RESUMO
Desmoplastic melanoma (DM), a type of spindle cell melanoma separated into pure desmoplastic melanoma (PDM) and mixed desmoplastic melanoma (MDM) subtypes, can be a diagnostic challenge and easily confused for dermal scar, especially PDM. We report a 65-year-old white man who received a left thumb amputation after an initial biopsy for melanoma, an unclassified type with epithelioid morphology. The amputation and sentinel lymph node specimens were significant for residual melanoma with epithelioid morphology, dermal scar, and a slightly expanded "scar-like" capsular area in one of seven lymph nodes, which was diffusely positive for SOX10 on reflex sentinel lymph node immunohistochemical protocol. On re-review of the amputation "scar" like area, a subsequent SOX10 stain confirmed the diagnosis of MDM in this area with epithelioid and spindle cell morphology, significantly upgrading the tumor stage. We share this case to highlight: (i) MDM, although exceptionally uncommon, can result in a pure spindle cell lymph node metastasis, (ii) to encourage increased utilization of SOX10 to assess sentinel lymph node biopsies, especially in the context of melanomas with a spindle cell component, and (iii) share an example of inattentional blindness which was fortunately identified by reflex sentinel lymph node immunohistochemical protocols.
Assuntos
Melanoma , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Melanoma/patologia , Metástase Linfática , Neoplasias Cutâneas/patologia , Cicatriz/patologia , Biópsia de Linfonodo Sentinela , Cegueira , Fatores de Transcrição SOXERESUMO
Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article.
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BACKGROUND: Perineuriomatous nevi are rare and diagnostically problematic. We report a series of eight perineuriomatous nevi to highlight the diagnostic features. METHODS: Cases were retrospectively reviewed and characterized. RESULTS: Median age was 42.5 years (range 25-64), with equal sex distribution. Lesions occurred on the arm (n = 4), trunk (n = 2), and head/neck (n = 2). Median size was 7.5 mm (range 5-12 mm). Clinical differential diagnoses included atypical nevus (3), blue nevus (1), neurofibroma (1), and dermatofibroma (1). Lesions were circumscribed, dome-shaped (5/8), and biphasic (8/8) with nested epithelioid cells and wavy spindled cells arranged in whorled fascicles in a myxocollagenous stroma. When present, junctional growth was lentiginous (4/8). No cases displayed pleomorphism or mitotic figures. The perineuriomatous component stained positively for epithelial membrane antigen (8/8 focal to diffuse) and CD34 (4/5 focal to diffuse). SOX10 and S100 protein stained all nevoid cells and in some cases a subset of intermingled spindled cells in perineuriomatous areas, where other melanocytic markers were negative. p16 protein expression was uniformly retained (3/3), and p53 negative (0/2). Nevoid cells in most lesions were positive for BRAFV600E (5/7). Ki67 was mildly elevated (~5%) in 3/3 cases. CONCLUSIONS: Recognizing the histopathologic and immunophenotypic features in these unusual nevi helps avoid overdiagnosis.
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Neoplasias de Bainha Neural/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Desmoplastic melanoma (DM) is an uncommon variant of melanoma that can be challenging to diagnose. Phenotypic variations in terms of the proportion of spindled cells and fibromucinous stroma have led to the subclassification of pure (>90% spindled cells) and mixed (<90% spindled cells admixed with epithelioid cells) histopathologic DM subtypes. This subclassification is not just semantic; several studies have underscored differences in clinical and prognostic behaviors of the subtypes. In this review, we parse the literature on DM subtypes with an emphasis on histopathologic, immunohistochemical, and genetic data to ascertain whether these factors influence and/or affect their differing biological behaviors. Demographics regarding age, location, and clinical behavior of the subtypes are detailed, as is the impact of dermoscopy as a diagnostic adjunct. Despite the plethora of markers used, our findings suggest that few differentiate between the DM subtypes. Differential expression of PD-L1 suggests that patients with the mixed subtype are likely better candidates for anti-PD/PD-L1 therapy. Significant differences between the subtypes in terms of neurofibromin expression and the frequency of TERT promoter mutations suggest that the subtypes have distinct genetic drivers. Thus, immunohistochemical and genetic analyses imply that these likely affect the biological behaviors of the DM subtypes.
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Melanoma/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/diagnóstico , Pele/patologia , Antígeno B7-H1/análise , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Procedimentos Cirúrgicos Dermatológicos , Dermoscopia , Testes Genéticos , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imuno-Histoquímica , Melanoma/genética , Melanoma/imunologia , Melanoma/terapia , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Regiões Promotoras Genéticas/genética , Pele/diagnóstico por imagem , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Telomerase/genética , Resultado do TratamentoRESUMO
The development of flat pigmented lesions on chronically sun-damaged (CSD) skin of the face may represent the clinical manifestation of a wide variety of hyperplastic/neoplastic melanocytic proliferations. We report the exceptional case of an acquired pigmented patch occurring on CSD skin, histopathologically characterized by diffuse hyperplasia of dendritic/spindled melanocytes in the superficial dermis within a widened band of actinic elastosis. This lesion was associated with a small focus of early invasive lentigo maligna melanoma (LMM). We show the melanocytic nature of the population of dermal pigmented cells by means of single and double immunohistochemical staining for melanocytic and histiocytic markers. The biologic significance of the focus of LMM within the hyperpigmented lesion (whether random collision phenomenon or causally related occurrence), as well as the pathogenesis of the whole dermal lesion are difficult to elucidate. Our case emphasizes the need for a better understanding of the pathophysiology of so-called dermal melanocytes.
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Sarda Melanótica de Hutchinson/diagnóstico , Melanócitos/patologia , Melanoma/patologia , Pele/efeitos da radiação , Luz Solar/efeitos adversos , Idoso de 80 Anos ou mais , Derme/patologia , Seguimentos , Humanos , Sarda Melanótica de Hutchinson/metabolismo , Sarda Melanótica de Hutchinson/patologia , Hiperpigmentação , Imuno-Histoquímica/métodos , Masculino , Melanócitos/citologia , Transtornos de Fotossensibilidade/patologia , Pele/patologia , Neoplasias Cutâneas/patologiaRESUMO
Desmoplastic melanoma (DM) is a rare melanoma variant that has unique biology and pathology compared with conventional melanoma (non-DM). Importantly, DM is classified into pure and mixed histologic subtypes, which have been correlated with outcomes. Management of DM broadly mirrors that of non-DM; however, there are unique considerations for DM that influence treatment approaches. This paper will provide a contemporary overview of this disease and will review the literature regarding the management of DM.
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Melanoma/classificação , Melanoma/cirurgia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/cirurgia , Gerenciamento Clínico , Humanos , Melanoma/patologia , Prognóstico , Neoplasias Cutâneas/patologiaRESUMO
Superficial malignant peripheral nerve sheath tumour (MPNST) is a rare, soft tissue neoplasm that shares morphological features and some molecular events with spindle/desmoplastic melanoma (SDM). Herein, we sought to identify molecular targets for therapy by using targeted RNA/DNA sequencing and gene expression of key immunological players. DNA and RNA from formalin-fixed paraffin-embedded tissue were extracted and processed. Massive high-throughput deep parallel sequencing was performed with the Oncomine comprehensive panel, enabling detection of relevant single-nucleotide variants, copy number variations, gene fusions and indels for 143 unique genes on the Ion torrent sequencer for clinical trial research programmes. Gene expression analysis was carried out with a customized 770-gene expression panel combining markers for 24 different immune cell types and 30 common cancer antigens, including key checkpoint blockade genes analysed with the Ncounter system. Fifty-one patients (SDM, 16/11; MPNST, 24; male, n = 37; female, n = 16) had sufficient DNA and RNA for testing. NF1 deleterious mutations and/or deep/homozygous deletions were identified in 73% of MPNSTs and 67% of SDMs, with 50% of the mutations involving the RAS-binding domain. Inactivating/deleterious mutations of TSC1/TSC2 were identified in 40% and 41% of MPNSTs and SDMs, respectively. Activating mutations affecting the EGFR-like and the negative regulatory domains of NOTCH1 and KDR (VEGFR2) were identified in 45% and 40% of SDMs and in 30% and 8% of MPNSTs, respectively. Differential gene expression and gene clustering analysis showed significantly perturbed immune pathway components, including nuclear factor-κB (NF-κB), JAK-STAT, and CXCL12-CXCR4, and differentially expressed CD274 and CTLA4, in both SDM and MPNST. Angiogenesis (KDR and NOTCH1) and mammalian target of rapamycin complex (mTORC) pathways offer a rationale for anti-angiogenic and selective mTORC inhibition as treatment strategies for MPNST and SDM. Cytokines and the JAK-STAT, TNF and NF-κB axes were perturbed in both SDM and MPNST. These pathways have been targeted in haematological malignancies and present promising targets for these tumours. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Melanoma/patologia , Neurilemoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Feminino , Perfilação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Análise de Sequência de RNA , Microambiente TumoralRESUMO
There are multiple, genetically distinct pathways that give rise to melanoma. Melanomas on sun-damaged skin (MSDS), including lentigo maligna and desmoplastic melanoma, have distinct genetic profiles and are uniquely linked to chronic ultraviolet exposure. In this article, we discuss the etiologies of lentigo maligna and desmoplastic melanoma, emerging diagnostic adjuncts that might be helpful for accurately identifying these lesions, and the clinical relevance of their frequent co-occurrence. We present unique and overlapping features of these entities and discuss challenges in MSDS management, including margin assessment, excision, and the potential role of nonsurgical therapy. Last, we address the role of immunotherapy in invasive disease. Understanding MSDS as distinct from melanoma arising on intermittently sun-exposed or sun-protected skin will ultimately help optimize patient outcomes.
Assuntos
Sarda Melanótica de Hutchinson/diagnóstico , Neoplasias Cutâneas/diagnóstico , Pele/patologia , Luz Solar/efeitos adversos , Antígeno B7-H1/genética , Biópsia , Procedimentos Cirúrgicos Dermatológicos , Dermoscopia , Diagnóstico Diferencial , Humanos , Sarda Melanótica de Hutchinson/etiologia , Sarda Melanótica de Hutchinson/terapia , Imiquimode/uso terapêutico , Imunoterapia/métodos , Margens de Excisão , Microscopia Confocal , Taxa de Mutação , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neurofibromina 1/genética , Proteínas Proto-Oncogênicas c-kit/genética , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Pele/diagnóstico por imagem , Pele/efeitos da radiação , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Positive staining for SOX10 and the S100 protein are often used in the evaluation of challenging melanocytic neoplasms including melanoma in patient samples. SOX-10 positivity of non-melanocytes in re-excision specimen could complicate the evaluation of invasive melanoma with an invasive desmoplastic component. Therefore, quantifiable data regarding the positivity of SOX-10 in scars will help dermatopathologists to better identify false positive staining. METHODS: A retrospective analysis was performed on 50 re-excision specimens from 2013 to 2017, with a diagnosis of squamous cell carcinoma (SCC) or squamous cell carcinoma in situ (SCCIS). Blocks of re-excision specimens containing scars were stained for SOX-10; results were evaluated by a board-certified dermatopathologist. The sum of the five highest numbers of high-power field (HPF) counts as a proxy for "SOX-10 stain factor," and cell morphological features were analyzed. MART-1 and CD68 immunohistochemical staining was performed to study possible lineage of these SOX-10 positive cells. RESULTS: All 50 specimens showed varying degrees of SOX-10 positivity for histiocytes. SOX-10 positive histiocytes were present in 86% of re-excision scar tissues, of which 71.3% had spindle-shaped or angulated nuclei, and 61.8% had nuclear sizes larger than typical lymphocytes (7 µm). Within the same area of scars, CD68 staining was floridly positive, where as MART-1 staining was overwhelmingly negative. CONCLUSIONS: This study illustrates a potential diagnostic pitfall of using SOX-10 to evaluate re-excision specimens of melanocytic neoplasms and also suggests a previously undescribed staining pattern in scars of SOX-10 positive cells that are not melanocytes. We postulate that such SOX-10 positive cells may represent a small fraction of histiocytes routinely found in scar tissue.
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Cicatriz/metabolismo , Derme/metabolismo , Histiócitos/metabolismo , Fatores de Transcrição SOXE/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Cicatriz/patologia , Derme/patologia , Feminino , Histiócitos/patologia , Humanos , Imuno-Histoquímica , Antígeno MART-1/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Coloração e RotulagemRESUMO
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoral PDL1 expression correlated with thickness (P = .0041); p53 expression (P = .019); Ki-67 proliferation index (P = .0018); and tumoral CD8 (P = .0084), stromal CD8 (P < .0001), and FoxP3 (P < .0001) T-cell counts. According to univariate analyses, PDL1 expression of 25% or higher correlated with shorter progression-free survival (P < .0001) and melanoma-specific survival (P = .034). According to multivariate analyses, PDL1 expression of 25% or more (P = .026) and mixed histology (P = .039) independently predicted shorter progression-free survival, and presence of lymphovascular invasion predicted shorter overall survival (P = .018). LIMITATIONS: Small study size. CONCLUSION: Tumoral and stromal CD8+ and FoxP3+ lymphocyte counts correlated with tumoral PDL1 expression, which is supportive of an adaptive immune response. PDL1 expression in desmoplastic melanoma was associated with tumor aggressiveness and progression. Although PDL1 expression is typically low in melanoma, its frequency and level of expression in desmoplastic melanoma may identify a subset of melanomas that are likely to respond to immunotherapy.
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Antígeno B7-H1/biossíntese , Melanoma/metabolismo , Melanoma/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To evaluate clinical, pathologic and genetic features of desmoplastic melanoma (DM). MATERIALS & METHODS: Analysis of all DM records from 1991 to 2015. RESULTS: The most common location of DMs was the head and neck (69%); median age and follow-up were 60.5 and 7.3 years, respectively. A familial predisposition for DMs and others malignancies was analyzed. Thin Breslow thickness (<4.5 mm) was associated with an intraepidermal component or a previous lentigo maligna, whereas high Breslow thickness (>4.5 mm) was observed in 'pure' DM. CONCLUSION: DM could progress from an early phase, characterized by an intraepidermal component, to late phase, characterized by a dermal nodule. This hypothesis correlates with melanoma genetic and NF1 mutation, which could be an early event in the progression of DM.
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Melanoma/diagnóstico , Melanoma/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Metástase Linfática , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100-positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major nerve, pre-existing neural benign tumor or the existence of stigmata suggestive of neurofibromatosis raised consideration of a DM. Careful attention should be paid to the presence of a firm dermal nodule and atypical scar lesions especially in sun-exposed areas (mainly head and neck region) in elderly patients associated with S100-positive spindle cell proliferation, solar elastosis and adjacent atypical melanocytic proliferation. In such cases, the possibility of a DM should be excluded with caution, especially if the tumor reveals a paucicellular morphology resembling various non-melanocytic neoplasms including malignant or benign peripheral sheath nerve tumors.
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BACKGROUND: The prognostic role Ki-67, p53, and p16 immunostains and RET (rearranged during transfection) polymorphism in desmoplastic melanoma has not been evaluated. OBJECTIVE: We sought to identify potential prognostic markers. METHODS: We performed Ki-67, p53, and p16 immunostains on 66 desmoplastic melanomas, and sequenced RET G691 polymorphism and recurrent mutations of 17 cancer genes in 55 and 20 cases, respectively. RESULTS: Recurrence and metastasis were documented in 11 of 66 (17%) and 26 of 66 (39%) patients, respectively. Death was noted in 25 of 55 (45%) patients. Ki-67 expression (≥10%, 43%) correlated with male gender (P = .009), ulceration (P = .002), and Breslow depth (P = .009). p53 Expression (≥50%, 28%) correlated with male gender (P = .002) and head and neck location (P = .0228). Using Kaplan-Meier plots, Ki-67 expression (P = .0425) and mitosis (P = .00295) correlated with overall survival, whereas vascular invasion (P = .0292) correlated with disease progression. There was a significant correlation between Ki-67 and p53 expression (P = .003). RET polymorphism was present in 10 of 46 (22%) cases and inversely correlated with Breslow depth (P = .024). LIMITATION: Our study is small and lacks power to perform a multivariate analysis. CONCLUSION: Although Ki-67 expression correlated with overall survival, additional studies are needed to determine whether Ki-67 would be an independent prognostic marker in addition to the current routine histopathologic assessment.
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Antígeno Ki-67/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Genes p16 , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Polimorfismo Genético , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Melanoma Maligno CutâneoRESUMO
Desmoplastic melanoma is an uncommon form of melanoma characterized by atypical spindled melanocytes and abundant collagen deposition. It typically presents in sun-damaged skin of the elderly as an amelanotic, indurated lesion. It has a higher tendency for local recurrence but lower risk of lymph node metastasis vs. conventional malignant melanoma. We report two cases in women aged 59 and 66 who presented with small scalp lesions clinically suggestive of alopecia. The differential diagnosis included alopecia areata, lupus erythematosus and lichen planopilaris. Biopsies performed according to alopecia protocol were reviewed at our institutions. Biopsies revealed atypical spindled and nested epithelioid melanocytes set in a sclerotic dermis with scattered lymphoid aggregates and immunohistochemical expression of S100 protein, features diagnostic of combined desmoplastic melanoma. Wide local excision with skin graft was performed on the older patient. Excision showed combined desmoplastic melanoma with a Breslow thickness of 8.5 mm with melanoma in situ identified in the adjacent epidermis. The other patient sought treatment elsewhere and was lost to follow up. These cases illustrate desmoplastic melanoma as an unusual etiology and dangerous clinical pitfall in patients with scar-like alopecia. To the authors' knowledge, these represent the second and third reported cases of desmoplastic melanoma presenting as primary alopecia neoplastica.
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Alopecia , Neoplasias de Cabeça e Pescoço , Melanoma , Proteínas de Neoplasias/metabolismo , Proteínas S100/metabolismo , Neoplasias Cutâneas , Idoso , Alopecia/metabolismo , Alopecia/patologia , Biópsia , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Desmoplastic melanoma (DM) is histologically characterized by a proliferation of spindle melanocytes dispersed in a collagenous stroma that can be mistaken for a variety of neoplasms. The purpose of this study was to analyze 40 cases of DM with a comprehensive panel of immunohistochemical markers (KBA.62, p16, Ezrin, WT-1, MITF-1, SOX-10, CD117, SOX-2, nestin, PNL2, p75, MART-1, gp100 and S100p) to obtain a more complete understanding of the potential use of these antibodies in the diagnosis of DM. We found that all cases of DM expressed p16, WT-1, SOX-10, nestin and S100p and 95% of cases expressed p75. There was variable expression with Ezrin, SOX-2, KBA.62, MART-1 and HMB-45. Most DMs did not express MITF-1, PNL2 and CD117. Conditions that may enter in the histologic differential diagnosis of DM, including dermal scars, fibromatosis and dermatofibromas were also studied. Nearly all control cases also stained positive for p16 but were negative for WT1, SOX10, nestin, p75 and S-100p, as well as for most of the other markers tested. We conclude that a panel of S-100p, WT1, SOX10, p75 and nestin may constitute the optimal panel with the most sensitive and specific combination of immunostain available for the diagnosis of DM.
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Melanoma/metabolismo , Melanoma/patologia , Proteínas de Neoplasias/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem/métodosRESUMO
BACKGROUND: Perineural invasion (PNI) in desmoplastic melanoma is associated with increased local recurrence and reduced disease-free survival. The biological mechanisms underlying PNI remain unclear although several lines of evidence implicate neurotrophins and their receptors. OBJECTIVES: We investigated the expression of p75NGFR and TrkA, and the presence of functional RET polymorphism (RETp) as they relate to PNI in desmoplastic melanoma. METHODS: In all, 43 cases of desmoplastic melanoma were immunohistochemically evaluated for TrkA and p75NGFR expression and RETp was detected by direct DNA sequencing. RESULTS: PNI was present in 67% of cases. On univariate analysis, p75NGFR was associated with PNI (expression detected in 79% of PNI-positive cases compared with 36% of PNI-negative cases, P = .005), increased Breslow depth (P = .007), and greater Clark level (P = .01). RETp was noted in 28% of cases but was not significantly associated with PNI (P = .27) or other histopathologic variables. TrkA expression was absent in all cases. PNI was associated with increased Breslow depth and Clark level (P = .01 and P = .009, respectively). Controlling for the association between p75NGFR and depth, p75NGFR remained associated with an increased propensity for PNI (odds ratio 4.68, P = .04). LIMITATIONS: The sample size was limited. CONCLUSION: In desmoplastic melanoma, p75NGFR expression is significantly associated with PNI and a more locally aggressive phenotype.
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Melanoma/patologia , Nervos Periféricos/patologia , Receptores de Fator de Crescimento Neural/análise , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Proteínas do Tecido Nervoso/análise , Polimorfismo Genético , Proteínas Tirosina Quinases/análise , Proteínas Proto-Oncogênicas c-ret/genética , Análise de Sequência de DNA , Melanoma Maligno CutâneoRESUMO
BACKGROUND: In the current study, the authors sought to evaluate outcomes, specifically with respect to adjuvant radiotherapy (RT), for patients with desmoplastic melanoma. METHODS: The records of 130 consecutive patients who presented between 1985 and 2009 with nonmetastatic desmoplastic melanoma and were treated curatively with either surgery alone (59 patients; 45%) or surgery and postoperative RT (71 patients; 55%) were retrospectively reviewed. Ages ranged from 21 years to 97 years (median age, 66 years). The location of the primary tumor was in the head and neck region in 62% of patients. Only 5 patients (4%) had lymph node involvement at the time of presentation. RESULTS: The median follow-up was 6.6 years (range, 11 months-24 years). Overall survival rates at 5 years and 10 years were 69% and 53%, respectively. Disease-specific survival rates were 84% and 80%, respectively, at 5 years and 10 years. The actuarial rate of local recurrence was 17% at 5 years and beyond. Of the patients who underwent surgery without receiving postoperative RT, 14 (24%) experienced local recurrence. Of the 71 patients treated with surgery and postoperative RT, 5 (7%) experienced local recurrence. In a Cox multivariate regression model, improved local control was significantly associated with the receipt of postoperative RT (P= .009). CONCLUSIONS: Surgery followed by postoperative RT appears to provide superior local control compared with surgery alone for patients with desmoplastic melanoma.
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Neoplasias de Cabeça e Pescoço/radioterapia , Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Desmoplastic melanoma is an extremely rare subtype of malignant melanoma comprising only 1% of all the cutaneous melanomas. Being amelanotic and owing to its histopathological features of spindle cells lying in a collagenized stroma, it is often misdiagnosed as a dermatofibroma or scar tissue. The present case study describes a case of desmoplastic melanoma of the chest wall where the final diagnosis could be arrived at only after an extensive immunohistochemical panel to exclude other spindle cell proliferations.