Granzyme K mediates IL-23-dependent inflammation and keratinocyte proliferation in psoriasis.

Psoriasis is an inflammatory disease with systemic manifestations that most commonly presents as itchy, erythematous, scaly plaques on extensor surfaces. Activation of the IL-23/IL-17 pro-inflammatory signaling pathway is a hallmark of psoriasis and its inhibition is key to clinical management. Granzyme K (GzmK) is an immune cell-secreted serine protease elevated in inflammatory and proliferative skin conditions.

PRAME Immunohistochemistry for Distinguishing Vulvar and Vaginal Melanoma From Benign Melanocytic Nevi.

Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities.

Incidence and profile of skin cancers in patients following ultraviolet phototherapy without psoralens: A retrospective cohort study.

Background: Psoralen + ultraviolet-A (PUVA) is associated with photocarcinogenesis. However, carcinogenic risk with other ultraviolet phototherapies remains unclear.

Objective: Evaluate whether phototherapy without psoralens increases skin cancer risk.

Small plaque psoriasis re-visited: A type of psoriasis mediated by a type-I interferon pathway.

TNFα-inhibitor-induced psoriasis is mediated by the type-I interferon pathway, of which IFNα, LL37 and IL-36γ are major players. A subset of patients treated with TNFα inhibitors develop small plaque psoriatic lesions. Small plaque psoriasis is similarly observed in patients on immune checkpoint inhibitors (ICI), and with concurrent systemic lupus erythematosus (SLE) or positive antinuclear antibody (ANA).

CD34 Staining as a Useful Tool in Disorders of Collagen Degeneration.

The human progenitor-cell antigen CD34 is expressed in dermal dendritic cells and is lost in several disorders affecting dermal collagen. The loss of CD34 immunohistochemical staining has been demonstrated to be helpful in the histologic diagnosis of morphea, lichen sclerosus, and the classic pattern of granuloma annulare. This study characterized CD34 expression in 2 sclerosing disorders affecting the subcutis: lipodermatosclerosis (LDS) and the sclerodermoid form of chronic graft-versus-host disease (ScGVHD).

Granzyme B inhibition reduces disease severity in autoimmune blistering diseases.

Pemphigoid diseases refer to a group of severe autoimmune skin blistering diseases characterized by subepidermal blistering and loss of dermal-epidermal adhesion induced by autoantibody and immune cell infiltrate at the dermal-epidermal junction and upper dermis. Here, we explore the role of the immune cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, granzyme B knockout or topical pharmacological inhibition significantly reduces total blistering area compared to controls.

Comparison of p53 immunohistochemical staining in differentiated vulvar intraepithelial neoplasia (dVIN) with that in inflammatory dermatoses and benign squamous lesions in the vulva.

Aims: Differentiated vulvar intraepithelial neoplasia (dVIN), the precursor lesion to human papillomavirus-independent vulvar squamous cell carcinoma (VSCC), can be difficult to distinguish from vulvar inflammatory dermatoses. Our goal was to determine if p53 could be a useful biomarker for dVIN, by characterizing p53 percentage, intensity and patterns of staining in dVIN and its histological mimics.

Methods And Results: We studied p53 immunohistochemical staining patterns in 16 dVIN cases and 46 vulvar non-neoplastic squamous lesions [12 lichen sclerosus (LS); seven lichen simplex chronicus; three lichen planus (LP); six psoriasis; 13 spongiotic dermatitis (SPO); and five candidiasis].

Scalp biopsy identifies systemic amyloidosis presenting as isolated telogen effluvium: A case report.

AL amyloidosis is a complication of B-cell dyscrasias and multiple myeloma, manifest as deposition of antibody fragments in many different organs, including the skin. We describe a rare case of this systemic disease which presented with isolated scalp alopecia. Further investigation led to the diagnosis of an occult plasma-cell dyscrasia, showing the benefit of including systemic amyloidosis in the differential diagnosis of alopecia.

Granzyme B is elevated in autoimmune blistering diseases and cleaves key anchoring proteins of the dermal-epidermal junction.

In healthy skin, epidermis and dermis are anchored together at the dermal-epidermal junction (DEJ), a specialized basement membrane pivotal for skin integrity and function. However, increased inflammation in the DEJ is associated with the disruption and separation of this junction and sub-epidermal blistering. Granzyme B (GzmB) is a serine protease secreted by immune cells.

Bullous Pemphigoid: A 10-Year Study of Discordant Results on Direct Immunofluorescence.

Background: Bullous pemphigoid (BP) is the most common subepidermal autoimmune disorder characterized by tense bullae. It is associated with circulating autoantibodies against BP antigen-1 and BP antigen-2. Diagnosis is based upon clinical, histopathologic, and immunopathologic examination.

Distinguishing Epidermolysis Bullosa Acquisita From Bullous Pemphigoid Without Direct Immunofluorescence.

Background: It has been postulated that periodic acid-Schiff staining of basement membrane can predict direct immunofluorescence patterns seen in epidermolysis bullosa acquisita and bullous pemphigoid. It has also been suggested that the type of inflammatory infiltrate or presence of fraying of basal keratinocytes may differentiate these two conditions.

Objective: In this study, we aimed to confirm these observations.

Amelanotic Lentigo Maligna Melanoma: Mohs Surgery as the Definitive Treatment of an Invisible Tumour.

Amelanotic lentigo maligna melanoma represents <2% of melanomas. Diagnosis is delayed owing to the lack of lesion pigmentation and advanced disease at presentation. Excision with appropriate margins is the treatment standard, but the starting point for such margins is often unclear.

Cytomegalovirus Scrotal Ulcer in a Renal Transplant Patient.

Background: Cytomegalovirus (CMV) is a highly prevalent herpesvirus that can present with cutaneous disease in immunocompromised individuals. This may reflect systemic involvement, which is associated with significant morbidity and mortality.

Objective: To report a case of cutaneous CMV in an immunocompromised patient and to discuss the differential diagnosis of genital ulcers.

Clinical Recognition of Melanoma in Dermatologists and Nondermatologists.

Background: The incidence of melanoma is increasing annually in Canada.

Objectives: This retrospective study was designed to assess the ability of physicians of different specialties to accurately recognize melanoma.

Methods: Pathology reports of biopsies submitted to Vancouver Coastal Health with clinical diagnoses of melanoma were reviewed (January to July 2013).

Lymphocytic panniculitis: an algorithmic approach to lymphocytes in subcutaneous tissue.

The diagnosis of panniculitis is a relatively rare occurrence for many practising pathologists. The smaller subset of lymphocyte-predominant panniculitis is further complicated by the diagnostic consideration of T cell lymphoma involving the subcutaneous tissue, mimicking inflammatory causes of panniculitis. Accurate classification of the panniculitis is crucial to direct clinical management as treatment options may vary from non-medical therapy to immunosuppressive agents to aggressive chemotherapy.

Multiple Cutaneous Creamy Papules and Nodules: A Case of Miliarial Gout.

Background: Tophaceous gout is the nonarticular deposition of monosodium urate resulting from a disorder in purine metabolism that causes an elevation of serum uric acid. Cutaneous variants of tophaceous gout include papular, nodular, ulcerative, and pustular forms.

Objective: We present a case of a 67-year-old man who presented with multiple cutaneous creamy white papules and nodules.