[The role of new molecular tests in the diagnosis of melanoma in a setting of congenital nævus in an infant].

Introduction: Congenital and infantile melanomas are extremely rare. We report a case of a child presenting at birth with a giant congenital nevus complicated by melanoma and on long-term follow-up with exploration using new immunohistochemistry and molecular biology tools.

Observation: A new-born girl presented at birth with a large congenital cervico-mandibular tumour with para-pharyngeal extension and underlying osteolysis.

Histopathology-guided mass spectrometry differentiates benign nevi from malignant melanoma.

Purpose: Distinguishing benign nevi from malignant melanoma using current histopathological criteria may be very challenging and is one the most difficult areas in dermatopathology. The goal of this study was to identify proteomic differences, which would more reliably differentiate between benign and malignant melanocytic lesions.

Methods: We performed histolpathology - guided mass spectrometry (HGMS) profiling analysis on formalin-fixed, paraffin embedded tissue samples to identify differences at the proteomic level between different types of benign nevi and melanomas.

Necrotic Keratinocytes Are Common in Psoriasis and Have a Predilection to the Upper Epidermis: A Quantitative and Comparative Analysis.

Background: The most salient histopathological features of psoriasis are epidermal hyperplasia, hypogranulosis, parakeratosis, dilated capillaries in dermal papillae, and intraepidermal and intracorneal neutrophils. Several additional "nonclassic" features of psoriasis have recently been reported, including necrotic keratinocytes (NK). To determine the diagnostic utility of NK, we characterized NK in a large cohort of psoriasis cases compared with psoriasiform spongiotic dermatitis (PSD) and normal skin.

Subcutaneous Panniculitis-Like T-Cell Lymphoma With Granulomas as the Predominant Feature.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma preferentially localized in the subcutaneous adipose tissue and composed of cytotoxic T cells with an α/β immunophenotype. The neoplastic T cells can be variably admixed with other inflammatory cells, including histiocytes, which can rarely form noncaseating granulomas. We present a case of SPTCL in which granulomas are the predominant feature, composing 75%-80% of the inflammatory infiltrate.

Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex-Mediated Activation of the NLRP3 Inflammasome.

Objective: High-expression alleles of macrophage migration inhibitory factor (MIF) are linked genetically to the severity of systemic lupus erythematosus (SLE). The U1 small nuclear RNP (snRNP) immune complex containing U1 snRNP and anti-U1 snRNP antibodies, which are found in patients with SLE, activates the NLRP3 inflammasome, comprising NLRP3, ASC, and procaspase 1, in human monocytes, leading to the production of interleukin-1β (IL-1β). This study was undertaken to investigate the role of the snRNP immune complex in up-regulating the expression of MIF and its interface with the NLRP3 inflammasome.

Quantitative assessment of neuropilin-2 as a simple and sensitive diagnostic assay for spitzoid melanocytic lesions.

There is a significant need for the development of diagnostic tools that can precisely distinguish Spitz nevi and spitzoid melanomas. Here, we report the development of a PCR-based quantitative diagnostic assay for spitzoid melanocytic lesions utilizing the expression ratio of neuropilin-2 and melan-A genes in primary tumor specimens. We find that the expression ratio of neuropilin-2/melan-A is significantly increased in spitzoid melanomas compared with Spitz nevi.

Proteomic Mass Spectrometry Imaging for Skin Cancer Diagnosis.

Mass spectrometry imaging can be successfully used for skin cancer diagnosis, particularly for the diagnosis of challenging melanocytic lesions. This method analyzes proteins within benign and malignant melanocytic tumor cells and, based on their differences, which constitute a unique molecular signature of 5 to 20 proteins, can render a diagnosis of benign nevus versus malignant melanoma. Mass spectrometry imaging may assist in the differentiation between metastases and nevi as well as between proliferative nodules in nevi and melanoma arising in a nevus.

Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma.

Histopathological interpretation of proliferative nodules occurring in association with congenital melanocytic nevi can be very challenging due to their similarities with congenital malignant melanoma and malignant melanoma arising in association with congenital nevi. We hereby report a diagnostically challenging case of congenital melanocytic nevus with proliferative nodules and ulcerations, which was originally misdiagnosed as congenital malignant melanoma. Subsequent histopathological examination in consultation by one of the authors (R.

Spitz nevi and Spitzoid melanomas: exome sequencing and comparison with conventional melanocytic nevi and melanomas.

We performed exome sequencing of 77 melanocytic specimens composed of Spitz nevi (n=29), Spitzoid melanomas (n=27), and benign melanocytic nevi (n=21), and compared the results with published melanoma sequencing data. Our study highlights the prominent similarity between Spitzoid and conventional melanomas with similar copy number changes and high and equal numbers of ultraviolet-induced coding mutations affecting similar driver genes. Mutations in MEN1, PRKAR1A, and DNMT3A in Spitzoid melanomas may indicate involvement of the protein kinase A pathway, or a role of DNA methylation in the disease.

A 65-Year-Old Female from Connecticut with Orf Infection.

The virus, which causes orf and induces acute pustular skin lesions in sheep and goats, is transmissible to humans yet is rarely observed in North America. We present a case of a 65-year-old female farmer from Connecticut who contracted orf from her sheep. The clinical and histopathologic features, important to arrive at the correct diagnosis of this uncommon yet important infection, are described.

Imaging mass spectrometry assists in the classification of diagnostically challenging atypical Spitzoid neoplasms.

Background: Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas.

Objective: We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior.

Methods: We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS.

Somatic Mosaicism in Blaschkolinear Inflammatory Disorders.

Linear lichen planus (LP) is a rare dermatologic disease in which lichenoid lesions conform to a blaschkolinear distribution, most commonly on the extremities. Linear discoid lupus erythematosus (DLE) is a cutaneous manifestation of lupus that also conforms to Blaschko's lines. Blaschkolinear disorders have been shown to result from somatic mosaicism, most recently in nevus sebaceus, epidermal nevi, and syringocystadenoma papilliferum.

Evidence for glycosylation as a regulator of the pigmentary system: key roles of sialyl(α2-6)gal/GalNAc-terminated glycans in melanin synthesis and transfer.

Unlabelled: The major regulators of melanogenesis are glycoproteins, however no role for glycosylation in the pathway has yet been described. We stained skin biopsies and melanocyte-keratinocyte co-cultures with a panel of 20 lectins as oligosaccharide markers. Notably, the Elderberry Bark Lectin (EBL/SNA) stained melanocytes in both systems.

Congenital nevi versus metastatic melanoma in a newborn to a mother with malignant melanoma - diagnosis supported by sex chromosome analysis and Imaging Mass Spectrometry.

A 37-year-old pregnant woman presented with a 2-cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2-mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm(2) and no ulceration.

Comparison of the expression of vimentin and actin in spitz nevi and spitzoid malignant melanomas.

Introduction: The differentiation between Spitz nevi (SN) and Spitzoid malignant melanomas (SMM) represents a challenge to dermatopathologists. We recently demonstrated differential expression of vimentin and Actin in SN and SMM by mass spectrometry (MS). We sought to investigate whether this differential expression could be detected using conventional immunohistochemistry or automated quantitative analysis (AQUA) of histological sections.

Clinical characteristics associated with Spitz nevi and Spitzoid malignant melanomas: the Yale University Spitzoid Neoplasm Repository experience, 1991 to 2008.

Background: Spitz nevi and Spitzoid malignant melanomas are uncommon and may be difficult to distinguish histopathologically. Identification of clinical features associated with these lesions may aid in diagnosis.

Objective: We sought to identify clinical characteristics associated with Spitz nevi and Spitzoid malignant melanomas.

Use of imiquimod for residual acral melanoma.

Recent reports suggest that topical imiquimod cream is an effective treatment option for certain types of melanomas. No reports exist on the efficacy of using imiquimod cream to treat melanoma located on the plantar surface of the foot. We present two patients with a melanoma of the foot who had residual melanoma following surgical excision with acceptable margins.

Staphylococcal Purpura Fulminans: Report of a Case.

Purpura fulminans (PF) is associated with several infections and most commonly with meningococcemia. However, there are only a few reports of this entity in association with toxic shock syndrome toxin-1-producing Staphylococcus aureus. We report a 53-year-old man who presented with fever, progressive hemodynamic instability, multiorgan failure, and thrombocytopenia following lobectomy for a solitary lung metastasis from rectal adenocarcinoma.

Subcutaneous histiocytoid Sweet's syndrome in a patient with myelodysplastic syndrome and acute myeloblastic leukemia.

Subcutaneous histiocytoid Sweet’s syndrome is a rare variant of histiocytoid Sweet’s syndrome (SS). We present a 68-year-old woman with subcutaneous histiocytoid SS in association with refractory myelodysplastic syndrome transformed to acute myeloblastic leukemia (AML), status post induction chemotherapy and with persistent blasts (50%) in the bone marrow and blood, accompanied with neutropenia. The patient presented to the emergency room with fever and altered mental status.

Clinicopathologic features and survival in Spitzoid malignant melanoma and conventional malignant melanoma.

Background: Although recent advances in genetics have revealed distinct mutational profiles and molecular signaling pathways associated with Spitzoid malignant melanoma (SMM), less is known about the clinicopathologic characteristics and behavior of SMM compared with conventional melanoma.

Objective: We sought to determine the clinicopathologic characteristics and mortality risk associated with SMM and conventional malignant melanoma.

Methods: We conducted a retrospective study of 30 patients with SMM and 30 patients with conventional melanoma.