Vol. 29. No. 3


The proper diagnosis and management of pigmented lesions and melanoma can be extremely challenging, but significant strides have been made on multiple fronts in our understanding of the best approaches to these lesions. In this issue, Arthur Sober and his colleagues describe the new changes to the AJCC staging system, Beth Ruben discusses the issues surrounding pigmented lesions of the nail, Kara Shah examines the risk of melanoma and neurocutaneous melanosis in congenital nevi, and Rossitza Lazova and Maria Miteva review the difficulties associated with management of Spitz nevi and the “atypical Spitzoid neoplasm.” Steven Wang and Pantea Hashemi review different imaging modalities, and Suephy Chen and her colleagues discuss the literature surrounding photoprotection measures and serum vitamin D levels. Hensin Tsao and his colleagues describe our current knowledge of the genetic determinants of melanoma predisposition, and the issue concludes with Keith Flaherty and Igor Puzanov’s review of the latest information regarding targeted therapy for metastatic melanoma. I hope that the reader will find the authors’ insights to be helpful when faced with similar situations in daily practice, and I thank all the authors for sharing their expertise. This issue is dedicated to Marie-France Demierre, who was to have been a contributor to this issue before her untimely passing. She was not only an excellent clinician, researcher, and teacher, but also a wonderful colleague and friend, and she is missed.

Implications of the 2009 American Joint Committee on Cancer Melanoma Staging and Classification on Dermatologists and Their Patients

Arthur J. Sober, MD | Charles M. Balch, MD | Mary Alice Nading, MD

The Melanoma Staging and Classification system was recently revised by the American
Joint Committee on Cancer (AJCC) and implemented effective January 2010 with changes
reflecting new prognostic data gleaned by the significantly larger patient population studied
for the 7th edition. This newest analysis yields important long-term outcome data as many
of the patients were followed for nearly 2 decades. Additions to edition 7 of the AJCC
Melanoma Staging classification highlight several important prognostic factors, particularly
the addition of mitotic rate for classifying thin melanomas, the presence of microtumor
burden in lymph nodes for stage III disease, and elevated lactate dehydrogenase levels in
patients with distant metastatic disease. Although the basic tumor-nodes-metastases (ie,
TNM) cancer classification model remains unchanged in this newest edition, the current
AJCC Melanoma Staging System has incorporated the latest prognostic data to accurately
stratify patients into staging categories. It is important for clinicians and dermatopathologists
to familiarize themselves with these changes so that patients are suitably managed
and referred to medical and surgical oncologists when appropriate.
Semin Cutan Med Surg 29:142-147 © 2010 Elsevier Inc. All rights reserved.


Pigmented Lesions of the Nail Unit: Clinical and Histopathologic Features

Beth S. Ruben, MD

Probably the most common reason to perform biopsy of the nail unit is for the evaluation of
irregular pigmentation, especially longitudinal melanonychia or pigmented bands. When narrow
and solitary, these are usually the product of melanocytic activation/hypermelanosis,
lentigines, or melanocytic nevi. Multiple pigmented bands are generally a benign finding, the
result of melanocytic activation, as seen in racial pigmentation in darker-skinned patients, for
example. In the context of an irregular, broad, heterogeneous or “streaky” band, the chief
concern is the exclusion of subungual melanoma. Before assessing the histologic features of
any such entities, it is important to understand the normal nail anatomy and melanocytic density
of nail unit epithelium, as well as the type of specimen submitted, and whether it is adequate to
undertake a proper histologic evaluation. The criteria for diagnosis and prognosis of melanoma of
the nail unit are still evolving, and a variety of factors must be weighed in the balance to make a
correct diagnosis. The importance of the clinical context cannot be overemphasized. There are also
nonmelanocytic conditions to be considered that may produce worrisome nail discoloration, such
as subungual hemorrhage, squamous cell carcinoma, and pigmented onychomycosis.
Semin Cutan Med Surg 29:148-158 © 2010 Elsevier Inc. All rights reserved.


The Risk of Melanoma and Neurocutaneous Melanosis Associated with Congenital Melanocytic Nevi

Kara N. Shah, MD, PhD

Congenital melanocytic nevi are commonly encountered in clinical practice. Although the
development of malignant melanoma arising in small and intermediate congenital melanocytic
nevi is rare, there is a significant risk of malignant degeneration associated with large
congenital melanocytic nevi, in particular those that arise on the torso in the so-called
“bathing trunk” distribution, where the risk is estimated to be about 2.5% to 5%. The risk
of malignant melanoma arising within a large congenital melanocytic nevus is highest in the
first 5 to 10 years of life and carries a significant mortality. Large congenital melanocytic
nevi, in particular those overlying the posterior axis and occurring in the context of multiple
satellite melanocytic nevi, are also associated with the development of neurocutaneous
melanosis, which may result in neurologic and neurodevelopmental sequelae and is associated
with a significant risk of primary central nervous system melanoma and death.
Semin Cutan Med Surg 29:159-164 © 2010 Elsevier Inc. All rights reserved.


Spitz Nevus and Atypical Spitzoid Neoplasm

Maria Miteva, MD | Rossitza Lazova, MD

Spitz nevus (SN) and Spitzoid malignant melanoma (SMM) represent benign and malignant
counterparts at both ends of the spectrum of Spitzoid lesions. Atypical Spitzoid neoplasm
(ASN) is a poorly defined and characterized category of melanocytic tumors with histologic
features of both benign Spitz nevi and malignant melanomas. The group of ASN represents
a mixture of Spitz nevi with atypical features and Spitzoid melanomas. However, at the
current moment in time, histopathologists are not capable of differentiating between the 2
in some cases and are forced to place them in this ambiguous category, where the behavior
of these lesions cannot be predicted with certainty. Because this group encompasses both
benign and malignant lesions, and perhaps also a separate category of melanocytic tumors
that behave better than conventional melanomas, some of these neoplasms can metastasize
and kill patients, whereas others have no metastatic potential, and yet others might
only metastasize to regional lymph nodes. Although diagnostic accuracy has improved over
the years, many of these lesions remain controversial, and there is still poor interobserver
agreement in classifying problematic Spitzoid lesions among experienced dermatopathologists.
The objective of this review article is to summarize the most relevant information
about SN and ASNs. At this time histologic examination remains the golden standard for
diagnosing these melanocytic neoplasms. We therefore concentrate on the histopathologic,
clinical, and dermoscopic aspects of these lesions. We also review the most recent
advances in immunohistochemical and molecular diagnostics as well as discuss the
controversies and dilemma regarding whether to consider sentinel lymph node biopsy for
diagnostically ambiguous melanocytic neoplasms.
Semin Cutan Med Surg 29:165-173 © 2010 Elsevier Inc. All rights reserved.


Noninvasive Imaging Technologies in the Diagnosis of Melanoma

Pantea Hashemi, MD | Steven Q. Wang, MD

The incidence of melanoma has increased during the last few years. Melanoma care and
survival can be improved by early diagnosis, which can be facilitated by the use of
noninvasive imaging modalities. Here we review 5 modalities available in clinical practice.
Total body photography is used to follow patients at high risk for melanoma by detecting
new lesions or subtle changes in existing lesions. Dermoscopy is an effective noninvasive
technique for the early recognition of melanoma by allowing clinicians to visualize subsurface
structures. Computer-assisted diagnostic devices are fully automated analysis systems
with the capacity to classify lesions as benign or malignant with limited involvement
from clinicians. Confocal scanning laser microscopy is an in vivo and noninvasive technology
that examines the skin at a resolution comparable to that of histology. Highresolution
ultrasound is an adjunct diagnostic aid mainly for the early detection of lymph
node metastasis. Applications and limitations of each technology are discussed.
Semin Cutan Med Surg 29:174-184 © 2010 Elsevier Inc. All rights reserved.