MIT family translocation renal cell carcinoma
The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MITF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCC were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: M.D. Pedram Argani Source Type: research
Outcome Prediction for Patients with Renal Cell Carcinoma
Outcome assessment for renal cell carcinoma is somewhat controversial. Despite numerous studies a very limited variety of features have been recognized as having prognostic significance in clinical practice. In this review tumor features considered to be of importance in outcome prediction for surgically treated patients with the three most commonly encountered morphotypes of renal cell carcinoma (clear cell, papillary and chromophobe renal cell carcinoma) are evaluated. In particular we have focused upon histologic subtype, sarcomatoid and rhabdoid differentiation, TNM staging, primary tumor size, tumor grade and the pres...
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Christine M. Lohse, Sounak Gupta, John C. Cheville Source Type: research
Issues and challenges associated with classifying neoplasms in percutaneous needle BIOPSIES of incidentally found small renal masses
Percutaneous needle core biopsy has become acceptable for classifying renal tumours and guiding patient management in the setting of an incidentally-detected small renal mass (SRM), defined as an asymptomatic, non-palpable mass < 4cm in maximum dimension. Long-held concerns preventing the incorporation of biopsies into routine patient care, including the perception of poor diagnostic yield and risks of complications such as bleeding or biopsy tract seeding, have largely been disproven. While needle biopsies for SRM’s have traditionally been performed in academic centres, pathologists based in non-academic centres can exp...
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Andrew J Evans, Brett Delahunt, John R Srigley Source Type: research
BRAF V600E Mutation-Specific Antibody: A Review
The significance of BRAF mutations in neoplasia was first recognized in 2002 when mutations were discovered in a broad range of cancers. Numerous subsequent studies expanded our understanding of BRAF V600E as a critical diagnostic, prognostic and predictive biomarker in many cancers. Additionally, the advent of small molecule inhibitors of BRAF V600E rendered assessment of BRAF mutation status essential in tumors such as melanoma. In clinical practice, evaluation of BRAF mutation status has routinely been performed by DNA-based assays utilizing polymerase chain reaction (PCR). (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Lauren L. Ritterhouse, Justine A. Barletta Source Type: research
Predictive Markers in Breast Cancer: An Update on ER and HER2 Testing and Reporting
Gene expression profiling of human tumors has provided a new paradigm for classifying breast carcinomas, predicting response to treatment and risk of recurrence. Estrogen receptor (ER), human epidermal growth factor 2 (HER2) receptor and proliferation-related genes are the main drivers of classification in many of the gene expression profiling tests for breast cancer. However, ER, progesterone receptor (PR) and HER2 receptor status remain essential in determining the need and type of adjuvant therapy. (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Benjamin C. Calhoun, Laura C. Collins Source Type: research
Soft tissue tumor pathology: New diagnostic immunohistochemical markers
Recent insights into the pathogenesis of various soft tissue tumors, along with the identification of recurrent molecular alterations characteristic of specific tumor types, have resulted in the development of many diagnostically useful immunohistochemical markers. In some cases, expression of these markers is significantly associated with distinctive clinical and histologic features, which may impart prognostic or predictive information. This review outlines new diagnostic immunohistochemical markers in soft tissue tumor pathology, emphasizing their utility in clinical practice and potential pitfalls, molecular correlates...
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Leona A. Doyle Source Type: research
HPV-related squamous cell carcinoma of the head and neck: an update on testing in routine pathology practice
Oropharyngeal squamous cell carcinoma caused by high risk types of human papillomavirus (HPV) is now a well-recognized tumor entity whose incidence is on the rise. Most HPV-related oropharyngeal squamous cell carcinomas have distinct histomorphology, and most patients fit a typical clinical profile. Importantly, HPV-related oropharyngeal carcinoma patients overall have significantly improved outcomes when compared to their HPV-negative counterparts, and the differences in tumor biology may soon lead to modifications in how they are treated. (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Justin A. Bishop, James S. Lewis, James W. Rocco, William C. Faquin Source Type: research
Predictive Value of Immunohistochemistry in Pre-Malignant Lesions of the Gastrointestinal Tract
Immunohistochemistry can be an important adjunct to histopathology for the diagnosis of pre-malignant lesions of the gastrointestinal tract and in patient risk stratification. The purpose of this review is to provide information and guidance on the usefulness of immunohistochemical markers that facilitate the diagnosis of dysplasia and help to predict risk for the development of carcinoma in pre-malignant lesions of the gastrointestinal tract. Particular emphasis is given to the role of immunohistochemistry in the assessment of epithelial dysplasia in the setting of Barrett’s esophagus and inflammatory bowel disease; sup...
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Changqing Ma, Reetesh K. Pai Source Type: research
Immunohistochemistry and in situ hybridization for the diagnosis and classification of squamous lesions of the anogenital region
Distinguishing anogenital squamous intraepithelial lesions from benign conditions and mimics may be problematic. Immunohistochemistry for surrogate markers of HPV infection, such as Ki-67, p16, and ProExTM C, may aid the diagnosis in equivocal cases. The main diagnostic pitfall in the diagnosis of LSIL is the occurrence of “pseudokoilocytes” in benign squamous mucosa, which may lead to overdiagnosis. When interpreted correctly, Ki-67 is a sensitive and specific marker for dysplasia in mature squamous epithelium and is therefore useful for confirmation of LSIL and condyloma. (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Edyta C. Pirog Source Type: research
Immunohistochemical Markers in lymphoid Malignancies: Protein Correlates of molecular alterations
Histomorphology, immunohistochemistry (IHC), and genetics are essential tools for the evaluation and classification of lymphoid malignancies. Advances in diagnostic techniques include the development of immunohistochemical assays that can serve as surrogates for genetic tests. We review the performance of select subset of assays that detect the aberrant expression of onco-proteins secondary to chromosomal translocations (MYC; BCL2), somatic mutations (BRAF V600E; NOTCH1), and gene copy number gains (PD-L1; PD-L2) in fixed tissue biopsy sections. (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Caleb Ho, Scott J. Rodig Source Type: research
Genotyping and immunohistochemistry of gastrointestinal stromal tumors: An update
Gastrointestinal stromal tumors (GISTs) were originally thought to harbor either KIT or platelet-derived growth factor receptor A (PDGFRA) mutations only. However, more recent discoveries have highlighted additional, less common oncogenic driver mutations including NF1, BRAF and succinate dehydrogenase (SDH) mutations. Genotyping GISTs has become more important since not all genotypes respond equally to FDA-approved tyrosine kinase inhibitors. GIST is a paradigm for personalized cancer therapy. Recent studies demonstrate how immunohistochemistry can be used both to diagnose GIST and to screen for specific mutations. (Sourc...
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Brian P. Rubin, Michael C. Heinrich Source Type: research
Evolving approach and clinical significance of detecting DNA mismatch repair deficiency in colorectal carcinoma
The last two decades have seen significant advancement in our understanding of colorectal tumors with DNA mismatch repair (MMR) deficiency. The ever-emerging revelations of new molecular and genetic alterations in various clinical conditions have necessitated constant refinement of disease terminology and classification. Thus, a case with the clinical condition of hereditary non-polyposis colorectal cancer as defined by the Amsterdam criteria may be one of Lynch syndrome characterized by a germline defect in one of the several MMR genes, or one of the yet-to-be-defined “Lynch-like syndrome” if there is evidence of MMR ...
Source: Seminars in Diagnostic Pathology - February 4, 2015 Category: Pathology Authors: Jinru Shia Source Type: research
Mesenchymal tumors of adult kidney
Mesenchymal tumors of the kidney, although infrequently encountered, constitute a wide spectrum of lesions. The relative rarity of these tumors means that in some instances criteria to differentiate between benign and malignancy are currently incompletely defined. More recently a variety of novel stromal tumors have been characterized, with hemagioblastoma and myopericytoma being notable examples. The identification of a subset of spindle cell tumors as synovial sarcoma, on the basis of the presence of a characteristic genetic translocation, has facilitated the correct classification of a number of tumors previously labell...
Source: Seminars in Diagnostic Pathology - February 3, 2015 Category: Pathology Authors: Hemamali Samaratunga, Brett Delahunt Source Type: research
Protein correlates of molecular alterations in lung adenocarcinoma: Immunohistochemistry as a surrogate for molecular analysis
Most clinically actionable alterations in lung adenocarcinomas are detected using molecular or cytogenetic techniques. However, many such alterations have a protein-level correlate that can be interrogated using immunohistochemistry. This review will summarize the therapeutic relevance of predictive biomarkers in lung adenocarcinoma including the oncogenes EGFR, MET, ALK, RET and ROS1 and tumor suppressors PTEN and LKB1 with an emphasis on established and emerging protein immunohistochemistry reagents and their promise in clinical practice. (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - February 3, 2015 Category: Pathology Authors: Lynette M. Sholl Source Type: research
HPV- and non-HPV-related subtypes of penile squamous cell carcinoma (SCC): Morphological features and differential diagnosis according to the new WHO classification (2015)
The majority of penile carcinomas are squamous cell carcinomas originating in the squamous mucosa covering the glans, coronal sulcus, or inner surface of the foreskin, the 3 latter sites comprising the penile anatomical compartments. There is a variegated spectrum of subtypes of penile squamous cell carcinomas according to recent classification schemes. Currently, because of etiological and prognostic considerations, 2 morphologically and molecularly distinctive groups of subtypes of penile SCCs based on the presence of HPV were delineated. (Source: Seminars in Diagnostic Pathology)
Source: Seminars in Diagnostic Pathology - December 29, 2014 Category: Pathology Authors: Diego F. Sanchez, Sofía Cañete, María José Fernández-Nestosa, Cecilia Lezcano, Ingrid Rodríguez, José Barreto, Isabel Alvarado-Cabrero, Antonio L. Cubilla Source Type: research
