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Cutaneous tumors of children.

Nevi are the most common tumors of childhood. Pigmented nevi are classified into blue nevi, intraepidermal nevi, junction nevi, intradermal nevi (or common mole) and combination types. Cutaneous malignant disease in children is rare. Malignant melanoma is rare before puberty. Wholesale removal of benign pigmented nevi in children should be condemned. However, junction nevi located on the palms, soles, genitalia or waistline-that is, in areas subject to frequent trauma-should be excised. Hemangiomas in infants are the most common tumors for which advice is sought. Not all hemangiomas regress spontaneously, and on occasion the persistence or progression of such a lesion may bring about life-long unsightly deformities. Therapy for this type of tumor is simple when given early in life. Hemangiomas involving the ears, nose, lips or eyelids should be treated at once, preferably within a month of the time they appear.

Administration, Cutaneous↗

Growth dynamics of acquired melanocytic nevi. Higher reactivity of proliferating cell nuclear antigen in junctional and compound nevi than intradermal nevi.

BACKGROUND: The histogenesis of acquired melanocytic nevi is still a matter of debate. OBJECTIVE: To provide data on the histogenesis, we investigated the lesional area of acquired melanocytic nevi and the proliferative activity of the nevus cells. METHODS: Proliferative activity was examined with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The lesional area of the nevus was estimated in histologic sections. RESULTS: Intradermal nevus was the largest of the acquired melanocytic nevi but had few PCNA-positive nevus cells. In contrast, junctional nevi were smallest and showed the highest PCNA positivity. Statistical analysis showed a significant inverse correlation between the largest lesional area and PCNA positivity. CONCLUSION: The findings of the present study are in accordance with an epidermal melanocytic origin of acquired melanocytic nevi.

Antigens, Neoplasm↗

Basal cell carcinoma and melanocytic nevus in the same lesion.

We report a case of basal cell carcinoma and intradermal melanocytic nevus in the same lesion. A review of the literature indicates that the simultaneous occurrence of two or more neoplasms in one specimen is a relatively infrequent finding. The pathogenesis of simultaneously occurring neoplasms remains the subject of speculation. Based on currently available evidence, we believe that the coexistence of lesions in this particular patient is most likely coincidental.

Aged↗

The intermediate filament peripherin is expressed in cutaneous melanocytic lesions.

Peripherin is an intermediate filament involved in growth and development of the peripheral nervous system and is localized to neurons, some other cells derived from neural tube and neural crest, and some neuroendocrine cells (e.g. beta cells of islets of Langerhans). Peripherin also has been demonstrated in neuroblastomas and cutaneous neuroendocrine (Merkel cell) carcinomas. The expression of peripherin by other cells derived from the neural crest is unknown. We evaluated by immunohistochemistry 74 cutaneous melanocytic lesions including primary invasive malignant melanoma (IMM), melanoma in situ (MIS), atypical nevus (nevus with architectural disorder and cytologic atypia of melanocytes) (AN), spindle and epithelioid cell nevus (Spitz nevus) (SN), blue nevus (BN), and common intradermal benign melanocytic nevus (BMN) for expression of peripherin. Peripherin was detected in a cytoplasmic distribution within tumor cells in 14/14 IMM and 8/10 MIS. For IMM, peripherin localized to both the intraepidermal and invasive dermal components. Peripherin was detected in 10/10 AN and 9/9 SN, being localized to the intraepidermal component and, focally, to the superficial dermal component of the lesions. The dendritic nevus cells in 15/15 BN also expressed peripherin. For most of the BMN, expression of peripherin was absent or limited to rare, scattered cells in the superficial portion of the lesions. Melanocytes in adjacent normal skin were not labeled in any of the lesions studied. These results indicate that expression of peripherin is common in both benign and malignant melanocytic lesions, but not in normal resting adult melanocytes. Among benign lesions, expression of peripherin in the dermal component is rare except in the dendritic cells of BN. These findings provide evidence that the expression of peripherin, a marker of neuronal differentiation, is maintained by IMM, MIS, and BN, but is lost in the normal maturational sequence of the dermal component of other melanocytic lesions.

Adult↗

Trichilemmal cyst under a compound melanocytic nevus.

Cystic dilatation of a hair follicle, folliculitis, abscess formation and epidermoid cysts are not infrequent findings in an intradermal melanocytic nevus. We herein report a trichilemmal cyst under a compound melanocytic nevus. To the best of our knowledge this association has not been previously reported.

Adult↗

Keratotic melanocytic nevus.

Thirty-five percent of 363 melanocytic nevi were found to have a keratotic epithelial architectural pattern that was mostly infundibular and not previously emphasized. Keratotic melanocytic nevi were commonly from the trunk of women, and most were associated with an intradermal melanocytic nevus. The clinical and histopathologic features as well as a review of the literature of these keratotic melanocytic nevi are presented.

Female↗

Pseudomelanoma: recurrent melanocytic nevus following partial surgical removal.

Histological markers enable the correct diagnosis of a pigmented lesion that histologically resembles a superficial spreading malignant melanoma and yet behaves in a wholly benign way. This pseudomelanoma occurs in young adults within a few weeks following partial surgical-shave excision of an intradermal melanocytic nevus.

Adolescent↗

Melanoma on dysplastic nevus spilus.

BACKGROUND: Nevus spilus is found with relative frequency. It is observed as as tan to brown macule serving as base to a speckle of smaller and darker maculo-papular elements. On rare occasions it turns into a malignant melanoma. PURPOSES: To describe one case with some characteristics different from routine observations and to revise the cases published reporting nevus spilus that turned into malignant melanoma, in order to point out the most frequent aspects. RESULTS: The 17 patients with nevus spilus and melanomas, including ours, were white, with ages between 35 and 56 years. Most of the cases were localized in the dorsal region. Five patients were men. Almost all nevus were congenital and their size ranged between 2 and 10 cm in diameter. Histologically, the speckled spots were junctional nevus, and few of them had dysplastic characteristics. Melanomas corresponded to the extensive superficial type MES; one of them was nodular. Some had systemic ganglial metastases and three of the patients are known to have died. Our patient had an intradermal cellular nevus on the man spot, and terminal hairs could be observed on it. The speckled elements were junctional nevus with dysplastic cells. CONCLUSIONS: Nevus spilus must be closely monitored, because it may turn into a malignant melanoma.

Adult↗

Congenital giant melanocytic nevus with pigmented epithelioid cells: a variant of epithelioid blue nevus.

Epithelioid-cell blue nevus is an unusual cytologic variant of blue nevus that has been recently described mostly in patients with Carney complex, although the lesion may also appear in patients with no evidence of Carney complex. This variant of blue nevus is composed of melanin laden large polygonal epithelioid melanocytes situated within the dermis. The neoplastic cells show no maturation with progressive descent and, in contrast with the usual stromal changes in blue nevi, epithelioid-cell blue nevus exhibits no dermal fibrosis. This report describes a congenital giant melanocytic nevus with pigmented epithelioid cells located on the back of a 2-year-old male. The lesion was present at birth and the patient had no evidence of Carney complex. Histopathologically, the lesion consisted of a large and entirely intradermal melanocytic nevus composed of heavily pigmented epithelioid melanocytes involving the full-thickness of dermis, but extending also to the subcutaneous fat and underlying soft tissues. Immunohistochemically, epithelioid neoplastic melanocytes expressed immunoreactivity for S-100 protein, HMB-45, Melan-A, NK1C3, and microphthalmia transcription factor (MiTF) antibodies. MIB-1 cellular proliferation marker was expressed in the nuclei of only a few scattered epithelioid melanocytes. This report demonstrates that epithelioid-cell blue nevus is a distinctive histopathologic variant of blue nevus that may also appear as a giant congenital melanocytic nevus.

Biomarkers, Tumor↗

Immunohistochemical expression of BCL-2 in melanomas and intradermal nevi.

The BCL-2 gene is the prototype of a newly described family of oncogenes involved in tumorigenesis by blocking apoptosis, or programmed cell death. Overexpression of BCL-2 protein was originally described in follicular B-cell lymphomas bearing the 14;18 translocation. BCL-2 overexpression has also been described in other lymphomas and more rarely in neoplasms outside the lymphoid tissue. The aim of this paper is to determine the immunohistochemical expression of BCL-2 in intradermal nevi and primary invasive and metastatic melanoma. Formalin-fixed and paraffin-embedded tissues from 4 cutaneous melanoma metastases, 10 primary invasive melanomas, and 10 intradermal melanocytic nevi were immunolabeled with monoclonal antibodies directed against BCL-2 protein (Dako, clone 124) and Ki-67 antigen (Amac, clone MIB-1), after antigen retrieval techniques. Morphologically normal epidermal melanocytes expressed BCL-2, as did nevi and melanomas in virtually all cells. However, whereas the labeling in normal melanocytes and nevus cells showed a uniformly strong reactivity, melanoma cells showed a variable but mainly weak reactivity. Ki-67 antigen expression was restricted to melanomas. The widespread expression of BCL-2 suggests that this oncoprotein cannot be involved in the malignant transformation of melanocytic cells. It seems likely that the decreased BCL-2 expression detected in melanomas may reflect one further step of tumor progression in melanocytic neoplasms.

Humans↗

Mucinous naevocellular naevi.

We report 4 cases of a naevocellular naevus variant containing abundant amounts of mucinous matrix. The mucinous matrix was Alcian blue (pH 2.5) and Halle's colloidal iron positive and mucicarmine and PAS negative. When the blocks of tumours were cut down, regions typical of common intradermal naevi were found in all 4 cases. The differential diagnosis with mucinous carcinoma of the skin and myxoid malignant melanoma is discussed.

Adenocarcinoma, Mucinous↗

Utility of a proliferation marker in distinguishing between benign naevocellular naevi and naevocellular naevus-like lesions with malignant properties.

In the present study we have investigated the utility of the proliferation marker MIB 1 in distinguishing between benign naevocellular naevi and naevocellular naevus-like lesions with malignant potential. Percentages of MIB 1 immunoreactivity in the intradermal portion of the lesions were determined. In benign congenital and acquired naevi, as well as in dysplastic naevi, there was no or only a slight intradermal melanocytic proliferation (0-2%), whereas vertical growth phase melanomas exhibited a substantial proliferative activity (11-48%). In five cases of naevus-lke lesions, which had all relapsed as unmistakable malignant melanomas (locally or metastatically) after primary surgery, there was also clear proliferative activity (9-67%). Our findings suggest that MIB 1 may be a useful tool in the routine histopathological examination of problematic naevocellular lesions.

Antibodies, Monoclonal↗

Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions.

Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein (TYRP1), Dopachrome tautomerase (DCT) and Pmel17 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation.

Adult↗

Acral melanocytic neoplasms: a histologic analysis of 158 lesions.

BACKGROUND: Acral nevi occasionally demonstrate pagetoid spread of melanocytes. This feature may be of considerable concern because it is commonly associated with melanoma. Other features of melanoma must be assessed to accurately classify these neoplasms as benign. OBJECTIVE: We examined acral melanocytic lesions, benign and malignant, to evaluate their features. METHODS: A retrospective analysis during 3 years was performed on 158 acral pigmented lesions diagnosed by the dermatopathology service. Blue nevi, intradermal nevi, lentigines, and Spitz nevi were excluded. The specimens were divided into three groups: benign nevi, benign nevi with pagetoid spread, and melanoma. They were evaluated for circumscription, symmetry, papillary dermal fibroplasia, bridging between rete ridges, inflammatory infiltrate, pagetoid spread, cytologic atypia, and mitotic activity. RESULTS: Most lesions (60%) were compound nevi and 84% were from the foot. Ten specimens were melanomas (6%) and 28 (18%) were nevi with architectural disorder. Pagetoid spread of melanocytes, often minimal, was found in 57 benign lesions. However, these nevi did not demonstrate the degree of pagetoid spread, cellular atypia, inflammation, and asymmetry found in malignant lesions. CONCLUSIONS: The presence of pagetoid spread of melanocytes is common in otherwise benign acral nevi. Other parameters of malignancy in these neoplasms must be evaluated to determine their biologic potential.

Epidermis↗

Immunohistochemical expression of retinoblastoma protein in cutaneous melanomas.

Retinoblastoma protein (pRB) is the product of a tumour-suppressor gene (rb) mapped to chromosome 13q14. pRB acts as a control checkpoint at the G1 phase of the cell cycle, preventing cells from entering into the S phase. Mutational inactivation of both normal alleles leads to loss of pRB expression and the development of malignant neoplasms. Absence of pRB occurs in retinoblastomas, sarcomas and several other types of tumours. The potential role of pRB in the pathogenesis of cutaneous melanoma is unknown, and was the subject of this investigation. Formalin-fixed, paraffin-embedded sections of four cutaneous melanoma metastases, 17 primary invasive melanomas and 10 predominantly intradermal melanocytic naevi were studied. Monoclonal antibodies directed against pRB and Ki-67 antigen were used after microwave heating of sections to restore antigenicity. pRB was not detected in morphologically normal epidermal melanocytes. In five naevi, only scattered cells (1%) expressed pRB, whereas in the other five naevi, pRB expression was undetectable. In contrast, pRB was detected in all primary and metastatic melanomas (5-70% of cells). Expression was always localized to nuclei. Ki-67 expression was detected only in the melanomas, with both cellular staining and regional localization similar to that shown by pRB in 13 of the 20 melanomas studied with both antibodies. pRB appears to be expressed at higher levels in melanomas than in benign naevi. It therefore seems unlikely that loss of rb expression is an important factor in the pathogenesis of melanoma.

Humans↗

Increased tenascin expression in melanocytic tumors.

Tenascin is a large extracellular matrix glycoprotein which is widely distributed in normal, hyperplastic and neoplastic tissues. Its function is unknown but it has been associated with the epithelial-stromal interactions, such as cell adhesion and movement which take place, e.g. in morphogenesis, cellular proliferation and neoplasia. In this study, we investigated tenascin expression in 70 benign, dysplastic and malignant melanocytic tumors by using immunohistochemistry and monoclonal anti-tenascin 143DB7C8 antibody on paraffin sections. In all types of benign nevi, both intradermal, compound and junctional, there was a moderate expression of tenascin at the dermoepidermal junction and in the papillary dermis. In dysplastic nevi, the fibrotic areas in the papillary dermis also showed a moderate staining for tenascin. Invasive malignant melanomas showed the strongest expression of tenascin. In addition to the staining at the dermo-epidermal junction and in the papillary dermis, there was a variable expression of tenascin in the reticular dermis. Intracytoplasmic tenascin was detected both in primary melanomas and melanoma metastases. In conclusion, we have shown that tenascin expression is moderately increased in benign and dysplastic melanocytic tumors and greatly increased in malignant melanomas and melanoma metastases. The function of tenascin may be related to the cellular-stromal interactions and it is possibly associated with the proliferation and spread of the melanocytic tumors.

Biopsy↗

Psammomatous malignant melanoma arising in an intradermal naevus.

AIMS: A wide variety of differentiation patterns may be found in malignant melanoma. Schwannian features are unusual, and mostly present in the desmoplastic variant. We report the first description of psammoma bodies in malignant melanoma. METHODS AND RESULTS: A malignant melanoma arose in an intradermal naevus of the scalp in a 51-year-old woman, displaying focal neural-like features in the form of rosette-like pseudo-meissnerian alveolar nests, as well as numerous psammoma bodies grouped in a few areas. Tumour cell immunostaining for S100, HMB45, NKI-C3, and vimentin was detected. In addition, both malignant and benign melanocytic cells showed widespread MART-1 immunoreactivity. Differential diagnosis with psammomatous melanotic schwannoma, a feature of Carney's complex, is particularly emphasized, since dermal variants of this nerve sheath neoplasm have been described. In addition, its potential relationship with cutaneous malignant melanotic neurocristic tumour is discussed. CONCLUSIONS: This is, to our knowledge, the first reported case of cutaneous malignant melanoma with psammoma bodies.

Antibodies, Monoclonal↗