Loren E. Golitz

Primary malignant melanoma of the oral cavity. A review of 177 cases.

Malignant melanoma of the oral cavity is rare, accounting for about 1% to 8% of all melanomas. There have been no prospective studies of melanoma in this location, and all previous papers have reported small numbers of cases or have retrospectively reviewed case reports from the literature. The authors report six new cases and review 171 cases published since the last major review in 1975. The classification of oral melanomas with radial growth phases is discussed.

Diffuse Neonatal Hemangiomatosis

Abstract: Diffuse neonatal hemangiomatosis is an often fatal disorder characterized by widespread capillary hemangiomas of the skin and visceral organs. Ultrasound and computed tomographic scans may be useful in determining the extent of visceral disease. The organs most commonly affected are the gastrointestinal tract, brain, liver, and lung. Complications include high‐output cardiac failure, gastrointestinal bleeding, hydrocephalus, and consumption coagulopathy. Despite therapy with corticosteroids, the mortality rate is high.

Vulvar clear cells of Toker: precursors of extramammary Paget's disease.

Clear cells of Toker are intraepithelial cells with clear to pale staining cytoplasm and bland cytologic features found with H&E staining in approximately 10% of normal nipples. Toker cells have been hypothesized as a precursor of extramammary Pagets disease (EMPD), although Toker cells have not been identified as a normal component of genital skin. Using immunohistochemistry, we studied 11 vulvectomies for the presence of Toker cells in association with mammary-like glands of the vulva (MLG). A retrospective study of 11 vulvectomies was performed using routine hematoxylin and eosin staining, as well as immunohistochemical staining for cytokeratin 7 (CK7). Control sections of skin not involving the milk line from age-matched patients were also examined. Four of eleven vulvectomies (36%) demonstrated Toker cells with CK7 staining. Toker cells were associated with the openings of the ducts of mammary-like glands of the vulva. Toker cells were not seen in control tissues. Toker cells occur as a normal constituent of genital skin in association with mammary-like glands of the vulva. Previous morphologic, immunohistochemical, and ultrastructural evidence have pointed to Toker cells as a precursor of EMPD. The demonstration of Toker cells in genital skin strengthens the evidence of their role in the development of EMPD.

Papillary mesenchymal bodies: A histologic finding useful in differentiating trichoepithehomas from basal cell carcinomas

To distinguish a basal cell carcinoma (BCC) from a trichoepithelioma can be difficult even for an experienced dermatopathologist. Previously reported differentiating histologic features are relative criteria that may be shared by both tumors. In a review of 30 consecutive cases each of trichoepitheliomas, keratotic BCC, and routine BCC, classic criteria were compared with papillary mesenchymal body formation. Papillary mesenchymal bodies are distinct fibroblastic aggregations that represent abortive attempts to form the papillary mesenchyme responsible for hair induction. Papillary mesenchymal bodies were observed in 93% of all trichoepitheliomas, 7% of all keratotic BCC, and 0% of all routine BCC. Hair bulb formation was observed in 30% of trichoepitheliomas and in none of the BCC. We conclude that papillary mesenchymal body formation is an easily recognizable histologic criterion that is more reliable in differentiating these two tumors than standard criteria, including epidermal connections, keratinization, calcification, foreign body reaction, fibrosis, stromal retraction, tumor mucin, ulceration, frondlike epithelial pattern, and the inflammatory response.

Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane

There has been a rapid emergence of numerous targeted agents in the oncology community in the last decade. This exciting paradigm shift in drug development lends promise for the future of individualized medicine. Given the pace of development and clinical deployment of targeted agents with novel mechanisms of action, dermatology providers may not be familiar with the full spectrum of associated skin-related toxicities. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents, and their intensity can be dose-limiting or lead to therapy discontinuation. In light of the often life-saving nature of emerging oncotherapeutics, it is critical that dermatologists both understand the mechanisms and recognize clinical signs and symptoms of such toxicities in order to provide effective clinical management. Part I of this continuing medical education article will review in detail the potential skin-related adverse sequelae, the frequency of occurrence, and the implications associated with on- and off-target cutaneous toxicities of inhibitors acting at the cell membrane level, chiefly inhibitors of epidermal growth factor receptor, KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors.

Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways.

The last decade has spawned an exciting new era of oncotherapy in dermatology, including the development of targeted therapies for metastatic melanoma and basal cell carcinoma. Along with skin cancer, deregulation of the PI3K-AKT-mTOR and RAS-RAF-MEK-ERK intracellular signaling pathways contributes to tumorigenesis of a multitude of other cancers, and inhibitors of these pathways are being actively studied. Similar to other classes of targeted therapies, cutaneous adverse effects are among the most frequent toxicities observed with mitogen-activated protein kinase pathway inhibitors, PI3K-AKT-mTOR inhibitors, hedgehog signaling pathway inhibitors, and immunotherapies. Given the rapid expansion of these families of targeted treatments, dermatologists will be essential in offering dermatologic supportive care measures to cancer patients being treated with these agents. Part II of this continuing medical education article reviews skin-related adverse sequelae, including the frequency of occurrence and the implications associated with on- and off-target cutaneous toxicities of inhibitors of the RAS-RAF-MEK-ERK pathway, PI3K-AKT-mTOR pathway, hedgehog signaling pathway, and immunotherapies.

Melanocytic nevi with focal atypical epithelioid cell components : a review of seventy-three cases

BACKGROUND We report a variant of melanocytic nevus that may be confused with melanoma. OBJECTIVE The purpose of this study is to describe the clinical, histologic, and biologic features of nevi with focal atypical epithelioid cell components (clonal nevi). METHODS Seventy-three cases were retrieved by reviewing lesions previously diagnosed as clonal, combined, deep penetrating, and inverted type-A nevi. Histologic features were assessed and referring physicians received a questionnaire about the presentation and outcome of each case. RESULTS Histologically, all cases had a biphasic pattern characterized by an ordinary nevus that contained a darkly pigmented collection of large distinct epithelioid melanocytes in the superficial dermis. Immunostains identified mutant p53 proteins in 50% of dermal clones (9 of 18) but not in ordinary nevus cells adjacent to the clones. We are not aware of any patient developing a malignant melanoma (mean follow-up 24.5 months), including 41 cases that were initially incompletely excised. CONCLUSION Clonal nevi are a distinct variant of melanocytic nevi and should be distinguished from malignant melanoma arising in a preexisting nevus.

Neutrophilic eccrine hidradenitis associated with induction chemotherapy

We report three new cases of neutrophilic eccrine hidradenitis associated with induction chemotherapy which resolves two major points. First, because two of our patients had testicular carcinoma; this firmly establishes that NEH is not exclusively seen in patients with acute myelogenous leukemia or Hodgkins lymphoma as previously reported. Second, because two of our patients did not receive cytarabine which has previously been suspected of being the causative agent, it is apparent that this disorder may be produced by more than one chemotherapeutic agent or combination of agents. The histologic features with a discussion of the spectrum of changes which may be seen are presented.

Pediatric melanoma : Are recent advances in the management of adult melanoma relevant to the pediatric population

Purpose Although melanoma in childhood is a rare condition, there is evidence that it is increasing in frequency. As advances are being made in the understanding and therapy of adult melanoma, we need to consider the relevance of these advances to the pediatric population. Patients and Methods We have reviewed our experience at the University of Colorado Health Sciences Center with the clinical parameters, therapy, and outcomes of melanoma in 27 patients age 16 years or younger and contrasted these to the adult experience. Results Most cases were diagnosed early with the median thickness of the primary melanoma being 0.75 mm. Six of seven patients who had lymph node metastases develop remain alive at a median follow-up of 62 months. Durable complete responses to a variety of therapies were seen in three of five patients with advanced disease outside the central nervous system. Our experience with sentinel node biopsy, adjuvant interferon, and new therapies for metastatic melanoma were also reviewed and appear to be relevant for younger patients. Conclusions The behavior of melanoma in the pediatric population at our center is similar to that seen in adults. The integration of recent advances in the staging and therapy of melanoma in adults would be of benefit to children with this condition.

Correlation of p16 and pRb expression with HPV detection in Bowen's disease.

Background:  Bowen’s disease is a form of cutaneous squamous cell carcinoma which may be caused by ultraviolet radiation, human papilloma virus (HPV) infection, or other causes. Although p16 over‐expression is a surrogate marker of HPV E7‐mediated catabolism of pRb in premalignant and malignant lesions of the cervical mucosa, the correlation of p16 and pRb expression with HPV detection in Bowen’s disease has not been well characterized.