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Melanocytic Proliferations (melanocytic + proliferation)
Selected AbstractsMelanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas.JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005A study of 226 cases Background:, Neurofibromatosis, type 1, is associated with cutaneous melanin pigmentation, but an association with ordinary melanocytic nevi has not been described. Methods:, This retrospective case-control study was designed to see if neurofibromas in patients with neurofibromatosis, type 1 (NF-1) differ from sporadic neurofibromas (SN) in their incidence of associated melanocytic nevi and other histologic features. Slides from 114 NF-1 were compared with 112 SN and 300 intradermal melanocytic nevi (IDN). Results:, Small lentiginous melanocytic nevi were identified over 13 NF-1 (11%) but no SN (P = 0.0002). Compared with other NF-1, NF-1 with nevi were more frequently associated with melanocytic hyperplasia, giant melanosomes and diffuse neurofibroma (P < 0.03). Compared with SN, NF-1 were also more frequently associated with melanocytic hyperplasia, lentigo simplex-like changes, diffuse neurofibroma and plexiform neurofibroma (P < 0.001). Sebaceous hyperplasia (14%), dermal elastosis (9%), lipomatous change (8%), epithelial cysts (4%) and keratin granulomas or folliculitis (3%) were not significantly different in prevalence between NF-1, SN and the control group of IDN. Conclusions:, This study suggests that there is a difference in the potential for melanocytic proliferation in NF-1 compared with SN. NF-1, SN and IDN are associated with a similar range of incidental histologic changes. [source] Large Atypical Melanocytic Nevi in Recessive Dystrophic Epidermolysis Bullosa: Clinicopathological, Ultrastructural, and Dermoscopic StudyPEDIATRIC DERMATOLOGY, Issue 4 2005Fernando Gallardo M.D. The lesion was clinically atypical and fulfilled the criteria for a malignant melanocytic proliferation. A complete surgical excision was performed. Histopathologic examination disclosed a compound melanocytic nevus without melanocytic atypia. Ultrastructural examination showed melanocytic cells located both at the roof and the floor of the blister. Several months later, three pigmentary lesions with a similar clinical appearance developed. Periodic clinical and dermoscopic examinations were recommended. Dermoscopic examination disclosed a globular pattern with brown globules and black dots distributed all over the lesions. The lesions also exhibited blue-greyish dots and multiple rounded white structures corresponding to milia-like cysts. No dermoscopic features suggestive of malignancy were noted. Acquired melanocytic nevi showing atypical clinical features have been reported to occur in areas of blistering in patients with epidermolysis bullosa. These nevi appear as large, asymmetrical pigmentary lesions with irregular borders. Initially, they are very dark in pigmentation, with color variegation and loss of pigment, and even becoming papillomatous over time. Histopathologic examination can show features of compound/junctional nevus as well as persistent/recurrent nevus. The concept of "epidermolysis bullosa nevus" has been proposed to define these peculiar lesions. The clinical, histopathologic and ultrastructural features of these nevi are reviewed. The usefulness of dermoscopic examination in the routine diagnosis and follow-up of these lesions are stressed. [source] Pathology of conjunctival melanocytic neoplasmsACTA OPHTHALMOLOGICA, Issue 2008SE COUPLAND Purpose To describe the classification, grading and staging of conjunctival melanocytic proliferation. Methods We have audited our experience with conjunctival melanomas, using a novel mapping system and have found shortcomings in the current Tumour Node Metastasis (TNM) staging system. We have also reviewed our cases of intra-epithelial melanocytic neoplasia and confirmed other authors' impressions that conjunctival ,primary acquired melanosis with atypia' is histologically similar to cutaneous in situ melanoma. To improve objectivity in the reporting of conjunctival intra-epithelial melanocytic neoplasia, we propose a scoring system based on pattern of melanocytic infiltration, density of melanocytes & degree of cellular atypia. Results The term ,conjunctival melanosis' should be used only to describe the slit-lamp appearance of hyperpigmentation. Histologically, this abnormality should be categorized as ,hypermelanosis' or ,melanocytosis'. Hypermelanosis can either be primary or secondary to ocular or systemic disease. Benign melanocytosis comprises conjunctival melanocytic hyperplasia and naevi. Malignant melanocytosis is essentially melanoma, which is primary (in situ or invasive) or secondary (i.e., spreading to conjunctiva from adjacent tissues) or rarely metastatic. We suggest that the TNM staging system for conjunctival melanoma should be revised to: (1) include a Tis stage; (2) take account of superficial extent, invasion of adjacent tissues and caruncular involvement, in stages TI to TIII; and (3) to sub-categorize TIV disease so that there is better correlation with likely mortality. Conclusion We have revised the classification of conjunctival melanocytic proliferations & improved the grading and staging of melanoma. These developments should be useful in treatment & research. [source] Bilateral diffuse uveal melanocytic proliferation and uterine cancer.ACTA OPHTHALMOLOGICA, Issue 3 2000A case report ABSTRACT. Purpose: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), a rare paraneoplastic syndrome causing visual loss in patients with systemic carcinoma. Results: A 70-year-old woman developed visual symptoms 13 months after surgery and local irradiation therapy for uterine cancer. Following bilateral external beam irradiation supplemented with subsequent drainage of subretinal fluid in the left eye, the visual acuity improved from 0.01 to 0.15 in this eye only. The visual acuity remained at this level until she died 4 1/4 years after the onset of eye symptoms. Conclusion: This is the fourth case that survived longer than 24 months after the onset of visual symptoms of the 22 previously reported cases with BDUMP. It demonstrates that radiotherapy may have a vision-preserving effect in this group of patients. The patient also developed two different paraneoplastic phenomena , a nephrotic syndrome before and BDUMP after treatment for uterine cancer. [source] Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridizationJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2010Klaus J. Busam A conjunctival melanocytic nevus may on occasion be difficult to distinguish from melanoma both clinically and histopathologically. An unambiguous correct diagnosis is critical because of major differences in management and prognosis. We evaluated a fluorescence in situ hybridization (FISH) assay, which has previously been shown to be of value for the diagnosis of melanocytic nevi and melanomas of the skin, using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and centromere 6 (CEP6), for its potential to assist in the distinction of conjunctival melanocytic nevi from melanomas. Four melanocytic nevi and eight melanomas of the conjunctiva were analyzed. Two of the melanomas were diagnostically problematic because of suboptimal histopathology. None of the conjunctival melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for a diagnosis of melanoma. All eight conjunctival melanomas (six unequivocal and two suspicious lesions) met FISH criteria for melanoma. Thus, results from FISH assay targeting 6p25, 6q23, 11q13 and centromere 6 correlated well with the histopathologic diagnoses and supported the histopathologic suspicion in two problem cases. The findings encourage further exploration of this technique as an ancillary method for the work-up of conjunctival melanocytic proliferations. Busam KJ, Fang Y, Jhanwar SC, Pulitzer MP, Marr B, Abramson DH. Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization. [source] Expression patterns of MITF during human cutaneous embryogenesis: evidence for bulge epithelial expression and persistence of dermal melanoblastsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2008Briana C. Gleason Background:, The mechanisms whereby melanocytes populate the epidermis and developing hair follicles during embryogenesis are incompletely understood. Recent evidence implicates an intermediate mesenchymal stage in this evolutionary process in which HMB-45-positive melanocyte precursors (,melanoblasts') exist both in intradermal as well as intraepithelial and intrafollicular compartments. The melanocyte master transcriptional regulator, microphthalmia transcription factor (MITF), identifies mature melanocytes as well as melanocyte precursor stem cells that reside in the bulge region of the hair follicle. Methods:, To better define the use of MITF expression in the evaluation of melanocyte ontogeny, human embryonic and fetal skin samples (n = 28) at 6,24 weeks gestation were studied immunohistochemically for expression of MITF and Mart-1. Adjacent step sections were evaluated to correlate staining patterns with cell localization in the intraepidermal, intrafollicular and intradermal compartments. Results:, At 6,8 weeks, MITF and Mart-1-positive cells were primarily intradermal with only rare positive cells in the epidermis. By 12,13 weeks, most of these cells had migrated into the epidermis, predominantly the suprabasal layers. Between 15,17 weeks, these cells localized to the basal layer and colonized developing hair follicles. Rare intradermal MITF and Mart-1 positive cells were found as late as week 20. At 18,24 weeks, MITF and Mart-1 positive cells were identified in the outer root sheath, bulge, and follicular bulge epithelium, in addition to the epidermis. Unexpectedly, weak but diffuse nuclear MITF expression was also present in the keratinocytes of the bulge area. Conclusions:, The in situ migratory fate of MITF/Mart-1-expressing cells in fetal skin involves a well-defined progression from intradermal to intraepidermal to intrafollicular localization. Occasional intradermal melanocytes may persist after the intraepithelial stages are completed, a finding of potential significance to melanocytic proliferations that may arise de novo within the dermis. Because MITF may play a role in stem cell maintenance, the presence of MITF in bulge epithelial cells suggests that it may be a novel marker for follicular stem cells of both epithelial and melanocytic lineage. [source] Histological evolution of lentiginous melanoma: a report of five new casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2007Tracy Davis Background:, The term lentiginous melanoma was recently used for atypical melanocytic proliferations sharing some histological features with lentigo maligna and associated with a protracted in situ stage before invasion. Lentiginous melanoma was characterized by predominantly single-cell lentiginous growth pattern with focal junctional nests and pagetoid spread, preservation of the dermoepidermal junction, limited cytological atypia, and lack of significant solar elastosis. We report five similar cases. Methods:, Histological review of routine sections with clinicopathological correlation. Results:, Three patients were male and two were female. The age at presentation ranged from 24 to 66 years. All lesions arose on the truck or proximal extremities. All five cases fulfilled histological criteria proposed for lentiginous melanoma. None of the lesions showed significant solar elastosis. One lesion was followed clinically and histologically for 16 years without intervening treatment. It had three local recurrences before culminating in invasive melanoma. Conclusions:, Our observations support recent efforts to distinguish lentiginous melanoma as a distinct clinicopathological entity. Lentiginous melanoma can remain in situ for a long time before invasion and may be considered an analogue of lentigo maligna occurring on non-severely sun-damaged skin. Familiarity with the histological features of this variant is important for its early recognition and treatment. [source] CD34+ Pigmented Fibrous Proliferations: The Morphologic Overlap Between Pigmented Dermatofibromas and Bednar TumorsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J. Chu McAllister Pigmented dermatofibrosarcoma protuberans (Bednar tumor) constitute 5,10% of all cases of dermatofibrosarcoma protuberans, and are usually considered mimics of melanocytic proliferations rather than fibrous lesions. We report two cases of pigmented fibrous proliferations that demonstrate features of both dermatofibromas and DFSP. The first case is a 19-year-old man with a three year history of a slowly growing pigmented lesion on the right arm. On clinical exam the lesion was a 7 mm firm pigmented papulonodular lesion. The second case is a 31-year-old woman with a 4,5 year history of a slowly enlarging, asymptomatic ,dark area' on the right buttock. On clinical exam the lesion is a 2 cm darkly pigmented flat nodule. Morphologically both lesions are primarily dermal proliferations of spindled cells admixed with pigmented dendritic melanocytes. The lesional cells trap collagen fibers at the periphery and there is basal cell hyperpigmentation. Adnexal structures are effaced but significant trapping of subcutaneous fat is not present. By immunohistochemistry both lesions show focal CD34 positivity but are negative for Factor XIIIa and melanocytic markers. Although overlap between dermatofibromas and DFSP is well documented in the literature, pigmented fibrous lesions with features of both entities are not well described. [source] Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship,JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2004Qing Li Background:, S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. Methods:, Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. Results:, Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p , 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p , 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = ,0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. Conclusions:, Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. [source] Blue Nevi of the Sinonasal Mucosa: A Report of Two Cases and Review of the Literature,THE LARYNGOSCOPE, Issue 2 2007Wen-Yu Chuang MD Abstract Blue nevi are uncommon melanocytic proliferations. They occur mostly in the skin and occasionally in mucosae. Blue nevi of the sinonasal mucosa are extremely rare with only two cases reported to date. We report two more cases and review the literature. Compared with sinonasal malignant melanomas, which usually present as symptomatic tumors, sinonasal blue nevi are asymptomatic lesions found incidentally. A biopsy is required for a definitive diagnosis. Although none of the four cases had recurrence, given a rare but possible occurrence of malignant transformation in cutaneous blue nevi, complete excision with follow up should be the treatment of choice. [source] Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesionsCANCER, Issue 9 2002M.D., Oriana Simonetti Ph.D. Abstract BACKGROUND Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a hierarchical role in regulating physiologic and pathologic angiogenesis. Moreover, the transformation from noninvasive to invasive carcinomas is accompanied by focal disruption and discontinuity of the basement membrane. Several groups of proteases have been implicated in tumor cell invasion, including the 72-kDa gelatinase A/Type IV collagenase (matrix metalloproteinase 2 [MMP-2]) and the 92-kDa gelatinase B/Type IV collagenase (MMP-9). METHODS The authors assessed the immunohistochemical expression of VEGF and metalloproteinases MMP-2 and MMP-9 in paraffin embedded biopsy specimens of malignant melanomas (18 invasive melanomas and 10 in situ melanomas); dysplastic nevi with architectural disorder and cytologic atypia of melanocytes; Spitz nevi; and compound or predominantly intradermal, ordinary, benign melanocytic nevi. RESULTS Strong cytoplasmic staining for VEGF was observed in melanoma cells in as many as 77% of primary invasive melanomas, whereas only 25% of the in situ melanomas exhibited a detectable immunoreactivity for VEGF. It is interesting to note that no immunoreactivity was shown by any nevi; Spitz nevi, in particular, showed negative immunoreactivity to VEGF. Invasive melanomas and in situ melanomas displayed coexpression of MMP-2 and MMP-9, although to a variable extent. In particular, high MMP-2 staining was observed in 14 of 18 invasive melanomas; moreover, strong MMP-2 expression also was observed in 60% of in situ melanomas, whereas the residual 40% of those melanomas showed a moderate level of positivity. CONCLUSIONS On the basis of the current data showing that malignant melanocytic tumors displayed strong VEGF expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF, VEGF also may be used as a discriminating factor to distinguish malignant melanoma from lesions of uncertain histology. Cancer 2002;95:1963,70. © 2002 American Cancer Society. DOI 10.1002/cncr.10888 [source] Pathology of conjunctival melanocytic neoplasmsACTA OPHTHALMOLOGICA, Issue 2008SE COUPLAND Purpose To describe the classification, grading and staging of conjunctival melanocytic proliferation. Methods We have audited our experience with conjunctival melanomas, using a novel mapping system and have found shortcomings in the current Tumour Node Metastasis (TNM) staging system. We have also reviewed our cases of intra-epithelial melanocytic neoplasia and confirmed other authors' impressions that conjunctival ,primary acquired melanosis with atypia' is histologically similar to cutaneous in situ melanoma. To improve objectivity in the reporting of conjunctival intra-epithelial melanocytic neoplasia, we propose a scoring system based on pattern of melanocytic infiltration, density of melanocytes & degree of cellular atypia. Results The term ,conjunctival melanosis' should be used only to describe the slit-lamp appearance of hyperpigmentation. Histologically, this abnormality should be categorized as ,hypermelanosis' or ,melanocytosis'. Hypermelanosis can either be primary or secondary to ocular or systemic disease. Benign melanocytosis comprises conjunctival melanocytic hyperplasia and naevi. Malignant melanocytosis is essentially melanoma, which is primary (in situ or invasive) or secondary (i.e., spreading to conjunctiva from adjacent tissues) or rarely metastatic. We suggest that the TNM staging system for conjunctival melanoma should be revised to: (1) include a Tis stage; (2) take account of superficial extent, invasion of adjacent tissues and caruncular involvement, in stages TI to TIII; and (3) to sub-categorize TIV disease so that there is better correlation with likely mortality. Conclusion We have revised the classification of conjunctival melanocytic proliferations & improved the grading and staging of melanoma. These developments should be useful in treatment & research. [source] Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in human malignant melanoma and their relation to angiogenesisCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2006Y.-T. Tu Summary Background., Angiogenesis is the major and key factor for growth and invasion of tumours, including malignant melanoma (MM), but the factors that contribute to tumour angiogenesis are still unclear., Objective., To study expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in human MM and their relation to angiogenesis. To investigate the correlation between eNOS and VEGF and the role of nitric oxide (NO) generated by eNOS in the process of mediating angiogenesis by VEGF. Methods., Tissue sections from 31 patients with MM were examined using immunohistochemistry and morphological quantitative analysis for protein expression of eNOS and VEGF. Microvessel density (MVD) was counted in endothelial cells in immunostained by anti-FVIII:RAg antibody. Results., Positive eNOS and VEGF immunostaining were observed in 77.4% and 83.9% of MM lesions, respectively, whereas pigmented naevi never expessed eNOS and VEGF. A positive correlation between eNOS and VEGF in MM was observed. Expression of eNOS and VEGF was positively correlated with MVD expression in MM, and MVD expression in MM was stronger than in pigmented naevi. Expression of eNOS and VEGF was not correlated with lymph node metastasis. Conclusions., On the basis of the current data showing that malignant melanocytic tumours displayed strong VEGF and eNOS expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF and eNOS, such expression may be used as a discriminating factor to distinguish malignant melanoma from pigmented naevi. Expression of eNOS and VEGF may contribute to angiogenesis of MM, eNOS probably plays an important role in mediating VEGF-induced angiogenesis. [source] |