Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15&#37;&#8211;20&#37; of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a &#8220;humanized&#8221; monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.

Sejal Shah

Beiyun Chen

Testing for HER2 in Breast Cancer: A Continuing Evolution

Despite ongoing advances in the treatment of gastroesophageal cancer, prognosis remains poor. The best promise to improve this poor survival is provided by new targeted agents. Of these, human epidermal growth factor receptor 2 (HER2) is currently in the spotlight. In this review, we provide an overview of recent developments in HER2 testing and results of clinical trials targeting HER2 in gastroesophageal adenocarcinoma. Based on the encouraging ToGA trial findings it is now expected that routine HER2 testing will be included in the diagnostic work-up of patients with advanced gastric cancer. With regard to this testing, overexpression of the HER2 protein seems to possess the best predictive properties. However, HER2 immunohistochemistry (IHC) is subject to assay and interobserver variability, so standardization and internal and external proficiency testing is an absolute prerequisite, especially as the IHC scoring system in gastric cancer is different from that of breast cancer. Further study is needed to investigate the clinical meaning of the significant heterogeneity observed in both gene amplification and protein overexpression in gastroesophageal cancer. Highly effective therapies for gastroesophageal cancer can only be accomplished by a multi-targeted approach, considering crosstalk between pathways and continuing to optimize chemotherapy.

Cathy B. Moelans

Paul J. van Diest

Anya N. A. Milne

G. Johan A. Offerhaus

HER-2/<i>neu</i> Testing and Therapy in Gastroesophageal Adenocarcinoma

Eosinophilic fasciitis (Schulman&#39;s syndrome) is a rare disease with specific clinical symptoms such as the groove sign which facilitate diagnosis. We report a typical case of eosinophilic fasciitis in an otherwise healthy 49-year-old man who presented with &#x0201C;prayer and groove signs&#x0201D;. Histological analysis showed sclerosis and eosinophilic infiltration of the fascia. The patient was successfully treated with systemic corticotherapy and Cyclosporine. A short review of the clinicopathological features of the lesions is presented.

Amandine Servy

Thierry Cl&#233;rici

Caroline Malines

Jean-Marie Le Parc

Jean-Fran&#231;ois C&#244;t&#233;

Eosinophilic Fasciitis: A Rare Skin Sclerosis

We analyzed the subgross distribution of the invasive component in 875 consecutive cases of breast carcinomas using large-format histology sections and compared the immunophenotype (estrogen and progesterone receptor expression, HER2 overexpression and expression of basal-like markers, CK5/6, CK14, and epidermal growth factor receptor) in unifocal, multifocal, and diffuse tumors. Histology grade and lymph node status were also analyzed. Unifocal invasive carcinomas comprised 58.6% (513/875), multifocal invasive carcinomas 36.5% (319/875), and diffuse invasive carcinomas 4.9% (43/875) of the cases. The proportion of lymph node-positive cases was significantly higher in multifocal and diffuse carcinomas compared to unifocal cancers, but no other statistically significant differences could be verified between these tumor categories. Histological multifocality and diffuse distribution of the invasive tumor component seem  to be negative morphologic prognostic parameters in breast carcinomas, independent of the molecular phenotype.

Tibor Tot

Gyula Pek&#225;r

Syster Hofmeyer

Maria Gere

Mikl&#243;s Tarj&#225;n

Dan Hellberg

David Lindquist

Molecular Phenotypes of Unifocal, Multifocal, and Diffuse Invasive Breast Carcinomas

Prognosis of invasive ductal carcinoma (IDC) strongly correlates with tumor grade as determined by Nottingham combined histologic grade.  While reporting grade as low grade/favorable (G1), intermediate grade/moderately favorable (G2), and high grade/unfavorable (G3) is recommended by American Joint Committee on Cancer (AJCC) staging system, existing TNM (Primary Tumor/Regional Lymph Nodes/Distant Metastasis) classification does not directly incorporate these data.  For large tumors (T3, T4), significance of histologic grade may be clinically moot as those are nearly always candidates for adjuvant therapy. However, for small (T1, T2) node-negative (N0) tumors, grade may be clinically relevant in influencing treatment decisions, but data on outcomes are sparse and controversial. This retrospective study analyzes clinical outcome in patients with small N0 IDC on the basis of tumor grade. Our results suggest that the grade does not impact clinical outcome in T1N0 tumors. In T2N0 tumors, however, it might be prognostically significant and relevant in influencing decisions regarding the need for additional adjuvant therapy and optimal management.

Mathew Purdom

Michael L. Cibull

Terry D. Stratton

Luis M. Samayoa

Edward H. Romond

Patrick C. Mcgrath

Rouzan G. Karabakhtsian

Should  Histologic Grade Be Incorporated into  the TNM Classification System for Small (T1, T2) Node-Negative Breast Adenocarcinomas?

Patients with HIV/AIDS have a higher risk of developing aggressive B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL). Lymphomas are rather heterogeneous in nature and in a few cases can switch their genetic or immunohistochemical phenotype, transform into other lymphomas or carry more than one malignant clone. In this report, we present the case of a 47-year-old man with HIV infection who was diagnosed with an apparent low-risk, early-stage DLBCL, but became refractory to therapy while undergoing treatment with rituximab-containing chemotherapy. We postulate that the development of his refractory disease occurred in the context of an immunohistochemical switch or the surge of a clone refractory to therapy. This phenomenon was not associated with a superinfection with EBV or HHV-8.

Jorge J. Castillo

Tina Rizack

Diana Treaba

Immunophenotypical Switch versus Tumor Heterogeneity in a Patient with HIV-Associated Diffuse Large B-Cell Lymphoma

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