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Dermatologic Manifestations of Internal Malignancy

Key Points Internal malignancy can involve the skin either directly or indirectly. Direct involvement is defined as tumor metastatic to the skin. Indirect involvement refers to changes in the skin that suggest the possibility of an underlying malignancy. Patients with direct involvement should be assumed to have an underlying neoplasm and must be evaluated accordingly. Patients with indirect involvement may not have an underlying neoplasm when…

Genetic Disorders Predisposing to Skin Malignancy

Key Points Several genodermatoses have a predisposition for the development of one or more types of skin cancers. Internal malignancies may also arise in a few. These diseases are caused by mutations in over 30 genes which normally function as tumor suppressors, repair of UV-damaged DNA, telomere length regulation, maintenance of cutaneous structural integrity, and susceptibility to mutagenesis by specific human papillomaviruses. Multidisciplinary management includes early…

Cutaneous Carcinogenesis Related to Dermatologic Therapy

Key Points Potential risks and benefits associated with phototherapy and drug therapy should be discussed with all patients. Screening examinations should be performed prior to prescribing a therapy with carcinogenic risk. Attention must be paid to treatment interactions that may increase carcinogenesis when multiple medications are prescribed. Introduction Any systemic treatment is associated with the risk of systemic side effects. The prudent physician must use caution…

Spitz nevus

Key Points Spitz nevi can be clinically and histopathologically distinguished from melanoma in a large majority of cases. Spitz nevi are predominantly seen in children and young adults, but recent studies have shown a broader age range than was previously appreciated. Spitz nevi are classically solitary, well circumscribed pink papules, but large, deeply pigmented, verrucous and other variations in appearance can occur. Spitz can be junctional,…

Genetic Testing for Melanoma

Key Points Approximately 10% of melanomas occur in family clusters. In North American populations, mutations in the CDKN2A gene are associated with up to a 76% lifetime risk for melanoma. CDKN2A may also increase the risk for pancreatic cancer to as much as 25%. Clinical genetic testing is available to identify families with mutations in the CDKN2A gene. In moderate to high melanoma incidence areas, referral…

Pregnancy and Melanoma

Key Points Pregnancy does not have an adverse effect on the prognosis of patients with stage I/II melanoma. There is some evidence that pregnant patients are diagnosed with thicker melanomas compared with non-pregnant controls, but this finding needs further study. Although estrogen receptor β expression has been observed in melanomas diagnosed in pregnant patients, clinical relevance needs to be elucidated. Recommendations for these patients regarding future…

Management of the Patient with Melanoma

Key Points Melanoma management should be tailored to the needs of each individual patient. Surgical excision is the cornerstone of melanoma management. Sentinel lymph node biopsy is currently a staging and prognostic tool in the management of melanoma. Adjuvant therapy should be considered in patients at high risk of recurrence. Single drug chemotherapy remains the standard treatment for advanced metastatic disease. Clinical trials should be strongly…

Pathology of Melanoma: Interpretation and New Concepts

Key Points It is essential that clinicians understand the appropriate methods for biopsy of lesions that are highly suspect for melanoma to enhance accurate diagnosis. Histopathologists who diagnose cutaneous melanoma must be aware of the many different histologic variants and the simulators of melanoma. Special stains and other techniques are valuable adjuncts to routine histology but no individual stain or special technique alone can distinguish between…

Prognostic Factors and Staging in Melanoma

Key Points Staging has significant impact on prognostic assessement, treatment decision-making, and clinical trial planning and analysis. Primary tumor (Breslow) thickness and ulceration continue to represent important prognostic factors for survival and define T-category strata in cutaneous melanoma. Mitotic rate, defined as mitoses per square millimeter, is an important independent prognostic factor, particularly for patients with thin (T1 ≤1 mm) melanoma, and replaces Clark level of…

The Importance of Early Detection of Melanoma, Physician and Self-Examination

Key Points The incidence of melanoma has been increasing faster than that of any other cancer in the United States. Early detection of melanoma is critical for better patient survival. Many early melanomas can be recognized with the help of the ABCDEs, and new evolving techniques using complex computer algorithms will augment the effectiveness of early diagnosis. Public and professional education, regular full-body skin examination by…

Congenital Melanocytic Nevi

Key Points Congenital melanocytic nevi (CMN) can have medical, cosmetic, and psychological consequences. The natural history of CMN may be dynamic and can include development of erosions and proliferative nodules during infancy, changes in pigmentation and topography, neurotization, and spontaneous regression. The risk of melanoma arising within a small or medium-sized CMN is low (<1% over a lifetime) and is extremely low before puberty. Melanoma develops…

Dysplastic Nevi

Key Points Clinically dysplastic nevi are an important risk factor for development of melanoma. The lesion represents a point on a clinicopathological continuum that spans banal nevus at one end and melanoma at the other. Individual dysplastic nevi rarely eventuate into melanoma. There appears to be a genetic basis for this lesion, the expression of which is under the influence of environmental factors. The lesion is…

Cutaneous T-cell Lymphoma: Mycosis Fungoides and Sézary Syndrome

Key Points Cutaneous T-cell lymphoma (CTCL) is a malignant neoplasia of T cells with homing features in the skin. Mycosis fungoides and Sézary syndrome are the most common variants of CTCL. Mycosis fungoides is often a slow-growing, indolent epidermotropic malignancy, while Sézary syndrome progresses rapidly. The clinical presentations of mycosis fungoides are protean including patches, plaques, tumors and erythroderma. Sézary syndrome is characterized by erythroderma, lymphadenopathy,…

Pseudolymphomas of the Skin

Key Points Cutaneous pseudolymphomas are benign inflammatory skin diseases that mimic malignant lymphomas either clinically, histopathologically, or both. Cutaneous pseudolymphomas should be classified precisely according to specific clinicopathologic entities. Integration of clinical, histopathologic, immunophenotypic and molecular genetic features is crucial for the diagnosis of cutaneous pseudolymphomas. Some non-lymphoid malignant neoplasms may simulate histopathologically the picture of a cutaneous lymphoma. Introduction Pseudolymphomas of the skin are benign…

Cutaneous Neoplastic Disorders Related to HPV and HIV Infection

Key Points Epidermodysplasia verruciformis (EV) is a genetic lifelong disease associated with specific human papillomaviruses (HPV) and multiple skin cancers. Immunosuppressed patients have an increased risk of developing EV lesions. Bowenoid papulosis presents as wart-like papules usually affecting the genitals of young sexually active adults. HPV genotype is detected in most lesions of bowenoid papulosis with HPV-16 being the most commonly identified. Progression of bowenoid papulosis…

Malignant Neoplasms: Vascular Differentiation

Key Points Clinical presentation is frequently a red- to purple-colored macule, plaque or nodule. Helpful diagnostic clues include sharp circumscription versus infiltrative edges of the neoplasm, size and multicentricity, as well as site of involvement, age, and other associated disease states such as immunosuppression, but biopsy is required to confirm diagnosis. Conservative excision is effective for benign lesions but other extensive treatment modalities may be needed…

Merkel Cell Carcinoma

Key Points Merkel cell carcinoma (MCC) is an uncommon neuroendocrine skin cancer with a 5-year disease-associated mortality of 46%. The reported incidence of MCC has tripled in the past 20 years and there are approximately 1500 new cases each year in the US. Risk factors include age over 50 years, profound immune suppression, UV exposure, and fair skin. Unfortunately, despite its lack of tenderness, MCC is…

Kaposi’s Sarcoma

Key Points Kaposi's sarcoma is a multicentric, mostly oligoclonic neoplastic proliferation of endothelial cells that have been infected and transformed by human herpesvirus-8. Four epidemiologic types of Kaposi's sarcoma are recognized: classic (typically found sporadically in elderly persons of Mediterranean descent), epidemic (AIDS-related), endemic (occurring in Africa), and iatrogenic (immunosuppression-associated, transplant-associated). While there are numerous clinical variants, the typical lesions are well-demarcated, smooth purple macules, plaques…

Sarcomas of the Skin

Key Points Sarcomas of the skin comprise numerous rare entities that commonly present as nodules or plaques. Cutaneous sarcomas exhibit differentiation toward a variety of mesenchymal lineages. Dermatofibrosarcoma protuberans, atypical fibroxanthoma, and cutaneous leiomyosarcoma are the most common types. Diagnosis is aided by key immunohistochemical, cytogenetic, and molecular diagnostic studies. Complete surgical extirpation is the mainstay of therapy. Radiotherapy is used as adjuvant therapy in select…