Focus Issue on Squamous Cell Carcinoma: Practical Concerns Regarding the 7th Edition AJCC Staging Guidelines

The 7th edition of the AJCC Cancer Staging Manual represents a dramatic shift in the way that cutaneous squamous cell carcinoma (cSCC) is staged, in that it is first attempt to incorporate evidence-based medicine into the staging guidelines for cSCC. In our opinion, the changes made to the seventh edition represent a significant improvement over previous editions and will ultimately lead to improved patient stratification, more accurate prognostic data, and a better framework to guide clinical decision making. However, there are a number of issues within the latest guidelines that require clarification or are impractical for clinical practice. The purpose of this paper is to highlight the key changes to the 6th edition staging manual as they pertain to cSCC, to point out impractical component of the 7th edition and/or aspects that require further clarification, and to make recommendations that address any current shortcomings to improve subsequent editions. Specific focus will be given to the inclusion of separate guidelines for cSCC and Merkel cell carcinoma (MCC), the incorporation of high-risk factors as modifiers of T stage, the addition of new guidelines for advanced T stage, and the changes in stratification of lymph node status. This paper is modified from a more comprehensive treatment of the staging of nonmelanoma skin cancer by Warner and Cockerell entitled “The new 7th edition American joint committee on cancer staging of cutaneous nonmelanoma skin cancer: a critical review,” in the American Journal of Clinical Dermatology (paper accepted, pending publication)

Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload.

Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system\u27s use of deep-learning-based confidence scoring as a criterion to consider the result as accurate yields an accuracy of up to 98%, and makes it adoptable in a real-world setting. Without confidence scoring, the system achieved an accuracy of 78%. We anticipate that our deep learning system will serve as a foundation enabling faster diagnosis of skin cancer, identification of cases for specialist review, and targeted diagnostic classifications

Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses

ABSTRACT Background: Human Polyomavirus 6 (HPyV6) and Human Polyomavirus 7 (HPyV7) are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. Objective: We determined whether biopsies showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. Methods: We screened biopsies showing "peacock plumage" histology by PCR for human polyomaviruses. Cases positive for HPyV 6 or 7 were then analyzed by immunohistochemistry, electron microscopy (EM), immunofluorescence, quantitative PCR, and complete sequencing, including unbiased, next generation sequencing (NGS). Results: We identified three additional cases of HPyV6 or 7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared to normal skin and the identification of intact virions by both EM and NGS support a role for active viral infections in these skin diseases. Limitation: This was a small case-series of archived materials. Conclusion: We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a unique histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatosis (H6PD and H7PD).

Hyptiogastrites electrinus Cockerell, 1917, from Myanmar (Burmese) amber: Redescription and its placement within the Evanioidea (Insecta: Hymenoptera)

© The Natural History MuseumThe wasp Hyptiogastrites electrinus Cockerell, 1917, from the Lower Cretaceous (Upper Albian) Myanmar (Burmese) amber is redescribed from the well-preserved holotype and its relationship with extant Aulacidae and Gasteruptiidae (Hymenoptera: Evanioidea) evaluated. Although the wing venation is identical to the majority of extant Hyptiogastrinae (Gasteruptiidae), phylogenetic analysis places H. electrinus as sister taxon to the Aulacidae s.str., (i.e. Aulacus + Pristaulacus). Thus, Hyptiogastrinae is confirmed as having a restricted Southern Hemisphere distribution (i.e. Australasia and South America). Consistent with this result, H. electrinus is included within a slightly more broadly defined Aulacidae rather than being placed in a new monotypic family. Characters that align this species with the Aulacidae include: having small circular eyes, percurrent Y-shaped notauli, pyramidal shape of the propodeum and the presence of a groove or ovipositor guide on the hind coxae.John T. Jennings, Andrew D. Austin and Nicholas B. Steven

Coleoptera and Arachnida from Florissant, Col.

p. 617-621 ; 24 cm

Primary care incidence and treatment of four neuropathic pain conditions: A descriptive study, 2002–2005

<p>Abstract</p> <p>Background</p> <p>Between 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain.</p> <p>Methods</p> <p>A descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia (n = 1,923); trigeminal neuralgia (1,862); phantom limb pain (57) and painful diabetic neuropathy (1,444) using computerised UK general practice records (THIN): May 2002 to July 2005.</p> <p>Results</p> <p>Primary care incidences per 100,000 person years observation of 28 (95% confidence interval (CI) 27–30) for post-herpetic neuralgia, 27 (95%CI 26–29) for trigeminal neuralgia, 0.8 (95%CI 0.6–1.1) for phantom limb pain and 21 (95%CI 20–22) for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants (post-herpetic neuralgia) or antiepileptics (trigeminal neuralgia and painful diabetic neuropathy) and opioid analgesics (phantom limb pain). The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain.</p> <p>Conclusion</p> <p>The incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached.</p

Phylogenomic analyses of the genus Drosophila reveals genomic signals of climate adaptation

Many Drosophila species differ widely in their distributions and climate niches, making them excellent subjects for evolutionary genomic studies. Here, we have developed a database of high-quality assemblies for 46 Drosophila species and one closely related Zaprionus. Fifteen of the genomes were newly sequenced, and 20 were improved with additional sequencing. New or improved annotations were generated for all 47 species, assisted by new transcriptomes for 19. Phylogenomic analyses of these data resolved several previously ambiguous relationships, especially in the melanogaster species group. However, it also revealed significant phylogenetic incongruence among genes, mainly in the form of incomplete lineage sorting in the subgenus Sophophora but also including asymmetric introgression in the subgenus Drosophila. Using the phylogeny as a framework and taking into account these incongruences, we then screened the data for genome-wide signals of adaptation to different climatic niches. First, phylostratigraphy revealed relatively high rates of recent novel gene gain in three temperate pseudoobscura and five desert-adapted cactophilic mulleri subgroup species. Second, we found differing ratios of nonsynonymous to synonymous substitutions in several hundred orthologues between climate generalists and specialists, with trends for significantly higher ratios for those in tropical and lower ratios for those in temperate-continental specialists respectively than those in the climate generalists. Finally, resequencing natural populations of 13 species revealed tropics-restricted species generally had smaller population sizes, lower genome diversity and more deleterious mutations than the more widespread species. We conclude that adaptation to different climates in the genus Drosophila has been associated with large-scale and multifaceted genomic changes