Faculty Bibliography

Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.

Pilomatricomas are benign adnexal tumors which differentiate towards hair matrix cells. These lesions present most often as firm nodular tumors in the upper extremities, head and neck areas, with rare cases reporting pilomatricomas appearing on the trunk. Pilomatricomas can range from 0.5 to 3 cm in diameter with the classification of "giant" pilomatricoma reserved for tumors exceeding 5 cm in diameter. Four histopathologic stages have been described: early, fully developed, early regressive, and late regressive, all of which involve anucleated squamous cells known as "ghost" or "shadow" cells. There are known associations of this pathology with other conditions, most notably myotonic dystrophy, sarcoidosis, Gardner syndrome, Turner syndrome, Steinart disease, sternal cleft, and coagulative defects. Rarely, pilomatricomas can degenerate into pilomatricoma carcinoma. Treatment of this condition is excision of the tumor and the prognosis is favorable with virtually no recurrence. Pilomatricomas are most often seen in patients in their first two decades of life. We report a case of a 41-year-old Asian woman with no significant medical history who presented with painful lesions on her upper extremities bilaterally. The patient denied a family history of similar lesions and was worried she had skin cancer. On clinical exam, the patient had on each upper extremity, a roundshaped, blue and white colored, firm nodule. The lesions were completely excised without complications and were consistent with pilomatricomas on histology. Prior to our observations, Fernandez-Flores et al reported a 28-year-old male with multiple pilomatricomas associated with seminoma which was diagnosed several months before the pilomatricomas. In another case, a 22-year-old woman, also with no medical history, presented with multiple pilomatricomas distributed on her forearm, trunk, and eyebrow. Nevertheless, multiple pilomatricomas in an older patient and in the absence of associated disorders remains rare, which may be a product of underreporting rather than actual incidence. This case highlights the importance of considering pilomatricomas in the differential diagnosis in the setting of multiple growths, even in older patients

Scedosporium apiospermum, a ubiquitous environmental mold, is increasingly reported as causing invasive fungal disease in immunocompromised hosts. It poses a therapeutic challenge due to its intrinsic resistance to traditional antifungals and ability to recur despite demonstrating susceptibility. We present an immunocompromised patient with a cutaneous S. apiospermum infection that disseminated despite treatment with voriconazole, the drug of choice. Adding echinocandins and GM-CSF provided partial recovery, indicating a potential synergistic role of dual-antifungal and immunotherapeutic agents.

Cutis verticis gyrata that involves only the face is a rare presentation of this even rarer cutaneous anomaly. We present a 61-year-old man, who developed primary essential progressive cutis verticis gyrata of the face.

We present a 53-year-old woman with diffuse macular amyloidosis. We discuss the clinical manifestations, pathophysiologic mechanisms, and associations of cutaneous macular amyloidosis.

A 56-year-old man presented with a 15-year history of scaly red plaques on the trunk and axillae. Skin biopsy was consistent with Hailey-Hailey disease. His condition was refractory to multiple therapies, which included topical and oral antibiotics and topical, intralesional, and oral glucocorticoids. Treatment with subcutaneous botulinum toxin type A at the axillae and on the back led to a nearly complete resolution of plaques in those areas. Botulinum toxin type A should be considered in patients with extensive Hailey-Hailey disease who are fail traditional therapies.

We present a 69-year-old man with type 2 diabetes mellitus and a five-year history of an eruption of follicular pustules, papules, and nodules, which was identified histopathologically as folliculocentric granuloma annulare (GA). Folliculocentric generalized GA is a rarely reported variant of GA, in which the the palisading histiocytes form focal granulomas in a follicular pattern. In this case, the GA may represent an isotopic phenomenon, with lesions developing in hair follicles that were previously affected by a suppurative folliculitis.

Nodular amyloidosis is the rarest form of primary cutaneous amyloidosis. We report the case of a 74-year-old woman with an eight-year history of asymptomatic, hyperpigmented plaques on the pretibial areas. A skin biopsy specimen showed deposits of amorphous eosinophilic material that extended throughout the dermis with apple-green birefringence with a Congo-red stain, which established a diagnosis of nodular amyloidosis. Patients with nodular amyloidosis should be evaluated for systemic disease and followed appropriately due to a small risk of progression to systemic amyloidosis.