XB130 deficiency enhances carcinogen-induced skin tumorigenesis.

XB130 is an adaptor protein that functions as a mediator of multiple tyrosine kinases important for regulating cell proliferation, survival, migration and invasion. Formerly predicted as an oncogene, alterations of its expression are documented in various human cancers. However, the exact role of XB130 in tumorigenesis is unknown.

Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2.

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate.

Cutaneous epithelioid angiomatous nodule: a report of a series including a case with moderate cytologic atypia and immunosuppression.

Background: Cutaneous epithelioid angiomatous nodule (CEAN) is a very rare and relatively recently recognized vascular proliferation characterized usually by minimal cytological atypia and accompanying mitotic activity. As such, CEAN represents an important diagnostic pitfall, which could lead to significant misdiagnosis and unnecessary treatment.

Methods: The clinicopathologic findings of 5 cases of CEAN were reviewed including a unique case with typical findings but also moderate cytologic atypia and brisk mitotic activity in a patient on immunosuppression.

Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma.

Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell-associated molecules that can be targeted by tumor immunotherapies.

Pyoderma Gangranosum-Like Blastomycosis.

Blastomyces dermatitidis is typically contracted through inhalation of the dimorphic conidia, resulting in pulmonary infection as well as extrapulmonary disease through hematogenous spread. Blastomycosis is considered one of the great mimickers in medicine, with verrucous cutaneous blastomycosis resembling skin malignancy and B dermatitidis pulmonary infections often confused with lung cancer. Cutaneous blastomycosis can also often mimic pyoderma gangrenosum and should be considered in the differential diagnosis in any suspected case.

Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient.

Trichodysplasia spinulosa (TS) is a rare dermatologic complication associated with the immunosuppressive therapy used in solid organ transplantation. The distinctive clinical manifestation of this condition is spiny follicular papules on the face, ears, extremities, and trunk. Histopathologically, abnormally maturing hair follicles with hyperkeratotic material are noted.

Gene of the month: BAP1.

The BAP1 gene (BRCA1-associated protein 1) is a tumour suppressor gene that encodes a deubiquitinating enzyme (DUB), regulating key cellular pathways, including cell cycle, cellular differentiation, transcription and DNA damage response. Germline BAP1 mutations cause a novel cancer syndrome characterised by early onset of multiple atypical Spitz tumours and increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma and various other malignancies. Recognising the clinicopathological features of specific BAP1-deficient tumours is crucial for early screening/tumour detection, with significant impact on patient outcome.

Cutaneous Strongyloides Infection Postchemotherapy.

Background And Objective: While clinical symptoms of strongyloidiasis are often nonspecific, larva currens (with erythematous, serpiginous, and pruritic papules and plaques) should prompt investigation including stool microscopy, serology, and skin biopsy of the lesion. Appropriate diagnosis and treatment with ivermectin is necessary, especially in the immunocompromised patient who is at increased risk for hyperinfection syndrome and disseminated disease.

Conclusion: We present a 61-year-old immunocompromised man with presentation of larva currens of cutaneous strongyloides infection without symptoms of hyperinfection or disseminated disease.

Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma.

Anti-PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown.

Malignant Melanoma of Vulva and Vagina: A Histomorphological Review and Mutation Analysis--A Single-Center Study.

Objectives: The aim of this work was to determine molecular characteristics and specifically, the frequency of BRAF, C-KIT, and NRAS mutations in vulvar and vaginal melanomas.

Methods: A retrospective review of all cases of vulvar and vaginal melanoma between 2002 and 2013 was performed. We reviewed the clinical and histological characteristics of all cases and performed genotyping studies on cases that had tissue available for the study, using next-generation sequencing.

Pathologic complete response to intralesional interleukin-2 therapy associated with improved survival in melanoma patients with in-transit disease.

Purpose: Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response.

Methods: We retrospectively collected the clinicopathological data of 31 consecutive patients who presented to a tertiary care cancer center for treatment of in-transit melanoma with intralesional IL-2.

Cutaneous polyarteritis nodosa sine nodosa.

Background And Objective: Cutaneous polyarteritis nodosa, a form of vasculitis affecting the small to medium sized arteries, most commonly presents as tender subcutaneous nodules over the lower legs and feet. Other features include livedo reticularis, skin ulcers and tender indurated plaques.

Conclusion: We report a 51-year old woman with a primarily livedo reticularis presentation of cutaneous polyarteritis nodosa without a nodular component.

Neuroendocrine carcinoma of the skin--an updated review.

Primary neuroendocrine carcinoma of the skin, or Merkel Cell carcinoma (MCC), is a rare but aggressive tumor. Many recent advances on the morphology, immunophenotype, and pathogenesis have come to light in recent years. This review highlights the clinical features, varying histologies, histogenesis, advances in molecular pathology, prognosis, and current management of MCC.

Identification of novel target proteins in sebaceous gland carcinoma.

Background: The aim of this study was to identify new target proteins in sebaceous gland carcinoma.

Methods: A tissue microarray containing 115 core biopsies was constructed and stained for proteins involved in carcinogenesis, angiogenesis, inflammation, and cell-to-cell contact. Two investigators independently determined protein expression of all antibodies.

Linear arrangement of neutrophils along the Basal layer in bullous pemphigoid: a unique histological finding.

Bullous pemphigoid is an inflammatory autoimmune subepidermal bullous disease with distinct immunohistological features. We report an unusual case of a 59-year-old woman with a bullous eruption whose lesional skin biopsy showed a subepidermal blister with a linear arrangement of neutrophils, mimicking linear IgA bullous dermatosis. However, direct immunofluorescence studies demonstrated IgG and C3 linear deposition along the basement membrane zone, compatible with bullous pemphigoid.

Virtual microscopy using whole-slide imaging as an enabler for teledermatopathology: A paired consultant validation study.

Background: There is a need for telemedicine, particularly in countries with large geographical areas and widely scattered low-density communities as is the case of the Canadian system, particularly if equality of care is to be achieved or the difference gap is to be narrowed between urban centers and more peripheral communities.

Aims: 1. To validate teledermatopathology as a diagnostic tool in under-serviced areas; 2.

Sebaceous gland carcinoma of the head and neck: the Princess Margaret Hospital experience.

Background: The purpose of this study was to identify prognostic factors predicting outcomes in sebaceous gland carcinomas.

Methods: We conducted a retrospective medical chart review of patients with sebaceous carcinomas of periorbital (n = 33) and extraorbital sites (n = 13).

Results: Patients with periorbital tumors had higher recurrence rates than did patients with extraorbital tumors (64% vs 23%; p = .

Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma.

Background: The purpose of this study was to determine the expression pattern of the Merkel cell polyomavirus (MCPyV) large T-protein antigen in patients with Merkel cell carcinoma.

Methods: A tissue microarray (TMA) containing 30 specimens was constructed and stained for the MCPyV large T protein. Immunohistochemical expression was determined semiquantitively and was compared to patients' outcome.

Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs).

Background: Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs).

Microangiopathic hemolytic anemia and leukoerythroblastic blood film heralding bone marrow metastatic gastroesophageal adenocarcinoma.

Despite modern technological advancements in laboratory hematology, the blood film remains an important diagnostic aid. Herein, we report the case of a patient with a history of gastric cancer, who presented seven years following apparently successful surgery and adjuvant chemo-radio-therapy, with blood film findings of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and leukoerythroblastosis (LEB). Although mimicking features of thrombotic thrombocytopenic purpura (TTP), subsequent bone marrow examination instead revealed an association with occult recurrence of necrotic, metastatic gastric adenocarcinoma.

Infundibular carcinoma of the skin: a distinct morphological and immunohistochemical entity.

This report describes a new entity which has been defined as infundibular carcinoma (IC) of the skin. This new entity must be distinguished from other basaloid carcinomas arising from the epidermis, the hair follicles or from sweat duct and glandular elements. Specific criteria have been used to define ICs.

Spindle cell melanocytic lesions: part II--an approach to intradermal proliferations and horizontally oriented lesions.

Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes show a dendritic cytomorphology and territorial isolation, lesional nevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies, and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may either be a characteristic feature or a divergent appearance.