Lisa M. Cohen

Lentigo maligna and lentigo maligna melanoma

Lentigo maligna (LM) is a pigmented lesion that occurs on the sun-exposed skin, particularly the head and neck areas, of an older patient. The lesion increases in size and at some point, often many years after its onset, may become lentigo maligna melanoma (LMM). For this reason, most authors consider LM a form of melanoma in situ. Treatment includes surgical or destructive modalities; the preferred form of therapy is surgical removal. Histopathologic features include a proliferation of atypical melanocytes along the basal layer of the epidermis and adnexal structures. This article discusses the clinical, histopathologic, and epidemiologic features of LM. The prognosis and treatment of LM are reviewed. Although the lifetime risk of the development of LMM is unclear, LMM is discussed briefly.

Array-CGH Reveals Recurrent Genomic Changes in Merkel Cell Carcinoma Including Amplification of L-Myc

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P=0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26% of tumors, a deletion of 13q14-21 was recurrent in 26% of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39% of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 4/4 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.

Atypical melanocytic nevi: Clinical and histopathologic predictors of residual tumor at reexcision

BACKGROUND The appropriate method for surgical management of melanocytic lesions with disordered architecture and melanocytic atypia (formerly dysplastic nevi) has been controversial. Physicians often reexcise these lesions after primary removal because of their potential relation to malignant melanoma. The outcomes of these reexcisions and the original biopsy specimens have not been previously examined. OBJECTIVE The purpose of this study was to examine reexcision specimens and their respective original specimens to determine whether there were any characteristics predictive of the presence of residual nevus cells (RNCs) on reexcision. METHODS One hundred eighty-nine reexcision specimens of atypical melanocytic lesions were evaluated for this study. The original specimens were examined for specific histopathologic features without knowledge of the findings on reexcision. Clinical characteristics were also examined. RESULTS Of the 189 reexcision specimens, 47 (24.9%) contained RNCs. The proportion of specimens with RNC on reexcision was significantly greater if the original lesion was removed by punch biopsy rather than by shave or elliptical excision (38.3% vs 22.0% vs 10.5%, respectively; p < 0.03). Lesions located on the chest had a higher likelihood of RNCs than those on the back or leg (52.2% vs 21.7%; p = 0.009; 52.2% vs 9.7%, p < 0.002, respectively). Mean age was greater in those with RNCs at reexcision than those without (43.6 vs 37.9 years, respectively; p < 0.0001). The proportion of specimens with RNCs at reexcision was greater in those that had both lateral margins involved than in those that had nevus cells in either one or neither of the lateral margins in the original biopsy specimens (39.7% vs 24.0% vs 7.8%, respectively; p = 0.0005). One of the 189 reexcision specimens (0.5%) contained melanoma, although the original histopathologic diagnosis was an atypical melanocytic nevus. CONCLUSION We identified several clinical and histopathologic factors that are strongly associated with the presence of RNCs on reexcision.

Clear Cell Fibrous Papule With Nki/c3 Expression: Clinical and Histologic Features in Six Cases

Fibrous papule of the nose is a common benign lesion of dermal fibroblast lineage. Two unusual variants have been described, namely, fibrous papule with granular cells and fibrous papule with clear fibrocytes. We report a second case series (six cases) of clear cell fibrous papule to add to the first series of 9 cases. Clinical and histologic features in our cases are similar to those in the first series. All of our specimens were dome-shaped, 2- to 5-mm skin-colored to slightly erythematous papules on the faces of three male and three female adults ranging from 18 to 48 years of age. All but one lesion were on the nose. Clinical differential diagnoses included fibrous papule, verruca, basal cell carcinoma, and a variety of other neoplasms. Histologically, dermal aggregates of clear cells with finely granular to vacuolated cytoplasm, and centrally located nuclei, were found. Most specimens also contained ectatic capillaries, and all showed evidence of irritation or trauma. Periodic acid-Schiff stain was negative in all specimens to which it was applied (5/6). Neural, melanocytic, and epithelial origins were eliminated by negative staining with S-100, Mart-1, cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen, performed on some of the specimens. A mesenchymal nature was confirmed in one specimen staining strongly positive for vimentin. Five of six cases stained positively for CD68, and all five cases studied were strongly and diffusely positive for NKI/C3. Factor XIIIa stain highlighted scattered dendritic cells within the lesion but was otherwise negative in all six cases studied. Recognition of this variant of fibrous papule is important to distinguish this benign lesion from other clear cell neoplasms.

Human papillomavirus type 11 in multiple squamous cell carcinomas in a patient with subacute cutaneous lupus erythematosus

Squamous cell carcinoma (SCC) is a rare complication of cutaneous lupus erythematosus (LE). Aside from the documented role of ultraviolet light, SCC may arise in areas of chronic scarring, such as in lesions of discoid LE. Iatrogenic immunosuppression associated with organ transplantation also results in a predisposition to SCC, often with multiple tumors. A role for certain human papillomaviruses (HPV) in the development of squamous cell carcinoma has been documented; specifically, HPV types 5 and 8 are detected in SCCs in patients with epidermodysplasia verruciformis and in recipients of organ transplants. HPV-11 is generally found in benign genital condylomata or laryngeal papillomas, but has not yet been associated with malignancy. We describe a patient with non-scarring cutaneous LE who was treated with azathioprine and prednisone and developed multiple SCCs. HPV-11 DNA and the target oncogenes neu and Ki-ras were detected in tumor tissue with the polymerase chain reaction. The HPV may have been involved in tumor induction and the azathioprine may have been involved in tumor promotion.

Intradermal melanocytic nevus with prominent Schwannian differentiation

Features of peripheral nerve sheath differentiation such as neuroid cords, nerve corpuscles, fascicle-like structures, and, exceptionally, palisading have been reported in melanocytic nevi. We report an intradermal melanocytic nevus with prominent Verocay-like bodies. The upper portion of the neoplasm was composed of typical round intradermal nevus cells, many of which were pigmented. Within the deeper portion, there was a nonpigmented spindle cell proliferation with prominent Verocay bodies, simulating a neurilemmoma. Typical nevus nests merged with neurilemmoma-like areas. The entire lesion stained positively for S-100 and Mart-1 proteins and negatively for HMB-45 stain. Diffuse Mart-1 positivity excluded a collision of a melanocytic lesion with a neurilemmoma. The histopathologic features of this nevus further support a close relation between nevus cells and Schwann cells.

De novo intraepidermal epithelioid melanocytic dysplasia: a review of 263 cases

Background: De novo intraepidermal epithelioid melanocytic dysplasia (DNIEMD) is a newly characterized lesion that is associated with a personal and/or family history of malignant melanoma (MM) and/or dysplastic nevi (DN). However, the biological significance is still uncertain and the persons predisposed to this lesion have not been adequately described.

Aminolevulinic Acid Photodynamic Therapy in the Treatment of Erosive Pustular Dermatosis of the Scalp: A Case Series

IMPORTANCE Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory skin condition that develops on sun-damaged skin in older individuals. Patients with EPDS present a therapeutic challenge because medical treatments and surgical modalities have met with limited success. Methyl aminolevulinate photodynamic therapy has been effective in 1 case but induced the disease in others. OBSERVATIONS Eight patients with EPDS with mean (range) age 84 (67-93) years underwent gentle curettage of the hyperkeratotic lesions followed by aminolevulinic acid photodynamic therapy (PDT) 1 to 2 weeks later. Lesions resolved in 6 patients, whereas 2 patients had residual lesions at 6-week follow-up and underwent a second cycle of curettage and aminolevulinic acid PDT with resolution. One patient experienced a partial recurrence 5 months after the procedure and was successfully retreated with curettage + aminolevulinic acid PDT. No adverse effects were noted, and patients were satisfied with the treatment. CONCLUSIONS AND RELEVANCE This series of patients demonstrated EPDS successfully treated with PDT. Lesions resolved in all patients with a protocol that included curettage followed by aminolevulinic acid PDT. Therefore, this protocol represents an efficacious modality for EPDS.

Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases

Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal–epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process.

Severe, ulcerative, lichenoid mucositis associated with secukinumab

Secukinumab is a new human monoclonal antibody targeting interleukin (IL)-17A, a cytokine involved in the pathogenesis of psoriasis. The US Food and Drug Administration approved secukinumab for psoriasis in 2015. Because the medication has been on the market for a short time, adverse events involving the oral mucosa are rarely reported. We report a case of severe, ulcerative, lichenoid mucositis associated with secukinumab use.