Syringomatous Tumour Presenting as Inversion of a Supernumerary Nipple

Syringomatous tumour (SyT) is a rare type of benign locally infiltrative tumour with debated origin. Because of the growth pattern, SyT can be mistaken for a malignant tumour, and it is therefore important to keep this diagnosis in mind. This case presents a woman with two supernumerary nipples on each side of the abdomen. One of the nipples was inverted with a small palpable firm mass in close relation to the nipple, leading to referral to the breast surgery department. SyT occurring in a supernumerary nipple and presenting with the symptoms described in this case has to our knowledge never been described previously

Poor response to neoadjuvant chemotherapy in metaplastic breast carcinoma.

Metaplastic breast carcinoma (MpBC) is a rare special histologic subtype of breast carcinoma characterized by the presence of squamous and/or mesenchymal differentiation. Most MpBCs are of triple-negative phenotype and neoadjuvant chemotherapy (NAC) is frequently utilized in patients with MpBC. The aim of this study was to evaluate response to NAC in a retrospective cohort of MpBCs. We identified 44 patients with MpBC treated with NAC at our center between 2002 and 2018. Median age was 48 years, 86% were clinical stage II-III, and 36% were clinically node-positive. Most (80%) MpBCs were triple-negative or low (1-10%) hormonal receptor positive and HER2 negative on pre-NAC biopsy. While on NAC, 49% showed no clinical response or clinico-radiological progression. Matrix-producing subtype was associated with clinico-radiological response (p = 0.0036). Post NAC, two patients initially ineligible for breast-conserving surgery (BCS) were downstaged to be eligible for BCS, whereas three patients potentially eligible for BCS before treatment became ineligible due to disease progression. Only one (2%) patient had a pathologic complete response (pCR). Among the 16 patients presenting with biopsy-proven clinical node-positive disease, 3 (19%) had nodal pCR. Axillary lymph node dissection was avoided in 3 (19%) patients who had successful axillary downstaging. Residual cancer burden (RCB) was assessed in 22 patients and was significantly associated with disease-free survival and overall survival. We observed a poor response or even disease progression on NAC among patients with MpBC, suggesting that NAC should be reserved for patients with inoperable MpBC

Molecular pathology in breast disease: diagnostic, prognostic, and therapeutic tools

Molecular testing in breast cancer gained increasing attention and importance as specific molecular results can tailor not only oncological decisions on systemic adjuvant or neoadjuvant or in metastatic setting, but increasingly serve in diagnostic routine histopathological services to differentiate between morphologically overlapping or ambiguous histological pictures. Diagnostic tools involve in most cases a broad spectrum of immunohistochemical panels, followed by entity-specific in situ hybridization probes and in given cases NGS-based sequencing. Workflow of which methodology is applied and in which order depends on the specific entity resp. on the given differential diagnosis in question. Regarding prognostic/predictive molecular testing, the choice of assay and the workflow are based on clinical algorithms and on the evidence of targeted therapies following the molecular alterations. In this review paper, we aim to address the use of molecular technics in [1] the histological diagnostic setting (such as subtyping of invasive carcinomas/malignant spindle cell tumors and sarcomas and some B3 lesions) and [2] in the context of adjuvant or neoadjuvant or other clinical settings with special focus of targeted therapies

Triple-negative breast cancer histological subtypes with a favourable prognosis

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

High rate of PIK3CA mutations but no TP53 mutations in low-grade adenosquamous carcinoma of the breast

International audienceLow-grade adenosquamous carcinoma of the breast (LGASC) is a rare variant of metaplastic carcinoma characterised by a favourable outcome and histologically composed of glandular and squamous elements in a spindle cell background typically associated with a lymphocytic stromal reaction. Because of its rarity, the immunophenotypic and genetic profile of LGASC has not been sufficiently characterised. The aim of this study was to gain insights into the molecular and phenotypic characteristics of LGASC

Quantitative Proteomic and Mutational Landscape of Metaplastic Breast Carcinoma and Generation of a 3D Organoid Model of Neoplastic Progression

Triple-negative breast cancer (TNBC) is considered to be the most aggressive and has worse prognosis compared to other breast cancers and accounts for roughly 18% of all epithelial cancers of the breast, or carcinomas. TNBC exhibits complex molecular heterogeneity both inter- and intratumorally and likely consists of several distinct molecular subgroups that are currently unknown. Metaplastic breast carcinoma (MBC) is even more aggressive than triple-negative breast cancer (TNBC) but also typically presents as triple-negative histologically, and is defined by the admixture of both invasive glandular and non-glandular “metaplastic” heterologous elements of spindle, squamous or sarcomatoid subtypes. The protein profiles underpinning the phenotypic diversity and metastatic behavior of MBC are unknown. We present a quantitative multi-subtype proteomic landscape of MBC, non-metaplastic TNBC, and normal breast from small yet well-annotated cohort of 27 patients, and also present the somatic mutational landscape on the same cohort. We used multiplex isobaric tandem mass tag (TMT) labeling for proteomics and quantified 5,798 proteins, and from whole-exome sequencing for genomics analysis we found 980 total somatic mutational variants. MBCs displayed increased epithelial-to-mesenchymal transition (EMT) and extracellular matrix (ECM) signaling, and reduced metabolic pathways compared to TNBC. We discovered subtype-specific profiles among MBCs including distinct upregulated profiles; translation and ribosomal events in spindle, inflammation and apical junctions in squamous, and extracellular matrix in sarcomatoid. Comparison of the proteomes of spindle MBC with MMTV-cre;Ccn6fl/fl spindle MBC mouse tumors revealed a shared spindle-specific signature of 17 upregulated proteins involved in translation (e.g. RPL4,6,18, P3H1, PYCR1). The somatic mutational landscape also revealed MBCs share common TP53 mutations, and in PLEC, MUC17, CRYBG2, and ZNF681. We identified that spindle and squamous MBC exhibit overlapping mutational profiles of genes involved in transcription, RNA metabolic processes and actin filament binding, while sarcomatoid tumors harbor distinct mutations in MAPK, WNT, protocadherin cluster genes, calcium binding and ECM organization. These data identify subtype-specific MBC protein profiles and mutational signatures that identified novel biomarkers for therapy. Three-dimensional (3D) cell culture has been widely used in recent decades, compared with monolayer (2D) culture, because they better mimic the in vivo state. 3D systems utilize different types of gels critical for their success, such as collagen or the reconstituted basement membrane, Matrigel, which has enabled recapitulation of tissue architecture and function that is more physiologic compared to 2D. However, conventional 3D models using gel-embedded platforms have large variability and slow transport of biomolecules to the matrix-encapsulated cells. Here, we developed a highly reproducible, 3D scaffold-free hanging drop method amenable for primary tissues including mouse and human tumors, and our analyses describe a one drop-one organoid format using MCF10A cells, a non-tumorigenic breast cell line. We attained high-yield production of uniform organoids that resemble normal human breast acini, express both mammary gland-specific and progenitor markers, and we developed treatment assays for EMT induction and neoplastic progression delivering rapid quantification of phenotypic and morphological changes. Integration of 3D methods with omics analyses is envisioned to enhance the study of neoplastic progression and generate novel targets of both MBC and TNBC tumors.PHDMolecular & Cellular PathologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155234/1/djomehri_1.pd