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Heat shock protein 27 is expressed in normal and malignant human melanocytes in vivo.

BACKGROUND: Heat shock proteins (HSPs) are a family of highly conserved proteins found ubiquitously in mammalian cells, believed to be regulators of normal cell physiology and the cellular stress response. In addition, the small 27-kDa heat shock protein (HSP27) has previously been found to be a differentiation marker for keratinocytes and a prognostic marker associated with increased survival in certain cancerous tumors. METHODS: Using immunohistochemistry on routinely processed paraffin sections, we examined skin biopsies from 15 invasive melanomas, 13 intradermal nevi, and two compound nevi immunostained with a mouse monoclonal antibody to HSP27. In addition, cultured melanocytes were heat stressed at 45 degrees C for 1 h and then fixed and immunostained in order to localize HSP27 expression intracellularly. RESULTS: We found cytoplasmic and strong perinuclear staining of HSP27 in melanocytes in normal skin, in melanomas, and in nevi. Nuclear reactivity was absent. In addition, in cultured non-malignant melanocytes, HSP27 expression relocated from the cytoplasm to the nucleus with heat stress. CONCLUSIONS: To our knowledge, this investigation is the first to demonstrate that HSP27 is expressed in melanocytes in normal skin, in nevi, and in non-malignant cultured melanocytes.

Adolescent↗

Naevogenesis: a hypothesis concerning the control of proliferation of melanocytes with special reference to the growth of intradermal naevi.

The pigmentary function of epidermal melanocytes depends on the donation of melanin granules to the surrounding surface structures. This involves transfer of cytoplasm (cytocrine transfer) from melanocytes to keratocytes, a process which requires competence of the donor cells and the availability of adjacent competent recipient cells. Donor cell competence involves the extension of dendrites and recipient cell competence consists of the ability of these cells to phagocytose peripheral portions of the melanocyte cytoplasm. Since there is a highly regulated mechanism for the control of cellular size which operates by inhibiting proliferation of cells that are below a critical volume, it is proposed that the continual removal of portions of the melanocyte cytoplasm by cytocrine transfer is responsible for inhibiting growth of the epidermal melanocyte population, accounting for their relatively low population density. It is proposed that inhibition of cytocrine transfer permits the proliferation of melanocytes. Cytocrine transfer may be inhibited by loss of competence of donor or recipient cells or by their relative displacement. Displacement of melanocytes into the dermis, out of range of potential recipient keratocytes, would, according to this hypothesis, result in melanocyte proliferation leading to the generation of localized aggregations of melanocytes (melanocytomas). It is proposed that this is the origin of acquired benign pigmented moles.

Cell Communication↗

Comparative expression of NFkappaB proteins in melanocytes of normal skin vs. benign intradermal naevus and human metastatic melanoma biopsies.

Nuclear factor kappa B (NFkappaB) is an essential regulator of gene transcription for hundreds of genes, including many critically involved in apoptosis. NFkappaB complexes containing cRel generally activate pro-apoptotic genes, while those with RelA activate anti-apoptotic genes. We have previously shown that NFkappaB binding by RelA is constitutively elevated in human metastatic melanoma cultures relative to normal melanocytes. Here we extended our investigation to immunohistochemical analysis of human tissue biopsies. We found that RelA expression is significantly elevated in melanocytes of human naevi and melanomas relative to normal skin, but expression of its inhibitor IkappaB-alpha is significantly lower in metastatic melanomas than in intradermal naevi. Antibodies specific for the nuclear localization signal of RelA also showed significantly increased staining in metastatic melanoma biopsies. Notably, in melanomas and in naevi, we also found that RelA is phosphorylated at serine 529, and this activated form accumulates in the nuclei of melanomas. This suggests that increased expression and phosphorylation of RelA occurs at the stage of the benign naevus, but IkappaB-alpha is able to sequester RelA in the cytoplasm and regulate RelA transcriptional transactivation. We also found that antibodies against cRel show a progressive increase in staining from naevi to melanoma. However, staining for IkappaB-epsilon, which primarily inhibits the nuclear localization of cRel was also progressively increased, and cRel expression was predominantly cytoplasmic in melanomas. These results confirm that the altered expression of RelA found in metastatic melanoma cells in tissue culture is relevant to human tumors and offer new insights into the deregulation of NFkappaB signaling.

Apoptosis↗

Surgical facial wounds: simple interrupted percutaneous suture versus running intradermal suture.

The purpose of this study is to compare the esthetics of scars resulting from small surgical facial wounds sutured either with simple interrupted percutaneous suture (SIPS) or with running intradermal suture (RIS). 93 small (0.6-1.9 cm) benign, facial new growths, mostly (86%) intradermal nevi were surgically removed. Forty-seven surgical wounds were sutured with SIPS and 46 with RIS. All surgical procedures were performed by the same dermatologic surgeon. For comparison, lesions were grouped in five facial areas. Other variables such as the age of the patient and type and size of lesions were similar in both groups. Evaluation of each scar was made blindly by two independent observers and by the patients. Judged by independent observers 90 days after surgery, excellent (45 %) to good (45%) results were obtained in similar proportion with either SIPS or RIS suturing in 90% of the patients. In the patients' self evaluation, excellent (85%) to good (14%) results were obtained in 99% of the cases. Suture marks and tracks present 30 days after surgery in 28% of scars sutured with SIPS disappeared 90 days after surgery. The esthetic results obtained by suturing small surgical facial wounds with SIPS or RIS were similarly good to excellent when observed 90 days after surgery. There was no advantage in using RIS over SIPS in the type of wounds described.

Adolescent↗

Pregnancy-associated melanoma occurring in two generations.

We report of a case of malignant melanoma occurring during pregnancy in a woman whose mother had a melanoma excised during pregnancy. There was no other family history of melanoma. To our knowledge, this has not been previously reported. A review of the recent literature suggests that pregnant women with melanoma do not have a worse prognosis when compared to matched controls, but may present with worse prognostic features.

Adult↗

Melanocytic activation in HIV-1 disease: HMB-45 staining in common acquired nevi. Military Medical Consortium for the Advancement of Retroviral Research.

BACKGROUND: An increase in pigmented lesions has been reported in HIV-1-infected patients. In a study of HIV-1-positive patients, we have seen patients who noticed new or changing pigmented lesions. OBJECTIVE: The goal of this study was to determine to what degree these pigmented lesions showed evidence of significant melanocytic proliferation as opposed to increased pigment production without significant melanocytic proliferation. METHODS: Biopsy specimens were studied with routine light microscopy and immunohistochemical stains including S-100 protein, HMB-45, and proliferating cell nuclear antigen. RESULTS: The lesions included two malignant melanomas and 42 benign melanocytic lesions. Significant staining of dermal melanocytes with HMB-45 was present in two of three melanomas and in 19 of 42 nevi. With stains for proliferating cell nuclear antigen there was a positive reaction in the dermal component of both melanomas and a negative reaction in the dermal cells of the nevi. CONCLUSION: In some HIV-1-infected patients there is stimulation of melanosome production without significant melanocyte proliferation.

Adult↗

Statistical evaluation of epiluminescence microscopy criteria for melanocytic pigmented skin lesions.

BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive technique by which the clinical diagnosis of pigmented skin lesions (PSL) can be improved. Many ELM criteria have been described, but their significance in the differential diagnosis of PSL has not yet been established. OBJECTIVE: The purpose of this study was to determine the value of ELM criteria in the differential diagnosis of PSL. METHODS: Two hundred one melanocytic PSL (61 common nevi, 60 dysplastic nevi, and 80 melanomas) were investigated with ELM for the presence of certain ELM criteria; their significance was determined by calculating the odds ratios. RESULTS: Individual ELM criteria have different weights of significance in the differential diagnosis of melanocytic PSL. Selected patterns of ELM criteria adjusted to the distinct types of PSL considerably improve the diagnostic accuracy of melanocytic PSL. CONCLUSION: The prevalence of certain distinct ELM criteria in a given melanocytic PSL has statistical value in differential diagnosis.

Confidence Intervals↗

Epidermal nevus syndrome and intraspinal hemorrhage.

The epidermal nevus syndrome (ENS) is a rare neurocutaneous disease characterized by extensive epidermal nevi and a wide variety of abnormalities involving brain, eyes, and skeleton. Neurological symptoms in ENS include seizures, paresis, and mental retardation and are usually ascribed to hemimegalencephaly and various migration disorders. It was suggested that in some patients neurological symptoms might be secondary to vascular abnormalities. We report a case of a patient with diagnosed ENS without any primary CNS lesions, who developed paraplegia resulting from spinal cord hemorrhage. The patient presented many vascular and skeletal anomalies.

Child↗

Argon laser therapy of benign tumors of the eyelid.

PURPOSE: To report the therapy of benign eyelid tumors with an argon laser as an alternative to surgery. METHODS: Forty-one patients with 47 benign tumors of the eyelid were included in this study. In all patients, the eyelid tumor was eliminated by argon laser. In 24 cases the lower eyelid and in 23 cases the upper eyelid was involved, including the lid margin in 17 cases. Laser spot size ranged from 150 to 500 microm. Argon laser power density varied between 4.1 and 61.1 W/mm2. Spots were counted between 40 and 1204. Twenty-seven of 41 patients treated were followed up; the mean follow-up period was 5.8 months (range, 3 to 24 months). Postoperatively, histologic confirmation was obtained in 42 cases of the 47 treated tumors. RESULTS: All patients were satisfied regarding the laser therapy and the cosmetic result. Remarkably, the wounds were dry after argon laser therapy. No infections of the wounds occurred; wounds were epithelialized after 2 to 3 weeks by a normal-appearing epithelium. The area of argon laser treatment was less pigmented than the surrounding skin and showed no obvious remarkable notches. As a complication, one patient developed a viral conjunctivitis. No relapses occurred during follow-up. CONCLUSIONS: Argon laser therapy of benign eyelid tumors may result in very satisfactory wound healing. Taking the short follow-up and the limited number of cases into account, it seems to be a useful alternative to traditional surgery, especially for tumors positioned close to the lacrimal papillae.

Adolescent↗

[Nevocytic nevi associated elastic fibers hyperplasia: a type of "twin nevus"].

BACKGROUND: In common intradermal or compound nevi, nevocytes may be associated with other kinds of cells, tissues or lesions. In rare cases, they are associated with notable hyperplasia of the elastic fibers. CASE-REPORTS AND RESULTS: In 11 nevi (10 intradermal or compound nevi and 1 blue nevus), we observed striking hyperplasia of the elastic fibers strictly limited to the nevi, with normal aspect of the elastic fibers in the surrounding reticular dermis. These fibers were thicker than normal elastic fibers and showed tight connexions with nevus cells. This hyperplasia was not clinically relevant. It was correlated neither with the age and sex of patients nor with the site of the excised nevi. It was seen in 0.1% of excised nevi. DISCUSSION: Hyperplasia of elastic fibers in some common nevi is a curiosity which may be classified together with other vascular, nervous, epithelial or connective twin lesions occasionally associated with the nevocytic nevi. It has to be added to the list of so-called "twin nevi".

Adolescent↗

Linear psoriasis with porokeratotic eccrine ostial and dermal duct nevus.

Linear psoriasis is an uncommon form of psoriasis characterized by the linear distribution of the psoriatic lesions. It usually follows the lines of Blaschko with unilateral involvement. Poro keratotic eccrine ostial and dermal duct (PEODD) nevus is another rare dermatosis that follows Blaschko's line. The pathogenesis of linear psoriasis and PEODD nevus is unclear, but both could be best explained by a specific somatic mutation. Hence, it has been suggested that the mutation responsible for PEODD nevus would constitute a rare but critical psoriasis gene. In the literature, 1 case of linear psoriasis with PEODD nevus was reported, which may support this suggestion. This article describes another case of linear psoriasis and PEODD nevus. A 7-year-old boy had a 4-month history of multiple psoriasiform plaques, arranged in linear distribution, and had congenital linear hyperkeratotic papules and pits on the right side of his trunk and right arm.

Child↗

Familial polythelia.

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Abnormalities, Multiple↗

Nail matrix nevi: a clinical and histopathologic study of twenty-two patients.

BACKGROUND: Because most dermatologists do not regularly perform biopsies of longitudinal melanonychia, even when the pigmentation presents as a single band, the true prevalence of nail matrix nevi is unknown. OBJECTIVE: Our purpose was to determine the prevalence of nail matrix nevi in white patients with longitudinal melanonychia involving a single digit and to determine whether longitudinal melanonychia caused by a nail matrix nevus can be clinically distinguished from longitudinal melanonychia from other causes. METHODS: From January 1989 to December 1994 we performed a nail biopsy on 100 of 128 consecutive white patients who had a single band of "idiopathic" longitudinal melanonychia. RESULTS: A nail matrix nevus was detected in 22 patients. A junctional nevus was found in 19 specimens and a compound nevus in three specimens. CONCLUSION: Nail matrix nevi in Caucasian patients are uncommon but not exceptional. The number of nevi presenting with longitudinal melanonychia exceeded that of melanoma. The diagnosis of nail matrix nevi is impossible clinically and always requires histopathologic study. The pathologic features of nail matrix nevi are similar to those of skin nevi except for their architectural pattern, which reflects the peculiar anatomy of the nail unit.

Adolescent↗

Epidermal nevus syndrome with hypermelanosis and chronic hyponatremia.

Epidermal nevus syndrome is seldom encountered, and its association with hypermelanosis and the chronic syndrome of inappropriate antidiuretic hormone secretion (SIADH) has never been reported. A male neonate who developed intractable seizures and hyponatremia soon after birth is reported. He had alopecic patches on the scalp at birth. Large areas of skin hyperpigmentation, and epidermal nevi developed gradually. The clinical picture of hypotonic hyponatremia, high urine osmolality, elevated urine sodium, and euvolemia was compatible with SIADH. The seizures did not correlate with the hyponatremia, and no other cause for the seizures could be identified. The hyponatremia became chronic and was treated with a direct supply of sodium chloride. The development of the patient was markedly delayed at the last visit when he was 1 year of age. It is suggested that hypermelanosis and chronic SIADH may also be a variant presentation of epidermal nevus syndrome.

Brain↗

Reduction of expression of tuberin, the tuberous-sclerosis-complex-gene-2 product in tuberous sclerosis complex associated connective tissue nevi and sporadic squamous and basal cell carcinomas.

BACKGROUND: Patients affected with tuberous sclerosis complex (TSC) are prone to the development of multiple benign tumors of the skin and other organs. Tuberin, the protein product of the tuberous-sclerosis-complex-2 tumor suppressor gene (TSC2) has been shown to inhibit cell proliferation. In TSC associated kidney tumors and sporadic brain tumors the loss/reduction of tuberin has been shown. METHODS: Specimens of nine squamous cell carcinomas (SCC) and five basal cell carcinomas (BCC) from patients without TSC and six biopsies of connective tissue nevi (CTN) of patients with TSC were obtained. Specimens were analyzed by immunoblotting for the expression of tuberin. RESULTS: Absent or reduced levels of tuberin were detected in the dermal parts of three of six shagreen patches, two of five BCC, and four of nine SCC. CONCLUSIONS: In tumors/hamartomas of patients with TSC the complete loss of TSC2 and tuberin is a mechanism which could be shown for CTN, thereby excluding the possibility of haploinsufficiency of TSC2. In a substantial number of cutaneous BCC and SCC the loss or downregulation of tuberin seems to be epigenetic, as alterations of TSC2 are not known in these tumors. The absence or reduction of tuberin might contribute to their proliferation.

Basal Cell Carcinoma↗