Search

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 WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Cutibacterium acnes (also known as Propionibacterium acnes) has long been implicated in the pathogenesis of acne, inspiring both therapeutic and personal care approaches aiming to control the disease by controlling the bacterium. The purported association has made people with acne feel dirty and led to the-at times excessive-use of cleansers, antiseptics and antibiotics for the condition. However, recent evidence seems to weaken the case for C. acnes' involvement. New genetics and molecular biology findings strongly suggest that abnormal differentiation of sebaceous progenitor cells causes comedones, the primary lesions in acne. Comodegenesis is initiated by androgens and is unlikely to be triggered by C. acnes, which probably doesn't affect sebaceous differentiation. Is there still a place for it in this understanding of acne? It is necessary to critically address this question because it has consequences for treatment. Antibiotic use for acne noticeably contributes to microbial drug resistance, which we can ill afford. In this Viewpoint, we explore if and how C. acnes (still) fits into the developing view on acne. We also briefly discuss the implications for therapy in the light of antibiotic resistance and the need for more targeted therapies. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) SMART Innovation Centre MvS is funded by the Biomedical Research Council (BMRC) A*STAR, BMRC-A*STAR-EDB IAF-PP for the Skin Research Institute of Singapore (H17/01/a0/004) and the Acne and Sebaceous Gland Program (H17/01/a0/008), and a SMART Innovation Grant. GBC is supported by the Innovation Centre and Antimicrobial Resistance IRG of the Singapore-MIT Alliance for Research and Technology Centre, supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) Program. He is also supported by a SMART Innovation Grant.

Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.

Folliculitis is an inflammatory process involving the hair follicle, frequently attributed to infectious causes. Malassezia, an established symbiotic yeast that can evolve to a skin pathogen with opportunistic attributes, is a common source of folliculitis, especially when intrinsic (e.g. immunosuppression) or extrinsic (high ambient temperature and humidity, clothing) impact on the hair follicle and the overlying skin microenvironment. Our aim was to critically review the pathophysiology and clinical characteristics of Malassezia folliculitis, to describe laboratory methods that facilitate diagnosis and to systematically review treatment options. Malassezia folliculitis manifests as a pruritic, follicular papulopustular eruption distributed on the upper trunk. It commonly affects young to middle-aged adults and immunosuppressed individuals. Inclusion into the differential diagnosis of folliculitis is regularly oversighted, and the prerequisite-targeted diagnostic procedures are not always performed. Sampling by tape stripping or comedo extractor and microscopic examination of the sample usually identifies the monopolar budding yeast cells of Malassezia without the presence of hyphae. However, confirmation of the diagnosis with anatomical association with the hair follicle is performed by biopsy. For systematic review of therapies, PubMed was searched using the search string "(malassezia" [MeSH Terms] OR "malassezia" [All Fields] OR pityrosporum [All Fields]) AND "folliculitis" [MeSH Terms] and EMBASE was searched using the search string: 'malassezia folliculitis.mp OR pityrosporum folliculitis.mp'. In total, 28 full-length studies were assessed for eligibility and 21 were selected for inclusion in therapy evaluation. Conclusively Malassezia folliculitis should be considered in the assessment of truncal, follicular skin lesions. Patient's history, comorbidities and clinical presentation are usually indicative, but microscopically and histological examination is needed to confirm the diagnosis. Adequate samples obtained with comedo extractor and serial sections in the histological material are critical for proper diagnosis. Therapy should include systemic or topical measures for the control of the inflammation, as well as the prevention of recurrences.

Aim To retrospectively assess the effectiveness and safety of BLES stereotactic biopsy of suspicious calcifications and investigate possible predictive factors for underestimation. Methods and materials Between January 2014 and January 2016, 400 biopsies of suspicious calcifications were performed in our Department using the BLES stereotactic device. The mean age of our population was 58.5 years (range 39-78 years). The final surgical results were used as gold standard. The effectiveness of the method was statistically evaluated. Mammographic size, grade, molecular type, and presence of comedo type/necrosis were assessed as predictive factors. Results 90/400 (22.5%) cases were cancers (20% invasive cancers, 80% non-invasive cancers). 38/400 cases were atypical lesions (9.5%). No underestimation was found in atypical lesions that underwent surgery (29/38 cases). Downgrade was achieved in 45.5% of cases (with complete removal in 34.4%), concordance in 43.3%, and upgrade was found in 15.5% of the cases; the initial mammographic size and the grade of the cancers were found to be statistically significant predictive factors. The total complication rate was 8.75%. Conclusions Breast lesion excision system is a highly accurate and safe stereotactic biopsy technique of suspicious calcifications with low underestimations and high downgrade/removal rates with the potential to alter the final surgical decision in selected cases.

A 20-year-old man presented with for 6-month history of facial acne. He had erythema and red papules on the face secondary to BPO-induced contact dermatitis. He was administered topical corticosteroid. Contact dermatitis improved with this treatment, and he had red papules, comedones, prominent postinflammatory hyperpigmentation (PIH), postinflammatory erythema (PIE), erosions and erythema associated with acne vulgaris. He was subsequently treated with oral minocycline 100 mg/d and topical adapalene and ozenoxacin lotion once daily for 3 months. The inflammatory lesions and comedo subsided; however, PIH, PIE, atrophic scar and erosion persisted. During 3 months, the patient underwent chemical peeling using 20% glycolic acid (GA) and subsequent vitamin C iontophoresis twice at 1-month intervals. He showed almost disappearance of red papules and comedones but persistent PIH, PIE and erosion after 3 months of treatment. He was thereafter prescribed topical glyceryl-octyl-ascorbic acid/ascorbyl 2-phosphate 6-palmitate/DL-a-tocopherol phosphate complex for local application twice daily for 3 months. After 7 months of treatment, PIH, PIE, erosion and atrophic scar faded significantly with only trace residual erosions, atrophic scar and PIH. Subsequently, he was prescribed local application of 2% isostearyl-L-ascorbic acid gel vitamin C gel twice daily for 3 months. After 15 months, PIH, PIE, erosion and atrophic scar disappeared completely with significant improvement. Comprehensive sequential therapy resulted in significant improvement. It is suggested that medical treatment using systemic and topical antimicrobials and topical adapalene reduces inflammatory lesions and comedones initially. Subsequent chemical peeling using GA and vitamin C iontophoresis could improve PIH. These synergistic effects might have contributed to the significant improvement observed in this case. Comprehensive sequential treatment using chemical peeling, vitamin C iontophoresis and topical vitamin C can be a useful treatment strategy for PIH in acne vulgaris.

BackgroundImpaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast cancer pathogenesis. This study aims to assess the role of FEN1 in breast ductal carcinoma in situ (DCIS).MethodsExpression of FEN1 protein was evaluated in a large (n = 1015) well-characterised cohort of DCIS, comprising pure (n = 776) and mixed (DCIS coexists with invasive breast cancer (IBC);n = 239) using immunohistochemistry (IHC).ResultsFEN1 high expression in DCIS was associated with aggressive and high-risk features including higher nuclear grade, larger tumour size, comedo type necrosis, hormonal receptors negativity, higher proliferation index and triple-negative phenotype. DCIS coexisting with invasive BC showed higher FEN1 nuclear expression compared to normal breast tissue and pure DCIS but revealed significantly lower expression when compared to the invasive component. However, FEN1 protein expression in DCIS was not an independent predictor of local recurrence-free interval.ConclusionHigh FEN1 expression is linked to features of aggressive tumour behaviour and may play a role in the direct progression of DCIS to invasive disease. Further studies are warranted to evaluate its mechanistic roles in DCIS progression and prognosis.

BACKGROUND Comedogenesis is defined as the process of the development of a new comedo, which is of great importance for the understanding of acne. OBJECTIVE To evaluate the formation and evolution of acne lesions from clinically unaffected skin of patients with mild-moderate acne to characterize the morphological changes and natural resolution by means of in vivo reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D-OCT). METHODS Ten patients with mild-moderate acne, not assuming any topical or systemic therapy, comprised between 12 and 30 years of age, were recruited. A target area of 4 × 4 mm of the face, without acne lesions at baseline, was selected. A set of standardized clinical pictures, RCM and D-OCT images were acquired weekly for 6 weeks and evaluated. RESULTS Seventy full sets of clinical, RCM and D-OCT images were analysed. The appearance of acne lesion is preceded by an increase of large bright follicles in the area corresponding to infundibular keratinization, followed by increment of inflammation parameter, such as increased of small bright cells upon RCM and vascular network upon D-OCT, which return to normal after the resolution of acute inflammation. CONCLUSION Acne skin dynamics is complex and seems characterized by the early increase in the number of dysmorphic pilosebaceous units and the hyperkeratinization of the acroinfundibulum of the pilosebaceous duct prior to the occurrence of inflammatory events around the follicle. The processes of hyperkeratinization and inflammatory phenomena may generate a pathologic vicious cycle, which characterizes acne through progressive worsening and a self-sustainment mechanism.

Background: Despite the numerous treatments available for acne vulgaris, not all are efficacious, and many patients experience psychological distress and various side effects from medications used to treat this condition. The objective of this study was to develop a new surgical technique for the treatment of acne. Methods: This surgical technique utilizes tweezers to widen the hair follicle to discharge comedo and pus completely and quickly from the acne. Results: Complete healing of acne was observed. Patients whose acne were cured within the range of 1-10, 1-20, and 1-50 treatments accounted for approximately 85%, 93%, and 99% of the 4566 patients, respectively. Conclusions: This newly developed surgical technique can be used as a basic treatment option for acne vulgaris. The implications of these findings include the prevention of patient psychological distress and avoidance of side effects of medications.

Background: The aim of the study was to retrospectively evaluate possible imaging and histopathology criteria that can be used in a clinical basis to assess the success of excision of suspicious calcifications using the breast lesion excision system (BLES).Methods: We investigated 400 BLES stereotactic biopsies of suspicious calcifications with the mean size of 15.38 mm (st. dev.= 13.579 mm, range 3-78 mm) using a 20 mm probe performed in our department between January 2014 and 2016. The mean age of our population was 58.5 years old (range 39-78 years). The pathology results of BLES specimens were compared with the final surgical results to assess excision success rates. Possible imaging and histopathology criteria for removal were statistically analyzed (mammographic size, disease free margins, grade, comedo phenotype, molecular type).Results: The results showed that 90/400 (22.5%) biopsies were cancers (80% DCIS) and 38/400 were lesions with cell atypia (9.5%) of which 29/38 had subsequent surgery and were included in the study. Excision was achieved in 31/90 cancers (34.4%) and in 23/29 lesions with cell atypia (76.3%). The imaging and histopathology criteria for BLES excision that could be potentially clinically assessed were the initial mammographic size (p

Diagnosis of breast preneoplastic and neoplastic lesions is difficult due to their similar morphology in breast biopsy specimens. To diagnose these lesions, pathologists perform immunohistochemical analysis and consult with expert breast pathologists. These additional examinations are time-consuming and expensive. Artificial intelligence (AI)-based image analysis has recently improved, and may help in ordinal pathological diagnosis. Here, we showed the significance of machine learning-based image analysis of breast preneoplastic and neoplastic lesions for facilitating high-throughput diagnosis. Images were obtained from normal mammary glands, hyperplastic lesions, preneoplastic lesions and neoplastic lesions, such as usual ductal hyperplasia (UDH), columnar cell lesion (CCL), ductal carcinoma in situ (DCIS), and DCIS with comedo necrosis (comedo DCIS) in breast biopsy specimens. The original enhanced convoluted neural network (CNN) system was used for analyzing the pathological images. The AI-based image analysis provided the following area under the curve values (AUC): normal lesion versus DCIS, 0.9902; DCIS versus comedo DCIS, 0.9942; normal lesion versus CCL, 0.9786; and UDH versus DCIS, 1.000. Multiple comparison analysis showed precision and recall scores similar to those of single comparison analysis. Based on the gradient-weighted class activation mapping (Grad-CAM) used to visualize the important regions reflecting the result of CNN analysis, the ratio of stromal tissue in the whole weighted area was significantly higher in UDH and CCL than that in DCIS. These analyses may provide a more accurate and rapid pathological diagnosis of patients. Moreover, Grad-CAM identifies uncharted important histological characteristics for newer pathological findings and targets of research for understanding diseases.

Dermoscopy and trichoscopy are non-invasive methods used as auxiliary tools in diagnostics of different dermatoses. To date, no systematic review concerning the utility of dermoscopy and trichoscopy in the diagnostics of primary cutaneous lymphomas has been published. The aim of this study was to summarize the current state of knowledge on this topic based on systematic search of PubMed database and related references published before 8th of August 2020. Besides dermoscopic features, type of dermoscope, polarization mode, magnification, number of cases and histopathological correlation were analysed. A total of 34 records were included into the final analysis, evaluating 141 patients diagnosed with primary cutaneous T-cell lymphomas and 70 patients with primary cutaneous B-cell lymphomas. Most of the analysed records evaluated dermoscopic features (n = 206); trichoscopy was analysed in only 5 cases. Structures most commonly observed in classical mycosis fungoides (n = 108) were fine short linear vessels/linear vessels, spermatozoa-like vessels and orange-yellow patchy areas. In folliculotropic mycosis fungoides (n = 12), most frequently observed were comedonal lesions/comedo openings/central keratotic plugs and white halo around hair follicles/perifollicular accentuation. Primary cutaneous marginal zone B-cell lymphoma (n = 42) and primary cutaneous follicle centre lymphoma (n = 20) most commonly presented with salmon-coloured background and fine short/linear irregular/serpentine vessels. For other PCL, with less than 10 cases reported in the analysed records, details have been provided in the article. Most observations analysed in this systematic review rely on findings from case reports/case series (with the level of evidence V) and lack a control group. A few studies provided information concerning technical aspects of dermoscopic/trichoscopic examination. The role of dermoscopy/trichoscopy in diagnostics of cutaneous lymphomas requires further studies, especially in entities where dermoscopic features have been described in only single or a few cases. However, it seems that this practical, accessory tool in future may provide additional clues during clinical assessment.

El acné es considerado una patología multifactorial inflamatoria crónica, que puede aparecer de forma espontánea y el estrés es una reacción adaptativa del organismo ante las situaciones del medio por lo q nuestro trabajo propone analizar la posible relación entre el estrés y la aparición de lesiones acneiformes en estudiantes de con carga académica alta que suele generar altos niveles de estrés en estudiantes de medicina en una universidad colombiana. Se realizo un estudio de corte transversal descriptivo donde se diseñó una encuesta tipo cuestionario que permitiera registrar y recolectar la información necesaria acerca de las condiciones sociodemográficas, alimentación, estrés y su relación con la presencia de acné. Fueron recolectados datos de 87 estudiantes que incluyeron los datos sociodemográficos, hábitos relacionados con la presencia de acné, frecuencia de uso de productos faciales, tipo de productos (maquillajes, mascarillas, recetas caseras), hábitos alimenticios, presencia de estresores como problemas familiares, frecuencia lidia con problemas de salud, horas de descanso, presencia del acné, tipos de acné y recaídas de acné. En conclusión, se evidencio una amplia relación entre el estrés y la presencia de acné, en época de evaluaciones parciales de la universidad, la falta de descanso, hábitos y estilos de vida poco saludables, así como consumo de comida chatarra, uso de cosméticos y distintos problemas de salud que aunque no desencadenan directamente la aparición de acné, influyen de manera significativa. Acne is considered a chronic inflammatory multifactorial pathology, which can appear spontaneously and stress is an adaptive reaction of the body to environmental situations, so our work proposes to analyze the possible relationship between stress and the appearance of acneiform lesions in students with a high academic load that usually generates high levels of stress in medical students at a Colombian university. A descriptive cross-sectional study was carried out where a questionnaire-type survey was designed to record and collect the necessary information about sociodemographic conditions, diet, stress, and their relationship with the presence of acne. Data from 87 students were collected that included sociodemographic data, habits related to the presence of acne, frequency of use of facial products, type of products (makeup, masks, homemade recipes), eating habits, presence of stressors such as family problems, frequency deal with health problems, hours of rest, presence of acne, types of acne and acne relapses. In conclusion, a broad relationship was evidenced between stress and the presence of acne, at the time of partial university evaluations, lack of rest, unhealthy habits and lifestyles, as well as consumption of junk food, use of cosmetics and other health problems that, although they do not directly trigger the appearance of acne, have a significant influence

Comedonal acne is a common skin disease characterized by cystic dilation of the hair follicle junctional zone. While the molecular mechanisms of acne pathogenesis are not well understood, an emerging hypothesis holds that imbalances in key signalling pathways may lead to abnormal fate determination of sebaceous progenitor cells. The subsequent accumulation of cells could then cause cyst formation in the hair follicle junctional zone and lower infundibulum, forming blackheads. This notion is supported by the observation that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes severe comedonic acne and seboatrophy by inducing fate changes in Lrig1-expressing stem cells, as well as recent human GWAS studies implicating the Wnt signalling pathway in acne. To test the possible involvement of Wnt signals in blackhead formation, we used an Lrig1-CreERT2 mouse line to modulate Wnt signalling in stem cells of the junctional zone, which are known to contribute to the junctional zone, infundibulum, and sebaceous glands. We find that persistent activation of Wnt signalling in the junctional zone leads to formation of comedone-like cysts with associated atrophic sebaceous glands. The cysts strongly express stem cell markers and can be partially reduced by treatment with all-trans retinoic acid, a well-established acne treatment, as well as by inhibition of Hedgehog signalling. In contrast, loss of Wnt signalling leads to enlargement of the junctional zone, infundibulum and sebaceous glands. These data lead us to suggest that abnormal Wnt signalling could be involved in acne pathogenesis by inhibiting differentiation and retaining junctional zone cells in a proliferative progenitor state, leading to their accumulation into comedones.

Objective: This study evaluated the histopathological features of ductal carcinoma in situ (DCIS), including cytological grade, architectural pattern and immunohistochemistry (IHC) in pure DCIS and DCIS associated with invasive carcinoma of no special type (ICNST). Methods: We evaluated a series of 232 cases of pure DCIS and DCIS associated with ICNST from a total of 399 breast carcinomas from a population consisting by women diagnosed with breast cancer and submitted to breast surgery from 2011 to 2015. Results: DCIS presented a mixed architectural pattern in most cases (56%); the solid subtype was the most common morphology (30%). High-grade DCIS was identified in 84/221 cases (38%), and comedonecrosis was present in 106/221 cases (48%). High-grade was more common in the solid subtype (61/155 cases, 39%, p < 0.001). Tumor size was greater in the presence of comedonecrosis than in the absence (mean 27 vs 20 mm, p = 0.009). Estrogen receptor (ER) was positive in 81% of cases with a cribriform pattern (p = 0.013). Greater locoregional recurrence was found in the comedonecrosis (15%) and micropapillary (19%) subtypes in DCIS associated with ICNST. Conclusion: We observed a greater relationship of ER with the low nuclear grade, while Ki-67 was related to the high-grade. DCIS presented a higher nuclear grade compared to ICNST. The less common pure pattern was the micropapillary, and the most common, the solid. Comedonecrosis was more frequent in the solid pattern. Our results showed that high-grade was more common in the solid and comedo subtype, and low-grade was more frequent in the cribriform.

Background: Benign melanocytic neoplasms have nests of melanocytic cells and show characteristic dermoscopic features. Clinical and dermoscopic features have not been studied previously in the Indian population. Aims: To study the clinical, epidemiological and dermoscopic patterns of benign melanocytic neoplasms. Methods: This was a descriptive, observational, single centre study. In 107 patients with melanocytic neoplasms, 167 lesions were clinically examined and studied under the dermoscope and histopathological examination was done when indicated. The lesions were broadly divided as acquired and congenital. Five main dermoscopic patterns were seen–globular, homogenous, reticular, parallel and streaks. If there were two of these patterns in a particular lesion, it was termed 'mixed pattern'. The presence of three or more patterns was called 'multicomponent pattern'. Various other features were also observed. Results: The majority of patients belonged to the third decade with a female preponderance. History of increased UV exposure and family history was significant in acquired nevi. The dermoscopic pattern progressed from predominantly reticular in junctional nevi to predominantly globular in compound nevi and lesser pigment in intradermal nevi, with more vascular structures. The congenital melanocytic nevi showed additional features of comedo- like lesions, milia- like cysts, perifollicular pigmentary changes and increased colour variation. Even though colour variation was observed in both acquired and congenital lesions, no signs of dysplasia were seen on histopathology. Limitations: A larger sample size is required, with follow up of lesions. No parallel studies in brown skinned population were found for exact comparison. Conclusion: Benign melanocytic proliferations are often neglected in our country. This study will help in understanding the course, clinical features and dermoscopic patterns of various benign melanocytic neoplasms, and will be a step forward towards research in our population. To the best of our knowledge, this is the first study of its kind in India.

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare dermatosis initially described as 'comedo nevus' and renamed 'PEODDN'; it has also been referred to as linear eccrine nevus with comedones, porokeratotic eccrine ostial and hair follicle nevus, and porokeratotic adnexal ostial nevus. PEODDN is usually present at birth or develops early in life. Rarely, PEODDN can develop in adults. The treatment of this puzzling condition is not standardized. We report herein a new case of adultonset PEODDN with dermatoscopic images. Our patient responded favorably to topical tazarotene.

INTRODUCTION Acne is an inflammatory disease of the pilosebaceous unit, which can be investigated in vivo using reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). OBJECTIVES By means of RCM and OCT to identify morphological characteristics of acne that may be associated with clinical acne severity. METHODS Patients with mild to moderate facial acne (n = 14, Investigators Global Assessment scale, IGA 1-3), and healthy participants (n = 7, IGA 0) were included in this explorative study. A total of 108 RCM image blocks and 54 OCT scans (each RCM and OCT image measuring 6 × 6 mm) were captured from lesional-, perilesional, and lesion-free skin areas. Acne lesions, infundibular regions of follicles and inflammation degree were compared in acne patients and healthy participants. RESULTS Combined use of RCM and OCT demonstrated infundibular morphology, acne lesions, and blood flow. RCM images of perilesional- and lesion-free skin in acne patients revealed follicle infundibula with hyperkeratinized borders and abundant keratin plugs, contrasting skin of healthy participants. Higher acne severity related to increased number of follicles with hyperkeratotic borders (P = 0.04) and keratin plugs (P = 0.006), increased infundibulum diameter (P

An 18-year-old female black leopard (Panthera pardus) showed renal failure, leukocytosis and presence of subcutaneous masses in the lower abdominal region and right shoulder; she eventually died. Histopathological observations included a mammary gland carcinoma with comedo, solid and tubulopapillary patterns in subcutaneous tissue, and highly proliferated tumor cells in systemic organs. The tumor cells were positive for cytokeratin AE1/AE3. The mammary gland tumor was diagnosed as intermediate-grade adenocarcinoma, based on a previously reported histological grading system of feline mammary carcinomas. Chronic interstitial nephritis was estimated to have been ongoing for 5 years, whilst acute necrotic pancreatitis in relation to tumor metastasis could have been the cause of death.

It is well known that comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ (DCIS) of human breast, but its molecular mechanisms remain largely unclear. Therefore, in this study, we first examined the gene expression profile of comedo DCIS based on microarray data and identified CYC1 as a gene associated with comedo necrosis. Cytochrome c1 (CYC1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production. However, the significance of CYC1 has not yet been examined in DCIS. We therefore immunolocalized CYC1 in 47 DCIS cases. CYC1 immunoreactivity was detected in 40% of DCIS cases, and the immunohistochemical CYC1 status was significantly associated with tumor size, nuclear grade, comedo necrosis, van Nuys classification, and Ki-67 labeling index. Subsequent in vitro studies indicated that CYC1 was significantly associated with mitochondrial membrane potential in MCF10DCIS.com DCIS cells. Moreover, CYC1 significantly promoted proliferation activity of MCF10DCIS.com cells and the cells transfected with CYC1 siRNA decreased pro-apoptotic caspase 3 activity under hypoxic or anoxic conditions. Considering that the center of DCIS is poorly oxygenated, these results indicate that CYC1 plays important roles in cell proliferation and comedo necrosis through the elevated oxidative phosphorylation activity in human DCIS.

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0–17), intermediate (18–30), and high (31) to predict chemotherapy benefit. Our goal was to determine the association between histomorphology, immunohistochemistry, and RR. We retrospectively identified 536 patients with ER+ and LN− breast cancers that underwent Oncotype testing from 2006 to 2013. Tumor size ranged from 0.2 cm to 6.5 cm (mean = 1.3 cm) and was uniform in all 3 categories. The carcinomas were as follows: ductal = 63.2%, lobular = 11.1%, and mixed = 35.7%. The RR correlated with the Nottingham grade. Increasing RR was inversely related to PR positivity but directly to Her2 positivity. Of the morphologic parameters, a tubular(lobular) morphology correlated only with low-intermediate scores and anaplastic type with intermediate-high scores. Other morphologies like micropapillary and mucinous were uniformly distributed in each category. Carcinomas with comedo intraductal carcinoma were more likely associated with high RR. Forty-four patients with either isolated tumor cells or micrometastases were evenly distributed amongst the 3 RR. While there was only 1 ER discrepancy between our immunohistochemistry (3+ 80%) and Oncotype, up to 8% of PR+ cases (mean = 15%, median = 5%) and 2% of HER2+ cases were undervalued by Oncotype.

In recent years, the detection rate of ductal carcinoma in situ (DCIS) has been greatly increased due to the wide application of mammography. DCIS is a non-invasive neoplastic lesion that encompassed a heterogeneous group of lesions characterized by mild to severe atypia in ductal hyperplastic tumor cells. To facilitate the selection of appropriate treatments and to predict the risk of recurrence of DCIS, pathologists divide DCIS into three grades based primarily on nuclear grade (low grade, intermediate grade and high grade) and intraductal necrosis (comedo or punctate). Imaging and clinical examination failed to identify the grade of DCIS due to lack of adequate resolution. Clinically, the histopathological gold standard "hematoxylin and eosin-stained (H and E) sections" is used to identify the grade of DCIS. But, hematoxylin and eosin-stained (H and E) sections has several shortcomings, including time-consuming and complicated pathological procedures, labor intensive, and some subjective errors. Multiphoton microscopy (MPM) based on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG), provides a label-free, low phototoxicity and high-resolution imaging method for label-free tissue samples. In this study, we used MPM to identify three different grades of human breast DCIS. Our results demonstrated that MPM can be rapidly used to identify three different grades of human breast DCIS on label-free tissue samples, via high-resolution imaging of intraductal proliferation of tumor cells, intraductal necrosis, and ductal basement membranes.

Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) are less understood. Our institutional database of 668 patients with pure DCIS from 2010 to 2018 was queried. TILs were evaluated by International TILs Working Group guidelines. Percentage of TILs was assessed from the densest focus (hotspot) in one high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses (to define sparse versus dense TILs), logistic, and Cox regression models. Sixty-nine patients with DCIS and TILs were evaluated, of whom 54 (78%) were treated by breast-conserving surgery. Thirteen (19%) patients had ipsilateral recurrence. Each recurrence (n = 13) was matched to four controls (n = 56) based on date of surgery. Median follow-up was 6.7 years. TILs were defined as sparse (

Mammographic breast density (MBD) is an independent risk factor for breast cancer. Information regarding the relationship of MBD and breast cancer biology in women with ductal carcinoma in situ (DCIS) is currently lacking. This study aimed to examine the clinicopathologic characteristics of DCIS in women stratified by MBD. A retrospective review was performed to identify women with pure DCIS who underwent preoperative mammography between 2010 and 2018. Clinicopathologic and demographic data were collected. For the purpose of analysis, MBD was categorized as “non-dense” (Breast Imaging-Reporting and Data System [BI-RADS] density categories A and B) or “dense” (BI-RADS C and D) according to its identification in radiology reports. Of 3227 patients with a breast cancer diagnosis enrolled in the institutional Breast Cancer Database during the study period, 658 (20%) had pure DCIS. Of these 658 patients, 42% had non-dense breasts, and 58% had dense breasts. Most lesions were non-palpable (92%) and detected by mammography (84%). Patients with dense breasts were more likely to be younger at the time of diagnosis (p

Collagen plays a key role in normal and malignant tissue homeostasis. While the prognostic significance of collagen fiber remodeling in invasive breast cancer has been studied, its role in ductal carcinoma in situ (DCIS) remains poorly defined. Using image analysis, we aimed to evaluate the prognostic significance of the geometric characteristics of collagen surrounding DCIS. A large well-characterized cohort of DCIS comprising pure DCIS (n = 610) and DCIS coexisting with invasive carcinoma (n = 180) were histochemically stained for collagen using picrosirius red. ImageJ software was used to assess collagen density, degree of collagen fiber dispersion and directionality in relation to DCIS ducts’ boundary. We developed a collagen prognostic index and evaluated its prognostic significance. A poor index was observed in 24% of the pure DCIS and was associated with determinants of high-risk DCIS including higher nuclear grade, comedo type necrosis, hormonal receptor negativity, HER2 positivity and high proliferation index. High collagen prognostic index was associated with the collagen remodeling protein prolyl-4-hydroxlase alpha subunit 2 and the hypoxia-related protein hypoxia inducible factor 1α. DCIS coexisting with invasive breast cancer had a higher collagen prognostic index than pure DCIS ( p

The comedo is the initial, primary lesion of acne. It is an impaction of corneocytes within sebaceous follicles. Comedones develop through the following stages.

Acne vulgaris is a chronic inflammatory condition characterized by comedo, papule, cyst, nodule and postinflammatory hyperpigmentation. Meanwhile, it is also induced by adverse event of drugs. Among them, acneiform folliculitis is a side effect of epidermal growth factor receptor (EGFR) inhibitor, which is an anticancer agent, and its incidence may occur in upward of 75 ∼ 100% of cases. The main method of acne vulgaris treatment is oral antibiotics, retinoids, topical medication and so on. However, it is limitation that teratogenicity caused by retinoids and antibiotic resistance increased by using antibiotics. In this study, we aimed to evaluate the clinical efficacy and safety of topical recombinant human (rh) EGF in treating facial acne vulgaris. Twenty three Koreans (age: 10 ∼ 29 years) with mild to moderate acne vulgar participated in the study and applied topical rhEGF cream (trouble control EGF) with 3 products (trouble control clarifying cleansing foam, trouble control all-clear filling toner, redroll calming moisture) on their face cetwice daily for four weeks. Several assessment methods were applied: Acne lesion counts score by investigator’s global assessment, efficacy and satisfaction score by subjects. Skin sebum output level, hydration level and redness level were also measured at each visit. At the final visit, skin sebum level, transepidermal water loss, skin redness statistically decreased and acne lesions (comedone, papule) were statistically reduced. No severe side effects were observed during the study. In conclusion, topical rhEGF seems to be an effective and safe adjuvant treatment option for mild acne vulgaris.

Objectives The goal of this study was to review the main lesion types of the nasal skin and appropriate treatment strategies rather than to present a comprehensive list of all diseases that affect the skin that can involve the nose. Methods We reviewed the main nasal skin lesion types and available treatment strategies. Nasal skin lesions were classified as benign, premalignant, or malignant. Results Benign lesions of the nose include nonmalignant tumoral lesions (i.e., freckles, comedo, adenoma sebaceum [Pringle disease], hydrocystoma, fibrous papules, sebaceous hyperplasia, and rhinophyma), autoimmune and inflammatory conditions (i.e., pemphigus, sarcoidosis, systemic lupus erythematosus, facial eosinophilic granuloma, rosacea, herpes zoster infection, leishmaniasis, and leprosy), and vascular lesions (i.e., telangiectasis, hemangioma, and spider nevus). Premalignant lesions are actinic keratosis and keratoacanthoma; and malignant tumors are melanoma, basal cell carcinoma, and squamous cell carcinoma. Regardless of whether or not they are malignant, all facial lesions can yield significant cosmetic discomfort that should be evaluated carefully before commencing any curative or corrective intervention. In general, benign lesions are treated with dermabrasive modalities, such as trichloroacetic acid, phenol, salicylate, and laser ablation. Electrocautery, cryosurgery, and surgical excision are also used, although these methods may result in scar formation, which can sometimes be more problematic than the original lesion itself. Conclusion Any disease that affects the skin, especially those diseases that are triggered by ultraviolet exposure, can involve the face and nose. Cosmetic defects due both to the lesion itself and the intervention must be discussed with the patient, preferably in the presence of a first-degree relative, before commencement of treatment. As a result of heterogeneity of skin lesions of the nose, appropriate education of general practitioners as well as otorhinolaryngologists is mandatory.

Background: Lichen planus (LP) is an autoimmune dermatosis characterized by pruritic violaceous flat-topped polygonal papules predominantly over the extremities but can also affect trunk, mucosa, scalp, palms, soles and nails. Dermoscopy is a novel non-invasive imaging modality and the presence of salient dermoscopic features will help to obviate the need for skin biopsies in many doubtful cases.Methods: This was a descriptive study of 108 cases of classical lichen planus cases conducted at a tertiary care hospital in South India over a period of one year. Dermoscopic examination of the LP lesions were carried out using DermLite DL3N and histopathological samples were analyzed in 35 cases.Results: The dermoscopic features were blue globules in 100%, Wickham’s striae in 92.6% and comedo like openings in 49.1%. Vascular patterns were noted only in 13%. On correlating Wickham’s striae in dermoscopy with wedge shaped hyper granulosis on histopathology using the chi-square test we found agreement (kappa value 0.242). We also found that dermoscopy was 93.75% sensitive and 33.33% specific regarding Wickham’s striae in relation to wedge shaped hyper granulosis. In 85% of cases blue globules were present dermoscopically and dermal melanophages were found histopathologically.Conclusions: Wickham’s striae can be considered as a diagnostic dermoscopic finding in lichen planus whereas findings like bluish pigmentation and vascular structures depended on the skin colour of the patient. We also found agreement between dermoscopic and histopathologic features namely Wickham’s striae with wedge shaped hyper granulosis and blue globules with dermal melanophages.

Ductal carcinoma in situ (DCIS) transition to invasive tumor is a big problem for breast cancer. The human MCF10DCIS.com cell line (abbreviated as MCF10DCIS) is derived from the human MCF10A breast epithelial cell line. The MCF10DCIS xenografts are similar to human high grade comedo DCIS. In the xenograft assay, MCF10DCIS cells form DCIS-like lesion, remain as DCIS-like lesion in the first several weeks, and then progress into invasive carcinoma. Thus, it is an excellent model to study human breast cancer transition from DCIS to invasive carcinoma. We investigated the role of CD44 in breast cancer transition from DCIS to invasive carcinoma by knockdown the expression of CD44 in the MCF10DCIS xenograft model. Our results show that knockdown of CD44 expression in the MCF10DCIS cells promotes DCIS transition to invasive carcinoma. Our finding is supported by a previous study that showed CD44 expression is higher in DCIS than in invasive breast carcinomas for human patients. Furthermore, we will present our ongoing studies for the underlying mechanisms. Our findings have important implications for breast cancer. Citation Format: Fang Liu, Jun Zhou, Tanima Kundu-Roy, Joseph Wahler, Jae Young So, Yong Lin, You-Rong Lou, Nicola J. Barnard, Isao Matsuura, Nanjoo Suh. CD44 inhibits the transition of ductal carcinoma in situ to invasive breast carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5052.

Summary Background Milia are small, hard, white superficial epidermal cysts measuring a few millimetres that can occur during skin healing due to occlusion of pilosebaceous units. Milia rarely occur on tattoos. However, cases of allergic reactions with hyperkeratosis and open comedones have been described in the literature, sometimes under the term “epidermal cysts”. Patients and methods We saw three patients who developed milia, including a 32-year-old man with eruptive milia 10 weeks after getting a black, red and green tattoo on his upper arm. Topical tretinoin was applied. We encountered two further cases of eruptive milia on black/grey tattoos. A fourth patient presented a massive hyperkeratotic reaction with retention comedones on the red/pink area of a tattoo. Discussion The occurrence of milia and acneiform allergic reactions after tattooing is rare. We collated a total of 13 cases from the literature, of which 8 involved milia. This condition occurred within 3 months following tattooing, with no particular correlation with any given colour, and generally without any allergic reaction (except in one case). Reactions comprising excessive acneiform hyperkeratosis and open comedones were noted with pink and red inks and were a complication in a setting of allergic inflammatory reaction. However, the histopathology of these reactions is poorly described in the literature. It seems inappropriate to diagnose the condition as “epidermal cysts” since the lesions are not in fact simple cysts but rather retention lesions occurring during an inflammatory reaction and are thus different from post-traumatic milia.

Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), −T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.

This study aimed to investigate the correlations of Estrogen Receptor (ER), Progesterone Receptor (PR), human epidermal growth factor receptor 2 (Her-2) and cytokeratin 5/6 (CK5/6) protein expression with histological characteristics features and prognosis of breast Ductal Carcinoma in situ (DCIS). Fortyeight cases of breast DCIS specimen were enrolled in this study. The samples were histologically typed and graded. The immunohistochemical analysis was performed to determine the expression of ER, PR, Her-2 and CK5/6 protein. Results showed that, the positive rates of ER and PR protein expression in non-comedo type DCIS group were significantly higher than those in comedo type DCIS group, respectively (P 0.05). There was significant difference of positive rate of ER, PR, Her-2 protein expression among histological grades I-III (P 0.05). The expression of ER protein was positively correlated with PR protein expression (r=0.764, P

The purpose of this report is to detail the unique occurrence of comedo-like trichoadenoma of the upper eyelid. A 54-year-old man underwent surgical resection of the lesions of the left upper eyelid that were suspected to be dilated pores. The lesions were studied with histopathological examination. Histopathology showed lesions in the dermis and epidermis containing keratinous cysts surrounded by interstitial edema and infiltration of lymphocytes. The lesions were finally diagnosed as trichoadenoma.