The complete sequencing of the human genome has ushered in an era of medical advances that was previously unimaginable. Scientists are continually discovering novel genetic and epigenetic mechanisms that are associated with human disease states and therapeutic responses. The ability to determine the underlying defect(s) in single-gene (Mendelian) diseases, many of which are rare, has improved both...
The rapid development of molecular biology in recent decades has dramatically changed the way we practice medicine. With the help of an impressive arsenal of new technologies, including high-throughput sequencing and microarrays, we are now well-equipped to probe into the molecular nature of diseases. Which set of genes are involved? What are the genetic and epigenetic alterations associated with...
Molecular techniques are being increasingly employed in the field of dermatology, significantly enhancing the management of cutaneous disorders. These applications have become important diagnostic tools, not only in the setting of genodermatoses, but also in a wide range of cutaneous malignancies and infectious diseases. In addition, molecular testing has been used to select treatment, assess therapeutic...
Skin tumors can arise as a result of cumulative genetic abnormalities, including chromosomal aberrations that can be described as either morphological (structural rearrangements) or molecular (copy number variations). Cytogenetic techniques have been used to examine both large and small chromosomal aberrations, and include karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization...
There are many possible indications and potential uses for molecular diagnostic techniques in the evaluation and management of melanocytic neoplasms. These include: (a) the identification of better diagnostic, staging, and prognostic markers; (b) the discovery of novel therapeutic targets; (c) the development of a molecular classification scheme, with the potential to stratify melanomas into subtypes...
The TNM staging categories and groupings of the updated 2009 American Joint Committee on Cancer (AJCC) Melanoma Staging System are outlined in Tables 6.1 and 6.2 [1]. “T ” parameters are defined by primary tumor thickness, ulceration, and mitotic status; “N” parameters by the number of lymph nodes with metastatic disease and extent of metastatic burden; and “M” parameters by the site(s) of the metastases...
Non-melanoma skin cancers (NMSC), which include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are among the most common human neoplasms, accounting for nearly as many human tumors as all other cancers combined. More than one million new cases of NMSC are diagnosed each year in the USA [1]. Although their growth is often slow when compared to other cancers, NMSC can be locally destructive...
Primary cutaneous sarcomas account for 14% of all sarcomas [1]. Partly owing to their relative rarity, diagnosis of these tumors is often challenging. All too often a pathologist is faced with a small biopsy, and has to differentiate a common benign mesenchymal tumor from its malignant counterpart, or classify a malignant tumor based on a limited tissue sample. Fortunately, basic science discoveries...
Technologies are being increasingly employed to identify the biological pathways, genes, and proteins involved in disease pathogenesis and progression. These investigations have uncovered diagnostic and prognostic biomarkers for a variety of cutaneous tumors. Molecular testing may have a role in the evaluation of tissue margins, clonal origin, and histogenesis of skin cancers.
More than 65% of all cutaneous lymphomas are T-cell disorders. Cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of non-Hodgkin lymphomas that share the common feature of malignant T-cell infiltration of the skin (Table 10.1) [1, 2]. The most common forms of CTCL are mycosis fungoides (MF) and its leukemic counterpart Sézary syndrome (SS), accounting for ∼44% and ∼3% of cases, respectively...
Southern blot analysis (SBA) and polymerase chain reaction (PCR)-based testing for monoclonal T-cell receptor gene rearrangements (TCR-GRs), fluorescence in situ hybridization (FISH) for t(2;5)(p23;q35), in situ hybridization for Epstein-Barr virus-encoded mRNA (EBER-ISH), and SBA for human T-cell lymphotropic virus type I (HTLV-I) provirus integration are the most common molecular techniques used...
Cutaneous lymphoproliferative disorders are a markedly heterogeneous group of diseases and represent one of the most challenging areas in dermatopathology. Careful correlation of clinical, histopathological, immunophenotypic, and molecular findings is essential for the accurate diagnosis and proper classification of these neoplasms [1]. There are several types of B-cell lymphoma which may show...
The diagnosis and classification of leukemia requires the integration of clinical features and light microscopic findings with the results of cytochemical, immunological (flow cytometry and/or immunohistochemistry), and molecular studies [1]. Immunophenotypic and genotypic technologies are commonly applied to peripheral blood (PB) and bone marrow (BM) specimens in the initial work-up and management...
Inflammatory disorders of the skin, including eczematous, psoriasiform, lichenoid-interface, autoimmune, and neutrophilic dermatoses, probably represent the group of cutaneous diseases in which molecular pathology currently has the least impact in daily clinical practice. Many of these diseases are readily diagnosed through the correlation of clinical features with histopathological findings on hematoxylin...
Dermatophytes are a unique group of fungi that infect keratinous tissue, including skin, hair, and nails, resulting in cutaneous mycoses called dermatophytoses, tinea, or ringworm infections. This closely-related group of organisms can be categorized into one of three genera: Trichophyton, Microsporum, and Epidermophyton. Species within these genera that do not invade keratinous tissue are, by definition,...
Identification of the pathogenic microbe is essential for selection of the most appropriate treatment in the majority of cutaneous infections. Historically, the diagnosis of cutaneous pathogens has been based on the results of immunological studies, lesional culture, and/or microscopic examination of tissue samples, in combination with histochemical stains (i.e., PAS, Gram) or immunohistochemical...
The normal wound healing response can be divided into (1) inflammatory, (2) proliferative, and (3) tissue remodeling (i.e., fibroplasia and maturation) phases that involve complex interactions between various cutaneous-derived and inflammatory cells, cytokines, and the extracellular matrix (ECM) [1–6]. Numerous studies continue to uncover the genetic, epigenetic (i.e., microRNA), cellular (including...
Primary alopecias of the scalp are divided into scarring and nonscarring types [1]. Scarring alopecias include: (a) lymphocytic (discoid lupus erythematosus [DLE], lichen planopilaris [LPP], pseudopelade of Brocq [PPB], central centrifugal cicatricial alopecia [CCCA]); (b) neutrophilic (dissecting folliculitis/cellulitis, folliculitis decalvans); and (c) combined (acne keloidalis) subtypes. Nonscarring...
This chapter discusses the molecular basis of inherited diseases in which the primary changes are manifest in the skin and its appendages (nails, hair, sweat glands, and sebaceous glands). The disorders have been subdivided into sections according to their clinical presentation and molecular basis, but this is not a fixed classification, as many diseases will fit into more than one category. With...