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Histopathology is the reference standard for diagnosing the presence and nature of many diseases, including cancer. However, analyzing tissue samples under a microscope and summarizing the findings in a comprehensive pathology report is time-consuming, labor-intensive, and non-standardized. To address this problem, we present HistoGPT, a vision language model that generates pathology reports from a patient’s multiple full-resolution histology images. It is trained on 15,129 whole slide images from 6705 dermatology patients with corresponding pathology reports. The generated reports match the quality of human-written reports for common and homogeneous malignancies, as confirmed by natural language processing metrics and domain expert analysis. We evaluate HistoGPT in an international, multi-center clinical study and show that it can accurately predict tumor subtypes, tumor thickness, and tumor margins in a zero-shot fashion. Our model demonstrates the potential of artificial intelligence to assist pathologists in evaluating, reporting, and understanding routine dermatopathology cases. Machine learning models represent an opportunity for the automatic generation of histopathology reports. Here, the authors develop HistoGPT, a vision language model that can generate reports from multiple gigapixel-sized whole slide images and also predict tumour thickness, subtypes, and margins, among other diseases.

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Therefore, five biopsies from four patients were analyzed histologically, immunohistochemically with anti-Vaccinia virus antibodies, and electron-microscopically. Notably, the early macular stage only showed subtle viropathic changes; it did not express of Orthopoxvirus proteins in immunohistochemistry and therefore can easily be missed histologically. In later stages, immunohistochemistry with anti-Vaccinia virus antibodies might be useful to distinguish mpox from differential diagnoses such as herpes virus infections. In the ulcerative stages, the identified occlusive vasculopathic changes could be an explanation for the severe pain of the lesions reported by some patients. Despite the small number of samples examined, our analysis suggests that the histological findings of mpox are highly dependent on the stage of the biopsied lesion. Therefore, knowledge of all different stages of histology is necessary to reliably diagnose mpox histologically, especially when molecular testing is not available.

A 43‐year‐old patient from Liberia presented with itching scaly plaques, impaired quality of life persisting for 9 months and intermittent joint pain in the knees. Personal and family history was unremarkable. Coexisting diagnoses included type 1 diabetes mellitus and liver cirrhosis due to chronic hepatitis B and D. The patient reported ongoing use of Tenofovir, Propranolol, Glargine and Aspart. Clinical examination showed disseminated brownish, partly confluent hyperkeratotic plaques distributed throughout the integument in a Fitzpatrick skin type V. A skin biopsy revealed histologically a psoriasiform dermatitis. Laboratory findings included lymphocytopenia and elevated liver values. Hepatitis B serology confirmed chronic hepatitis B. Considering the clinical and histopathological findings Psoriasis vulgaris was diagnosed and psoriatic arthritis was ruled out by a rheumatologist. After consulting with the hepatologist, systemic therapy with Apremilast was initiated. Despite an initial positive response, gastrointestinal side effects led to a switch to therapy with Tildrakizumab, with regular monitoring of transaminases and HBV DNA. Despite an initial positive treatment response, a secondary loss of efficacy occurred prompting a switch to Risankizumab. Psoriasis is a chronic inflammatory systemic disease significantly impacting quality of life, necessitating optimal long‐term management. In this case, therapy with Apremilast and biologic therapy targeting IL‐23 blockade, even with concurrent hepatitis B, was well tolerated and effective. However, the evidence on the safety of modern psoriasis therapies in known chronic infections remains limited. Noteworthy in this case report is the patient's dark skin type. Diagnosing inflammatory dermatoses in People of Colour is challenging due to less visible erythema and other clinical nuances, exacerbating the already poorer healthcare for People of Colour. This case aims to raise awareness about the need for increased representation of People of Colour in education, presentations and clinical trials to ensure better care for this patient population. A 43‐year‐old Liberian patient presented with itching scaly plaques and known hepatitis B and D. Histologically and clinically a Psoriasis vulgaris was diagnosed. The initial therapy with Apremilast was switched to Tildrakizumab due to side effects, and later to Risankizumab due to secondary loss of efficacy. Managing psoriasis in dark skin is challenging due to subtle clinical signs. This case highlights the need for better representation of People of Color in medical education and research for improved care.

Ultraviolet B (UVB) radiation induces mutagenic DNA photoproducts, in particular cyclobutane pyrimidine dimers (CPDs), in epidermal keratinocytes (KC). To prevent skin carcinogenesis, these DNA photoproducts must be removed by nucleotide excision repair (NER) or apoptosis. Here we report that the UVB-sensitive transcription factor aryl hydrocarbon receptor (AHR) attenuates the clearance of UVB-induced CPDs in human HaCaT KC and skin from SKH-1 hairless mice. Subsequent RNA interference and inhibitor studies in KC revealed that AHR specifically suppresses global genome but not transcription-coupled NER. In further experiments, we found that the accelerated repair of CPDs in AHR-compromised KC depended on a modulation of the p27 tumor suppressor protein. Accordingly, p27 protein levels were increased in AHR-silenced KC and skin biopsies from AHR −/− mice, and critical for the improvement of NER. Besides increasing NER activity, AHR inhibition was accompanied by an enhanced occurrence of DNA double-strand breaks triggering KC apoptosis at later time points after irradiation. The UVB-activated AHR thus acts as a negative regulator of both early defense systems against carcinogenesis, NER and apoptosis, implying that it exhibits tumorigenic functions in UVB-exposed skin. In fact, AHR −/− mice developed 50% less UVB-induced cutaneous squamous cell carcinomas in a chronic photocarcinogenesis study than their AHR +/+ littermates. Taken together, our data reveal that AHR influences DNA damage-dependent responses in UVB-irradiated KC and critically contributes to skin photocarcinogenesis in mice.

As in general pathology, digitalization is also inexorably making its way into dermatopathology. This article examines the current state of digitalization in German dermatopathology laboratories based on the authors' own experiences, the current study situation, and a survey of members of the Dermatological Histology Working Group (ADH). Experiences with the establishment of a digital laboratory workflow, artificial intelligence (AI)-based assistance systems, and whole slide images (WSI)-based training programs are discussed. Digitalization in dermatopathology is an opportunity to simplify and accelerate processes, but there are some hurdles to overcome.

ABSTRACTTherapeutic options of anogenital warts (AGW) at the urethral meatus are limited and often require effortful and time-consuming procedures under general anesthesia. Here, we present two cases of AGW at the urethral meatus, which we have successfully treated with low-dose topical ingenol mebutate-gel.

Ingenol mebutate (IM) is highly effective in the treatment of human papillomavirus (HPV)-induced anogenital warts (AGW) leading to fast ablation within hours. However, the exact mode of action is still largely unknown. We performed dermoscopy, in vivo confocal microscopy (CLM), histology, immunohistochemistry, and immunofluorescence to gain insights in mechanisms of IM treatment in AGW. In addition, we used in vitro assays (ELISA, HPV-transfection models) to further investigate in vivo findings. IM treatment leads to a strong recruitment of neutrophils with thrombosis of small skin vessels within 8 h, in a sense of immunothrombosis. In vivo and in vitro analyses showed that IM supports a prothrombotic environment by endothelial cell activation and von Willebrand factor (VWF) secretion, in addition to induction of neutrophil extracellular traps (NETosis). IM superinduces CXCL8/IL-8 expression in HPV-E6/E7 transfected HaCaT cells when compared to non-infected keratinocytes. Rapid ablation of warts after IM treatment can be well explained by the observed immunothrombosis. This new mechanism has so far only been observed in HPV-induced lesions and is completely different from the mechanisms we see in the treatment of transformed keratinocytes in actinic keratosis. Our initial findings indicate an HPV-specific effect, which could be also of interest for the treatment of other HPV-induced lesions. Larger studies are now needed to further investigate the potential of IM in different HPV tumors.

Background The coronavirus disease 2019 (COVID‐19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain‐like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear. Patients and methods 6821 employees and patients were vaccinated at our institutions between February and June 2021. Every patient received two doses of the mRNA-1273 vaccine in our hospitals, and reported back in case of any side effects which were collected in our hospital managed database. Results Eleven of 6821 vaccinated patients (0.16%) developed delayed skin reactions after either the first or second dose of the mRNA-1273 vaccine against SARS-CoV-2. Eight of 11 patients (73%) developed a rash after the first dose, while in 3/11 (27%), the rash occurred after the second dose. More females (9/11) were affected. Four of 11 patients required antihistamines, with two needing additional topical steroids. All the cutaneous manifestations resolved within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second dose. There were no long-term cutaneous sequelae in any of the affected individuals. Conclusion Our data suggests that skin reactions after the use of mRNA-1273 vaccine against SARS-CoV-2 are possible, but rare. Further studies need to be done to understand the pathophysiology of these lesions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Radiotherapy remains a mainstay of cancer treatment. However, radiotherapy can also elicit acute and chronic adverse effects, including dermal inflammation and skin fibrosis. A comprehensive understanding of the underlying fibrotic processes remains elusive, and currently, no established treatment options exist. Canonical Wnt signaling has emerged as a significant player in fibrotic conditions. The Dickkopf (DKK) protein family comprises key modulators of Wnt signaling. To define the function of DKK3 in radiation-induced skin damage, we combined complementary in vivo and in vitro approaches, including a 3D human skin model, mice with cell-type-specific Dkk3 deletions, and irradiated human skin specimens. Our study revealed the pivotal role of DKK3 in regulating the response of the skin to radiation, with diminished DKK3 significantly mitigating radiation-induced skin damage. We found that radiation increases DKK3 expression in basal keratinocytes, leading to elevated ROS levels, TGF-β-mediated Wnt activation, epidermal hyperplasia, and subsequent skin fibrosis. Increased keratinocyte expression of DKK3 also drives macrophage polarization toward a CD163 high CD206 high profibrotic M2 phenotype, activating myofibroblasts and leading to fibrosis. Notably, DKK3 deficiency in keratinocytes markedly reduces radiation-induced dermal hyperplasia and fibrosis, identifying DKK3 as a key regulator of cutaneous radiation responses. These findings position DKK3 as a promising upstream modulator of TGF-β signaling for mitigating radiation-induced dermatitis and fibrosis, with potential relevance to other fibrotic diseases.