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2.
Australas J Dermatol ; 60(3): 209-213, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30773625

RESUMO

BACKGROUND: The recommended method for histopathological diagnosis of cutaneous melanoma is excisional biopsy, although partial biopsies (shave and punch) are often used. Following a partial biopsy, treatment guidelines recommend a narrow excisional biopsy to plan definitive management. There is limited evidence on the benefits of direct wide local excision (WLE) following diagnostic partial biopsies. METHODS: Retrospective cohort study of cutaneous melanoma cases, from two tertiary referral centres from January 2013 to December 2015. Demographic and histopathological data, including tumour thickness (T-stage) from initial biopsy and subsequent excisions, were collected. Logistic regression was used to examine histopathological T-staging between biopsy and subsequent excisions (upstaging). RESULTS: 2304 melanomas (2157 patients) were identified; 455 shave, 308 punch, 14 incisional and 1527 excisional biopsies. Out of 1527, 5 (<1%) excisional biopsies were upstaged from original biopsy T-stage to final WLE; compared to 28/455 (6%) for shave, 45/308 (15%) for punch and 2/14 (14%) for incisional biopsies. Histopathology upstaging were increased with punch (OR, 52.1; 95% CI, 20.5-132.4. P < 0.001) and shave biopsy (OR, 20.0; 95% CI, 7.7-52.0. P < 0.001) compared to excisional biopsy. Upstaging rates of 9.4% for desmoplastic (OR, 6.9; 95% CI, 2.4-19.7. P < 0.001) and 21.9% for acral lentiginous (OR, 18.4; 95% CI, 6.9-49.2. P < 0.001) melanomas were elevated compared to 1.4% for superficial spreading melanoma. CONCLUSIONS: In most cases, partial biopsy (particularly shave biopsy) can provide sufficient information to plan for definitive surgical melanoma management. Punch and incisional biopsies have elevated upstaging rates, a consideration in planning therapy. Partial biopsies of desmoplastic or acral lentiginous melanomas have high rates of upstaging and should have a complete excision prior to definitive treatment.

3.
Nat Genet ; 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30429576

RESUMO

In the version of this article originally published, the main-text sentence "In three patients of European ancestry, we identified the germline variant encoding p.Ile97Met in TIM-3, which was homozygous in two (P12 and P13) and heterozygous in one (P15) in the germline but with no TIM-3 plasma membrane expression in the tumor" misstated the identifiers of the two homozygous individuals, which should have been P13 and P14. The error has been corrected in the HTML, PDF and print versions of the paper.

4.
Nat Genet ; 50(12): 1650-1657, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30374066

RESUMO

Subcutaneous panniculitis-like T cell lymphoma (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation that adversely affects survival1,2. T cell immunoglobulin mucin 3 (TIM-3) is a modulator of immune responses expressed on subgroups of T and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants altering highly conserved residues of TIM-3, c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met), each with specific geographic distribution. The variant encoding p.Tyr82Cys TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while p.Ile97Met TIM-3 occurs in patients with European ancestry. Both variants induce protein misfolding and abrogate TIM-3's plasma membrane expression, leading to persistent immune activation and increased production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß, promoting HLH and SPTCL. Our findings highlight HLH-SPTCL as a new genetic entity and identify mutations causing TIM-3 alterations as a causative genetic defect in SPTCL. While HLH-SPTCL patients with mutant TIM-3 benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences.

5.
J Geriatr Oncol ; 9(5): 488-493, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29398454

RESUMO

OBJECTIVES: Melanoma treatment in the elderly can entail complex decision making. This study characterizes the presentation, management, and outcome of melanoma in the very elderly. METHOD: Retrospective review of all patients in their 85th year or older presenting to a tertiary referral cancer centre between 2000 and 2012 with American Joint Committee on Cancer stages 0-II cutaneous melanoma. RESULTS: 127 patients, 26 with in-situ disease and 101 with stages I-II disease, were included. For invasive primary disease, the median age was 87years (IRQ=86-89). Most patients had melanomas with poor prognoses at diagnosis: 49.5% were ulcerated, 68.3% mitotically active (mitotic rate≥1), and the median tumor thickness was 3.7mm (IQR=1.7-5.8). Nodular melanomas were the most frequent subtype (31.7%, 32/101). Only 66.3% received an excision margin≥10mm. Suboptimal excision margins were associated with increased risk of local recurrence (HR=6.87, 95% CI=5.53-8.20, p=0.0045) but not poorer disease specific survival (DSS, p=0.37) or overall survival (OS, p=0.19). Sentinel node biopsy (SNB) did not influence survival (DSS, p=0.39, OS, p=0.78). Median OS was 33months. Overall, one-third (34.7%) of patients died from causes other than melanoma during the follow up period. In patients aged ≥90 only 1 patient (4.3%) died from melanoma, while 10 patients (43.5%) died of other causes. CONCLUSIONS: Older patients have thick, mitotically active and frequently ulcerated melanomas. An excision margin≥10mm should be considered to reduce risk of local recurrence. SNB did not impact on survival. With increasing age, patients will more commonly die of causes other than melanoma regardless of the extent of surgical care.

7.
Australas J Dermatol ; 58(4): e207-e215, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27283245

RESUMO

BACKGROUND: Squamous cell carcinoma of the scalp is a common clinical problem in an aging population. Despite its high incidence, little has been documented regarding treatment or outcomes. METHODS: We retrospectively analysed 235 cases treated with curative intent at Peter MaCallum Cancer Centre between 1998 and 2010. The cohort was analysed for its characteristics, management, survival and prognostic factors. RESULTS: The patients were primarily male (88%) with a median age of 79 years (range 53-98 years). There was a high proportion of immunosuppressed patients (29%) and stage T2 (48%) tumours. Management included surgery (45%), radiotherapy (28%) and surgery and adjuvant radiotherapy (26%). Median follow up from treatment was 4.5 years. Estimated 5-year overall survival (OS), disease-specific survival and progression-free survival (PFS) were 59, 94 and 51%, respectively. The 5-year cumulative incidence of local and regional relapse was 11 and 7%, respectively. There were four patients who developed distant metastases and died of their disease. Statistically significant prognostic factors identified for poor outcomes for OS and PFS were T2 stage (hazard ratio [1.7 and 2.1) and immunosuppression (HR 3.3 and 3.4). CONCLUSIONS: We conclude the presence of immunosuppression and T2 stage is prognostic for survival. Further research to establish treatment principles is warranted.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/etiologia , Couro Cabeludo , Neoplasias Cutâneas/terapia , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Carcinoma de Células Escamosas/secundário , Procedimentos Cirúrgicos Dermatológicos , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Resultado do Tratamento
8.
Australas J Dermatol ; 56(2): 134-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25482351

RESUMO

Eruptive disseminated Spitz naevus (EDSN) is a rare entity and has never been documented in a South-east Asian individual (of Indian origin) previously. We report an adolescent with this condition which, to our knowledge, has only been previously reported a few times.


Assuntos
Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/patologia , Adolescente , Feminino , Humanos , Índia
9.
Australas J Dermatol ; 56(4): 303-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25331085

RESUMO

Pityriasis rosea is a common skin condition that presents acutely with asymptomatic, scaly and oval plaques, usually in a well-recognised distribution over the trunk. Two men developed ovoid, scaly and annular lesions limited to the radiotherapy field during treatment for pelvic malignancies and without a preceding herald patch. Other causes of the eruption were excluded on clinical and pathological grounds and the histopathological features were consistent with a pityriasis rosea-like eruption. In both cases the lesions resolved spontaneously by 8 weeks. These are the first reported cases of a localised pityriasis rosea-like eruption arising during radiotherapy.


Assuntos
Adenocarcinoma/radioterapia , Pitiríase Rósea/etiologia , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Neoplasias Retais/radioterapia , Humanos , Linfoma Folicular/radioterapia , Masculino , Pessoa de Meia-Idade
10.
Australas J Dermatol ; 55(2): 132-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24032760

RESUMO

Immunoglobulin type gamma 4 (Ig)G4-related disease (IgG4-RD) is a relatively recently described clinical entity characterised by elevated levels of serum IgG4 and tissue infiltration of IgG4+ plasma cells in various organ systems. Cutaneous involvement is rare but is becoming increasingly appreciated; typically presenting as erythematous papules and/or nodules that are commonly pruritic. We report a case of IgG4-RD presenting with persistent pruritic papules and unilateral parotid swelling. His serum IgG4 level was elevated and a histological examination of his skin biopsies found a lymphoplasmacytic infiltration with an excess of IgG4+ non-clonal plasma cells. The patient was intolerant of oral prednisolone, however complete resolution of the cutaneous lesions was achieved with the anti-CD20 antibody, rituximab.


Assuntos
Imunoglobulina G/sangue , Dermatopatias/patologia , Anticorpos Monoclonais Murinos/uso terapêutico , Humanos , Imunoglobulina G/análise , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Plasmócitos/química , Plasmócitos/patologia , Rituximab , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia
11.
Australas J Dermatol ; 55(1): e1-3, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23190403
13.
Clin Cancer Res ; 14(14): 4500-10, 2008 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-18628465

RESUMO

PURPOSE: Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat. EXPERIMENTAL DESIGN: Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was considered excessively toxic, and subsequent patients were treated at the expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4, 8, and 24 h after administration were subjected to microarray gene expression profiling and real-time quantitative PCR of selected genes. RESULTS: Patients attained a complete response (n = 2), attained a partial response (n = 4), achieved stable disease with ongoing improvement (n = 1), and progressed on treatment (n = 2). Microarray data showed distinct gene expression response profiles over time following panobinostat treatment, with the majority of genes being repressed. Twenty-three genes were commonly regulated by panobinostat in all patients tested. CONCLUSIONS: Panobinostat is well tolerated and induces clinical responses in CTCL patients. Microarray analyses of tumor samples indicate that panobinostat induces rapid changes in gene expression, and surprisingly more genes are repressed than are activated. A unique set of genes that can mediate biological responses such as apoptosis, immune regulation, and angiogenesis were commonly regulated in response to panobinostat. These genes are potential molecular biomarkers for panobinostat activity and are strong candidates for the future assessment of their functional role(s) in mediating the antitumor responses of panobinostat.


Assuntos
Antineoplásicos/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases , Ácidos Hidroxâmicos/uso terapêutico , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Acetilação/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Histona Desacetilases/efeitos dos fármacos , Histonas/efeitos dos fármacos , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Indóis , Linfoma Cutâneo de Células T/genética , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Panobinostat , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/genética
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