histological type. Histological special types of breast cancer account for up to 25% of all invasive breast cancers. The histopathological characteristics of these cancers might be driven by specific genetic alterations, providing direct evidence for genotypic-phenotypic correlations between morphological patterns and molecular changes in breast cancer. We review the historical aspects of breast cancer taxonomy, discuss the possible origins of the diversity of breast cancer and propose an approach for the identification of novel therapeutic targets on the basis of histological special types of breast cancer.

Histological and molecular types of breast cancer: is there a unifying taxonomy?

Triple-negative breast cancer is viewed clinically as an aggressive subgroup of breast cancer. In fact, most triple-negative breast cancers are poor-prognosis tumors with a complex genomic landscape. However, triple-negative disease is vastly heterogeneous, encompassing multiple entities with marked genetic, transcriptional, histologic, and clinical differences, with neoplasms in this group ranging from low to high grade. Among the less common low-grade triple-negative lesions, two large subgroups, both with a rather indolent behavior, can be distinguished: a low-grade triple-negative breast neoplasia family, which includes nonobligate precursors of triple-negative breast cancer, and, despite being low-grade, harbors the complex genomic landscape of usual triple-negative breast cancer, and the salivary gland-like tumors of the breast, lacking all the cardinal molecular features of conventional triple-negative breast cancer and underpinned by specific fusion genes or hotspot mutations, which may be of diagnostic and possibly therapeutic utility. Progression to high-grade triple-negative breast cancer likely occurs in both subgroups but at different rates. In this review, we describe the heterogeneity of triple-negative disease, focusing on the histologic and molecular features of the low-grade lesions. Recognition that triple-negative breast cancer is an operational term and that triple-negative disease is heterogeneous and includes low-grade forms driven by distinct sets of genetic alterations is germane to the successful implementation of precision medicine.

The Spectrum of Triple-Negative Breast Disease: High- and Low-Grade Lesions.

Papillary lesions comprise a wide spectrum of lesions in terms of their clinical presentation, morphologic appearance, malignant potential, and clinical behavior. Their defining feature is that of a fibrovascular stromal core lined by epithelial and myoepithelial cells, attached to the wall of the duct and extending into the duct lumen. Papillary lesions are often diagnostically challenging both on core biopsy and in excision specimens. Much of the difficulty arises from the many different terminologies that are used to describe the various entities that are included under the umbrella term of papillary lesions. Separation of papillary lesions into categories with a meaningful clinical outcome is most appropriate; however, there is a relative paucity of well-designed outcome studies with substantial cohort numbers to provide information in this regard. We use a pragmatic approach to the classification of papillary lesions in our practice, as we will outline in this review. We will also discuss controversies surrounding papillary lesions and focus on management of these lesions on core biopsy and in excision specimens.

Papillary lesions of the breast: a review.

The World Health Organization’s new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast carcinomas which is still principally based on histological features and follows the traditions of histological typing. It gives a subjective and critical view on the WHO classifications and their changes over time, and describes the changes related to some of the most common or challenging breast carcinomas: in situ carcinomas, invasive breast carcinomas of no special type, lobular, cribriform, tubular, mucinous, papillary, metaplastic carcinomas and carcinomas with medullary pattern and those with apocrine differentiation are discussed in more details. Although the 5th edition of the classification is not perfect, it has advantages which are mentioned along with problematic issues of classifications.

https://www.pathologica.it/article/download/96/126

Histological type and typing of breast carcinomas and the WHO classification changes over time.

Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.

Triple-Negative Breast Cancer Histological Subtypes with a Favourable Prognosis.

Five cases of a hitherto undescribed breast tumor having histologic features similar to those of the tall cell variant papillary thyroid carcinoma are described. They were composed of columnar mitochondrion-rich to oxyphilic cells arranged in nests, papillae, and follicle-like structures. In addition, the neoplastic cells showed numerous nuclear grooves and, in two cases, nuclear pseudo-inclusions. None of the patients had previous concomitant or subsequent evidence of a thyroid tumor. Immunohistochemistry further excluded a metastasis from the thyroid in the four cases tested, as they were consistently thyroglobulin and thyroid transcription factor 1 negative.

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases.

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Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases.