MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness

Recent Updates in the Treatment of Erythema Multiforme

Erythema multiforme (EM) is an immune-mediated condition that classically presents with discrete targetoid lesions and can involve both mucosal and cutaneous sites. While EM is typically preceded by viral infections, most notably herpes simplex virus (HSV), and certain medications, a large portion of cases are due to an unidentifiable cause. EM can be confused with other more serious conditions like Stevens–Johnson syndrome (SJS); however, clinical research has provided significant evidence to classify EM and SJS as separate disorders. Treatment of EM is highly variable, depending on the etiology, the involvement of mucosal sites, and the chronicity (acute vs. recurring) of the disease. If the etiology or causal medication/infection is identified, then the medication is stopped and/or the infection is treated prior to initiating symptomatic treatment. Treatment for acute EM is focused on relieving symptoms with topical steroids or antihistamines. Treatment for recurrent EM is most successful when tailored to individual patients. First line treatment for recurrent EM includes both systemic and topical therapies. Systemic therapies include corticosteroid therapy and antiviral prophylaxis. Topical therapies include high-potency corticosteroids, and antiseptic or anesthetic solutions for mucosal involvement. Second-line therapies for patients who do not respond to antiviral medications include immunosuppressive agents, antibiotics, anthelmintics, and antimalarial

Unilateral swelling and hyperpigmented papules

Lymphangioendothelioma, also known as acquired progressive lymphangioma, is a rare vascular neoplasm of lymphatic origin. Although in light-skinned individuals lesions typically present as erythematous to violaceous papules or plaques, in dark-skinned patients lesions often appear hyperpigmented. Histopathologic distinction of lymphangioendothelioma from early Kaposi sarcoma and angiosarcoma is imperative considering the therapeutic and prognostic implications. Herein, we present a 71-year-old woman with slowly progressive hyperpigmented papules and histopathology demonstrating thin-walled vascular spaces interspersed between collagen bundles, consistent with lymphangioendothelioma. We describe the clinical and histologic findings of this rare entity and highlight histologic mimics that might result in diagnostic delay

Histopathology of Hidradenitis Suppurativa: A Systematic Review

Hidradenitis suppurativa (HS) is a chronic inflammatory scarring disease felt to be related to occlusion of the hair follicle unit in intertriginous areas. We perform a systematic review on HS histopathology to evaluate current knowledge and discuss future directions. PubMed and Scopus databases were searched for relevant articles published from January 1985 to January 2021 that discussed the pathology of HS. Additional articles were identified by hand-searching, which entailed manually scanning selected journals. A total of 355 citations were identified in the primary search within the main databases. Two hundred and seventy-nine articles were excluded after a review of titles, abstracts, and duplicates. Sixty-one studies did not meet the inclusion criteria or were found to be duplicates, resulting in a total of 15 articles for analysis. Three articles were hand-searched. This comprehensive systematic review of the histopathology of HS confirms a high prevalence of follicular occlusion, follicular hyperkeratosis, and hyperplasia of the follicular epithelium. These findings support the central role of follicular occlusion in the development and progression of HS while providing a potential path to directing therapeutics against follicular occlusion

A Previously Unrecognized Granulomatous Variant of Gamma-Delta T-Cell Lymphoma

Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an extremely rare and aggressive T-cell neoplasm with complex heterogeneity. We present a series of two patients who presented with firm, subcutaneous nodules and were diagnosed with PCGD-TCL. In both cases, biopsies demonstrated a both superficial and deep adnexotropic infiltrate comprised of angiocentric, medium- to large-sized atypical lymphocytes. The infiltrate extended into the panniculus. Immuno–histochemical stains highlighted atypical lymphocytes that expressed CD3, CD8 and CD56 but were negative for EBV ISH. A brisk histiocytic response with focal aggregation into granulomas was highlighted with a PG-M1 stain. The atypical lymphocytes were positive for gene rearrangements on a TCR delta stain and negative for βF-1. CT and PET scan in one of the two patients demonstrated diffuse, subcutaneous, ground-glass foci; hypermetabolic soft tissue nodules; and lymphadenopathy in the lungs, as well as splenomegaly. A diagnosis of histiocyte-rich PCGD-TCL was rendered. A histiocyte-rich, granulomatous variant of γδ T-cell lymphoma is extremely rare. Its potentially misleading resemblance to inflammatory granulomatous conditions could pose a diagnostic pitfall in this already challenging condition. This variant may resemble granulomatous mycosis fungoides and granulomatous slack skin syndrome, but it has a distinct, aggressive clinical outcome

Racial disparities of delay in diagnosis and dermatologic care for hidradenitis suppurativa

Hidradenitis suppurativa is a chronic, debilitating skin disease that disproportionately affects African Americans, and care-related factors may contribute to this disparity. In this study, we investigated delay in diagnosis and dermatologic care for HS at an urban Midwestern Academic Center. A retrospective chart review of 1,190 patients with 3 or more encounters for HS between 1/1/2002 and 3/19/2019 was conducted. A total of 953 patients were included in statistical analysis. A mean (standard deviation) delay in diagnosis was 4.1 ± 7.0 years. For white patients the delay in diagnosis was 3.2 ± 6.3 years, for Black patients 4.8 ± 7.0 years, for Hispanic patients 4.7 ± 5.8 years, and for other races 4.9 ± 7.4 years (p \u3c0.001). Among the 932 patients with known specialist visit types, 500 (53.6%) had seen dermatology including 222 (47.8%) of Black patients, 242 (59.5%) of white patients, 24 (64.9%) of Hispanic patients, and 12 (50%) patients of other races (p=0.003).White patients and Hispanic patients saw a dermatologist an average of 3.0 years after first presentation of HS and Black patients saw a dermatologist on average 5.0 years after first presentation (p=0.004). Of the patients who did see dermatology, 44.9% of Black patients, 31.6% of white patients, 23.1% of Hispanic patients, and 30.8% of other races saw surgery before dermatology (p\u3c.001). Our results indicate that non-white patients have a longer delay in diagnosis than their white counterparts and that Black patients do not see dermatology as early in their disease course as other racial groups. Black patients also see surgery more often than white patients before seeing dermatology, which could suggest greater disease severity at presentation and diagnosis or difficult access to dermatology

Polarization of Macrophages in Granulomatous Cutaneous T Cell Lymphoma Granulomatous Mycosis Fungoides Microenvironment

Polarization of tumor associated macrophages (TAMs) has been shown to have prognostic significance in different cancer types. This study evaluates the macrophage subtypes that predominates in GMF. Cases of GCTCL from 2007–2020 were identified (n = 6), clinical data was extracted from the electronic medical record, and all pathology slides were reviewed to confirm the diagnosis. Immunohistochemistry (IHC) studies were performed to characterize M1 and M2 macrophage polarization. CD68 (PGM1), pSTAT1, and CD163 were used as pan macrophage, M1, and M2 markers, respectively. The macrophages with positive staining at hot spot per high power field were counted and recorded for data analysis. The average age of patients was 60.5 years [range, 21–78], five patients (83%) were women and 1 (17%) was a man. Five patients were Caucasian (83%), and 1 was Black/African American (17%). Two patients had late stage GMF with M2 (CD163) predominance and the other three had early stage GMF with M1 (pSTAT1) predominance. Our study suggests that macrophage polarization present in GMF tends to be M1 in early stages and M2 in advanced stages. Additional studies are needed to further elucidate the microenvironment of macrophages present in GMF. Such findings may lead to prognostic and therapeutic advances in GMF

Epidermolytic hyperkeratosis of the vulva

Vulvar epidermolytic hyperkeratosis is a benign entity that mimics other malignant and inflammatory vulvar dermatoses clinically and histologically requiring careful clinical pathologic correlation for diagnosis

Histopathologic spectrum of morphea

Morphea is an autoimmune skin disease with protean clinical manifestations. Histologic features are similarly variable, and skin biopsies may be nondiagnostic. A single-institution retrospective cohort study was conducted. Morphea patients who had a biopsy in 2005-2015 were included, and a histopathological review was conducted by 2 pathologists. There were 51 biopsy specimens from 40 subjects. The most common histologic features were dermal sclerosis (90%), dermal thickening (78%), collagen homogenization (86%), a superficial and deep infiltrate (76%), a moderate-abundant inflammatory infiltrate (73%), and periadnexal fat loss/decreased skin appendages (71%). Twenty-four specimens were not diagnostic of morphea. In these specimens, the main clues to diagnosis included the presence of dermal sclerosis (79%), subtle collagen homogenization (75%), dermal thickening (58%), moderate-to-abundant plasma cells (50%), and perineural inflammation (50%). There were no statistically significant differences between active and inactive lesions, nor untreated and treated lesions. The histopathologic features of morphea are variable and a high proportion of biopsies are not diagnostic. Clinicians and pathologists should have a high degree of suspicion to correctly make the diagnosis of morphea

Epidermolytic hyperkeratosis of the vulva

Vulvar epidermolytic hyperkeratosis is a benign entity that mimics other malignant and inflammatory vulvar dermatoses clinically and histologically requiring careful clinical pathologic correlation for diagnosis