Marilin Rosa

Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

BACKGROUND Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. METHODS A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. RESULTS During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. CONCLUSIONS This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

Male Breast: Clinical and Imaging Evaluations of Benign and Malignant Entities with Histologic Correlation

Breast cancer is an uncommon disease in men. As a result, the diagnosis may not initially be considered. Understanding the common benign and malignant entities affecting the male breast is critical for timely and accurate diagnosis in the primary care setting. Most patients present with a palpable breast mass or pain. The usual etiology is gynecomastia, the most common breast condition in males, but breast cancer must always be excluded through careful imaging evaluation when physical examination findings are suspicious or inconclusive. Imaging of the male breast generally relies on mammography and ultrasound, with mammography employed as the initial imaging modality of choice and ultrasound when a mass is detected or suspected. Here we describe the normal male breast anatomy and present an evaluation algorithm for the male patient with breast signs or symptoms. The most common benign and malignant entities are described.

Use of Immunohistochemical Stains in Epithelial Lesions of the Breast.

BACKGROUND During the last few decades, immunohistochemistry (IHC) has become an integral part of pathology. Although hematoxylin and eosin (H & E) stain remains the fundamental basis for diagnostic pathology of the breast, IHC stains provide useful and sometimes vital information. Moreover, considering the role of hormonal therapy in hormone receptor-positive breast tumors, as well as the availability of targeted chemotherapeutic agents for HER2-positive cases, IHC studies represent a major part of workups. METHODS A literature search was performed to explore the uses of IHC stains related to the diagnoses of breast lesions and prognostic/predictive information. RESULTS Selective use of IHC stains in conjunction with H & E examination helps resolve most diagnostic issues encountered by surgical pathologists during their day-to-day practice. Pathologists should be familiar with the use of each immunostain and its limitations to avoid interpretative errors. CONCLUSIONS IHC stains help guide the differential diagnosis of challenging epithelial lesions of the breast. They should be selectively and judiciously used and their findings must be interpreted with the differential diagnoses in mind and with an understanding of possible pitfalls.

Recurrent Systemic Anaplastic Lymphoma Kinase-Negative Anaplastic Large Cell Lymphoma Presenting as a Breast Implant-Associated Lesion.

A woman aged 48 years presented with fevers, chills, weight loss, and night sweats. She had significant lymphadenopathy of the left neck as well as the left axilla. Her history was significant for bilateral breast augmentation with textured silicone implants more than 25 years ago. Excisional biopsy of a cervical lymph node revealed large, atypical cells positive for CD4 and CD30 and negative for Epstein-Barr virus-encoded ribonucleic acid, CD2, CD3, CD5, CD7, CD8, CD15, CD20, pan-keratin, S100, anaplastic lymphoma kinase (ALK), and paired box 5. These findings were consistent with Ann Arbor stage IIIB ALK-anaplastic large cell lymphoma (ALCL). The patient was started on 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone. She initially had no signs or symptoms of breast involvement; however, after developing seroma during the clinical course, the patient underwent capsulectomy and removal of the intact, textured silicone implants. Pathological evaluation demonstrated ALK-ALCL in the left breast capsule with cells displaying a significant degree of pleomorphism with binucleated forms and numerous mitoses. Fluorescence in situ hybridization confirmed the tumor was negative for t(2;5). She presented 8 weeks later showing evidence of recurrent systemic disease.

Breast Carcinomas with Neuroendocrine Features (Neuroendocrine Carcinomas of the Breast)

Breast carcinomas with neuroendocrine features (NEC) have only been recently recognized as a separate diagnostic entity by the World Health Organization classification. This category of tumors encompasses neuroendocrine tumor, well differentiated; neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and invasive breast carcinoma with neuroendocrine differentiation. Because of the lack of specific clinical or imaging features, diagnosis of NEC depends upon recognition of its histologic growth pattern and immunohistochemical (IHC) staining for neuroendocrine markers. Histologic features that suggest neuroendocrine differentiation include low nuclear grade, palisading of nuclei at the periphery of the tumor, and sparse cellular stroma. A number of diagnostic criteria have been proposed to render this diagnosis. Currently, it is accepted that the tumors should display morphological features similar to neuroendocrine carcinomas of the lung and gastrointestinal (GI) tract and/or should have proven neuroendocrine differentiation using IHC markers. An important issue when diagnosing breast carcinomas with neuroendocrine features is that it is necessary to differentiate them from metastatic neuroendocrine tumors to the breast. This distinction has important clinical implications and will directly impact patient care. In this review, we will highlight the pathological, molecular, and clinical characteristics of NEC in the breast as well as discuss the most current available literature.

Invasive Breast Carcinoma Tumor Size on Core Needle Biopsy: Analysis of Practice Patterns and Effect on Final Pathologic Tumor Stage

Introduction In the absence of nodal metastasis, pathologic tumor (pT) size remains one of the most important factors in adjuvant treatment decisions and patient prognosis in breast cancer. The aim of this study was to evaluate the effect of core needle biopsy (CNB) tumor size on final pT stage. Materials and Methods Our information system was searched to identify all patients who underwent excisional procedures for invasive breast carcinoma from January 1, 2014 to December 31, 2015. The tumor size on CNB and final excision, the number of cases in which the CNB size was larger, and the percentage of cases in which using the CNB tumor size changed the final pT stage were recorded. Results From 1380 primary breast excisions/mastectomies, a total of 870 cases were included. In 82 (9.4%) the CNB tumor size was larger (63 of 82 cases) or no residual tumor was identified on excision (19 of 82 cases). From these 82 cases, 40 (48.7%) were properly staged on the basis of CNB tumor size, 16 (19.5%) were not staged, and 26 (31.7%) were staged using the final excision tumor size. Change in stage occurred in 7 of these 26 patients. Conclusion Our study revealed that in most cases, the largest tumor size is found in the excision/mastectomy specimen. However, in 9.4% (82 of 870), the CNB contains the most accurate tumor size for pT staging. On the basis of our results, including the largest linear tumor extent on the CNB report is recommended. Micro‐Abstract In this study we evaluated the effect of core needle biopsy (CNB) tumor size on final pathologic tumor (pT) stage. The laboratory information system was retrospectively reviewed for breast excisional specimens. In 82 of 870 cases (9.4%) the CNB contains the most accurate tumor size for pT staging. Including the largest linear tumor extent on the CNB report is recommended.

Expression of Her-2/neu in extrahepatic cholangiocarcinoma

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Her-2 Expression in Gastroesophageal Intestinal Metaplasia, Dysplasia, and Adenocarcinoma.

Overexpression of human epidermal growth factor receptor 2 protein (Her-2) in Barrett neoplasia is significant for targeted therapy with trastuzumab. Here, we studied the frequency of Her-2 overexpression in Barrett adenocarcinoma and precursor lesions. Retrospective formalin-fixed paraffin-embedded tissue samples of 25 normal (NM) esophageal mucosa, 50 Barrett esophagus (BE) without dysplasia, 49 BE with low-grade dysplasia (LGD), 50 BE with high-grade dysplasia (HGD), and 50 invasive adenocarcinoma (ICA) were used. A BE tissue microarray was built and analyzed by Her-2 immunohistochemistry (IHC) and Her-2 dual in situ hybridization (DISH). Her-2 IHC expression was negative in NM and low in 26% of BE (IHC score: 1+) and in 24.5% of LGD (IHC score: 1 to 2+). Her-2 overexpression was seen in 28% of HGD and in 24% of ICA (IHC score: 2 to 3+). Her-2 DISH was negative in NM and BE but positive in 6% of LGD, 20% of HGD, and 18% of ICA. Differences in Her-2 DISH positivity between NM and HGD or ICA were statistically significant (P=0.02), but those between NM and LGD or HGD and ICA were not (P=0.2). Although Her-2 overexpression results in ICA were similar to previous reports, the finding of 28% in HGD was unexpected and may have clinical implications. Positive Her-2 DISH in 6% of LGD is novel, suggesting a role of Her-2 during BE progression.