A comparison of mast cells in skin biopsies of cutaneous mastocytosis with other inflammatory dermatoses: A study of 33 cases.

BACKGROUND: Histopathologic criteria for diagnosis of cutaneous mastocytosis include 20 mast cells per high-power field or clusters of 15 mast cells. We aimed to determine the specificity of these criteria for cutaneous mastocytosis in comparison with inflammatory disorders of mast cell activation. METHODS: Twenty-six cases of spongiotic dermatitis or urticaria were identified from 2021 to 2022. Recuts were stained with mast cell tryptase and slides were reviewed for the presence of 20 mast cells per high-power field and for clusters of 15 mast cells. In addition, seven cases of mastocytosis were reviewed for the same criteria. RESULTS: Twelve of 26 cases (46.1%) of spongiotic dermatitis/urticaria had at least 20 mast cells per high-power field. Three of 26 cases (11.5%) of spongiotic dermatitis/urticaria had a cluster of 15 mast cells. Six of seven cases (85.7%) of mastocytosis had at least 20 mast cells per high-power field; four of seven cases (57.1%) of mastocytosis had a cluster of 15 mast cells. CONCLUSIONS: In our study, the finding of 20 mast cells per high-power field was nonspecific as a single criterion for cutaneous mastocytosis. The finding of clusters of 15 mast cells was more specific but not sensitive.

The mixed spongiotic and interface reaction pattern: A study of clinical and histopathologic findings.

BACKGROUND: Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern. METHODS: Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified. RESULTS: The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04). CONCLUSIONS: The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

Increased MxA protein expression and dendritic cells in spongiotic dermatitis differentiates dermatomyositis from eczema in a single-center case-control study.

BACKGROUND: Dermatomyositis (DM) is conventionally characterized by interface dermatitis (ID) on skin histopathology. A subset of DM patients has skin biopsies showing spongiotic dermatitis (SD), a histopathology more commonly seen in eczema. In this study, we aimed to (a) identify the percentage of clinically diagnosed DM patients with SD skin biopsies, (b) identify cytokine and cell markers that can help determine if a SD skin biopsy is consistent with DM. METHODS: In this case-control study, biopsy specimens from ten DM patients with SD (DM-SD) were compared to specimens from ten healthy controls, ten patients with eczema, and 12 patients with DM with ID (DM-ID). Specimens were stained by immunohistochemistry for MxA, IFN-ß, CD11c, and BDCA2. One-way ANOVA with Bonferroni's multiple comparison test was used to compare protein expression between groups. RESULTS: Eleven of 164 (6.7%) patients with a clinical diagnosis of DM at our tertiary care center were identified as having SD. MxA, IFN-ß, CD11c, and BDCA2 protein expression was significantly higher in DM-SD compared to eczema and healthy controls. Expressions of MxA, IFN-ß, and BDCA2 were not significantly different between DM-SD and DM-ID. CONCLUSION: Increased MxA, IFN-ß, CD11c, and BDCA2 protein expression may aid in distinguishing between DM-SD and eczema and warrants further investigation.

[Report of the first case of tinea corporis bullosa by Trichophyton tonsurans]. / Bericht des ersten Falls einer bullösen Tinea corporis durch Trichophyton tonsurans.

Blister formation in tinea corporis is rare. Bullous tinea is usually evoked by zoophilic dermatophytes. A 20-year-old woman presented in our out-patient department with a painful pruritic bullous skin eruption at the left forearm. Clinically, a 4â€¯× 3 cm symmetrical plaque with sharp borders and peripheral versiculation and serous crusts was seen. Histologically there was a marked spongiotic dermatitis with fungal elements in periodic acid stain (PAS). By fungal culture, PCR and gene sequencing Trichophyton (T.) tonsurans was identified. To the best of our knowledge, this is the first published case of T. tonsurans as the causative agent of bullous tinea corporis.

Clinicopathologic overlap of psoriasis, eczema, and psoriasiform dermatoses: A retrospective study of T helper type 2 and 17 subsets, interleukin 36, and ß-defensin 2 in spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated dermatitis.

BACKGROUND: T helper (Th) type 17 and Th2 cells mediate psoriasis and eczema, respectively. Some dermatoses exhibit overlapping clinicopathologic features, and their immunopathology is relatively unexplored. OBJECTIVE: To determine whether Th17 and Th2 subsets and interleukin (IL) 36 and ß-defensin 2 (BD-2) markers of IL-17 signaling expression can discriminate between biopsy samples of psoriasis and eczematous/spongiotic dermatitis and to use those markers to immunophenotype cases with clinicopathologic overlap. METHODS: A retrospective study was performed on biopsy samples of psoriasis, eczema/spongiotic dermatitis, sebopsoriasis, tumor necrosis factor α inhibitor-associated psoriasiform dermatitis, and ambiguous cases diagnosed as spongiotic psoriasiform dermatitis. Dual CD4/GATA3 and CD4/RORC, IL-36, and BD-2 immunohistochemistry was performed. RESULTS: IL-36 and BD-2 were strongly expressed in biopsy samples of psoriasis compared with eczema/spongiotic dermatitis. No significant differences were observed in the percentages of Th2 and Th17 cells between disease types. Strong expression of IL-36 and BD-2 was observed in a subset of spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated psoriasiform dermatitis biopsy samples. LIMITATIONS: This was an exploratory study with a small sample size. No multiple testing adjustment was done. Clinical follow-up was limited. CONCLUSIONS: In cases with clinicopathologic overlap between psoriasis and spongiotic dermatitis, IL-36, and to a lesser extent BD-2, may be used to assess for a psoriasis-like/IL-17 phenotype, which could inform therapeutic clinical decisions.

Eczematous graft-vs-host disease: A report of three cases and review of the literature.

Graft-vs-host disease (GVHD) is the most common complication following hematopoietic cell transplantation, which affects skin frequently. Acute and chronic forms of GVHD manifest commonly as maculopapular to morbilliform eruptions and sclerotic or lichen-planus-like lesions, respectively; however, atypical presentations such as eczema-like GVHD may occur at times. We describe three cases of GVHD with diverse and polymorphous cutaneous eruptions including pompholyx-like and vasculitis-like rash as well as erythematous plaques and papulosquamous eruptions, with skin biopsy showing unifying histopathological findings with concurrent changes of spongiotic dermatitis and vacuolar interface reaction with apoptotic keratinocytes. In addition, the clinical and pathological features of previously reported cases of eczema-like GVHD are reviewed. It is emphasized that the course of the disease can be variable and successful management often involves a combination of multiple therapeutic modalities including immunosuppression with or without ultraviolet therapy. These cases highlight the importance of meticulous clinicopathological correlation with careful exclusion of mimicking conditions to arrive at the correct diagnosis.

Erosive pustular dermatosis of the scalp: A neutrophilic folliculitis within the spectrum of neutrophilic dermatoses: A clinicopathologic study of 30 cases.

BACKGROUND: It is general opinion that histopathology is nonspecific and of little value in diagnosing erosive pustular dermatosis of the scalp (EPDS). OBJECTIVES: Clinicopathologic correlation of erosive pustular dermatosis of the scalp. METHODS: We reviewed the clinical and pathologic records of patients with a clinicopathologic diagnosis of EPDS between 2011 and 2016 at the Dermatopathology Unit of Turin University. RESULTS: Thirty elderly patients with EPDS were identified (22 men and 8 women). Androgenetic alopecia was present in 19 of 30 patients. Triggering factors included mechanical trauma in 10 of 30 cases, surgical procedures in 4 of 30 cases, and herpes zoster in 1 of 30 cases. Three patients were affected by autoimmune disorders. The vertex was the most common location. Disease presentation varied markedly from tiny, erosive, scaly lesions to crusted and hemorrhagic plaques, mimicking pustular pyoderma gangrenosum. The pathologic changes differed according to lesion type and disease duration. Interestingly, a spongiotic and suppurative infundibulo-folliculitis was observed in 8 of 30 cases. LIMITATIONS: This was a retrospective study. CONCLUSIONS: We believe that the primary lesion of erosive pustular dermatosis of the scalp is a spongiotic, pustular superficial folliculitis. The clinicopathologic similarities with other neutrophilic dermatoses, such as pustular pyoderma gangrenosum, suggest this condition should be included in this spectrum, where pathergy plays a pathogenetic role.

Spontaneously regressing brain lesions in Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder caused by an inborn error of cholesterol synthesis that affects the development of many organ systems. Malformations in the central nervous system typically involve midline structures and reflect abnormal growth and differentiation of neurons and supporting cells. Despite these defects in central nervous system development, brain tumor formation has only rarely been reported in association with SLOS. We present three individuals with SLOS and lesions in the basal ganglia or brainstem detected by MRI that were concerning for tumor formation. However, the individuals' clinical and neurological course remained stable, and the lesions regressed after several years. These lesions have similarities to spongiotic changes observed in individuals with neurofibromatosis type 1 (NF1). Notably, impaired activity of small GTPases is present in both SLOS and NF1, perhaps giving mechanistic insight into the formation of these lesions.

Progression of undiagnosed cutaneous lymphoma after anti-tumor necrosis factor-alpha therapy.

BACKGROUND: Cutaneous lymphoma diagnosed after anti-tumor necrosis factor-α therapy (anti-TNF-α) has been reported in the literature, yet a clear link between both events remains elusive. OBJECTIVE: To review our experience with cutaneous lymphoma diagnosed during or after the use of anti-TNF-α therapies. METHODS: This is a multicenter retrospective study and a literature review. RESULTS: A total of 22 cases, including 20 cutaneous T-cell lymphomas (CTCLs) and 2 cutaneous B-cell lymphomas, were identified. In the CTCL group, 75% of the patients received an anti-TNF-α agent for a presumed inflammatory skin condition. Mycosis fungoides and Sézary syndrome were the most common subtypes of CTCL diagnosed. Advanced disease (stage IIB to IVA) was commonly seen at time of diagnosis and required aggressive therapy, including stem cell transplant in 3 patients; 2 patients in whom cutaneous B-cell lymphomas was diagnosed had an indolent course. A total of 31 cases were gathered from a literature search. LIMITATIONS: This is a retrospective study. CONCLUSIONS: Our findings suggest that the disease of most of the identified patients was misdiagnosed as psoriasis or eczema; therefore, a comprehensive morphologic and molecular review of skin biopsy specimens and peripheral blood samples should be considered before initiation of anti-TNF-α therapy in patients with poorly defined dermatitis or atypical presentations of psoriasis.

Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study.

BACKGROUND: Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized. OBJECTIVE: To assess the nature of dermatitis after exposure to a PD-1/PD-L1 inhibitor and oncologic outcomes associated with dermatitis. METHODS: Retrospective, matched, case-control study conducted at a single academic center. RESULTS: The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). The overall tumor response rate was 65.0% for the case patients and 17.0% for the controls (P = .0007) (odds ratio, 7.3; 95% confidence interval, 2.3-23.1). The progression-free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan-Meier analysis (P < .0001 and .0203, respectively). LIMITATIONS: The retrospective design and relatively small sample size precluded matching for all cancer types. CONCLUSIONS: Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The value of PD-1/PD-L1-related dermatitis in predicting cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.

Feasibility study in teledermatopathology: An examination of the histopathologic features of mycosis fungoides and spongiotic dermatitis.

BACKGROUND: Digital pathology offers numerous advantages, allowing remote information sharing using whole slide imaging (WSI) to digitize an entire glass slide (GS) at high resolution, creating a digital slide (DS). METHODS: In this study, we examine the concordance in diagnoses made on 40 digital slides (DSs) vs traditional GSs in differentiating between spongiotic dermatitis (SD) and patch/plaque-stage mycosis fungoides (MF). RESULTS: Greater interobserver concordance rate in final diagnosis of SD vs MF was observed with the utilization of DS (86.7%) compared with the utilization of GS (80%). Intraobserver concordance rate between the diagnoses rendered by a particular dermatopathologist on GS and DS was 86.7%. For all histopathological criteria, a correlation in the magnitudes of interobserver vs intraobserver discordances suggests that discordance between glass vs digital evaluation of these criteria may be largely expected subjective read variation independent of the media. Discordance in identification of histopathological features did not have a statistically significant link to discordance in diagnosis for 7 out of the 8 features. CONCLUSIONS: The similarity between interobserver and intraobserver discordances suggests that WSI does not introduce additional barriers or variability to accurately identify histopathologic feature and to discriminate between MF and SD beyond interobserver variability.

Psoriasiform dermatitides: A brief review.

Psoriasis vulgaris (PV)-the prototypical "psoriasiform" dermatitis-may assume a spectrum of histologic appearances, depending on whether it has been treated or not. Because of that relative lack of morphological uniformity, other skin disorders that feature epidermal acanthosis, with or without associated inflammation, may be confused diagnostically with PV. This brief review considers the clinicopathologic attributes of PV and its imitators, including chronic spongiotic dermatitides, lichen simplex chronicus, prurigo nodularis, pityriasis rubra pilaris, psoriasiform secondary syphilis, and Reiter syndrome.

Localized Juvenile Spongiotic Gingival Hyperplasia: Report of Two Cases.

OBJECTIVE: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a painless gingival swelling that histologically exhibits hyperplasia of the non-keratinized stratified squamous epithelium, intercellular edema and spongiosis of the spinus layer, and exocytosis of inflammatory cells. LJSGH pathogenesis remains to be elucidated, while a possible origin from the gingival sulcus epithelium is nowadays proposed. STUDY DESIGN: We report two cases of LJSGH with immunohistochemical evaluation of cytokeratins (CKs) 18 and 19. RESULTS: Both cases concerned 12-year-old boys, who presented with a well-circumscribed bright red pedunculated papillary swelling on the marginal gingiva of the left maxillary lateral incisor. With the provisional diagnosis of LJSGH, the lesions were excised under local anesthesia and histological examination supported the final diagnosis of LJSGH. In both cases, the lesional epithelium showed intense and mild positivity for CK19 and CK18, respectively, while the adjacent normal gingival epithelium expressed CK19, but not CK18, only in the basal cell layer. The postoperative course was uneventful in both patients and no recurrence has been reported. CONCLUSION: LJSGH is a recently introduced entity that is worth attention in the clinical pediatric dentistry. Clinical and histological examination is required for the final diagnosis, while immunohistochemistry has shed light to LJSGH pathogenesis.

Localized juvenile spongiotic gingival hyperplasia possibly originates from the junctional gingival epithelium-an immunohistochemical study.

AIMS: To immunohistochemically evaluate the cytokeratin (CK) pattern of expression in localized juvenile spongiotic gingival hyperplasia (LJSGH) as compared with the gingival epithelium (GE). METHODS AND RESULTS: Ten cases of LJSGH were semiquantitatively evaluated for the immunohistochemical pattern of CK1/10, CK4, CK8/18, and CK19. GE controls were taken from 10 cases of reactive gingival fibroepithelial hyperplasia. GEs showed mean positivity rates of 80% for both CK1/10 and CK4, and 5% for both CK8/18 and CK19. LJSGHs showed mean positivity rates of 65% for CK19, 60% for CK8/18, 30% for CK4, and 5% for CK1/10. The differences between LJSGHs and GEs were statistically significant (P < 0.01). CONCLUSIONS: The LJSGH pattern of CK expression is reminiscent of the profile described in the literature for the junctional epithelium (JE). Possibly, JE exteriorized from the gingival sulcus would be more prone to irritation from a variety of sources, resulting in inflammation and hyperplasia, with the subsequent development of LJSGH.

Reflectance Confocal Microscopy for Inflammatory Skin Diseases.

In vivo reflectance confocal microscopy (RCM) is a relatively novel non-invasive tool for microscopic evaluation of the skin used prevalently for diagnosis and management of skin tumour. Its axial resolution, its non-invasive and easy clinical application represents the goals for a large diffusion of this technique. During the last 15 years, RCM has been demonstrated to be able to increase the sensibility and sensitivity of dermoscopy in the diagnosis of skin tumours integrating in real time clinic, dermoscopic and microscopic information useful for the definition of malignancy. Despite to date, no large comparative studies on inflammatory skin diseases has been published in the literature, several papers already showed that RCM has a potential for the evaluation of the descriptive features of the most common inflammatory skin diseases as psoriasis, lupus erythematosus, contact dermatitis and others. The aim of the application of this technique in non-neoplastic skin diseases has been prevalently focused on the possibility of clinical diagnosis confirmation, as well as therapeutic management. Moreover, the use of RCM as driver for an optimised skin biopsy has been also followed in order to reduce the number of unsuccessful histopathological examination. In this review article we describe the confocal features of the major groups of inflammatory skin disorders focusing on psoriasiform dermatitis, interface dermatitis and spongiotic dermatitis.

Localized juvenile spongiotic gingival hyperplasia featuring unusual p16INK4A labeling and negative human papillomavirus status by polymerase chain reaction.

BACKGROUND: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a distinct type of gingival hyperplastic lesion with specific clinicopathologic features. Evaluation of the morphological characteristics of LJSGH indicates the potential role of human papillomavirus (HPV) infection as an underlying etiopathogenetic mechanism. METHODS: All cases of LJSGH from 2008 to present were retrieved. Clinical and demographic data were collected. HPV status was investigated by p16INK4A immunohistochemistry and HPV-Polymerase chain reaction (PCR). RESULTS: Twenty-one cases of LJSGH were identified, 14 (66.7%) affecting males and seven (33.3%) females (M:F = 2:1, age range: 8-36, mean: 13 years). All lesions were well-demarcated, exophytic, erythematous, and hemorrhagic with granular or slightly papillary surface. Preponderance for the maxillary gingiva (19, 90.5%) was observed. Two (9.5%) patients presented with recurrence 20 and 21 months after excision (mean follow-up: 18.7 months). Histopathologically, all LJSGH lesions featured epithelial hyperplasia with intense neutrophilic exocytosis and spongiosis. All cases demonstrated positivity for p16INK4A with the majority of specimens (47.6%) intensely decorated in >50% of the overlying epithelium with focal immunostaining observed in 47.6% and diffuse in 52.4%. Thirteen cases (61.9%) were negative for HPV DNA by PCR, while two (9.5%) were suspicious for the presence of low levels of HPV DNA but definitive genotyping was not possible. One case (4.8%) displayed positivity for HPV-31. The remaining five cases failed the PCR reaction. CONCLUSIONS: Human papillomavirus does not participate in the pathogenesis of LJSGH. P16INK4A expression in the absence of detectable HPV DNA can likely be attributed to the intense inflammation associated with LJSGH.

Interface dermatitis along Blaschko's lines.

Linear dermatoses are fascinating entities that likely reflect embryologically derived cutaneous mosaicism, even when they occur after childhood. Adult blaschkitis is a rare, relapsing inflammatory dermatitis that most often presents in middle age. It presents clinically as a pruritic eruption of linear papules, vesicles and plaques, and is most commonly found to have features of spongiotic dermatitis on pathology. However, the clinical and histopathologic presentation of lichen striatus in adults may be similar to those of adult blaschkitis. A case in which 'blaschkitis' was suspected clinically is presented, in which the biopsy showed non-characteristic microscopic features resembling erythema multiforme--a finding rarely reported in the literature to date. We present this case and a brief review of the most commonly acquired linear eruptions following Blaschko's lines with the goal of expanding the histopathologic findings that may be encountered in adult blaschkitis. Moreover, the clinical and histopathologic overlap between the entities of blaschkitis and lichen striatus is explored, acknowledging that these entities may exist on a clinicopathologic spectrum. In the diagnosis of linear eruptions, clinicopathologic correlation is important for arriving at an accurate final diagnosis.

Challenges in diagnosing spongiotic dermatitis: A complex case report.

This case study presents a challenging case of spongiotic dermatitis manifesting in the vaginal region. Spongiotic dermatitis, characterized by fluid buildup causing skin swelling, poses diagnostic difficulties due to its resemblance to other skin conditions. A 64-year-old female initially misdiagnosed with various genital infections underwent multiple treatments without relief. With Sexually Transmitted Diseases (STD) tests being negative, a biopsy later revealed spongiotic dermatitis. Histological examination confirmed characteristic features of spongiotic dermatitis, guiding definitive diagnosis. Following confirmation of spongiotic dermatitis through biopsy, the patient received appropriate treatment, leading to the resolution of symptoms. This case underscores the importance of biopsy in diagnosing spongiotic dermatitis amidst variable clinical presentations, highlighting the need for further research to understand spongiotic dermatitis prognosis and clinical manifestations.

A Cross-Sectional Study of Epidemiological and Clinical Aspects of Pityriasis Rosea along with Dermoscopic Analysis and Histopathology Correlation.

Background: Pityriasis Rosea (PR) is a common, yet enigmatic, dermatological condition characterized by a distinctive clinical presentation. Despite its prevalence, the aetiology and pathogenesis of PR remain elusive. Aims: To study the epidemiological and clinical aspects of patients with PR. To study dermoscopic findings and carry out histopathological correlation. Methods: A cross-sectional study of 50 patients was conducted. A detailed clinical history was taken and an examination was done followed by a dermoscopy. Quantitative data like age and duration of disease are presented with the help of standard deviation. Qualitative risk factors, like gender, age groups, symptomatology, site of lesion, findings or cutaneous examination, dermoscopy findings, and histopathology findings, are presented with the help of frequency and percentages. Results: PR shows male preponderance and mean age of occurrence being 30.8 ± 15.7 years. Forty per cent of patients had an atypical clinical presentation. The most frequently seen dermoscopy findings were diffuse red background (58%), peripheral collarette scale (62%), and peripheral dotted vessels (50%). On histopathology, the most common findings were spongiosis (44%), parakeratosis (38%), irregular acanthosis (34%), perivascular lymphocytic infiltrate (56%), and red blood cell extravasation (36%). Limitations: Sample size was less due to COVID. As this was a corss-sectional study follow up of patients could not be done. Conclusion: While the diagnosis of PR is clinical, it is difficult in atypical cases where dermoscopy comes to the aid. It also helps identify the age of lesions, thus helping decide the treatment strategy for patients. Biopsy remains the gold standard in ruling out other differentials of PR.