Utilizzo dell'esame dermoscopico nella valutazione clinica e nel follow up dei nevi melanocitici in sede acrale dell'età pediatrica: studio retrospettivo osservazionale

La dermoscopia, metodica non invasiva, di pratico utilizzo e a basso costo si è affermata negli ultimi anni come valido strumento per la diagnosi e il follow up delle lesioni cutanee pigmentate e non pigmentate. La presente ricerca è stata incentrata sullo studio dermoscopico dei nevi melanocitici a localizzazione palmo-plantare, acquisiti e congeniti, in età pediatrica: a questo scopo sono state analizzate le immagini dei nevi melanocitici acrali nei pazienti visitati c/o l’ambulatorio di Dermatologia Pediatrica del Policlinico Sant’Orsola Malpighi dal 2004 al 2011 per definire i principali pattern dermoscopici rilevati ed i cambiamenti osservati durante il follow up videodermatoscopico. Nella nostra casistica di immagini dermoscopiche pediatriche abbiamo notato un cambiamento rilevante (inteso come ogni modificazione rilevata tra il pattern demoscopico osservato al baseline e i successivi follow up) nell’88,6% dei pazienti ed in particolare abbiamo osservato come in un’alta percentuale di pazienti (80%), si sia verificato un vero e proprio impallidimento del nevo melanocitico e in un paziente è stata evidenziata totale regressione dopo un periodo di tempo di 36 mesi. E’ stato interessante notare come l’impallidimento della lesione melanocitaria si sia verificata per lo più in sedi sottoposte ad una sollecitazione meccanica cronica, come la pianta del piede e le dita (di mani e piedi), facendoci ipotizzare un ruolo del traumatismo cronico nelle modificazioni che avvengono nelle neoformazioni melanocitarie dei bambini in questa sede.

Residual visual processing following real or virtual lesions to primary visual pathways

Lesions to the primary geniculo-striate visual pathway cause blindness in the contralesional visual field. Nevertheless, previous studies have suggested that patients with visual field defects may still be able to implicitly process the affective valence of unseen emotional stimuli (affective blindsight) through alternative visual pathways bypassing the striate cortex. These alternative pathways may also allow exploitation of multisensory (audio-visual) integration mechanisms, such that auditory stimulation can enhance visual detection of stimuli which would otherwise be undetected when presented alone (crossmodal blindsight). The present dissertation investigated implicit emotional processing and multisensory integration when conscious visual processing is prevented by real or virtual lesions to the geniculo-striate pathway, in order to further clarify both the nature of these residual processes and the functional aspects of the underlying neural pathways. The present experimental evidence demonstrates that alternative subcortical visual pathways allow implicit processing of the emotional content of facial expressions in the absence of cortical processing. However, this residual ability is limited to fearful expressions. This finding suggests the existence of a subcortical system specialised in detecting danger signals based on coarse visual cues, therefore allowing the early recruitment of flight-or-fight behavioural responses even before conscious and detailed recognition of potential threats can take place. Moreover, the present dissertation extends the knowledge about crossmodal blindsight phenomena by showing that, unlike with visual detection, sound cannot crossmodally enhance visual orientation discrimination in the absence of functional striate cortex. This finding demonstrates, on the one hand, that the striate cortex plays a causative role in crossmodally enhancing visual orientation sensitivity and, on the other hand, that subcortical visual pathways bypassing the striate cortex, despite affording audio-visual integration processes leading to the improvement of simple visual abilities such as detection, cannot mediate multisensory enhancement of more complex visual functions, such as orientation discrimination.

High sensitivity analysis of BRAF mutations in neoplastic and non-neoplastic thyroid lesions

The clonal distribution of BRAFV600E in papillary thyroid carcinoma (PTC) has been recently debated. No information is currently available about precursor lesions of PTCs. My first aim was to establish whether the BRAFV600E mutation occurs as a subclonal event in PTCs. My second aim was to screen BRAF mutations in histologically benign tissue of cases with BRAFV600E or BRAFwt PTCs in order to identify putative precursor lesions of PTCs. Highly sensitive semi-quantitative methods were used: Allele Specific LNA quantitative PCR (ASLNAqPCR) and 454 Next-Generation Sequencing (NGS). For the first aim 155 consecutive formalin-fixed and paraffin-embedded (FFPE) specimens of PTCs were analyzed. The percentage of mutated cells obtained was normalized to the estimated number of neoplastic cells. Three groups of tumors were identified: a first had a percentage of BRAF mutated neoplastic cells > 80%; a second group showed a number of BRAF mutated neoplastic cells < 30%; a third group had a distribution of BRAFV600E between 30-80%. The large presence of BRAFV600E mutated neoplastic cell sub-populations suggests that BRAFV600E may be acquired early during tumorigenesis: therefore, BRAFV600E can be heterogeneously distributed in PTC. For the second aim, two groups were studied: one consisted of 20 cases with BRAFV600E mutated PTC, the other of 9 BRAFwt PTCs. Seventy-five and 23 histologically benign FFPE thyroid specimens were analyzed from the BRAFV600E mutated and BRAFwt PTC groups, respectively. The screening of BRAF mutations identified BRAFV600E in “atypical” cell foci from both groups of patients. “Unusual” BRAF substitutions were observed in histologically benign thyroid associated with BRAFV600E PTCs. These mutations were very uncommon in the group with BRAFwt PTCs and in BRAFV600E PTCs. Therefore, lesions carrying BRAF mutations may represent “abortive” attempts at cancer development: only BRAFV600E boosts neoplastic transformation to PTC. BRAFV600E mutated “atypical foci” may represent precursor lesions of BRAFV600E mutated PTCs.