More people are living with and beyond a cancer diagnosis. There is limited understanding of the long-term effects of cancer and cancer treatment on quality of life and personal and household ...finances when compared to people without cancer. In a separate protocol we have proposed to link de-identified data from electronic primary care and hospital records for a large population of cancer survivors and matched controls. In this current protocol, we propose the linkage of Patient Reported Outcomes Measures data to the above data for a subset of this population. The aim of this study is to investigate the full impact of living with and beyond a cancer diagnosis compared to age and gender matched controls. A secondary aim is to test the feasibility of the collection of Patient Reported Outcomes Measures (PROMS) data and the linkage procedures of the PROMs data to electronic health records data.
This is a cross-sectional study, aiming to recruit participants treated at the Leeds Teaching Hospitals National Health Service Trust. Eligible patients will be cancer survivors at around 5 years post-diagnosis (breast, colorectal and ovarian cancer) and non-cancer patient matched controls attending dermatology out-patient clinics. They will be identified by running a query on the Leeds Teaching Hospitals Trust patient records system. Approximately 6000 patients (2000 cases and 4000 controls) will be invited to participate via post. Participants will be invited to complete PROMs assessing factors such as quality of life and finances, which can be completed on paper or online (surveys includes established instruments, and bespoke instruments (demographics, financial costs). This PROMs data will then be linked to routinely collected de-identified data from patient's electronic primary care and hospital records.
This innovative work aims to create a truly 'comprehensive patient record' to provide a broad picture of what happens to cancer patients across their cancer pathway, and the long-term impact of cancer treatment. Comparisons can be made between the cases and controls, to identify the aspects of life that has had the greatest impact following a cancer diagnosis. The feasibility of linking PROMs data to electronic health records can also be assessed. This work can inform future support offered to people living with and beyond a cancer diagnosis, clinical practice, and future research methodologies.
Prognosis in patients with sentinel node (SN)-positive melanoma correlates with several characteristics of the metastases in the SN such as size and site. These factors reflect biologic behavior and ...may separate out patients who may or may not need additional locoregional and/or systemic therapy.
Between 1993 and 2008, 1,080 patients (509 women and 571 men) were diagnosed with tumor burden in the SN in nine European Organisation for Research and Treatment of Cancer (EORTC) melanoma group centers. In total, 1,009 patients (93%) underwent completion lymph node dissection (CLND). Median Breslow thickness was 3.00 mm. The median follow-up time was 37 months. Tumor load and tumor site were reclassified in all nodes by the Rotterdam criteria for size and in 88% by the Dewar criteria for topography.
Patients with submicrometastases (< 0.1 mm in diameter) were shown to have an estimated 5-year overall survival rate of 91% and a low nonsentinel node (NSN) positivity rate of 9%. This is comparable to the rate in SN-negative patients. The strongest predictive parameter for NSN positivity and prognostic parameter for survival was the Rotterdam-Dewar Combined (RDC) criteria. Patients with submicrometastases that were present in the subcapsular area only, had an NSN positivity rate of 2% and an estimated 5- and 10-year melanoma-specific survival (MSS) of 95%.
Patients with metastases < 0.1 mm, especially when present in the subcapsular area only, may be overtreated by a routine CLND and have an MSS that is indistinguishable from that of SN-negative patients. Thus the RDC criteria provide a rational basis for decision making in the absence of conclusions provided by randomized controlled trials.
Background. Sulfites are in widespread use as preservatives/antioxidants. There is increasing recognition of allergic contact dermatitis caused by sodium metabisulfite; however, contact allergy to ...sodium sulfite is less well recognized.
Objectives. We sought to establish the prevalence of positive patch test reactions to sodium sulfite in our patient population and investigate its relationship with sodium metabisulfite.
Methods. Over a 4‐month period, 183 patients referred for patch testing were tested with sodium sulfite 1% pet. in addition to sodium metabisulfite 1% pet., which already forms part of our baseline series.
Results. Positive allergic reactions occurred to sodium metabisulfite in 5.5% of the tested patients and to sodium sulfite in 3.8% of the tested patients. Sixty per cent of patients with a positive reaction to sodium metabisulfite were positive to sodium sulfite. Only 1 patient (0.6%) with a negative reaction to sodium metabisulfite showed a positive reaction to sodium sulfite.
Conclusions. This study shows that the majority of patients with positive reactions to sodium metabisulfite are also positive to sodium sulphite. Routinely patch testing with sodium sulfite is probably unnecessary, as most patients with positive reactions will also react to sodium metabisulfite. Clinicians should consider advising patients to avoid sodium sulfite and other sulfites when a positive allergic reaction to sodium metabisulfite occurs.
Gene expression studies in melanoma have been few because tumors are small and cryopreservation is rarely possible. The purpose of this study was to evaluate the Illumina DASL Array Human Cancer ...Panel for gene expression studies in formalin-fixed melanoma primary tumors and to identify prognostic biomarkers.
Primary tumors from two studies were sampled using a tissue microarray needle. Study 1: 254 tumors from a melanoma cohort recruited from 2000 to 2006. Study 2: 218 tumors from a case-control study of patients undergoing sentinel node biopsy.
RNA was obtained from 76% of blocks; 1.4% of samples failed analysis (transcripts from <250 of the 502 genes on the DASL chip detected). Increasing age of the block and increased melanin in the tumor were associated with reduced number of genes detected. The gene whose expression was most differentially expressed in association with relapse-free survival in study 1 was osteopontin (SPP1; P = 2.11 x 10(-6)) and supportive evidence for this was obtained in study 2 used as a validation set (P = 0.006; unadjusted data). Osteopontin level in study 1 remained a significant predictor of relapse-free survival when data were adjusted for age, sex, tumor site, and histologic predictors of relapse. Genes whose expression correlated most strongly with osteopontin were PBX1, BIRC5 (survivin), and HLF.
Expression data were obtained from 74% of primary melanomas and provided confirmatory evidence that osteopontin expression is a prognostic biomarker. These results suggest that predictive biomarker studies may be possible using stored blocks from mature clinical trials.
Abstract ‘It needs sometimes, the eye of faith to recognize the narrow band of black which borders the inflamed part’. – Hutchinson J. Notes towards the formation of clinical group of tumors. Am J ...Med Sci 1886; 91: 470. This groundbreaking observation by Sir Jonathan Hutchinson in 1886, initially termed the ‘melanotic whitlow’, refers to pigmentation change in the nailfold, often accompanied by painful inflammation. Historically such lesions were considered traumatic; however, through careful clinical observation and meticulous documentation, Hutchinson recognized that this manifestation could be associated with malignancy. The melanotic whitlow later evolved into the eponymous Hutchinson sign, which we continue to use in today’s assessment of melanonychia. Sir Jonathan Hutchinson was born in 1882 in Selby, emerging from a modest background to become a pioneering figure in 19th-century medicine. He was a distinguished British surgeon and pathologist with an interest in dermatology, ophthalmology, neurology and the study of syphilis. More than a clinician, Hutchinson was a dedicated teacher, writer and philanthropist, actively sharpening medical education and research, with his medical bibliography consisting of over 1000 published reports. His work traversed a diverse range of medical domains, with numerous eponyms across various fields attributed to him. In dermatology, we commonly know him for Hutchinson freckle (lentigo maligna) and use Hutchinson sign to describe the periungual extension of a longitudinal pigmented band onto the nailfold, typically representing progression of subungual melanoma. Although it remains a crucial diagnostic marker of subungual melanoma, our understanding of this phenomenon and our ability to detect it have evolved over the last century. Over time the term ‘pseudo-Hutchinson sign’ has been coined as a mimic of Hutchinson sign due to the reflection of pigmentation of the nailbed and nail matrix through a transparent nailfold. This is seen in nonmelanoma conditions such as Bowen disease, ethnic melanonychia, nail naevi, subungual haematoma, Peutz–Jeghers or Laugier–Hunziker syndrome, and other inflammatory pathologies. Further evolution of this eponym can also be attributed to the advent of dermoscopy. The aptly named micro-Hutchinson sign, describes the dermoscopic detection of subtle cuticular pigmentation, often elusive to conventional naked-eye examination, and is thought to be indicative of malignancy. Hutchinson’s detailed description of the melanotic whitlow has contributed significantly to our assessment of nail pigmentation and melanoma. From his first description of the ‘narrow band of black’ to Hutchinson sign, we now have three variations of this eponymous term, used widely by modern-day dermatologists and aiding in the analysis of melanonychia.
To use gene expression profiling of formalin-fixed primary melanoma samples to detect expression patterns that are predictive of relapse and response to chemotherapy.
Gene expression profiles were ...identified in samples from two studies (472 tumors). Gene expression data for 502 cancer-related genes from these studies were combined for analysis.
Increased expression of DNA repair genes most strongly predicted relapse and was associated with thicker tumors. Increased expression of RAD51 was the most predictive of relapse-free survival in unadjusted analysis (hazard ratio, 2.98; P = 8.80 × 10(-6)). RAD52 (hazard ratio, 4.73; P = 0.0004) and TOP2A (hazard ratio, 3.06; P = 0.009) were independent predictors of relapse-free survival in multivariable analysis. These associations persisted when the analysis was further adjusted for demographic and histologic features of prognostic importance (RAD52 P = 0.01; TOP2A P = 0.02). Using principal component analysis, expression of DNA repair genes was summarized into one variable. Genes whose expression correlated with this variable were predominantly associated with the cell cycle and DNA repair. In 42 patients treated with chemotherapy, DNA repair gene expression was greater in tumors from patients who progressed on treatment. Further data supportive of a role for increased expression of DNA repair genes as predictive biomarkers are reported, which were generated using multiplex PCR.
Overexpression of DNA repair genes (predominantly those involved in double-strand break repair) was associated with relapse. These data support the hypothesis that melanoma progression requires maintenance of genetic stability and give insight into mechanisms of melanoma drug resistance and potential therapies.
Abstract A 3-year-old boy with type IV skin presented in May 2021 with a 5-month history of a pigmented line in his right fourth fingernail. Examination revealed a 1-mm uniform darkly pigmented band ...(1.2 mm at proximal aspect) of triangular longitudinal melanonychia with positive pseudo-Hutchinson and negative Hutchinson sign. A clinical diagnosis of benign subungual naevus was made. The patient had a background of neurofibromatosis type 1 and ganglioglioma of the brainstem and right cerebellar peduncle treated with chemotherapy. First- and second-line regimens – vincristine plus carboplatin in 2019–2020, and TPCV (thioguanine, procarbazine, lomustine and vincristine) in 2020 to April 2021 – had been trialled unsuccessfully before dermatology review. In October 2021, the patient commenced trametinib 0.5 mg once daily for his progressive ganglioglioma. Within 4 months, the longitudinal melanonychia had involuted significantly. Dermoscopy demonstrated faded melanonychia with a small residual blueish linear pigmentation remaining proximally (reduced to 0.8 mm). Pseudo-Hutchinson sign was now negative. The patient’s trametinib was discontinued for around 10 days in July 2022 due to mucositis and sepsis and his melanonychia subsequently darkened and extended further distally over the following 3 months. In November 2022 his trametinib dose was decreased to 0.37 mg due to ongoing mucositis and infection. However, the dark band was not as pronounced as at the initial presentation. He remained on the reduced trametinib dose, and by January 2024 the melanonychia had faded and appeared as a 1-mm uniform pale-brown longitudinal streak. He also developed multiple new naevi on his face, trunk, buttocks and genital area during this period. Trametinib, a mitogen-activated protein kinase kinase (MEK) inhibitor, has been used in targeted therapies against various malignancies, including in combination with BRAF inhibitors against metastatic melanoma. A lesser-reported complication of targeted therapies includes ‘lightening’ of pigmented naevi. Hypopigmentation, or involution or regression has been reported in patients receiving single-agent BRAF inhibitor or combined BRAF–MEK therapy. However, ours is the first reported case of a single-agent MEK inhibitor causing regression of a subungual naevus as a side-effect. The mechanism behind naevus involution in patients receiving targeted therapy is unclear, with proposed models focusing on the impact of BRAF rather than MEK inhibition. This case highlights a stark temporal relationship between trametinib therapy and the involution and subsequent redevelopment of a benign longitudinal melanonychia. This adds to our growing understanding of the impact of targeted therapies on melanocytic naevi, which patients and doctors should be aware of.
Abstract Mole mapping is an effective way to facilitate the early detection of melanoma in high-risk patients with multiple and/or atypical naevi. Current UK guidance recommends baseline photography ...(preferably dermoscopic) and clinical review for monitoring National Institute for Health and Care Excellence. Assessing melanoma. Available at: https://www.nice.org.uk/guidance/ng14/chapter/Recommendations#assessingmelanoma (last accessed 20 March 2024). Our aim was to evaluate the use of a mole-mapping device with artificial intelligence (AI) in our National Health Service specialist pigmented lesion clinic and to compare this to standard medical photography. We carried out a pilot in January 2023 comparing our current photography software, Medical Image Manager (MIM), to the Canfield IntelliStudio Gen3 with DermaGraphix® (Canfield Imaging Systems, Fairfield, NJ, USA). The IntelliStudio combines a semiautomated photoacquisition system with mole-tracking software, allowing linked comparison of two-dimensional macro and dermoscopic images. The software flags new or changed lesions, and AI known as DExI version 1.0 (Dermatology Explained Intelligence) risk stratifies lesions as low or high risk for malignancy. The technology was assessed on its efficiency of use, its ability to identify new or changed naevi, and the accuracy of DExI. Twelve patients with multiple and/or atypical naevi were recruited: seven had multiple visits and eight had images captured with both the IntelliStudio and standard photography by the clinical photography team. On average DermaGraphix® was 5.4 times faster (P = 0.03) and needed 54% fewer clicks per lesion (P = 0.02) compared with MIM to assess all marked naevi, macro and dermoscopically. Consultants identified lesions for dermoscopy ranging from 2 to 32 per patient (mean 11.9). The number of lesions per patient identified by DermaGraphix® ranged from 152 to 2721 (mean 700) and naevi counts ranged from 45 to 749 (mean 255). The software flagged a few new and changed lesions in most patients with follow-up images. The toggle function allowed these to be rapidly identified as either benign inflammatory lesions or false positives, mainly attributable to variable body positioning and artefacts such as clothing. DExI identified 13 lesions as high risk for malignancy, 5 of which scored as low risk on another visit. These lesions were reviewed by dermatologists; all were clinically stable and benign. In conclusion, the IntelliStudio was considered a time-efficient and user-friendly system. A key benefit is the linking of dermoscopic images to the body map using automated markerless tracking, viewed on a single-page dashboard. Specialists can rapidly compare sequential images using the toggle function. Although this pilot suggests that DExI is not yet clinically reliable, a newer version is now available. We conclude that the IntelliStudio is a superior mole-mapping system compared with MIM for monitoring high-risk patients in a tertiary pigmented lesion clinic.
Abstract A 43-year-old man presented with a long-standing back lesion causing irritation and bleeding. A presumed pedunculated seborrhoeic keratosis was shave excised by his general practitioner; ...however, histology revealed a BRCA1-associated protein (BAP1)-inactivated melanocytoma (BIM) with melanoma transformation. Histologically, BIMs are identified by the presence of a dermally located expansile clone of epithelioid melanocytes, sometimes associated with a pre-existent conventional naevus. Clones have abundant amphophilic cytoplasm and nuclear polymorphism with distinct cell membranes. BAP1 immunohistochemistry showing loss of nuclear expression in altered melanocytes confirms the diagnosis. BIMs typically harbour a BRAF V600E mutation as the initial oncogenic driver, with subsequent biallelic loss of the BAP1 gene leading to BAP1 protein inactivation. They typically run a benign, indolent course, with no cases with distant metastasis previously reported. Our case had BAP1-inactivated clones with typical BIM morphology. However, there was also a dominant, aggressive, BAP1-inactivated subclone with 15 mitoses, Ki67 > 10%, ulceration, P16 loss and PRAME positivity. These features are unusual for BIMs and are considered high risk in conventional melanoma subtypes. Overlying this was a junctional component with focal architectural and cytological atypia, bordering on melanoma in situ. Next-generation sequencing showed an NRAS driver mutation. DNA methylation profiling showed more than three copy number variations: 8q12.1q24.3, 90.2-Mb gain; whole chromosome 9 loss; 9p21.3, 3-Mb biallelic loss including CDKN2A and CDKN2B (whole genes); and 11q22.3q25, 31.7-Mb loss. There was no significant family history, and germline BAP1 genetic testing was negative. The patient underwent narrow margin excision followed by wide local excision. Sentinel lymph node biopsy was not offered due to previous pulmonary emboli and obesity. After 11 months he reported persistent abdominal pain. Computed tomography showed widespread metastatic disease (right axillary lymph nodes, brain and liver). Lymph node biopsy revealed atypical naevoid to epithelioid cells with focal cytoplasmic pigmentation and mitotic activity lying within fibrous stroma. Immunohistochemistry demonstrated strong diffuse expression of SOX-10 and melan-A, with loss of BAP1 expression. We report the first case of BIM with melanoma transformation (malignant BAP1 inactivated tumour) resulting in stage IV melanoma. Our centre has identified four further lesions in three patients with similar histological presentation. Two patients with three lesions developed locoregional recurrence. Our cases demonstrate that not all BIMs run a benign to indolent course. Identifying high-risk features as seen in these cases will aid future risk stratification.
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