Benign Inflammatory Dermatoses Research Articles

A-114 Deep learning-based classification of early-stage mycosis fungoides and benign inflammatory dermatoses on hematoxylin and eosinstained whole-slide images: a retrospective, proof-of-concept study

A-114 Deep learning-based classification of early-stage mycosis fungoides and benign inflammatory dermatoses on hematoxylin and eosinstained whole-slide images: a retrospective, proof-of-concept study

Deep Learning–Based Classification of Early-Stage Mycosis Fungoides and Benign Inflammatory Dermatoses on H&E-Stained Whole-Slide Images: A Retrospective, Proof-of-Concept Study

The diagnosis of early-stage mycosis fungoides (MF) is challenging due to shared clinical and histopathological features with benign inflammatory dermatoses (BIDs). Recent evidence has shown that deep learning (DL) can assist pathologists in cancer classification, but this field is largely unexplored for cutaneous lymphomas. This study evaluates DL in distinguishing early-stage MF from BIDs using a unique dataset of 924 hematoxylin and eosin-stained whole-slide images from skin biopsies, including 233 early-stage MF and 353 BID patients. All MF patients were diagnosed after clinicopathological correlation. The classification accuracy of weakly-supervised DL models was benchmarked against three expert pathologists. The highest performance on a temporal test set was at 200x magnification (0.25 μm per pixel resolution), with a mean area-under-the-curve of 0.827 ± 0.044 and a mean balanced accuracy of 76.2 ± 3.9%. This nearly matched the 77.7% mean balanced accuracy of the three expert-pathologists. Most (63.5%) attention heatmaps corresponded well with the pathologists’ region-of-interest. Considering the difficulty of the MF versus BID classification task, the results of this study show promise for future applications of weakly-supervised DL in diagnosing early-stage MF. Achieving clinical-grade performance will require larger multi-institutional datasets and improved methodologies, such as multimodal DL with incorporation of clinical data.

Mycosis fungoides with spongiosis: a case report

BackgroundMycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). CTCL are an uncommon, heterogeneous group of non-Hodgkin lymphomas (NHLs) of T- and B-cell origin where the skin is the primary organ of involvement. It is characterized by malignant CD4+ T-cells infiltrating the skin and other organs, leading to progressive skin and systemic involvement. Histopathologically, MF is characterized by atypical lymphocytes demonstrating epidermotropism without spongiosis. Spongiosis is the histological hallmark of intercellular epidermal edema, viewed as clear spaces within the epidermis, and is very common in benign inflammatory dermatoses. Very few studies have reported MF in sub-Saharan Africa (SSA). We are reporting a case of MF with a rare presentation of spongiosis treated successfully with a low dose total skin electron beam therapy (TSEBT) followed by maintenance therapy of low dose Methotrexate (MT) at the Ocean Road Cancer Institute (ORCI) in Tanzania. This is the first case of MF to be managed with low-dose TSEBT in Tanzania. The authors wish to create awareness of the disease among physicians and pathologists and expand on the data paucity in SSA.Case descriptionWe are reporting a case of a 31-year-old male of African origin who self-referred to our oncology center with a 4-year history of skin rashes throughout the body, which was unresponsive to topical steroid treatment. The biopsy was taken, and the patient was diagnosed with MF CD 3 positive with spongiosis. The patient was treated with radiotherapy, whereby he received low dose total skin electron beam therapy (TSEBT) 12 Gy in 3 fractions at a daily dose of 4 Gy, followed by maintenance therapy of low dose Methotrexate and attained an excellent therapeutic response.ConclusionSpongiosis is an infrequent presentation of MF. Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with MF, which could be administered safely multiple times during a patient's disease with an acceptable toxicity profile. Lack of tendency to perform skin biopsies and cost constraints in assessing multiple immunophenotypic markers lead to missing the diagnosis. Diagnosis and treatment of MF in resource-limited countries is challenging.

Mycosis Fungoides Palmaris et Plantaris Progressing to Complete Early-Stage Disease Improved with Phototherapy

Mycosis fungoides is the most common form of cutaneous T cell lymphoma. In this article, the authors describe a case of a 53-year-old female who presented with multiple pruritic, slightly erythematous and hyperpigmented, variably shaped macules, and patches and plaques, with scaling on the bilateral hands and feet. The lesions resembled various benign inflammatory dermatoses, such as contact dermatitis and superficial dermatophytosis, and were treated as such until hyperpigmented, variably shaped macules and patches appeared on the legs and with a bathing trunk distribution. Histopathologic and immunohistochemical findings were consistent with early mycosis fungoides. The patient has improved with full body narrowband ultraviolet B phototherapy, combined with a psoralen ultraviolet A soak for the hands and feet. This case highlights the importance for physicians to recognise that mycosis fungoides may occur with different presentations, and may not present in its classic form. The patient’s quality of life may be improved with early diagnosis.

Portable System for In-Clinic Differentiation of Skin Cancers from Benign Skin Lesions and Inflammatory Dermatoses

The exquisite sensitivity of Raman spectroscopy for detecting biomolecular changes in skin cancer has previously been explored; however, this mostly required analysis of excised tissue samples using bulky, immobile laboratory instrumentation. In this study, the technique was translated for clinical use with a portable Raman system and customized fiber optic probe and applied to differentiation of skin cancers from benign lesions and inflammatory dermatoses. The aim was to provide an easy-to-use, easy-to-manage assessment tool for clinicians to use in their daily patient examination routine to perform rapid Raman measurements of skin lesions invivo. Using this system, >867 spectra were measured invivo from 330 patients with a wide variety of different benign skin lesions (n= 603), inflammatory dermatoses (n= 140), and skin cancers (n= 124). Ethnicities represented were 70% European; 16% Asian; 6% Māori; 5% Pacific people; and 4% Middle East, Latin American, and African. Accurate differentiation of skin cancers from benign lesions and inflammatory dermatoses was achieved using partial least squares discriminant analysis, with area under curve for the receiver operator curves for external validation sets ranging from 0.916 to 0.958. This study shows evidence for robust clinical translation of Raman spectroscopy for rapid, accurate diagnosis of skin cancer.

Histology-based classifier to distinguish early mycosis fungoides from atopic dermatitis.

Histopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the inclusion of all available diagnostic parameters. To identify the most impactful histological criteria for a predictive diagnostic model to discriminate MF from atopic dermatitis (AD). In this multicentre study, two cohorts of patients with either unequivocal AD or MF were evaluated by two independent dermatopathologists. Based on 32 histological attributes, a hypothesis-free prediction model was developed and validated on an independent patient's cohort. A reduced set of two histological features (presence of atypical lymphocytes in either epidermis or dermis) was trained. In an independent validation cohort, this model showed high predictive power (95% sensitivity and 100% specificity) to differentiate MF from AD and robustness against inter-individual investigator differences. The study investigated a limited number of cases and the classifier is based on subjectively evaluated histological criteria. Aiming at distinguishing early MF from AD, the proposed binary classifier performed well in an independent cohort and across observers. Combining this histological classifier with immunohistochemical and/or molecular techniques (such as clonality analysis or molecular classifiers) could further promote differentiation of early MF and AD.

Two cases of granuloma faciale showing rosettes.

Granuloma faciale (GF) is a rare benign chronic inflammatory dermatosis often difficult to distinguish clinically from other diseases, both inflammatory and neoplastic. Dermoscopy can be a helpful diagnostic tool and indeed several dermoscopic criteria observed in GF have been described in literature. We present two patients affected by GF in which we have observed rosettes.

Cell adhesion molecule 1 expression in mycosis fungoides versus parapsoriasis versus inflammatory dermatosis: an immunohistochemical comparative study.

Cell adhesion molecule 1 (CADM1) is one of the immunoglobulin super family adhesion molecules, that is proposed to contribute in the pathogenesis of various types of cutaneous T-cell lymphoma, including mycosis fungoides (MF). In this work, we decided to examine the immunohistochemical expression of CADM1 in MF specimens compared to premycotic parapsoriasis, benign inflammatory dermatosis and normal control skin specimens. 125 participants were enrolled (50 MF, 25 parapsoriasis, 25 inflammatory dermatosis, and 25 healthy controls). Patients were selected from the Outpatient Clinic of Dermatology and Venereology Department, Tanta University Hospitals. From all, 4mm punch skin biopsies were taken and examined for CADM1 immunohistochemical expression. The current study revealed statistically significant upregulation of CADM1 expression in MF specimens in comparison to parapsoriasis, inflammatory dermatosis, and normal control specimens. Additionally, there was statistically significant positive correlation between CADM1 expression and progression of TNMB staging of MF disease. Therefore, it is possible to recommend CADM1 as a beneficial diagnostic immunohistochemical marker for differentiation between early stages of MF and both the premycotic parapsoriasis and benign inflammatory dermatosis. Moreover, it may be of value in early detection of neoplastic transformation of parapsoriasis as well as in assessment of MF progression.

437 Single-cell RNA sequencing reveals specific T cell and fibroblast populations that can distinguish early mycosis fungoides from parapsoriasis and atopic dermatitis lesions

The diagnosis of early mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is often delayed due to clinical and histopathological similarities with benign inflammatory dermatoses. Moreover, its clear delineation from the spectrum of so-called “parapsoriasis” is still controversial. For further insight on a molecular level, we performed single-cell RNA sequencing to profile skin biopsies from patients presenting clinically with small- or large-patch dermatitis and compared them to atopic dermatitis (AD) lesions and healthy control (HC) individuals.

454 Digital quantitative detection of methylated DNA biomarkers: A helpful tool in the early diagnosis of Sézary syndrome

Sézary syndrome (SS) is an aggressive type of cutaneous T-cell lymphoma. Diagnosing SS can be challenging, especially in early stages of disease. Previously, in a genome-wide study, we showed that promoter hypermethylation of PROM1, G0S2, CMTM2, PAM, GNMT and NEXN is frequently observed in late stages of disease, but is neither found in healthy donors nor in benign erythrodermic inflammatory dermatoses (EID) patients. In this study, we evaluated the diagnostic value of these biomarkers in early stages of disease.

Hist-O-01 - Artificial intelligence-assisted probability scoring for differentiation of early mycosis fungoides and benign inflammatory dermatoses on H&E stained pathology slides of skin biopsies

Hist-O-01 - Artificial intelligence-assisted probability scoring for differentiation of early mycosis fungoides and benign inflammatory dermatoses on H&E stained pathology slides of skin biopsies

Chronicles of A.I. Pospelov Moscow Dermatovenerology and Cosmetology Society (MDCS was founded on October 4, 1891). Bulletin of the MSDC № 1145

On December 21, 2021, the 1145th meeting of the Moscow Society of Dermatovenereologists and Cosmetologists named after A.I. Pospelov took place.
 The meeting was held in a face-to-face format traditionally in the countries of the V.A. Rakhmanov Skin Clinic. There were 110 participants. Accepted as a member of the MSDV 4 people.
 Clinical observations of linear IgA-dependent dermatosis, systemic lupus erythematosus, annular granuloma were presented. Two scientific reports were heard ― about foot mycetoma; about skin reactions to tattoos.
 Linear IgA-dependent bullous dermatosis is a rare immune ― mediated vesicular skin disease characterized by the presence of homogeneous linear fixation of IgA along the basement membrane. Trigger factors: medications (vancomycin, cephalosporins, diclofenac, captopril, etc.); infectious diseases; vaccination against influenza; exposure to ultraviolet rays; paraneoplastic process (5% of cases) in lymphoproliferative diseases; inflammatory bowel diseases (ulcerative colitis and Crohns disease). The differential diagnosis in adults is Durings herpetiform dermatitis, Levers bullous pemphigoid, an atypical form of multiform exudative erythema; in children ― bullous impetigo, genetic epidermolysis bullosa.
 Systemic lupus erythematosus is a multisystem connective tissue disease with lesions of the skin and mucous membranes, joints, kidneys, heart, lungs and central nervous system. Systemic glucocorticoids, hydroxychloroquine, azathioprine, cyclophosphamide, belimumab, rituximab are used in the treatment.
 Annular granuloma is a benign inflammatory dermatosis of unknown etiology, which is characterized by the development of flesh colored or red papules on the skin, often arranged in the form of rings. Fractional laser action is used in the treatment.
 Mycetoma is a one sided, slightly painful dense tumor-like infiltrate limited on the foot or hand, edema with the formation of granulomas, microabcesses, the formation of fistulas and the release of actinomycetes or fungal mycelium from them. Differential diagnosis: chronic arthritis, arthrosis, sprain and rupture of ligaments, synovitis, chronic and postoperative osteomyelitis, bacterial mycetoma, botryomycosis, tumors, cold abscess, phlegmon, post-injection infiltrate, etc.
 Tattooing is a subspecies of avant ― garde art and a way of changing appearance, in which the integrity of the skin is violated with the help of various piercing tools and a persistent indelible pattern is applied by introducing a coloring agent. The pigments trapped in the tattoo partially exit through the lymph and are deposited in the regional lymph nodes. The nodes are imperceptibly colored along with the skin. A certain amount of pigment nanoparticles can enter the bloodstream and theoretically cause harm somewhere in the body.

Prevalence of T-cell antigen losses in mycosis fungoides and CD30-positive cutaneous T-cell lymphoproliferations in a series of 153 patients

Mycosis fungoides (MF) and primary cutaneous CD30-positive T-cell lymphoproliferative disorders (CD30LPD) are the most frequent primary cutaneous T-cell lymphomas. Our objective was to study pan-T-cell antigens and PD-1 expression in a large cohort of MF and CD30LPD with a special interest in antigen losses as a diagnostic tool. We retrospectively reviewed 160 consecutive samples from 153 patients over a 3 year period, including 104 with MF and 49 with CD30LPD. As controls, benign inflammatory dermatoses (BID, n=19) were studied. A semi-quantitative evaluation of CD2, CD3, CD4, CD5, CD7, CD8 expression was performed. PD-1 and double stainings (CD3+CD7 and PD-1+CD7) were performed in a subset of MF cases. CD8+ MF was frequent (23%) and CD7 was the most frequently lost antigen in both MF (45%) and CD30LPD (86%), while no significant T-cell antigen loss was observed in BID. CD7 loss was less frequent in folliculotropic MF (p<0.001). PD-1 was variably expressed in MF with no differences with BID. The CD3+/CD7- and PD-1+/CD7- neoplastic lymphocytes were highlighted by the use of chromogenic double staining experiments in MF with a CD7 loss identified with single staining. Multiple pan T-cell antigen losses were mostly seen in CD30LPD with CD2 being the most frequently preserved marker (90%). While PD-1 does not discriminate between MF and BID, CD7 is frequently lost in MF infiltrates as well as other pan-T-cell antigens in CD30LPD, which can be used as routine markers for diagnosis. We recommend the use of CD7 in addition to CD3, CD4 and CD8 as a minimal immunohistochemical panel for MF assessment, and the use of double stainings for CD3 and CD7 in difficult cases.

TOX Outperforms FOXP3, CD4 and GATA3 in Histopathological Diagnosis of Early Mycosis Fungoides.

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The early stage of MF is a difficult diagnostic case, as it is often confused with many benign inflammatory dermatoses (BID). The study aimed to evaluate the diagnostic utility of TOX, FOXP3, CDD4 and GATA3 in differentiating early stages of MF from histologically overlapping BID lesions. A retrospective cross-sectional study was performed, in which immunohistochemistry (IHC) was used to evaluate the expression of TOX, FOXP3, CD4 and GATA3 in formalin-fixed paraffin-embedded (FFPE) sections of skin lesions from 30 cases with BID and 30 patients with early-stage MF. The association between TOX expression and early-stage MF was statistically significant (P < 0.001). TOX had the highest sensitivity of 96.77% and accuracy of 85.71% in diagnosis of MF; followed by CD4 with sensitivity of 85.71% and accuracy of 78.95%; and then, GATA3 with sensitivity of 76.7% and finally FOXP3 with sensitivity of 70.0%. TOX is suggested to be of higher diagnostic value in the early stages of MF than the conventionally used CD4 and other markers examined.

From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis.

Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential role in the genesis of cancer out of genes expression dysregulation. Objectives: Due to the heterogeneity of MF and LPP and the scarcity of the cases, there are an exceedingly small number of studies that have identified molecular changes in these pathologies. We aim to identify and compare DNA copy number alterations and gene expression changes between MF and LPP to highlight the similarities and the differences between these pathologies. Materials and Methods: The patients were prospectively selected from University Clinic of Dermatology and Venereology Timișoara, Romania. From fresh frozen skin biopsies, we extracted DNA using single nucleotide polymorphism (SNP) data. The use of SNP array for copy number profiling is a promising approach for genome-wide analysis. Results: After reviewing each group, we observed that the histograms generated for chromosome 1–22 were remarkably similar and had a lot of CNAs in common, but also significant differences were seen. Conclusions: This study took a step forward in finding out the differences and similarities between MF and LPP, for a more specific and implicitly correct approach of the case. The similarity between these two pathologies in terms of CNAs is striking, emphasizing once again the difficulty of approaching and differentiating them.

GFI-1 overexpression promotes cell proliferation and apoptosis resistance in mycosis fungoides by repressing Bax and P21.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. The majority of patients with advanced stage MF are resistant to conventional chemotherapy and thus have a poor prognosis. The transcriptional repressor growth factor independence-1 (GFI-1) serves an important role in the development of T-cells. The results of the present study demonstrated that the expression of GFI-1 at different clinical stages of MF was significantly higher compared with benign inflammatory dermatoses, and there was a significant association with disease progression. Gene knockdown of GFI-1 results in the inhibition of Hut-78 cell proliferation and clone formation in vitro, cell cycle arrest and spontaneous apoptosis, upregulation of cell cycle-related P21, as well as the apoptosis-related proteins Bax and Caspase-3, and downregulation of CDK2. Using luciferase assays, and mutational analysis, it was demonstrated that GFI-1 directly regulated the transcription of P21. The results of the present study highlighted a potential molecular therapeutic approach for the treatment of advanced MF.

The value of five blood markers in differentiating mycosis fungoides and Sézary syndrome: a validation cohort*

Clinical and histological diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF) is challenging in clinical routine. We investigated five blood markers previously described for SS (T-plastin, Twist, KIR3DL2, NKp46 and Tox) in a prospective validation cohort of patients. We included 447 patients in this study and 107 patients were followed up for prognosis. The markers were analysed by reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) on peripheral blood leucocytes and CD4+ T cells in a cohort of consecutive patients with early MF, erythrodermic MF and SS and compared with patients presenting with benign inflammatory dermatoses (BID) and erythrodermic BID. The markers were assessed in parallel to gold standard values such as CD4/CD8 ratio, loss of CD7 and CD26 membrane expression and CD4 absolute values. Sensitivity and specificity were analysed by receiver operator characteristic curves. The prognostic value of selected markers was analysed on a subset of patients. This study was conducted in one centre. We defined cut-off values for each marker. T-plastin, Twist and KIR3DL2 had the best validity. SS may be overrepresented. The combination of T-plastin and Twist was able to differentiate between erythrodermic MF or BID and SS. The additional analysis of KIR3DL2 may be useful to predict the prognosis. We propose T-plastin, Twist and KIR3DL2 measured by RT-qPCR as new diagnostic markers for Sézary syndrome.

Sequential Use of Topical Imiquimod and Photodynamic Therapy in Extramammary Paget’s Disease: Disease and Treatment Update and Review of the Literature

Extramammary Paget’s disease (EMPD) represents an intraepithelial carcinoma whose diagnosis is often delayed as it can be easily misdiagnosed as a benign inflammatory dermatosis. Surgery is considered to be the standard treatment, but all surgical modalities are associated with high local recurrence rates. We give concern of this disease through the description of a case of primary EMPD in an 83-year-old lady treated with an alternative modality of treatment: the sequential use of topical imiquimod and photodynamic therapy. Topical treatments can be an alternative, and when used in combination, it allows increasing tolerance and, therefore, treatment compliance and satisfactory outcomes.

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas.

Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.

SEVERE POLYMORPHIC ERUPTION OF PREGNANCY DEVELOPING IN A LATE TERM PRIMIGRAVIDA: A CASE REPORT AND REVIEW OF LITERATURE

Polymorphic eruption of pregnancy [PEP] is a benign inflammatory dermatosis of pregnancy of unknown etiology developing in the third trimester as an intensely pruritic rash and inflamed striae with peri-umbilical sparing. It is a self-limiting condition which resolves after delivery and has no maternal or fetal adverse effects. There are no specific investigations. Diagnosis is based on history and typical clinical features. Emollients, topical corticosteroids and oral antihistamines provide symptomatic relief, though a few patients with severe symptoms may require a short course of oral or injectable corticosteroids. Autologous hemotherapy is a safe option and can be considered in severe conditions.