Mouse-INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy.

Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS prognosis remains unclear. To address this gap, we developed an in vivo model, Mouse-INtraDuctal (MIND), in which patient-derived DCIS epithelial cells are injected intraductally and allowed to progress naturally in mice. Similar to human DCIS, the cancer cells formed in situ lesions inside the mouse mammary ducts and mimicked all histologic subtypes including micropapillary, papillary, cribriform, solid, and comedo. Among 37 patient samples injected into 202 xenografts, at median duration of 9 months, 20 samples (54%) injected into 95 xenografts showed in vivo invasive progression, while 17 (46%) samples injected into 107 xenografts remained non-invasive. Among the 20 samples that showed invasive progression, nine samples injected into 54 xenografts exhibited a mixed pattern in which some xenografts showed invasive progression while others remained non-invasive. Among the clinically relevant biomarkers, only elevated progesterone receptor expression in patient DCIS and the extent of in vivo growth in xenografts predicted an invasive outcome. The Tempus XT assay was used on 16 patient DCIS formalin-fixed, paraffin-embedded sections including eight DCISs that showed invasive progression, five DCISs that remained non-invasive, and three DCISs that showed a mixed pattern in the xenografts. Analysis of the frequency of cancer-related pathogenic mutations among the groups showed no significant differences (KW: p > 0.05). There were also no differences in the frequency of high, moderate, or low severity mutations (KW; p > 0.05). These results suggest that genetic changes in the DCIS are not the primary driver for the development of invasive disease. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Nail-patella syndrome: "nailing" the diagnosis in three generations.

Nail-patella syndrome (NPS) is a hereditary disorder characterized by fingernail changes, elbow dysplasia, hypoplastic patellae, and presence of iliac horns. Clinical presentation can be subtle, and the spectrum of presentation often makes NPS a challenging diagnosis. Herein, we describe three family members with nail-patella syndrome who presented with different features and varying severity. The opportunity to recognize this rare syndrome in three linear generations provided a unique insight into NPS, and a moment to appreciate the random and unpredictable clinical presentation.

Porokeratosis ptychotropica: a rare variant that is commonly misdiagnosed.

Porokeratosis ptychotropica (PP) is a rare variant of porokeratosis characterized by pruritic, scaly papules and plaques localized to the perianal and gluteal cleft regions. Clinically, PP resembles other common disorders, resulting in frequent misdiagnosis. The diagnosis of PP often takes several years to make, therefore many reported cases in the literature described the late stages of PP. We report a case of PP diagnosed at an early stage. By presenting our patient, we aim to raise further awareness of PP to avoid a delay in diagnosis, thus preventing long term complications of this rare entity.

The use of virtual reality in non-burn dermatological care - a review of the literature.

AIM: Virtual Reality (VR) is the artificial depiction of a three-dimensional (3D) environment using computer-generated technology which allows users to interact with a simulated setting. VR has been used in a variety of clinical scenarios due to its efficacy as a distraction intervention, reducing anxiety and pain associated with medical procedures. The aim of this review is to provide clinicians with an overview of VR use in clinical dermatology. METHODS: A search on VR use in clinical dermatology was conducted using PubMed Medline, Embase, Cochrane, Google Scholar and ClinicalTrials.Gov in July 2019. Results related to burn care were excluded. RESULTS: This review identifies studies that utilized VR in the management of skin diseases and discusses considerations for its future use. CONCLUSION: The findings of these studies indicate that VR has beneficial effects as a complementary tool in the treatment of dermatological conditions.

Leclercia adecarboxylata catheter-related bacteraemia in an immunocompromised patient.

A 34-year-old man on active chemotherapy was hospitalised with fever, chills and rigours after power-washing a pig pen on a farm. His blood cultures grew Leclercia adecarboxylata, a gram-negative rod in the Enterobacteriaceae family, which has been isolated from a variety of environments including soil, surface water, as well as in the gastrointestinal flora of farm animals. The likely source of infection was his tunnelled central venous catheter exposed to water contaminated by faeces when he was washing the pig pen. While there have been several cases reported of catheter-related L. adecarboxylata bacteraemia, to our knowledge there are very few reports of infection spread in this manner.

BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression.

The molecular processes by which some human ductal carcinoma in situ (DCIS) lesions advance to the more aggressive form, while others remain indolent, are largely unknown. Experiments utilizing a patient-derived (PDX) DCIS Mouse INtraDuctal (MIND) animal model combined with ChIP-exo and RNA sequencing revealed that the formation of protein complexes between B Cell Lymphoma-9 (BCL9), phosphoserine 727 STAT3 (PS-727-STAT3) and non-STAT3 transcription factors on chromatin enhancers lead to subsequent transcription of key drivers of DCIS malignancy. Downregulation of two such targets, integrin ß3 and its associated metalloproteinase, MMP16, resulted in a significant inhibition of DCIS invasive progression. Finally, in vivo targeting of BCL9, using rosemary extract, resulted in significant inhibition of DCIS malignancy in both cell line and PDX DCIS MIND animal models. As such, our studies provide compelling evidence for future testing of rosemary extract as a chemopreventive agent in breast cancer.