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Romanian Journal of Morphology and... 2021Malignant tumors of the oral cavity have a growing incidence, most being squamous cell carcinomas, generally called oral cancers (OCs), clinically detected at various...
Malignant tumors of the oral cavity have a growing incidence, most being squamous cell carcinomas, generally called oral cancers (OCs), clinically detected at various stages of natural evolution. The increased incidence in Romania in recent years and the lack of conclusive data have led to the development of this study. The main purpose of this study was to assess the molecular profile of tumors, the types of blood vessels associated with the tumor, and expression of tumor immunomarkers. Regarding morphological findings, focal epithelial hyperplasia, dysplastic lesions, typical mitoses, perineural invasion, parakeratosis and keratosis beads, intracytoplasmic keratinization were observed. Microvascular density was higher in the tumor area compared to the peritumoral area. Lymphovascular invasion was identified in 13% of cases, which also presented regional lymph node metastases. Podoplanin expression was identified in 79% of cases which were tested positive for the D2-40 immunomarker. All p53-positive cases co-expressed epidermal growth factor receptor (EGFR), half of the EGFR-positive cases co-expressed p53, and co-expression of CD117 and p63 was identified in 80% of EGFR-positive∕cytokeratin 5 (CK5)-positive cases being proposed the basal-like subtype of OCs, defined as EGFR-positive∕CK5-positive, CD117-positive and p63-positive. Results support the need for molecular classification of OCs based on of tumor immunomarker expression and gene analysis.
Topics: Carcinoma, Squamous Cell; ErbB Receptors; Head and Neck Neoplasms; Humans; Immunohistochemistry; Mouth Neoplasms; Romania; Squamous Cell Carcinoma of Head and Neck; Tumor Suppressor Protein p53
PubMed: 35673812
DOI: 10.47162/RJME.62.4.05 -
Journal of Advanced Research Dec 2023Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively...
INTRODUCTION
Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a comprehensive perception of the underlying mechanisms and the predisposing factors for this disorder.
OBJECTIVES
Here, we investigated rumen epithelial cell heterogeneity, differentiation trajectories, and cornification to clarify the rumen epithelial keratinization process and discern the key ruminal metabolites contributing to rumen epithelial parakeratosis.
METHODS
Twenty-four 14-day-old lambs were divided into three groups, including only milk feeding, milk plus alfalfa hay feeding, and milk plus corn-soybean concentrate starter feeding. At 42 days of age, the lambs were slaughtered, and rumen tissues were collected for single-cell RNA-sequencing (scRNA-seq), immunofluorescence, and quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples were collected for metabolomic analyses. Rumen epithelial organoid was used to verify the key ruminal metabolites contributing to parakeratosis.
RESULTS
As expected, we observed that concentrate starter introduction resulted in rumen epithelial parakeratosis. Moreover, scRNA-seq analysis revealed a developmental impediment in the transition from differentiated keratinocytes to terminally differentiated keratinocytes (TDK) in lambs with concentrate starter introduction. Immunofluorescence and qRT-PCR analyses further verified the location and expression of marker genes of TDK. Metabolomic analysis showed a robust positive correlation between ruminal butyrate levels and rumen epithelial keratinization. More importantly, we successfully established a rumen organoid model capable of facilitating the study of the keratinization process in the rumen epithelia and further confirmed that high dose butyrate indeed contributed to rumen epithelial parakeratosis.
CONCLUSION
Collectively, concentrate starter introduction induces ruminal epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation in a neonatal lamb model. These findings enhance our understanding of rumen epithelial keratinization and provide valuable insights for addressing rumen epithelial parakeratosis using early nutritional intervention strategies.
PubMed: 38128723
DOI: 10.1016/j.jare.2023.12.016 -
Diagnostics (Basel, Switzerland) Dec 2022Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features...
Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features with chronic eczema, hyperkeratotic hand dermatitis and allergic contact dermatitis. The present study aims to characterize the histologic features of PP on a series of 21 cases. The following morphological features and their distribution were included: parakeratosis, dilated vessels in papillary dermis, psoriasiform acanthosis with elongation of rete ridges, perivascular lymphocytic infiltrate, decrease/loss of granular layer, Munro's microabscesses, spongiform pustules of Kogoj, spongiosis and lymphocytic exocytosis. The main diagnostic clues and histologic differential diagnoses are also discussed.
PubMed: 36553078
DOI: 10.3390/diagnostics12123071 -
Iranian Journal of Pathology 2022Nevus comedonicus (NC) is a rare developmental anomaly of the folliculosebaceous apparatus, which appears as numerous dilated papules containing firm, darkly pigmented,...
Nevus comedonicus (NC) is a rare developmental anomaly of the folliculosebaceous apparatus, which appears as numerous dilated papules containing firm, darkly pigmented, horny plugs. It appears shortly after birth and mostly before the age of 10; however, late-onset cases have been reported. There is no gender or racial predilection. Moreover, NC can be a component of nevus comedonicus syndrome, a neurocutaneous disorder with skeletal, ocular, and central nervous system abnormalities. EHK properties in NC are not a common finding and are rarely seen in association with each other. This paper reports a healthy, 27-year-old young woman who has been developing numbers of asymptomatic unilateral linear skin lesions on her chest, waist, right thigh, and popliteal fossa in a unilateral linear pattern over ten years. Skin biopsy revealed dilated follicular ostia with orthokeratotic hyperkeratosis, columns of parakeratosis, cornoid flagellation, epidermolytic hyperkeratosis, and mild acanthosis on its wall.
PubMed: 35463735
DOI: 10.30699/IJP.2022.542761.2767 -
International Ophthalmology May 2021To observe and describe the anterior segment optical coherence tomography features of limbally localised non-malignant epithelial mass lesions METHODS: Thirteen patients...
PURPOSE
To observe and describe the anterior segment optical coherence tomography features of limbally localised non-malignant epithelial mass lesions METHODS: Thirteen patients (age: 66.9 ± 16.3 years) with conjunctival mass suggesting ocular surface squamous neoplasia with biomicroscopic examination were imaged using anterior segment ocular coherence tomography (anterior segment optical coherence tomography)/Cirrus HD-OCT, Model 4000, Carl Zeiss Meditec, Inc., Dublin, CA, and Spectralis HRA + OCT system, Heidelberg Engineering, Vista, CA/. Cases with ocular surface squamous neoplasia-like anterior segment optical coherence tomography (hyperreflective, thickened epithelium and an abrupt transition from normal to abnormal) were included in the study. Maximal thickness of the epithelium was measured. Histological diagnosis was gained from an excisional or incisional biopsy or impression cytology specimens.
RESULTS
In six patients (age: 68.5 ± 15.4 years) with ocular surface squamous neoplasia-like anterior segment optical coherence tomography features, the histological diagnosis was other than ocular surface squamous neoplasia (papilloma, parakeratosis and a keratotic plaque with mild dysplasia), and ocular surface squamous neoplasia in seven cases (age: 65.6 ± 18.0 years). The maximal epithelial thickness was between 250 and 859 µm in non-ocular surface squamous neoplasia cases and between 252 and 596 µm in ocular surface squamous neoplasia cases.
CONCLUSION
Non-malignant epithelial lesions can mimic ocular surface squamous neoplasia on anterior segment optical coherence tomography.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Eye Neoplasms; Humans; Middle Aged; Tomography, Optical Coherence
PubMed: 33694094
DOI: 10.1007/s10792-021-01743-y -
International Journal of Molecular... Aug 2021Both agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we...
Both agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we hypothesized that epidermal PPARγ would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. -/- mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in -/- mouse skin included , , and . RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for , which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (). Transcripts for were detected in -/- mouse skin, but transcripts for and were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPARγ plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.
Topics: Animals; Cells, Cultured; Dermatitis; Epidermis; Homeostasis; Inflammation; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Organ Specificity; PPAR gamma; Skin Physiological Phenomena
PubMed: 34445339
DOI: 10.3390/ijms22168634 -
Head and Neck Pathology Dec 2020Benign alveolar ridge keratosis (BARK), the intraoral counterpart of cutaneous lichen simplex chronicus, is a reactive hyperkeratosis caused by trauma or friction that...
Benign alveolar ridge keratosis (BARK), the intraoral counterpart of cutaneous lichen simplex chronicus, is a reactive hyperkeratosis caused by trauma or friction that presents as a poorly demarcated white papule or plaque on the keratinized mucosa of the retromolar pad or alveolar ridge mucosa (often edentulous). This is a clinical and histopathologic analysis of BARK including evaluation of p53 expression in selected cases. One hundred and sixty-seven cases of BARK were identified from 2016 to 2017 and 112 (67.1%) occurred in males with a median age of 56 years (range 15-86). The retromolar pad was affected in 107 (64.1%) cases and the edentulous alveolar mucosa in 60 (35.9%) cases, with 17.4% of the cases presenting bilaterally. BARK showed hyperkeratosis often with wedge-shaped hypergranulosis and occasional focal parakeratosis. The epithelium exhibited acanthosis and surface corrugation with tapered rete ridges often interconnected at the tips. The study for p53 performed in 12 cases showed less than 25% nuclear positivity. BARK is a distinct benign clinicopathologic entity caused by friction, which should be clearly distinguished from true leukoplakia, a potentially malignant disorder.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alveolar Process; Biomarkers; Female; Humans; Jaw Diseases; Keratosis; Male; Middle Aged; Tumor Suppressor Protein p53; Young Adult
PubMed: 32180128
DOI: 10.1007/s12105-020-01151-1 -
The Journal of Investigative Dermatology May 2020Many psoriasis patients treated with biologics do not achieve total skin clearance. These patients possess residual plaques despite ongoing biologic treatment. To...
Many psoriasis patients treated with biologics do not achieve total skin clearance. These patients possess residual plaques despite ongoing biologic treatment. To elucidate mechanisms of plaque persistence despite overall good drug response, we studied 50 subjects: psoriasis patients with residual plaques treated with one of three different biologics, untreated patients, and healthy controls. Skin biopsies from all subjects were characterized using three methods: mRNA expression, histology, and FACS of hematopoietic skin cells. Although all three methods provided evidence of drug effect, gene expression analysis revealed the persistence of key psoriasis pathways in treated plaques, including granulocyte adhesion and diapedesis, T helper type17 activation pathway, and interferon signaling with no novel pathways emerging. Focal decreases in parakeratosis and keratinocyte proliferation and differential reduction in IL-17 producing CD103 T cells, but no change in CD103 tissue-resident memory T cells were observed. Of note, antitumor necrosis factor increased the interferon signaling pathway already present. Interestingly mast cells were the dominant source of IL-22 in all psoriasis subjects. These data suggest that while subtle differences can be observed in drug-treated plaques, underlying biologic mechanisms are similar to those present in untreated psoriatic lesions.
Topics: Adult; Biological Products; Cells, Cultured; Chronic Disease; Disease Progression; Female; Humans; Immunologic Memory; Inflammation; Interleukins; Male; Mast Cells; Middle Aged; Parakeratosis; Phenotype; Psoriasis; Th17 Cells; Young Adult; Interleukin-22
PubMed: 31715177
DOI: 10.1016/j.jid.2019.09.027 -
Diseases of the Esophagus : Official... Apr 2023Endoscopic eradication therapy (EET) is an effective treatment for Barrett's esophagus (BE); however, disease recurrence remains problematic requiring surveillance...
Endoscopic eradication therapy (EET) is an effective treatment for Barrett's esophagus (BE); however, disease recurrence remains problematic requiring surveillance post-treatment. While data regarding predictors of recurrence are limited, uncontrolled reflux may play a significant role. Our aim was to develop a scoring system based on histopathologic reflux in surveillance biopsies following EET to identify patients at high risk for recurrence of BE. Patients were identified from two centers in the treatment with resection and endoscopic ablation techniques for BE consortium. Hematoxylin and eosin-stained slides of surveillance biopsies post-EET were assessed for histologic changes associated with reflux from a cohort of patients who also underwent pH-metry (derivation cohort). We developed a novel scoring system (Recurrent Epithelial Changes from Uncontrolled Reflux [RECUR]) composed of dilated intercellular spaces, epithelial ballooning, basal cell hyperplasia, and parakeratosis, to identify patients with abnormal esophageal acid exposure. This scoring system was then used to grade surveillance biopsies from patients with or without recurrence of BE following EET (validation cohort). Of 41 patients in the derivation cohort, 19.5% had abnormal acid exposure times (AET) while on proton pump inhibitor therapy. The mean (SD) RECUR score for patients with AET <4% was 4.0 (1.6), compared with 5.5 (0.9) for AET ≥4% (P = 0.015). In the validation cohort consisting of 72 patients without recurrence and 64 patients with recurrence following EET, the RECUR score was the only significant predictor of recurrence (odds ratio: 1.36, 95% confidence interval: 1.10-1.69, P = 0.005). Histologic grading of surveillance biopsies using the RECUR scoring system correlates with BE recurrence following EET.
Topics: Humans; Esophagoscopy; Neoplasm Recurrence, Local; Barrett Esophagus; Metaplasia; Gastroesophageal Reflux; Esophageal Neoplasms
PubMed: 36446594
DOI: 10.1093/dote/doac078 -
Modern Pathology : An Official Journal... Oct 2020Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently...
Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words "verruciform" and "verrucous" were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Female; Humans; Middle Aged; Vulvar Neoplasms
PubMed: 32427961
DOI: 10.1038/s41379-020-0573-5