Update of pathophysiology and treatment options of seborrheic keratosis.

Seborrheic keratosis (SK) is a common, benign tumor that can occur on everybody site and can be conservatively managed. Cosmetic concerns, especially when a lesion involves the facial area, are the most common reason for excision. SK shows male gender preponderance and increasing age is an independent association with the condition. Even though more prevalent in the elderly, it has also been reported in younger age groups like adolescents and young adults. Precise pathogenesis is still obscure, but ultra-violet exposure represents a predisposing factor to SK by altering the biochemical concentration and expression of factors like Glutamine deaminases, endothelin, and stem cell factor. Moreover, the accumulation of amyloid-associated protein has also been postulated. Involvement of genitalia has been associated with human papillomavirus infection. Recently, Merkel cell polyomavirus nucleic acid was also detected in SK. Several oncogenic mutations involving FGFR-3 and FOXN1 have been identified. SKs are usually classified clinically and histologically. Dermatoscopy is a noninvasive alternative diagnostic technique widely used in differentiating SK from other benign and malignant tumors. In terms of treatment, topical agents, shave dissection, cryosurgery, electrodesiccation, laser application and curettage under local anesthesia are safe methods for eradication of SKs, mostly for cosmetic purposes. Though generally safe, the latter techniques may occasionally cause post-procedure depigmentation, scarring, and recurrence. Nanosecond-pulsed electric field technology is a promising new technique with fewer side-effects.

Scurvy and Tinea Corporis Simulating Leukocytoclastic Vasculitis.

ABSTRACT: Leukocytoclastic vasculitis (LCV) is a small vessel inflammatory condition considered to be caused by circulating immune complexes and often occurs after an acute infection or exposure to a new medication, although it may be associated with an underlying systemic disease or be idiopathic in nature. It is important to determine the etiology, identify the extent of the disease for early intervention and appropriate management, and treat and/or eliminate the underlying cause. Here, we report cases of scurvy and tinea corporis that presented with histopathologic features of LCV and had significant clinical improvement with treatment of the underlying etiologies. These cases emphasize that histopathologic features of early evolving LCV may be seen in other settings including scurvy and tinea corporis. Appropriate treatment of the underlying condition is important for optimized patient management.

Corrigendum: Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month followup of negative test results and utility data from a large US registry study.

The revised version of the article corrected Figure 2. This change appears in the revised online PDF copy of this article.

Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study.

The Pigmented Lesion Assay (PLA, sensitivity 91-95%, specificity 69-91%, negative predictive value ?99%) is a commercially available, non-invasive gene expression test that helps dermatologists guide pigmented lesion management decisions and rule out melanoma. Earlier studies have demonstrated high clinical utility and no missed melanomas in a 3-6-month follow-up period. We undertook the current investigations to provide 12-month follow-up data on PLA(-) tests, and to further confirm utility. A 12-month chart review follow-up of 734 pigmented lesions that had negative PLA results from 5 US dermatology centers was performed. Thirteen of these lesions (1.8%) were biopsied in the follow-up period and submitted for histopathologic review. None of the lesions biopsied had a histopathologic diagnosis of melanoma. The test's utility was studied further in a registry (N=1575, 40 US dermatology offices, 62 participating providers), which demonstrated that 99.9% of PLA(-) lesions were clinically monitored, thereby avoiding a surgical procedure, and 96.5% of all PLA(+) lesions were appropriately biopsied, most commonly with a tangential shave. This long-term follow-up study confirms the PLA's high negative predictive value and high utility in helping guide the management of pigmented lesions to avoid unnecessary surgical procedures.

Primary low-grade neuroendocrine carcinoma of the skin: An exceedingly rare entity.

Low-grade neuroendocrine tumors (NETs), also known as carcinoid tumor, commonly arise from the gastrointestinal (GI) and pulmonary tracts, but rarely occur in the skin. Cutaneous NET typically occurs as metastases or high-grade primary lesions, called Merkel cell carcinoma. In the few cases described in literature, primary low-grade neuroendocrine carcinomas of the skin (LGNECS) are usually indolent cutaneous nodules, presenting on the head and trunk of elderly patients. LGNECS tumors are histologically similar to its counterparts arising in other anatomic locations. As there is no NET cut-off for the skin due to their rarity, the GI scale was used instead; low-grade NETs have a Ki-67 proliferative index of less than 3%. The distinction between primary and metastatic NET, however, is not absolute and can be difficult. A primary vs metastatic NET diagnosis relies on clinical exclusion of a NET in other, more common, anatomic locations. Here, we present a case of an LGNECS on the scalp of a 72-year-old female patient. Whole body imaging failed to identify any octreotide-avid lesions elsewhere in the patient, aside from 2 positive cervical lymph nodes, which were confirmed with a node dissection and histologic evaluation. This is the 19th reported case of LGNECS and the 2nd reported case of LGNECS with nodal metastasis.

Cutaneous malignancies simulating seborrheic keratoses: An underappreciated phenomenon?

BACKGROUND: Seborrheic keratosis (SK), a common and benign entity, is generally diagnosed clinically without the need for a biopsy. Given their variable appearance, SK may mimic cancer clinically and require biopsy for clinically equivocal cases. A clinician may also choose to perform biopsies on SK based on other circumstances, such as cosmetic reasons or SK being in an inconvenient and irritative location. METHODS: Dermatopathology samples from 2015 obtained from private and university locations were retrospectively assessed. Cases included in the study were those with "SK" or "ISK" (irritated seborrheic keratosis) and no other diagnosis in the clinical data. Cases with modifiers suggestive of malignancy such as "SK rule out others," changing, growing and so on were excluded. A total of 4361 eligible cases were identified and used for analysis. RESULTS: Of the 4361 cases identified as only "SK" or "ISK" in the clinical data, 3759 (86.2%) were, in fact, SK or ISK. A total of 466 (10.7%) were an assortment of non-malignancy diagnoses such as dermatofibroma. There were 136 (3.1%) cases histologically diagnosed as malignancies. The majority (9/136 cases; 67%) were in situ or invasive squamous cell carcinoma; 24.3% (33/136) were basal cell carcinoma and 8.8% (12/136) were melanoma. CONCLUSION: SK may mimic cancer even in clinically unsuspicious cases.

Novel Cutaneous Manifestations of Pleuroparenchymal Fibroelastosis.

Pleuroparenchymal fibroelastosis (PPFE) is a rare progressive disease that manifests as parenchymal fibrosis of the upper lobe and pleura. Approximately 100 cases have been reported. Cutaneous manifestations of PPFE have not previously been described. Diagnosis is dependent on histologic identification of fibrosis with atypical elastic fibers, necessitating an invasive peripheral lung wedge biopsy.A 68-year-old male with a history of pleuroparenchymal fibroelastosis presented with an asymptomatic, telangiectatic erythematous eruption on bilateral lower extremities. Biopsies demonstrated a subtle perivascular infiltrate with marked increase in atypical elastic fibers, similar to the elastosis in the patient's lungs.This is the first documented case of cutaneous manifestations in PPFE. Clinicians need to be aware that cutaneous eruptions clinically simulating telangiectasia macularis eruptiva perstans but lacking a mast cell infiltrate histologically, may have increased abnormal elastic fibers. Thus, early recognition of these lesions in patients with an undefined restrictive lung disorder, may facilitate the diagnosis of PPFE in some patients.

Characterization of tissue and slide artifacts from automated embedding systems.

With recent technological advances and cost reductions, automated embedding systems are rapidly becoming routine in the processing of skin biopsy specimens. The efficiency advantages of this technique are due in part to the use of patented sectionable cassettes that hold formalin-fixed tissue from the time of grossing through tissue sectioning. In this process, the final paraffin block contains both the tissue and the cassette, which are sectioned and stained in unison. Here, we report the multiple tissue and slide artifacts commonly seen with automated embedding systems that are unique to this method of tissue processing. The most frequently observed tissue changes are patterned molding of the biopsy specimen around the cassette material. The most common slide artifacts are due to the presence of geometrically shaped polarizable cassette material adjacent to or overlying the stained tissue. As many of these artifacts strongly resemble the shapes seen in the classic 1980s video game, Tetris, we propose the term of Tetris-like artifacts for these findings. Although we remain confident that use of an automated embedding system does not decrease diagnostic reliability, increased familiarity with the standard appearance of slides processed using this technique will help avoid confusion when evaluating these cases.

Sarcoidosis Resembling Angiokeratomas: A Case Report.

Sarcoidosis, a multifaceted systemic disorder characterized histologically by the presence of non-caseating granulomas, has a wide array of cutaneous manifestations. We describe a case of a 74-year-old woman with a complex medical history, who presented with asymptomatic hyperpigmented papules on her lower extremities. Histological examination of a punch biopsy specimen showed nodular and angiocentric patterns of granulomatous inflammation consistent with sarcoidosis, and chest radiography demonstrated bilateral hilar opacities, supporting the diagnosis. To our knowledge, this specific cutaneous presentation of sarcoidosis has not been described before, and it can easily be mistaken for other conditions. Therefore, this case underscores the importance of recognizing atypical cutaneous morphologies of sarcoidosis, particularly in patients with complex medical histories, to facilitate accurate diagnosis and timely intervention. We aim to increase awareness among clinicians regarding the diverse manifestations of sarcoidosis, thereby enhancing diagnostic acumen and patient care.

Iterative refinement of a histologic algorithm for burn depth categorization based on 798 consecutive burn wound biopsies.

INTRODUCTION: Our group previously reported a burn biopsy algorithm (BBA-V1) for categorizing burn wound depth. Here, we sought to promulgate a newer, simpler version of the BBA (BBA-V2). METHODS: Burn wounds undergoing excision underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn wounds assessed as likely to heal by 21 days were imaged within 72 h of injury and at 21 days. A sample of 798 burn wound biopsies were classified by both BBAV1 and BBAV2 algorithms. For nonoperative burn wounds, the proportion of healing versus nonhealing pixels at 21 days after injury were compared. RESULTS: The 798 biopsies were classified by BBAV1 as 24% SPT, 47% DPT, 28% FT and by BBAV2 as 3% SPT, 67% DPT, and 30% FT (p < 0.0001). Overall, the proportion of biopsies whose wound reclassification changed from a nonoperative to operative pathway was 21% (95% CI: 18-24%). Nonoperative wounds judged at injury as being SPT contained 12.8 million pixels. Repeat 21-day imaging revealed 11.3 million healed pixels (accuracy = 89.6% (95% CI: 89.59-89.62)). CONCLUSIONS: BBA-V2 was associated with a significantly higher concordance with visual assessment for burn wounds clinically judged as deep partial and full thickness.

Pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation.

Actinic keratoses are proliferations of transformed neoplastic keratinocytes in the epidermis that are the result of cumulative ultraviolet (UV) radiation from sun exposure. They are commonly found on sites of sun-exposed skin such as the face, balding scalp, and back of the hand. Although UV exposure does exert certain beneficial effects on the skin, excessive exposure to UV radiation induces multiple cascades of molecular signaling events at the cellular level that produce inflammation, immunosuppression, failure of apoptosis, and aberrant differentiation. Cumulatively, these actions result in mutagenesis and, ultimately, carcinogenesis. This article provides a brief overview of the key mediators that are implicated in the pathobiology of actinic keratosis. Three evolutionary possibilities exist for these keratoses in the absence of treatment: (1) spontaneous remission, which can be common; (2) remaining stable, without further progression; or (3) transformation to invasive squamous cell carcinoma, which may metastasize. Because the effects of UV radiation on the skin are complex, it is not yet fully clear how all of the mediators of actinic keratosis progression are interrelated. Nonetheless, some represent potential therapeutic targets, because it is clear that directing therapy to the effects of UV radiation at a number of different levels could interrupt and possibly reverse the mechanisms leading to malignant transformation.

Uveitis and desquamating rash of the palms and soles.

Syphilis, a sexually transmitted disease caused by the spirochete Treponema pallidum, can affect nearly every organ system in the body. In particular, skin manifestations of secondary syphilis are common but nonspecific and can be a true masquerader of other skin disorders. Concomitant infection with HIV has been increasing and may cause even more unusual skin presentations. We present a patient with the atypical combination of palmoplantar keratoderma and ocular symptoms that closely resembled reactive arthritis (or Reiter's syndrome). When evaluating patients with HIV infection, clinicians should maintain a high level of suspicion for syphilis to accurately diagnose and treat this curable but potentially fatal disease.

Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis.

The intermittent use of dilute sodium hypochlorite "bleach baths" has shown efficacy as adjunctive therapy for atopic dermatitis (AD). This feasibility study evaluated the clinical response and patient acceptability of treatment with a cleansing body wash containing sodium hypochlorite in children with AD. This was a 12-week open-label feasibility study of 18 children with AD conducted in a pediatric dermatology outpatient clinic between May 2011 and July 2012. Children with moderate to severe AD, defined as an Investigator Global Assessment (IGA) score of at least 3 on a 5-point scale, who were age 6 months and older and had lesional cultures positive for Staphylococcus aureus at baseline were included. Patients were instructed to wash 3 days/week for 12 weeks with the sodium hypochlorite-containing cleansing body wash. During the study period, patient's individualized topical and systemic treatment regimens were continued. Clinical response to treatment was measured using an IGA score and the percentage of body surface area (BSA) affected. Parents were also administered a retrospective questionnaire evaluating acceptability of the product. There was a statistically significant reduction in IGA score at all time points, with an overall mean reduction from baseline to final measurement using the last observation carried forward in all patients of 1.0 (p = 0.001, n = 18). Similarly the mean reduction of BSA affected was 14.8% (p = 0.005, n = 18). Parents reported that the body wash was significantly easier to use than traditional bleach baths (p < 0.001). The significant reductions in clinical disease severity scores with use of this formulation are encouraging.

Id-like reaction to BCG therapy for bladder cancer.

Id reaction, also known as autoeczematization, is the development of dermatitis that is distant to an initial site of infection or sensitization. Clinical findings typically include an acute, intensely pruritic maculopapular or papulovesicular eruption that most frequently involves the extremities. Histology typically reveals spongiotic dermatitis that often is vesicular, and eosinophils may be present in the infiltrate. Id reactions can result from inflammatory skin conditions such as stasis dermatitis as well as infectious entities including mycobacterial infections. BCG live therapy consists of an attenuated strain of Mycobacterium bovis that is utilized as a first-line treatment of superficial transitional cell carcinomas. We report the case of an id-like reaction in a 90-year-old man who developed an intensely pruritic, scaly, erythematous eruption on all 4 extremities 2 weeks after starting weekly intravesical use of BCG therapy for superficial transitional cell carcinoma. A representative biopsy demonstrated spongiotic dermatitis with overlying scaling and an eosinophilic infiltrate. The eruption resolved after discontinuation of BCG therapy and treatment with topical corticosteroids.

Clinical update on cutaneous and subcutaneous sarcomas.

BACKGROUND: Cutaneous sarcomas are uncommon cancers that can have a wide range of clinical symptoms and lead to considerable cutaneous as well as systemic morbidity. AIM: The objective of this review article is to discuss epidemiology, clinical features, diagnosis, and therapy of different types of cutaneous sarcomas. MATERIAL AND METHODS: Literature was screened to retrieve articles from PubMed/Medline and Google Scholar and related websites. Cross-references from the relevant articles were also considered for review. Review articles, clinical studies, systematic reviews, meta-analyses, and relevant information from selected websites were included. RESULTS AND DISCUSSION: Cutaneous sarcomas have a negative effect on the quality of life. In their diagnosis, clinical presentation and histological evaluation are crucial. Complete surgical removal is the solution for more or less all cutaneous and subcutaneous sarcomas. The prognosis for cutaneous sarcomas is generally favorable since they tend to recur locally with distant metastases only on rare occasions. Patients having advanced disease should be treated in the setting of clinical trials if possible; choices include radiation therapy and systemic medicines. The value of innovative immunotherapy cannot be determined decisively at this time due to a paucity of relevant trials. CONCLUSION: As cutaneous sarcomas are rarely diagnosed based on clinical findings, histology plays an important role in the diagnosis. They have a relatively favorable prognosis if treated properly. Patients should be treated at specialized centres.

Artificial intelligence in Dermatopathology.

INTRODUCTION: Ever evolving research in medical field has reached an exciting stage with advent of newer technologies. With the introduction of digital microscopy, pathology has transitioned to become more digitally oriented speciality. The potential of artificial intelligence (AI) in dermatopathology is to aid the diagnosis, and it requires dermatopathologists' guidance for efficient functioning of artificial intelligence. METHOD: Comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar." Articles published in English language were considered for the review. RESULTS: Convolutional neural network, a type of deep neural network, is considered as an ideal tool in image recognition, processing, classification, and segmentation. Implementation of AI in tumor pathology is involved in the diagnosis, grading, staging, and prognostic prediction as well as in identification of genetic or pathological features. In this review, we attempt to discuss the use of AI in dermatopathology, the attitude of patients and clinicians, its challenges, limitation, and potential opportunities in future implementation.