Background Anti-programmed cell death (PD)-1 therapy is emerging as the backbone of new standard of care immunotherapy for metastatic melanoma. Immune-related cutaneous events are observed in these ...patients. Objective We sought to describe cutaneous adverse events observed in patients with metastatic melanoma on anti-PD-1 therapy. Methods We reviewed the clinical and histologic information of all patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at Westmead Hospital, Sydney, Australia, from May 2012 to February 2015. Results Of the 82 patients included in the study, 34 had dermatology assessments. Forty (49%) developed a form of anti-PD-1-associated cutaneous adverse events. In all, 17% developed lichenoid reactions and eczema, and 15% developed vitiligo. An estimated 25% of patients were expected to develop their first lichenoid reactions within 8.3 months, and eczema and vitiligo within 10.3 months of therapy. These adverse events tend to appear together in patients on anti-PD-1 therapy. Limitations The study was from a single center and clinical information was reviewed retrospectively in patients not referred to dermatology. Conclusion Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo.
Background BRAF inhibitors (BRAFi) cause paradoxical activation of the MAPK pathway in keratinocytes resulting in cutaneous squamous cell carcinoma (cuSCC). Objective We sought to examine the ...clinical factors involved in BRAFi-induced cuSCC development. Methods We studied 134 patients with BRAF-mutant metastatic melanoma treated with a BRAFi at Westmead Hospital, Sydney, Australia. Details of cuSCC development and associations with melanoma clinicopathologic features and treatment outcome were examined. Results In all, 32 (24%) patients developed 110 cuSCC after commencing treatment. In all, 61 (55%) cuSCC developed within the first 3 months. Age was the only independent risk factor for cuSCC development. After 3 months of therapy 4% of patients younger than 40 years developed cuSCC compared with 33% who were older than 60 years, and the hazard ratio of developing a cuSCC increased by 1.7 (95% confidence interval 1.3-2.3) per decade ( P < .001). BRAFi cuSCC occurred more often in sun-protected areas (42%) compared with sporadic cuSCC (21%) ( P < .001). cuSCC was not associated with progression-free survival. Limitations The study was from a single center and patients were also at risk of sporadic cuSCC. Conclusion Most BRAFi-induced cuSCC develop within 3 months of BRAFi therapy. The only independent risk factor is increasing age. cuSCC may present in anatomical locations with low ultraviolet exposure such that thorough dermatologic assessment is required.
Thyroid cancer is the most common endocrine cancer, with papillary thyroid carcinoma (PTC) accounting for the majority of these cases. Cerebellar metastasis is rarely the presenting feature and ...confers poor prognosis. Genetic mutations in this setting are most commonly TERTp, in contrast to BRAFV600E in the majority of PTC. We report the case of an 82 year‐old male who presented with a symptomatic right cerebellar lesion and underwent surgical resection to demonstrate metastatic PTC. Extensive workup with computed tomography, neck ultrasound and FDG‐PET was suggestive of a left thyroid primary lesion, with FNA confirming PTC. However, total thyroidectomy demonstrated incidental microMTC (medullary thyroid microcarcinoma, defined as tumour <10mm) without any evidence of PTC, whereas the left level VI neck dissection demonstrated a 30mm nodule of PTC without identifiable normal thyroid or lymph node tissue.
Although PTC has overall good survival, brain metastasis is rare and confers poor prognosis. Incidental microMTC in thyroidectomy specimens for PTC is also rare, and there is lack of evidence to support routine RET mutation testing in these patients.
Paraneoplastic bullous pemphigoid is a rare paraneoplastic syndrome. Rash is pruritic, with erythematous eruption of large subepidermal bullae over skin and often mucosal surfaces. We present an 84y ...woman with a three week history of erythematous rash, and 48hrs of bullae. A left clear cell renal cell carcinoma was identified on CT imaging during the presentation. Subsequent removal of the tumour resulted in resolution of bullous pemphigoid symptoms. This first-of-kind case and successful result strengthens the association between renal cell carcinoma and paraneoplastic bullous pemphigoid, arguing for a high degree of clinical suspicion in unexplained presentations of bullous pemphigoid.
This letter presents a 16-kb antifuse macro in a 5-nm high-K, metal-gate FinFET CMOS for the first time. Bootstrap high-voltage scheme (BHVS), read endpoint detection (REPD), and pseudodifferential ...sensing (PDS) are proposed to lower intrinsic bit error rate (BER) below 1 ppm for in-field programming and achieve ten years of data retention at 125 °C.
Background: Telepathology can potentially be utilized as an alternative to having on-site pathology services for rural and regional hospitals. The goal of the study was to validate two ...small-footprint desktop telepathology systems for remote parathyroid frozen sections. Subjects and Methods: Three pathologists retrospectively diagnosed 76 parathyroidectomy frozen sections of 52 patients from three pathology services in Australia using the “live-view mode” of MikroScan D2 and Aperio LV1 and in-house direct microscopy. The final paraffin section diagnosis served as the “gold standard” for accuracy evaluation. Concordance rates of the telepathology systems with direct microscopy, inter-pathologist and intra-pathologist agreement, and the time taken to report each slide were analyzed. Results: Both telepathology systems showed high diagnostic accuracy (>99%) and high concordance (>99%) with direct microscopy. High inter-pathologist agreement for telepathology systems was demonstrated by overall kappa values of 0.92 for Aperio LV1 and 0.85 for MikroScan D2. High kappa values (from 0.85 to 1) for intra-pathologist agreement within the three systems were also observed. The time taken per slide by Aperio LV1 and MicroScan D2 within three pathologists was about 3.0 times (P < 0.001, 95% confidence interval CI: 2.8-3.2) and 7.7 times (P < 0.001, 95% CI: 7.1-8.3) as long as direct microscopy, respectively, while MikroScan D2 took about 2.6 times as long as Aperio LV1 (P < 0.001, 95% CI: 2.4-2.7). All pathologists evaluated Aperio LV1 as being more user-friendly. Conclusions: Telepathology diagnosis of parathyroidectomy frozen sections through small-footprint desktop systems is accurate, reliable, and comparable with in-house direct microscopy. Telepathology systems take longer than direct microscopy; however, the time taken is within clinically acceptable limits. Aperio LV1 takes shorter time than MikroScan D2 and is more user-friendly.
The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value.
To determine whether ...development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival.
A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1.
In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model.
Single-center study.
This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.
The innovative blockade of immune checkpoints with targeted immunotherapies, such as monoclonal antibodies against programmed cell death-1, is pioneering the treatment for advanced melanoma. ...Potential adverse events of particular interest associated with immunotherapy are of an inflammatory or immune-related nature. Reported dermatological side effects mostly comprise nonspecific rash and pruritus. This is a report of a 75-year-old man with metastatic melanoma who was initially administered pembrolizumab at 10 mg/kg every 3 weeks. He developed spongiotic dermatitis that was partially treated with topical steroids after cycle 3. Pembrolizumab cycles were stopped because of disease progression after cycle 6. On the 30-day follow-up, the patient presented with extensive erythematous papules and plaques, in addition to a few intact and ruptured vesicles and bullae over the upper and lower limbs, especially over the knees and elbows. Both punch skin biopsies (haematoxylin and eosin and direct immunofluorescence studies) confirmed a bullous pemphigoid diagnosis. He was treated with a tapering dose of oral prednisone, resulting in rapid clinical improvement after only a week of treatment, which was switched to dexamethasone following the diagnosis of new brain metastases.
We report a 77-year-old male with biopsy proven adnexal adenocarcinoma where there was only mass deposit of basement membrane material in the therapeutic excision. To our knowledge, this finding is ...extremely rare and has not been previously described in the literature and necessitates distinction from other conditions which cause eosinophilic hyaline deposits within the dermis.
There are reported cases of diphencyprone used in treating cutaneous metastases of melanoma. Here, we report a patient with previous primary melanoma on his left back treated with surgical excision ...and lymphadenectomy, followed by radiotherapy for the recurrent tumor on the primary site. Despite radiotherapy and treatment with dabrafenib and trametinib, in-transit metastases have developed and topical diphencyprone was applied to these metastases. Six weeks later, the patient developed fever and a spreading erythematous tender indurated plaque covering the left side of the body including axillae, back, and flank, clinically suggestive of cellulitis. Systemic antibiotic therapy did not improve the condition and a biopsy showed sparse lymphocytic infiltrate. With the diagnosis of possible acute lymphedema, a CT scan was requested that showed significant axillary lymph node metastasis. The fever was considered secondary to dabrafenib and trametinib therapy. This case highlights that, in patients with lymphadenectomy, atypical forms of lymphedema on the body may appear. Truncal lymphedema is an infrequent event.
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