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J R Marsden

Publications and source records attributed to J R Marsden.

At least 19 recordsLinked to original sources
PubMed2006

Imiquimod in the treatment of lentigo maligna.

BACKGROUND: Lentigo maligna (LM) is treated to prevent progression to lentigo maligna melanoma (LMM). Surgery remains the treatment of choice, although topical immunotherapy with imiquimod has recently become a popular alternative. OBJECTIVES: In this review, we have analysed the published literature relating to the use of imiquimod for LM, in order to understand better the utility of this treatment. METHODS: All English language studies relating to the use of imiquimod for LM were analysed up to January 2006. RESULTS: Eleven case reports and four open-label studies were identified, comprising a total of 67 patients who completed treatment with imiquimod for LM. There was significant variability in treatment schedules and regimens. Eight patients failed to respond, with LMM developing in two of these. In certain cases there were discrepancies between clinical and histological response with some patients clearing clinically but not histologically, and vice versa. Follow-up periods were short, exceeding 12 months in only five cases. CONCLUSIONS: Although imiquimod clearly has an effect on LM, this analysis of available studies has helped to identify concerns about its use. Without controlled evidence and prolonged follow up, the use of imiquimod for LM must still be considered experimental.

Aminoquinolines↗
PubMed2005

Management of melanoma metastasis to the breast: case series and review of the literature.

BACKGROUND: Metastases to the breast from extramammary cancers are rare; melanoma is one of the malignancies that can metastasize to the breast. OBJECTIVES: To examine the records of a series of patients with a previous diagnosis of melanoma and a metastasis to the breast, and review the published literature of this condition. METHODS: We report details of eight female patients with breast metastases from melanoma seen over a 36-month period from 2001. All patients were female aged 28-84 years (median 58). The breast lump was investigated by core-cut biopsy or fine needle aspiration, with or without a mammogram. RESULTS: The time between diagnosis of the primary melanoma and the occurrence of a breast metastasis ranged from 13 to 180 months (median 62). In three patients the breast lump was the first sign of recurrence of melanoma. In three patients melanoma had previously relapsed in regional lymph nodes and in two patients it had already relapsed as locoregional and distant subcutaneous metastases before metastasizing to the breast. In two patients presenting via the breast clinic, the lump was subsequently confirmed on excision to be melanoma in an intramammary lymph node. In seven patients, a lumpectomy was performed after histological confirmation; one of these also had a level 1-3 axillary dissection. The eighth patient deteriorated clinically before further surgery was possible. Six patients developed further metastases within 1-5 months of breast lump detection. In one case a second 9 mm breast lump in the deeper tissue of the same breast was detected on a computed tomography scan and has been removed using stereotactic surgery. Four patients have died. CONCLUSIONS: Presentation is usually with a palpable mass without skin changes. Investigation must include histology or cytology to confirm the diagnosis. Management of melanoma metastasis to the breast is discussed; in this series it was surgical unless there were many metastases.

Adolescent↗
PubMed2003

Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma.

PURPOSE: To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or locoregional metastases. PATIENTS AND METHODS: In this randomized controlled trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three times per week for 2 years or until recurrence) on overall survival (OS) and recurrence-free survival (RFS) was compared with that of no further treatment in radically resected stage IIB and stage III cutaneous malignant melanoma. RESULTS: The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1), respectively. There was no significant difference in OS or RFS between the interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18; P =.6; and OR, 0.91; 95% CI, 0.75 to 1.10; P =.3; respectively). Male sex (P =.003) and regional lymph node involvement (P =.0009), but not age (P =.7), were statistically significant adverse features for OS. Subgroup analysis by disease stage, age, and sex did not show any clear differences between interferon-treated and control groups in either OS or RFS. Interferon-related toxicities were modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals (15%) from interferon treatment due to toxicity. CONCLUSION: The results from this study, taken in isolation, do not indicate that extended-duration low-dose interferon is significantly better than observation alone in the initial treatment of completely resected high-risk malignant melanoma.

Adolescent↗
PubMed2002

Dermatofibrosarcoma protuberans treated by micrographic surgery.

Dermatofibrosarcoma protuberans is an uncommon cutaneous tumour which rarely metastasises. However, local recurrence following apparently adequate surgical excision is well recognised, presumably as a result of sub-clinical contiguous growth, for which micrographically controlled excision would be a logical treatment. A retrospective study of all patients treated by micrographic surgery, from April 1995-March 2000, at a tertiary skin oncology centre. Twenty-one patients (11 males), age 14 to 71 years with dermatofibrosarcoma protuberans on the trunk (10 patients), groin (four), head and neck (four), and limbs (three) were treated. In 15 patients one micrographic layer cleared the tumour, and four were cleared with two layers. For one patient the second stage was completed by conventional excision guided by positive margins. Another patient with a multiply recurrent perineal dermatofibrosarcoma protuberans, not cleared in one area after two layers, died from a pulmonary embolus before total clearance could be achieved. There was no correlation between tumour size and lateral excision margin. No recurrence was observed during the follow-up, from 21 to 80 months, median 47 months. The study provides further support for micrographic surgery as the treatment of choice for dermatofibrosarcoma protuberans.

Adolescent↗
PubMed2002

Chloroma (aleukaemic leukaemia cutis) initially diagnosed as cutaneous lymphoma.

A 65-year-old man presented in 1997 with a nodule on his back; histology showed apparent high grade T-cell lymphoma, treated after excision with radiotherapy. He relapsed with lesions on the thigh and buttock in 1998 and was treated with CHOP chemotherapy with a complete response. Further relapse occurred in 1999 with a nodule on his thigh again; he received CNOP (doxorubicin substituted with mitozantrone). At no stage was there clinical, bone marrow or radiological evidence of extra cutaneous disease. In November 2000 he presented with widespread indurated plaques and violaceous nodules. Biopsies repeated with extensive immunohistological staining diagnosed aleukaemic leukaemia cutis. Our patient was diagnosed with cutaneous T-cell lymphoma (CTCL) on the basis of clinical and haemotoxylin & eosin appearances. The correct diagnosis was made after extensive immunohistological studies (including myeloid markers) of repeat biopsies. This case illustrates the importance of diagnostic review in atypical CTCL. There is a high incidence of progression to acute myeloid leukaemia.

Aged↗
PubMed2002

Multiple cutaneous plasmacytomas following an autologous peripheral stem cell transplant.

We describe the unusual development of multiple cutaneous plasmacytomas following treatment of IgA lambda myeloma with myeloablative therapy and a peripheral blood stem cell autograft. Cutaneous metastatic spread was evident despite bone marrow remission. Treatment with an autograft may have contributed to the cutaneous relapse.

Hematopoietic Stem Cell Transplantation↗
PubMed1999

Successful treatment of acquired perforating dermatosis with rifampicin in an Asian patient with sclerosing cholangitis.

Acquired perforating dermatosis (APD) is a very rare disorder which has been described in association with systemic diseases such as diabetes mellitus, HIV infection or lymphoma. In this report we describe a patient with APD associated with sclerosing cholangitis and diabetes mellitus who was successfully treated with rifampicin. A 33-year-old Indian woman with a history of extensive pancreatic surgery, sclerosing cholangitis and insulin dependent diabetes mellitus was referred to our unit with intractable pruritus. She was treated with cholestyramine, ursodeoxycholic acid, several analgesics, UVB therapy, topical steroids, sedative antihistamines and plasmapheresis without significant improvement. Increasingly severe itching was associated with papular skin changes limited initially to the lower limbs but which later involved her entire body. Biopsy of a representative lesion showed the changes of APD. She was subsequently treated with rifampicin which produced a dramatic resolution of pruritus within 3 weeks and the skin changes progressively resolved over subsequent months. In this newly described association of APD with sclerosing cholangitis, rifampicin treatment appeared to be efficient in ameliorating pruritus and the papular skin changes typical of APD.

Adult↗
PubMed1999

Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours.

AIMS: Compelling evidence from cell culture studies implicates cadherins in the neoplastic progression of melanocytic tumours but few reports describe the expression of cadherins and the related transmembrane proteins, catenins, in a full range of benign and malignant excised melanocytic tumours. METHODS: Using immunohistochemistry and western blotting after tissue fractionation, the pattern of expression of cadherins/catenins was studied in a range of surgically excised melanocytic tumours, from dysplastic naevi to stage III cutaneous metastatic malignant melanoma. RESULTS: Appropriate membranous expression of E-cadherins and P-cadherins is seen in dysplastic naevocytes with an epithelioid phenotype and is largely maintained with malignant transformation to radial growth phase melanoma and primary vertical growth phase malignant melanoma. Loss of membranous E-cadherin is seen in a small number of vertical growth phase melanomas only when metastasis has occurred. However, there is a concomitant dramatic loss of membranous P-cadherin expression in all melanomas at the same stage. A minority of metastatic melanomas show de novo membranous N-cadherin expression in comparison with dysplastic naevi and primary melanoma. Membranous expression of the desmosomal cadherin, desmoglein, was not seen in any tumour studied. Frequently, beta catenin is aberrantly produced in the cytoplasm of cells in dysplastic naevi and metastatic malignant melanoma, with an implied compromise to adhesive function. Furthermore, membranous gamma catenin expression was not seen in any of the 70 melanocytic tumours studied, implying obligatory transmembrane binding of cadherins to beta catenin for maintenance of adhesive function. CONCLUSIONS: The most important alterations in membranous cadherin and catenin expression are seen late in the biological progression of melanocytic tumours at the stage of "in transit" or regional lymph node metastasis, with implications for tumour growth, invasion, and dissemination.

Blotting, Western↗
PubMed1996

Does palpability of primary cutaneous melanoma predict dermal invasion?

BACKGROUND: Relatively few studies have addressed the question of whether clinical estimation of melanoma thickness by palpation can accurately predict its histologic thickness. If palpability was a reliable predictor of dermal invasion, it could be used to define the surgical margin. OBJECTIVE: We sought to determine whether clinical elevation of melanoma could be used to predict the presence or absence and the degree of dermal invasion in patients with stage 1 cutaneous melanoma. METHODS: Melanomas in 165 patients were categorized by one observer as flat, just palpable, palpable, or nodular. This was compared with histologic measurements of tumor thickness. RESULTS: Overall there was significant correlation between the degree of palpability of melanoma and the presence or absence of dermal invasion (p<0.001), Breslow thickness (p<0.0001), and Clark level (p<0.001). However, the relation between palpability and Breslow thickness for invasive melanomas less than 1 mm thick was weaker (n=62, p=0.053), and the correlation between elevation and Clark level was not significant for invasive melanomas less than 4 mm thick (n=111, p>0.999). CONCLUSION: We conclude that palpability of melanoma is an inadequate guide to the presence or absence and degree of dermal invasion in melanomas less than 1 mm thick and cannot be used to determine the surgical margin.

Adolescent↗
PubMed1995

Thalidomide-induced neuropathy and genetic differences in drug metabolism.

A pharmacogenetic predisposition to thalidomide-induced neuropathy has been investigated. Differences of drug metabolism were examined in 16 patients with severe orogenital ulceration, who were treated with thalidomide (< or = 200 mg/day) for 0.3-5.0 years. Eight had evidence of early peripheral neuropathy according to nerve conduction studies. Rates of C-hydroxylation, N-acetylation, and conjugation reactions with sulphate, glucuronide and glycine, were tested with the probe compounds debrisoquine, sulphadimidine, paracetamol and aspirin, respectively. Urinary drug metabolites were analysed by high pressure liquid chromatography. Results were compared with 16 healthy age- and sex-matched volunteers. Of the patients 6.25% and 13.3% of the controls had a poor Debrisoquine Hydroxylator Ratio (DMR); none of the patients with neuropathy had a poor DMR as compared to 12.5% without neuropathy. Of the patients 40.0% and 35.7% of the controls were slow acetylators; 28.6% with neuropathy were slow acetylators as opposed to 50% without neuropathy. Similarly, there were no significant differences in rates of conjugation between groups. All unaffected patients were active smokers, whereas only two of those with neuropathy smoked. Cumulative dose or duration of therapy were unrelated to risk of neuropathy. In conclusion, changes of nerve conductivity are a frequent and unpredictable adverse effect of thalidomide (< or = 200 mg/day), although smoking may have a protective action against their development. Nerve conduction studies are required before and during treatment, irrespective of the prescribed dose.

Acetylation↗
PubMed1995

Urticaria pigmentosa and acute lymphoblastic leukaemia.

Childhood urticaria pigmentosa is generally considered to have a good prognosis with the majority of cases undergoing spontaneous resolution. However, there have been a number of reports of haematological malignancies occurring in association with urticaria pigmentosa. We describe a child with extensive urticaria pigmentosa and a congenital cardiac anomaly who developed acute lymphoblastic leukaemia and suggest a possible common aetiology.

Heart Ventricles↗
PubMed1994

Classification of CEA-related positivity in primary and metastatic malignant melanoma.

Using a panel of antibodies to carcinoembryonic antigen (CEA), in paraffin-processed biopsy material patchy, predominantly membranous positivity was seen on tumour cells in 70 per cent of cases of superficial spreading melanoma, 60 per cent of nodular melanomas, and 75 per cent of secondary deposits studied with unabsorbed polyclonal anti-CEA only. No staining was seen using monoclonal anti-CEAs. Localization of CEA to the cell membrane was confirmed with confocal microscopy. Immunoblotting of fresh frozen material detected CEA of around 180 kD in both primary and metastatic melanomas migrating with an apparent molecular weight of between 150 and 200 kD, indicating variable glycosylation of the protein. Recognition of an adhesive role for CEA with roles in immunolocalization and immunotherapy emphasizes the importance of more precise classification of CEA-related positivity in human tumours.

Carcinoembryonic Antigen↗