Cutaneous gangrene, vascular calcification, and hyperparathyroidism.

We describe the development of necrotic ulcers with underlying vascular calcification in a 72-year-old man who had chronic renal failure. These lesions had surrounding ecchymoses. The patient had a normal serum calcium concentration, an elevated parathyroid hormone level, and findings consistent with a parathyroid adenoma on ultrasonography. We consider this another case of a characteristic cutaneous syndrome secondary to underlying vascular calcification and hyperparathyroidism.

Follicular mucinosis: histopathologic review of 33 cases.

Among 33 patients with the histologic diagnosis of follicular mucinosis (alopecia mucinosa) made at our institution between 1982 and 1989, 9 had mycosis fungoides diagnosed concomitantly. Three other patients had lymphoproliferative disorders, and two had Kaposi's sarcoma. Analysis of biopsy features such as epidermal lymphocytic exocytosis, periappendageal infiltrate, and deposition of mucin revealed no predominant finding that distinguished a benign course from mycosis fungoides. A predominance of eosinophils in the infiltrate was suggestive of benign follicular mucinosis rather than mycosis fungoides. Gene rearrangement studies detected three clones in three patients with follicular mucinosis; two were in patients with mycosis fungoides, and one was in a patient with dermatitis. The outcome of these three patients is pending further follow-up. No histopathologic or clinical features distinguished these patients from the others.

Malignant blue nevus: a report of eight cases.

Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision.

Necrobiotic xanthogranuloma.

We reviewed 32 cases of necrobiotic xanthogranuloma and 16 cases from the world literature. Necrobiotic xanthogranuloma is a destructive dermal and subcutaneous xanthogranuloma that most frequently involves the face (periorbital region) and trunk. Monoclonal gammopathy is common (IgG-kappa in 23 cases and IgG-lambda in nine cases), and cryoglobulins have also been found. Low complement levels, anemia, and leukopenia are frequently present. Bone marrow examination shows plasma cell proliferation and, rarely, true myeloma. We describe mucosal, muscle, and systemic lesions, including xanthogranulomatous myocardial lesions. The clinical course is chronic and often progressive. Low-dose chlorambucil treatment is safe and effective, but individual patients have responded to treatment with corticosteroids, melphalan, local radiation, and plasma exchange.

Deep penetrating nevus.

BACKGROUND: Deep penetrating nevus is a variant of melanocytic nevi with histologic features that may be alarming and can be mistaken for malignant melanoma. We are presenting a review of the clinical findings and the histologic features of deep penetrating nevus in a series of 14 cases. OBSERVATIONS: Deep penetrating nevus occurs most commonly over the acral skin of young adults. Clinically, the lesions were diagnosed as pigmented nevus, blue nevus, or malignant melanoma. Histologically, deep penetrating nevus shows a wedge-shaped lesion extending to the deep dermis and the subcutaneous fat tissue. Nests and fascicles of pigmented melanocytes extended deep at the periphery of blood vessels, nerves, and the cutaneous adnexa. Low-grade cellular atypia is present and mitoses are rare. CONCLUSIONS: Deep penetrating nevus is a variant of benign pigmented nevi with deep dermal and subcutaneous involvement. The pattern should be recognized and differentiated from malignant melanoma.

Chronic lupoid leishmaniasis. Evaluation by polymerase chain reaction.

BACKGROUND: The cutaneous lesions in chronic lupoid leishmaniasis resemble those of lupus vulgaris, both clinically and histologically. The differential diagnosis is difficult and may depend on the detection of a few Leishmania amastigotes in the histologic sections, the growth of the promastigotes in cultures, or the identification of amastigotes by other techniques. Polymerase chain reaction was used to detect Leishmania amastigote DNA in tissue samples obtained from 65 patients with chronic lupoid leismaniasis, and the results were confirmed by Southern blot analysis. OBSERVATIONS: The histologic findings of a predominantly epithelioid cell granuloma surrounded by lymphocytic infiltrate in chronic lupoid leishmaniasis are very similar to those observed in lupus vulgaris. Extensive histologic examination of the sections in this series revealed occasional macrophages containing a few amastigotes in only 12 cases. Cultures in NNN medium yielded Leishmania promastigotes in 20 cases. Polymerase chain reaction studies using a Leishmania-specific primer identified Leishmania DNA in 30 of 63 cases, and those using a Mycobacterium tuberculosis primer were found to be negative for mycobacteria in 47 cases tested, including 11 cases with a positive tuberculin skin reaction. CONCLUSIONS: The histologic findings in chronic lupoid leishmaniasis resemble those of lupus vulgaris. Polymerase chain reaction studies were useful in identifying amastigotes in 30 (47.6%) of 63 cases. This study confirms the presence of DNA molecules of Leishmania amastigotes in samples of formalin-fixed, paraffin-embedded granulomatous tissue obtained from patients with chronic lupoid leishmaniasis.

Osteoma cutis and hemihypertrophy: a case report.

We report an interesting case of a patient with multiple ipsilateral osteoma cutis lesions and contralateral hemihypertrophy. These two features have not been described together previously. We also review the dermatologic findings described with hemihypertrophy.

Onychomycosis.

Treatment options for onychomycosis are expanding, making accurate and prompt diagnosis of greater importance. Diagnosis of onychomycosis can be made by direct examination of potassium hydroxide-prepared nail clippings, culture, and histologic examination. We compared culture of nail clippings to histologic examination and show that histologic examination is a quick and reliable alternative.

Cheilitis due to treatment with simvastatin.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are very common and effective treatments for hyperlipidemia. Epidermal cholesterol synthesis has been shown to be essential for maintaining the cutaneous barrier function. We present two patients who experienced cheilitis after beginning treatment of hyperlipidemia with simvastatin (Zocor). The rash resolved after discontinuation of medication and subsequent treatment with topical moisturizers and topical corticosteroids. We suspect that skin barrier dysfunction may occur in the mucosa from inhibitors of HMG-CoA reductase in a manner analogous to the epidermis.

Epidermotropic metastatic malignant melanoma.

Epidermotropic metastatic malignant melanoma can simulate a primary malignant melanoma. However, since therapeutic management can be drastically different for these two lesions, care must be taken in evaluating them. We report a woman with forty-eight metastatic lesions of malignant melanoma, twenty-two of which were removed and found on histologic examination to be epidermotropic metastatic malignant melanoma.

Engineering a waste management enzyme to overcome cancer resistance to apoptosis: adding DNase1 to the anti-cancer toolbox.

Cancer treatment is often complicated by resistance to conventional anti-cancer treatment and to more recently developed immunotherapy and gene therapy. These therapeutic modalities aim at activating death pathways within cancer cells. Attempts to activate the apoptotic death pathway, by overexpressing proapoptotic signals, are compromised by cancer defense mechanisms, which disrupt the apoptotic-signaling cascade downstream of the overexpressed component. Here, we describe a therapeutic option of triggering apoptosis without activating the apoptotic-signaling cascade or using the native apoptosis executioner nuclease. We have engineered Deoxyribonuclease-1 (DNase1), a waste-management enzyme, by deleting its signal peptide, adding a nuclear localization signal, and mutating its actin-binding site. Apoptosis studies and colony-forming assay for assessing cell viability were conducted in apoptosis-resistant Mel-Juso human melanoma cells. The modified DNase1 reduced cell viability by 77% relative to controls. It also induced typical microscopic features of cellular apoptosis, such as Terminal Transferase dUTP Nick-End Labeling-positive cells and DNA fragmentation. Quantification of apoptosis by Laser scanning cytometry demonstrated high-killing efficiency of 70-100%. The results suggest that this modified DNase1 can efficiently eliminate apoptosis-resistant cancer cells through apoptosis. Coupled to different tissue-specific gene expression elements, this recombinant DNase1 may serve as a platform for eliminating a variety of cancer types.

Dapsone therapy of cicatricial pemphigoid.

Dapsone and the related sulfapyridine have been valuable therapeutic agents in many inflammatory disease states although the exact mechanism of action remains unclear. In patients with mild CP or the localized (gingival or ocular) variants, dapsone has been shown to be a relatively safe, first drug of choice in therapy before commencing treatment with systemic corticosteroids and/or immunosuppressive agents. In patients with extensive, severe, or rapidly progressive CP, initial therapy with corticosteroids in a dose of 1 to 2 mg/kg/d of prednisone plus immunosuppressive agents such as azathioprine or cyclophosphamide in a dose of 2 to 3 mg/kg/d are recommended.

Management of superficial squamous cell carcinoma of the lip with Mohs micrographic surgery.

Forty-one patients were treated with Mohs micrographic surgery for well-differentiated superficial squamous cell carcinoma of the lip; 34 had closure of their surgical site by a mucosal advancement flap, and five were allowed to heal by second intention. Cases were limited to T1N0M0 or T2N0M0, these being early superficial lesions. Primary closure by mucosal advancement provides cosmetic and functional healing for these lesions. The combination of Mohs micrographic excision and mucosal advancement closure may be considered standard office or outpatient surgical management of these common tumors.

Malignant melanoma in childhood.

Six cases of malignant melanoma in children 14 years of age and younger are reported. The six cases were diagnosed among 850,000 consecutive skin biopsy specimens and consultation slides examined within a 32-year period. This series included an infant born with neurocutaneous melanosis, a child with malignant melanoma developing in a large congenital nevus at the age of 13 years, a superficial spreading malignant melanoma, Clark Level III, in a child with many dysplastic nevi, and three cases with primary nodular malignant melanoma, two of which showed histologic features of Spitz nevus. A review of the literature indicates that malignant melanoma in childhood is rare, and no large series have been investigated. It is not known whether the genetic and the environmental factors incriminated in the development of malignant melanoma in adults play a role in childhood melanomas. Data on the incidence of childhood melanoma in the population, the clinical and the histologic variations, and the prognosis are not adequate. A multiinstitutional study is needed to gather a large enough series to provide this information.

Syringoma-like sweat duct proliferation in scalp alopecias.

We have reviewed a series of 585 scalp biopsies taken for histologic evaluation of hair loss and have looked for syringoma-like eccrine sweat duct proliferation. This feature was found in 6 specimens with scarring alopecia and one each with alopecia areata and female-pattern alopecia. Syringoma-like sweat duct proliferation appears to play no role in the etiology of hair loss.

Angiomyolipoma.

Angiomyolipoma is a benign tumor, usually of the kidney, that is frequently associated with tuberous sclerosis. Extrarenal tumors are rare. Cutaneous lesions have only recently been reported. We report a case of cutaneous angiomyolipoma with results of clinical, histologic, and immunohistochemical evaluation.

Phakomatosis pigmentovascularis: report of a case.

Phakomatosis pigmentovascularis is a rare cutaneous malformation characterized by a combination of melanocytic nevi and nevus flammeus. We report a 16-year-old boy with extensive and predominantly unilateral skin involvement combining features of speckled melanocytic nevi over a background of nevus flammeus. A brief review of the literature and classification of this phakomatosis is presented.

Carbon dioxide laser vaporization of recalcitrant symptomatic plaques of Hailey-Hailey disease and Darier's disease.

Carbon dioxide laser vaporization of localized, recalcitrant intertriginous plaques was done in two patients with Hailey-Hailey disease and two patients with Darier's disease. After treatment, only one patient had recurrence in one treatment site. All patients had significant clinical and symptomatic improvement. Destructive treatment must include the follicular infundibulum in Darier's disease, because histologically this was the focus of recurrent disease at one treated site. We suggest carbon dioxide laser vaporization for the treatment of chronic, localized, symptomatic plaques of Hailey-Hailey or Darier's disease, if medical therapy has been ineffective.