Line-field confocal optical coherence tomography: a new tool for non-invasive differential diagnosis of pustular skin disorders.

BACKGROUND: The spectrum of pustular skin disorders (PSD) is large and particularly challenging, including inflammatory, infectious and amicrobial diseases. Moreover, although pustules represent the unifying clinical feature, they can be absent or not fully developed in the early stage of the disease. The line-field confocal optical coherence tomography (LC-OCT) is a recently developed imaging technique able to perform a non-invasive, in vivo, examination of the epidermis and upper dermis, reaching very high image resolution and virtual histology. OBJECTIVES: We aimed to investigate the potentialities of LC-OCT in the non-invasive differential diagnosis of a series of 11 PSD with different aetiology, microscopic features, body location and incidence rates. MATERIALS AND METHODS: Complete LC-OCT imaging (i.e. 2D/3D frames, videos) was performed on a total of 19 patients (10 females and 9 males) aged between 35 and 79 years. Images were blindly evaluated and compared with corresponding histopathologic findings. RESULTS: The LC-OCT imaging was able to detect with high accuracy the pustule structure including shape, margins, morphology and cellular content, along with peculiar epidermal and adnexal alterations in each condition, including: Acute Generalized Exanthematous Pustulosis, Generalized pustular psoriasis, Generalized pustular figurate erythema, Subcorneal Pustular Dermatosis, Intraepidermal IgA pustulosis, Palmoplantar pustulosis, Palmoplantar pustular psoriasis. Herpetic whitlow, Acrodermatitis continua of Hallopeau, Vesicopustular Sweet syndrome and Vesicopustular Eosinophilic cellulitis, with pustular appearance, were also compared. CONCLUSIONS: The new LC-OCT can represent a rapid, non-invasive and painless tool which can help differentiating among PSD of different aetiology and microscopic morphology in clinical mimickers in daily practice.

Melanoma arising from a plaque-type blue naevus with subcutaneous cellular nodules of the scalp.

Plaque-type blue naevus (PTBN) is a very rare variant of blue naevus (BN). The potential malignancy of subcutaneous cellular nodules (SCN) in PTBN was discovered in 2012, and there is currently no clear consensus on prognostic factors or management guidelines of such lesions. PTBN on the scalp have not been described in the literature. We report the clinical, histopathological and immunohistological features of a 50-year-old man who presented with a 30-year history of scalp PTBN, with malignant proliferation of nodular elements and fatal outcome 8 years later. This case suggests that long-term monitoring of patients with PTBN is required. Early surgical removal of such lesions should be considered, especially in the presence of any case of enlargement or change.

NADPH oxidase activation and 4-hydroxy-2-nonenal/aquaporin-4 adducts as possible new players in oxidative neuronal damage presents in drug-resistant epilepsy.

A correlation between epilepsy and cellular redox imbalance has been suggested, although the mechanism by which oxidative stress (OS) can be implicated in this disorder is not clear. In the present study several oxidative stress markers and enzymes involved in OS have been determined. In particular, we examined the levels of 4-hydroxy-2-nonenal protein adducts (HNE-PA), a by-product of lipid peroxidation, and the activation of NADPH oxidase 2 (NOX2), as cellular source of superoxide (O(2)(-)), in surgically resected epileptic tissue from drug-resistant patients (N=50). In addition, we investigated whether oxidative-mediated protein damage can affect aquaporin-4 (AQP4), a water channel implicated in brain excitability and epilepsy. Results showed high levels of HNE-PA in epileptic hippocampus, in both neurons and glial cells and cytoplasmic positivity for p47(phox) and p67(phox) suggesting NOX2 activation. Interestingly, in epileptic tissue immunohistochemical localization of AQP4 was identified not only in perivascular astrocytic endfeet, but also in neurons. Nevertheless, negativity for AQP4 was observed in neurons in degeneration. Of note, HNE-mediated post-translational modifications of AQP4 were increased in epileptic tissues and double immunofluorescence clearly demonstrated co-localization of AQP4 and HNE-PA in epileptic hippocampal structures. The idea is that sudden, disorderly, and excessive neuronal discharges activates NOX2 with O(2)(-) production, leading to lipid peroxidation. The resulting generation of HNE targets AQP4, affecting water and ion balance. Therefore, we suggest that seizure induces oxidative damage as well as neuronal loss, thereby promoting neuronal hyperexcitability, also affecting water and ion balance by AQP4 modulation, and thus generating a vicious cycle.

Dermoscopy and digital dermoscopy analysis of palmoplantar 'equivocal' pigmented skin lesions in Caucasians.

BACKGROUND/AIM: The diagnosis of palmoplantar melanoma is often delayed and misdiagnosis is common, due to frequently unusual clinical presentation. We used a digital dermoscopy analyzer with a series of palmoplantar pigmented skin lesions (PP-PSL), and we compared sensitivity, specificity and diagnostic accuracy obtained with digital dermoscopy analysis (DDA) and classical dermoscopy. METHODS: Digital dermoscopy images of 107 PP-PSL were retrospectively obtained from the database of images of 3 Italian centers. The lesions (25 melanomas and 82 nevi) were all removed because of the presence of clinical and/or dermoscopic suspicious features. All digital images were analyzed using appropriate algorithms, and the diagnostic accuracy of the model was calculated. For comparison, dermoscopic images were clinically evaluated by two dermatologists and the Cohen ĸ concordance with DDA was calculated. RESULTS: The stepwise logistic regression analysis selected only 5 parameters out of 49. The logistic model achieved a sensitivity of 96% and a specificity of 87.8%. The Cohen ĸ concordance, evaluated by the Landis and Koch scale, supplied a substantial agreement between dermoscopy and DDA. CONCLUSIONS: DDA might be a useful diagnostic instrument in the evaluation of preselected PP-PSL. However, these findings should be confirmed in a formal clinical trial.

Supero-lateral orbitotomy for resection of spheno-orbital meningioma: a case report.

Spheno-orbital meningioma have traditionally been defined as secondary tumors of the orbit originating from the dura of the sphenoid wing bone. Nevertheless, pathologic findings reveal a distinct periorbital component as a defining feature of these lesions. These tumors are characterized by an intraosseous mass growth leading to a significant hyperostosis involving the sphenoid wing, the orbital roof, the lateral orbital wall and the middle fossa cranial base and to a thin, usually soft-tissue growth at the dura. We report here on the extension of the primary tumor into the orbital cavity and present the surgical approach performed.

A case of primary localized cutaneous infection due to Fusarium oxysporum.

Fusarium is a ubiquitous hyalohyphomycete isolated from food, widespread in the environment (plants, soil) and present at all latitudes. Fusarium oxysporum and Fusarium solani are the most frequent pathogenic species, followed by F. moniliforme and F. chlamydosporum. Infections due to this mold may be disseminated or localized. Localized forms include cutaneous and subcutaneous infection, onychomycosis, endophtalmitis, otitis, sinusitis, arthritis, osteomyelitis, and brain abscess. Disseminated forms are those in which two or more noncontiguous sites may be involved. These latter are observed in patients with severe neutropenia. Wounds, digital ulcers, onychomycosis, and paronychia are the typical cutaneous portal of entry. We report a case of primary localized cutaneous infection due to Fusarium in a 29-year-old woman presenting with a nodular lesion, partially ulcerated, asymptomatic on the first finger of the left hand, appeared 4 months earlier. Histological examination showed spongiosis and acanthosis in the stratum corneum, ulceration and inflammation with prevalently mononucleate cells and septate and branched fungal structures in the epidermis and in dermis. The fungus was identified as Fusarium oxysporum by culture of biopsy fragments on Sabouraud dextrose agar with chloramphenicol. The culture was deposited in the culture collection of the mycology section of IHEM, Brussels (IHEM21984 col no. 125). The patient had normal immune status and was successfully treated with surgical excision. Recovery was confirmed at follow-up 8 months later.

Papillary glioneuronal tumor of the fourth ventricle: case report and review of the literature.

Rosette-forming glioneuronal tumour (RGNT) of the fourth ventricle is a relatively new entity recently described. Neuronal and mixed neuronal-glial tumours have been incorporated in the same category in the WHO Classification of Nervous System Tumours. This category comprises heterogeneous neoplasms composed of neuronal and glial cells with various grades of differentiation. We present a case of papillary glioneuronal tumor occurring in a 44-year-old man with an unusual hemorrhagic onset. The clinical, morphological and immunohistochemical features are discussed and the published literature is reviewed.

Pterygomaxillary extension of orbital pseudotumor. Case report.

Idiopatic pseudotumor (IP) is a non-specific, non-neoplastic, inflammatory process without identifiable local or systemic causes. IP most commonly affects the orbit, comprising 5% to 8% of all orbital masses with occasional extension to other areas of the skull base. The ophthalmology literature has detailed reviews of IP as a space-occupying intraorbital lesion, but lesion involving only the skull base and sparing the orbit is exceptional. Understanding the presentation, work-up, and characteristics of the lesion is important for proper diagnosis and treatment. We report a rare case of orbital IP with extension into infratemporal fossa. Clinical and radiological findings and surgical approach are discussed.

Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin-induced changes in vitro and differential expression in melanocytic lesions.

Calpains are cysteine proteases comprising members ubiquitously expressed in human tissues and other tissue-specific isoforms. Alterations of calpain 3 (p94), the muscle-specific isoform that contains three peculiar sequences (NS, IS1 and IS2), are strictly associated to the limb-girdle muscular dystrophy type 2A, in which a myonuclear apoptosis has been documented. Our recent demonstration of a proapoptotic role of ubiquitous calpains in drug-induced apoptosis of melanoma cells prompted us to investigate the expression of calpain 3 in human melanoma cell lines undergoing apoptosis and in melanocytic lesions. In melanoma cell lines, we have identified two novel splicing variants of calpain 3 (hMp78 and hMp84): they have an atypical initiation exon and a putative nuclear localization signal, the shorter one lacks IS1 inset and both proteins are extremely unstable. Virtually, both isoforms (prevalently as cleavage forms) are localized in cytoplasm and in nucleoli. In cisplatin-treated preapoptotic cells, an increase of both transcription and autoproteolytic cleavage of the novel variants is observed; the latter event is prevented by the inhibitor of ubiquitous calpains, calpeptin, which is also able to protect from apoptosis. Interestingly, among melanocytic lesions, the expression of these novel variants is significantly downregulated, compared with benign nevi, in the most aggressive ones, i.e. in vertical growth phase melanoma and, even more, in metastatic melanoma cells, characterized by invasiveness properties and usually highly resistant to apoptosis. On the whole, our observations suggest that calpain 3 variants can play a proapoptotic role in melanoma cells and its downregulation, as observed in highly aggressive lesions, could contribute to melanoma progression.

Benign orbital pseudolymphoma. Case report.

Orbital pseudolymphomas are uncommon benign tumors composed of reactive lymphocytes. The typical clinical presentation is painless onset of ptosis, proptosis, diplopia, or eyelid swelling. Virtually any adnexal structure can be affected, but lacrimal gland, orbital soft tissue, or extraocular muscles are the usual sites of involvement. Historically, treatment has been with oral corticosteroids or localized radiotherapy. We present a case of benign orbital pseudolymphoma.

Primary hepatic epithelioid hemangioendothelioma progressively responsive to interferon-alpha: is there room for novel anti-angiogenetic treatments?

Primary hepatic epithelioid hemangioendothelioma (HEH) is a rare, low-grade malignant neoplasm of endothelial origin, with an unpredictable clinical course and prognosis. No standard therapeutic strategies are still available for HEH, due to the infrequency of the disease and to its variable natural history that limit the identification of the most effective treatment. In the absence of metastatic disease, surgical resection or liver transplantation represent the treatment of choice for HEH, while several antineoplastic agents have been proposed in the presence of metastatic nonresectable disesase. Herein, we describe the biological characterization and the clinical course of a primary HEH progressively responsive to treatment with intermediate doses of interferon-alpha (IFN)-alpha2a. Furthermore, based on the newly-identified expression of endoglin (CD105) on HEH, we discuss the clinical potential of novel anti-angiogenetic approaches to the disease.

Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defects.

We evaluated a 11-year-old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work-up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments.

A risk scoring system for the differentiation between melanoma with regression and regressing nevi.

BACKGROUND: Spontaneous regression of melanomas is relatively common, its prevalence ranging from 10 to 35%. However, regressing nevi can exhibit worrisome feature and simulate melanoma both clinically and dermoscopically. Thus, the presence of regression can represent a confounding factor. OBJECTIVE: To investigate the frequency of dermoscopic patterns of "regression" in a series of benign and malignant melanocytic skin lesions, and to design an integrated scoring system. Scoring classifiers are very effective in selecting the significant parameters for discriminating two clinical conditions, thus can rapidly calculate a patient's risk for a given disease. METHODS: We selected a series of 95 regressing melanocytic lesions, including 50 regressing nevi and 45 melanomas with regression. For each lesion, 12 dermoscopic variables (i.e. five types of regression structures, five atypical pigmentation structures, atypical vascular pattern and pink areas) were examined by three expert in dermoscopy (blinded to the histological diagnosis). The dermoscopic evaluation was then combined with patient age, gender, body site and the maximum diameter of lesion. Concordance analysis with Cohen's kappa was performed between the three clinicians. A risk scoring system was designed by the leave-one-out cross-validation procedure to ensure model prediction power. RESULTS: The predictive score model revealed a sensitivity of 97.8% and a specificity of 75.5% in discriminating nevi and melanomas with regression. Using the score model, the diagnostic performance of the examiners increased by an average of 23.7% in sensitivity and 5.9% in specificity, compared with standard dermoscopic pattern analysis. CONCLUSIONS: We assessed the validity of an integrated risk scoring model as a new methodological approach that could help the dermatologist in the differentiation between melanoma with regression and regressing nevus. Future studies could test the setting up of a score model over an even more complex pool of data obtained from different skin lesions with various diagnostic devices.

Malignant hypercalcemia in vulvar cancer.

Humoral hypercalcemia of malignancy (HHM) is a common paraneoplastic syndrome, most often associated with squamous cell carcinoma of the lung, esophagus, kidneys and breast, but rarely with vulval cancer. In most patients, HHM is associated with over-production of a peptide analogue of parathormone (parathyroid hormone-related protein, PTHrP). The case of a 70-year-old patient with massive squamous cell epithelioma of the vulva complicated by HHM is reported. To our knowledge, this is the first documented case with high serum concentrations of PTHrP and immunohistochemical confirmation of PTHrP production by neoplastic cells.