MOLECULAR DERMATOLOGY AND PATHOLOGY
Introduction
The entire scope of clinical medicine is being transformed
by the integration of molecular medicine. Rapid advancements
in the basic sciences are quickly being converted
into clinically applicable tests; providing physicians with a
heavy armament of newly developed diagnostic, prognostic,
and theragnostic assays to improve patient care. In our modern
era, a significant proportion of these tools are based on
advances in molecular medicine. As a result, clinical dermatologists
and dermatopathologists are observing new trends
and standards of practice. Significant transitions are taking
place, including, but not limited to: (1) moving from generalized
treatment for all melanoma patients to evaluation for
specific activating mutations in oncogenic drives and selection
of targeted therapy; (2) moving from diagnosis by standard
microscopy alone to integration of molecular testing for
specific diagnostic chromosomal translocations for soft-tissue
tumors, (3) providing more precise diagnostic and prognostic
information; (4) identifying potentially treatable infectious
causes of certain cutaneous lymphomas, for example, the
Epstein–Barr virus; and (5) improving risk assessment for borderline/
spitzoid melanocytic tumors by identifying characteristic
cytogenetic aberrations.
For the vast majority of dermatologists and dermatopathologists
trained in traditional clinical medicine, the sheer
volume of newly identified gene mutations, chromosomal
aberrations, and related molecular tests, even within a focused
area of specialization, is truly overwhelming. As in
many aspects of life, such rapid and transformative changes
may be met with welcome or resistance. Fear that new technological
advancements may replace years of clinical training
is a recurring theme in modern medicine. A critical concept is
that these advancements are meant to supplement not replace
the clinical expertise that dermatologists and dermatopathologists
have acquired in their specialties. Independent
of clinical dermatologists or dermatopathologists, advancements
in molecular medicine will continue to be integrated
into clinical medicine at an increasingly rapid pace.
The greatest threat is not the technologic advancements
but rather the loss of certain aspects of our practice to other
specialties that better embrace the molecular revolution. Dermatologists
and dermatopathologists must take leadership
roles in integrating molecular medicine into the specialty.
Otherwise, there is a risk of losing the primary roles of dermatologists
and dermatopathologists in the diagnosis and
management of cutaneous infectious diseases to infectiousdisease
specialists, cutaneous lymphomas to oncologists, genodermatoses
to pediatric geneticists, and so forth.
The clinical expertise that dermatologists and dermatopathologists
have acquired in our specialty positions should
be used to define and develop the roles for molecular tools in
our specialty. In this issue of Seminars in Cutaneous Medicine
and Surgery, I am proud to present a series of articles highlighting
advancements in molecular medicine in dermatology
and dermatopathology. These articles review many of the
advancements in molecular medicine in our field. I believe
the articles substantiate our ability as a specialty to take on
leadership roles in molecular medicine. Furthermore, I am
hopeful that this issue provides a stronger foundation in molecular
medicine, allowing practicing dermatologists and
dermatopathologists to retain their primary roles in cutaneous
medicine.
Hereditary Nonmelanoma Skin Cancer
Cutaneous basal and squamous cell carcinomas are among the most frequent malignancies
in the white population, with the annual incidence estimates ranging from 1 million to
3.5 million cases in the United States. These tumors can occur either sporadically or in the
context of hereditary genodermatoses with cancer predisposition, such as basal cell nevus
syndrome, xeroderma pigmentosum, epidermolysis bullosa, or oculocutaneous albinism.
Different genes and signaling pathways have been shown to play a central role in the
development and growth of these tumors. This article overviews the clinical features,
diagnostic criteria, and the most recent data on genetic routes of the major hereditary
syndromes predisposed to the development of nonmelanoma skin cancer.
Semin Cutan Med Surg 31:204-210 © 2012 Frontline Medical Communications
The Role of Molecular Testing in the Diagnosis of Cutaneous Soft Tissue Tumors
A number of soft tissue tumors are characterized by recurring genetic abnormalities. The
identification of these abnormalities has advanced our understanding of the biology of
these tumors and has led to the development of molecular tests that are helpful diagnostically.
This review will focus on the application of molecular diagnostic testing in select
mesenchymal tumors of the dermis and subcutis.
Semin Cutan Med Surg 31:221-233 © 2012 Frontline Medical Communications
The Role of Molecular Analysis in Cutaneous Lymphomas
The purpose of this review is to summarize the most important molecular techniques for the
diagnosis of cutaneous lymphomas. When making a diagnosis, we are looking for the solid
clinicopathological correlation. Molecular analysis includes immunophenotyping and clonality
analysis, and is important for 2 principal reasons: (1) to confirm the diagnosis in cases
where the clinical and/or pathological presentations are nondiagnostic, and (2) to further
characterize the nature of the lymphoma. More specifically, we are trying to discern
whether the lymphoma is primarily cutaneous or systemic with secondary skin involvement,
and we are also attempting to subclassify the tumor. Recently, many techniques have
provided a more accurate diagnosis of cutaneous lymphomas and some prognostic implications,
including polymerase chain reaction, fluorescence in situ hybridization, and flow
cytometry. Fluorescence in situ hybridization is not routinely used in the diagnosis of
cutaneous lymphoma, but many studies have shown potential future applications in various
areas. Other techniques, such as comparative genomic hybridization, are still confined to
the research arena, but have added some insight into the molecular pathogenesis of
cutaneous T-cell lymphoma.
Semin Cutan Med Surg 31:234-240 © 2012 Frontline Medical Communications
Polymerase Chain Reaction-Based Molecular Diagnosis of Cutaneous Infections in Dermatopathology
Conventional methods, including microscopy, culture, and serologic studies, are a mainstay in
the diagnosis of cutaneous infection. However, owing to limitations associated with these
techniques, such as low sensitivity for standard microscopy and in the case of culture delay in
diagnosis, polymerase chain-reaction based molecular techniques have taken on an expanding
role in the diagnosis of infectious processes in dermatopathology. In particular, these assays
are a useful adjunct in the diagnosis of cutaneous tuberculosis, atypical mycobacterial infection,
leprosy, Lyme disease, syphilis, rickettsioses, leishmaniasis, and some fungal and viral
infections. Already in the case of tuberculosis and atypical mycobacterial infection, standardized
polymerase chain-reaction assays are commonly used for diagnostic purposes. With time,
additional molecular-based techniques will decrease in cost and gain increased standardization,
thus delivering rapid diagnostic confirmation for many difficult-to-diagnose cutaneous
infections from standard formalin-fixed paraffin-embedded tissue specimens.
Semin Cutan Med Surg 31:241-246 © 2012 Frontline Medical Communications
Molecular Diagnosis of Infection-Related Cancers in Dermatopathology
The association between viruses and skin cancer is increasingly recognized in a number of
neoplasms, that is, cutaneous squamous cell carcinoma, Kaposi sarcoma, nasopharyngeal
carcinoma, and Merkel cell carcinoma, as well as hematolymphoid malignancies such as
adult T-cell leukemia/lymphoma and NK/T-cell lymphoma (nasal type) and post-transplant
lymphoproliferative disorders. Molecular assays are increasingly used to diagnose and
manage these diseases. In this review, molecular features of tumor viruses and related host
responses are explored. The tests used to identify such features are summarized. Evaluation
of the utility of these assays for diagnosis and/or management of specific tumor types
is presented.
Semin Cutan Med Surg 31:247-257 © 2012 Frontline Medical Communications