Cytologic atypia of benign inflammatory versus neoplastic cutaneous squamous lesions.

BACKGROUND: Cytologic atypia encompasses several features of abnormal cellular morphology. We sought to quantify these features in benign and premalignant/malignant squamous cell lesions to better characterize criteria for malignancy. METHODS: We conducted a rater-blinded observational study in which histopathology slides were evaluated under light microscopy, and the presence and relative quantity of 24 distinct cytological features were recorded, along with respective diagnoses. Each slide was evaluated, and the ratings were recorded and analyzed. RESULTS: The most helpful findings, whose presence in high numbers indicates an increased likelihood that the tissue sample is premalignant/malignant, were: (1) pleomorphic parakeratosis; (2) pleomorphic nuclei in the epithelium; (3) irregular nuclei; (4) thick refractile nuclear envelope; (5) presence of nuclear hyperchromasia (dark gray); (6) peripheral nucleoli; and (7) nucleolar stems. Higher values of round or oval nuclear shape and vesicular nuclei increase the likelihood that the tissue sample is benign. CONCLUSIONS: Certain nuclear features have a higher association with premalignancy/malignancy and may guide histologic evaluation of a given lesion. These findings can be used in combination with architectural features and clinical history to add to a complete diagnostic picture.

Spiny keratoderma: A review of case reports and histopathological descriptions.

Spiny keratoderma (SpK) is a rare skin condition characterized by spine-like papules on the palms and soles. The condition is identified under several names such as "music box spine keratosis" and "palmoplantar filiform hyperkeratosis," creating ambiguity in the diagnostic and histopathologic features of the disease. In this study, we reviewed 84 cases of SpK to examine patient demographics, medical history, clinical and histopathological descriptions, and sporadic versus hereditary onset. Notably, the most used histopathological terms were "parakeratosis" and "hypogranulosis," and the most used clinical terms were "spine" and "hyperpigmented." The average age at presentation was 60.1 years with the majority of cases in males. Only 29.8% of cases were associated with a family history of SpK and underlying malignancies were present in 28.6% of cases. This review investigates the frequency of histopathologic and clinical terms used to describe SpK to provide insight into the clinical and histopathological characteristics of this rarely reported condition.

Comparison of reflectance confocal microscopy and line-field optical coherence tomography for the identification of keratinocyte skin tumours.

BACKGROUND: Reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT) are non-invasive imaging devices that can help in the clinical diagnosis of actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC). No studies are available on the comparison between these two technologies for the identification of the different features of keratinocyte skin tumours. OBJECTIVES: To compare RCM and LC-OCT findings in AK and SCC. METHODS: A retrospective multicenter study was conducted. Tumours were imaged with RCM and LC-OCT devices before surgery, and the diagnosis was confirmed by histological examinations. LC-OCT and RCM criteria for AK/SCC were identified, and their presence/absence was evaluated in all study lesions. Gwet AC1 concordance index was calculated to compare RCM and LC-OCT. RESULTS: We included 52 patients with 33 AKs and 19 SCCs. Irregular epidermis was visible in most tumours and with a good degree of agreement between RCM and LC-OCT (Gwet's AC1 0.74). Parakeratosis, dyskeratotic keratinocytes and both linear dilated and glomerular vessels were better visible at LC-OCT than RCM (p < 0.001). Erosion/ulceration was identified with both methods in more than half of the cases with a good degree of agreement (Gwet AC1 0.62). CONCLUSIONS: Our results suggest that both LC-OCT and hand-held RCM can help clinicians in the identification of AK and SCC, providing an in vivo and non-invasive identification of an irregular epidermis. LC-OCT proved to be more effective in identifying parakeratosis, dyskeratotic keratinocytes and vessels in this series.

Hyperkeratotic erythema multiforme variant in 17 dogs.

BACKGROUND: A new canine subgroup defined as 'old-dog' or 'hyperkeratotic' erythema multiforme (HKEM) with marked hyperkeratosis and parakeratosis has been proposed without any detailed description of larger case series. OBJECTIVES: We report herein the signalment, clinical signs, treatment outcome, and histopathological and immunological findings in 17 dogs with HKEM. ANIMALS: Inclusion criteria were the presence of (i) scaly skin lesions with or without crusting; and (ii) microscopic lesions typical of EM (i.e. a panepidermal cytotoxic lymphocytic dermatitis with or without basal keratinocyte apoptosis); and (iii) microscopic ortho- and/or parakeratotic hyperkeratosis affecting the interfollicular epidermis. MATERIALS AND METHODS: Clinical questionnaires and skin biopsies were reviewed. Polymerase chain reactions for epidermotropic viruses and direct immunofluorescence were performed. RESULTS: Various breeds were affected with an over-representation of males in their mid-to-late adulthood (median age 9 years). Generalised skin lesions included multifocal-to-coalescing, linear and annular macules and plaques with erythema and adherent firm crusting. Microscopic lesions were specific for EM and featured prominent superficial epidermal apoptosis with lymphocytic satellitosis and parakeratosis. No drug triggers were identified. Polymerase chain reactions for canine herpesvirus polymerase gene, canine parvovirus and canine distemper virus were negative in all HKEM and canine erosive EM (15 dogs) biopsies. Lesions failed to respond to oral and/or topical antimicrobials. Complete remission of signs was achieved in 9 of 17 dogs (53%) using immunosuppressive regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Hyperkeratotic erythema multiforme (HKEM) is a chronic, persistent and clinically distinctive erythema multiforme (EM) variant that differs from 'classic' vesiculobullous erosive-to-ulcerative EM in dogs.

Histopathologic features of inverse psoriasis.

BACKGROUND: Inverse psoriasis represents a less commonly described form of psoriasis in intertriginous areas. The pathologic findings of inverse psoriasis are typically grouped in with those of plaque psoriasis, as the histopathologic features specific to inverse psoriasis have not received significant investigation. METHODS: A single institution, retrospective cohort study was performed to review biopsy slides for psoriasis occurring in typical intertriginous areas. Patient's charts were reviewed and only those where the clinical diagnosis of inverse psoriasis was also favored were included. RESULTS: Twelve patients met inclusion criteria: 58% male and 42% female, 18 to 86 years of age. Classic features of psoriasis such as hypogranulosis, confluent parakeratosis, and thinning of the suprapapillary plate were seen in 100%. Regular psoriasiform acanthosis and dilated tortuous dermal vessels were seen in 92%. Neutrophils were present in the scale in 83% and in the dermis in 100%. Features considered atypical for psoriasis included spongiosis in 83%, eosinophils in 67%, and focal serum in the scale in 42%. CONCLUSIONS: While inverse psoriasis commonly exhibits features considered to be classic for psoriasis, it is not unusual for inverse psoriasis to show features considered atypical for plaque psoriasis such as dermal eosinophils, epidermal spongiosis, and focal serum in the scale.

Hyperkeratotic flexural erythema (more commonly known as granular parakeratosis) with use of laundry sanitizers containing benzalkonium chloride.

BACKGROUND: Hyperkeratotic flexural erythema (HKFE), also known as granular parakeratosis, is a scaly, erythematous or brown eruption, which usually occurs in the intertriginous and flexural areas. It has been linked to the use of benzalkonium chloride (BAK). AIM: To review the clinical presentation of patients diagnosed with HKFE who had been exposed to laundry sanitizer containing BAK, and the therapies trialled to treat these patients. METHODS: This was a retrospective cases series of 45 patients seen by dermatologists in Victoria, Australia. Information was collected on clinical presentation, investigation and management. RESULTS: The patients varied in age from 18 months to 89 years. The rash typically presented as a symmetrical erythema with characteristic multilayered brownish epidermal scaling. The most common location of the rash was the inguinal/anogenital area (32 of 45 patients; 71.1%) and there was a female predominance. Regarding treatment, topical corticosteroids were frequently prescribed and antibiotics were trialled in 11 patients; however, the condition resolved spontaneously over time in all patients with use of emollients, along with cleaning of the washing machine by running an empty wash, and repeated washing or sometimes disposal of BAK-contaminated clothing. CONCLUSION: This large case series highlighted the characteristic clinical presentation of HKFE in the setting of BAK used in laundry sanitizer, demonstrating a potential causal link. Further studies are required to evaluate the role of the skin microbiome.

The pits.

A 71-year-old woman presented with a rash in the bilateral axillae. Histopathology showed hyperkeratosis and parakeratosis with retention of basophilic keratohyalin granules.

Erythematous flexural eruption in a young man.

A young man presented with a 2-week history of well-defined erythematous plaques symmetrically distributed in multiple intertriginous areas. He had received topical corticosteroids, antifungals and oral prednisolone without improvement. Histopathological examination revealed confluent parakeratosis with retention of basophilic keratohyalin granules within the stratum corneum. Click here for the corresponding questions to this CME article.

Epidermal Hyperproliferation With Less Prominent Dermal Inflammation Is the Unique Histopathological Feature of the Refractory Lesions in Psoriasis Treated With Ustekinumab.

ABSTRACT: Although ustekinumab (UST) shows excellent efficacy in treating psoriasis, not all patients have a complete clearance rate. The purpose of this study was to investigate the histopathological characteristics of refractory psoriasis lesions in patients with excellent response to UST. Fifty-seven patients with newly diagnosed psoriasis and 66 patients with a 75% reduction in the Psoriasis Area and Severity Index score after UST treatment were included. Computer-aided image analysis was performed to measure the epidermal thickness, horny layer thickness, number of dermal vessels, and dermal inflammatory cell infiltration rate. Parakeratosis was scored using a 4-point scale. These measurements were compared between the refractory lesions of UST-treated patients and the untreated lesions of newly diagnosed patients after the adjustment for confounding factors. The dermal inflammatory cell infiltration rate was significantly lower in the refractory lesions (P = 0.022). Meanwhile, the epidermal thickness, horny layer thickness, grade of parakeratosis, and dermal vessel count did not differ between the groups (P = 0.125, 0.719, 0.542, and 0.758, respectively). Subgroup analyses were performed within the UST-treated group after dividing them into 2 groups according to the number of treatments or treatment response rates. None of these features were significantly different between the subgroups. This study suggests that the reduction of dermal inflammation by UST was not sufficient to ameliorate the epidermal changes and implies the role of the interleukin-23-independent downstream cytokine pathway in causing the refractory lesions among patients who responded well to UST. The continuation of UST treatment might not further improve epidermal alterations.

Hyperkeratotic flexural erythema/granular parakeratosis responding to doxycycline.

Hyperkeratotic flexural erythema (HKFE), also termed granular parakeratosis (GP), is a rare skin condition thought to be linked to a skin barrier dysfunction process, however the exact cause of this is yet to be determined. Management options are varied, with no consensus on treatment. Several previous reports have recorded successful treatment with amoxycillin-clavulanic acid combination. We propose the use of oral doxycycline in addition to topical coconut oil compound as a treatment option in therapy resistant HKFE.

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Regulates Epidermal Keratinization under Psoriatic Skin Inflammation.

Psoriasis is an autoinflammatory/autoimmune skin disease and the epitome of an exaggerated primary inflammatory response in the surface barrier tissue. Despite the efficacy of dimethyl fumarate, an electrophilic drug for psoriasis management, there is a paucity of mechanistic evidence in vivo. In response to electrophiles, the Kelch-like erythroid cell-derived protein with cap-n-collar homology-associated protein 1/nuclear factor erythroid 2-related factor 2 (NRF2) system mediates a myriad of cytoprotective mechanisms, including the regulation of excessive inflammatory response and epidermal differentiation. Because the psoriasiform tissue reaction comprises neutrophil infiltration and parakeratotic scaling, it is hypothesized that Nrf2 not only regulates inflammatory responses but also maintains epidermal differentiation, a hallmark of epidermal homeostasis. By using the imiquimod-induced cutaneous inflammation model, an exaggerated inflammatory response and impaired epidermal differentiation in Nrf2-/- mice was detected. Dimethyl fumarate treatment in Nrf2+/+ mice attenuated a psoriasiform tissue reaction and rescued epidermal differentiation, which was not observed in Nrf2-/- mice. In accordance with the fact that psoriasis plaques form well-demarcated parakeratotic lesions in association with the psoriasiform tissue reaction, the lesional skin showed reduced expression levels of NRF2 and its downstream target genes compared with nonlesional skin. In conclusion, Nrf2 attenuates the psoriasiform tissue reaction and underscores the mechanistic legitimacy of the electrophile-based approach for the management of psoriasis.

Psoriasis on the Leg: Site-specific Histopathological and Immuno-histochemical Features and Diagnostic Difficulties.

The histopathology of psoriasis can lack classical features on certain anatomical sites. The aim of this study was to detail the histopathology and immunophenotype of psoriasis on the legs, in order to differentiate it from other inflammatory dermatoses, such as stasis dermatitis. The histopathology of psoriasis on the legs was retrospectively compared with psoriasis on the trunk and stasis dermatitis. Statistically, psoriasis on the legs was significantly less likely to show typical histological criteria of psoriasis, such as regular hyperplasia, suprapapillary thinning, and "kissing vessels". The most valuable criteria to distinguish psoriasis on the legs from stasis dermatitis were the presence of neutrophils in the cornified layer and staggered parakeratosis. In addition, an immunohistochemical panel (Ki-67, Bcl-2alpha, S100A7, CD3, MPO, CK10, CK16) revealed that staining with Ki-67 and MPO could be diagnostically useful. Since the cornified layer contains important histopathological clues to differentiate psoriasis on the legs from stasis dermatitis, clinicians should refrain from unnecessary rubbing during disinfection before taking a biopsy.

Axillary Granular Parakeratosis.

We describe a case of an 85-year-old Caucasian female who presented to the dermatology clinic with pruritic, scaly hyperpigmented papules and plaques with surrounding erythema in the left axilla. Based on the history and physical examination, there was concern for possible varicella zoster infection, and the patient was started on valacyclovir 1000 mg three times daily for seven days. A shave biopsy was taken from the left axilla to confirm a diagnosis. Microscopic examination revealed compact hyperparakeratosis with keratohyalin granules throughout the parakeratotic stratum corneum as well as admixed eosinophils within the stratum corneum. The epidermis was acanthotic with irregular hyperplasia of the rete ridges. These microscopic findings supported a diagnosis of axillary granular parakeratosis, a benign skin condition caused by a defect in epidermal differentiation. Granular parakeratosis is seemingly rare but is felt to be an underreported condition. It is important for clinicians to be aware of the disease in order to correctly identify the lesions and reassure patients of its benign nature and provide appropriate treatment recommendations.

Aluminum Chloride-Induced Apoptosis Leads to Keratinization Arrest and Granular Parakeratosis.

Aluminum chloride (AlCl3) is the main active ingredient in commonly used antiperspirant. Antiperspirant use may cause a rare keratinization disease, granular parakeratosis (GP), then AlCl3 may be associated with the etiology of GP. The objective of this study is to elucidate the skin effect of topical aluminum application using a mouse model. We sprayed 20% aluminum chloride every day on the depilated mice skin and analyzed the skin clinically, histopathologically, and immunohistologically. We have succeeded in the histological replication of GP on mouse skin. The basophilic granules in the stratum corneum contained filaggrin, and processing of profilaggrin to filaggrin was disrupted in aluminum-treated mouse skin (Al-mouse). In Al-mouse, cytochrome c and cleaved-caspase 3 were upregulated mainly in the granular layer, and caspase 3 p20 subunit was upregulated. TUNEL-positive cells increased significantly in the Al-mouse from the granular to the horny layer. Caspase 3 inhibitor inhibited granular parakeratotic change of Al-mouse. Our results indicated that aluminum-induced apoptosis leads to keratinization arrest and acceleration of nuclear degradation before completion of profilaggrin processing. This could lead to retention of the basophilic granules composed of underprocessed profilaggrin in the horny layer of Al-mouse skin, the hallmark of GP.

Mucinous Syringometaplasia: Surrounding Acanthosis With Hyperkeratosis Tends to Conceal the Change.

A 57-year-old man had a 2-year history of a painful nodule on the right sole. Physical examination revealed an 8 × 8 mm hyperkeratotic plaque with a central fissure. Excisional biopsy disclosed epithelial invagination surrounded by the acanthotic epidermis with parakeratotic hyperkeratosis and focal hypergranulosis. The invaginated epithelium lacked a cornified layer and was composed of a mixture of small basaloid squamous cells and goblet cells showing tubular structures. The patient was diagnosed with mucinous syringometaplasia. Our literature review established that surrounding acanthosis with hyperkeratosis typically tends to conceal mucinous syringometaplastic changes. Because mucinous syringometaplasia often presents as an asymptomatic papule/nodule with no distinct ulcer, fissure, or depressed area, cases may be overlooked.

Dermatomyositis: Histopathologic findings of parakeratosis and dermal edema revisited.

The cutaneous manifestations of dermatomyositis range from classical in the case of heliotrope rash and Gottron papules to less common papulosquamous and edematous/vesiculobullous lesions; histopathologic descriptions are dominated by interface dermatitis. We present a case of dermatomyositis with a combination of common and rare skin findings, both clinically and histologically. Increased awareness of papulosquamous and edematous lesions of dermatomyositis can help direct patient care. Although uncommon, confluent parakeratosis and dermal edema can be manifestations of dermatomyositis.

Degree of Skin Barrier Disruption Affects Lipid Organization in Regenerated Stratum Corneum.

Previously, a skin barrier repair model was developed to examine the effect of formulations on the lipid properties of compromised skin. In this model, the lipid organization mimics that of several skin diseases with impaired skin barrier and less dense lateral lipid organization. In addition, parakeratosis was occasionally observed. The present study investigated whether the extent of initial barrier disruption affects lipid organization and parakeratosis in regenerated stratum corneum. After barrier disruption and stratum corneum regeneration the fraction of lipids adopting a less dense lateral organization gradually increased with increasing degree of barrier disruption. Only when 75% of the stratum corneum was removed, were parakeratosis and a change in lamellar organization observed. This demonstrates the possibility of using the skin barrier repair model to study the effects of formulations on compromised skin in which the presence of parakeratosis and lipid organization can be modified by the extent of barrier disruption.

A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis.

Hereditary nasal parakeratosis (HNPK), described in the Labrador Retriever breed, is a monogenic autosomal recessive disorder that causes crusts and fissures on the nasal planum of otherwise healthy dogs. Our group previously showed that this genodermatosis may be caused by a missense variant located in the SUV39H2 gene encoding a histone 3 lysine 9 methyltransferase, a chromatin modifying enzyme with a potential role in keratinocyte differentiation. In the present study, we investigated a litter of Greyhounds in which six out of eight puppies were affected with parakeratotic lesions restricted to the nasal planum. Clinically and histologically, the lesions were comparable to HNPK in Labrador Retrievers. Whole genome sequencing of one affected Greyhound revealed a 4-bp deletion at the 5'-end of intron 4 of the SUV39H2 gene that was absent in 188 control dog and three wolf genomes. The variant was predicted to disrupt the 5'-splice site with subsequent loss of SUV39H2 function. The six affected puppies were homozygous for the variant, whereas the two non-affected littermates were heterozygous. Genotyping of a larger cohort of Greyhounds revealed that the variant is segregating in the breed and that this breed might benefit from genetic testing to avoid carrier × carrier matings.