Riccardo G. Borroni

Risk of acute postoperative hypertension after topical photodynamic therapy for non-melanoma skin cancer

Topical photodynamic therapy with methyl aminolevulinate (MAL‐PDT) is a non‐surgical treatment for actinic keratoses, Bowens disease and basal cell carcinoma. MAL‐PDT is particularly useful in elderly patients, who often present co‐morbidities and/or in whom surgical excision could be contraindicated. MAL‐PDT is generally well tolerated; the most frequent acute adverse events include pain and burning sensation localized to the treatment area. We describe our observation of the occurrence of acute postoperative hypertension (APH) and hypertensive crisis, after a MAL‐PDT.

A novel mutation of the glomulin gene in an Italian family with autosomal dominant cutaneous glomuvenous malformations

Abstract:  Glomuvenous malformations (GVM) are hamartomas characterized histologically by glomus cells, which should be distinguished from glomus tumors. Familial GVM are rare, often present as multiple lesions, and exhibit familial aggregation, with autosomal dominant transmission. GVM are caused by mutations of the glomulin (GLMN) gene on chromosome 1p21‐p22. Their development is thought to follow the ‘two‐hit’ hypothesis, with a somatic mutation required in addition to the inherited germline mutation. We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions. A second somatic ‘hit’ mutation in GLMN was not discovered in our family. We further provide histological, immunohistochemical and electron microscopic data exhibiting the classic features of GVM. The diagnosis of GVM is critical because of distinction from venous malformations and blue rubber bleb nevus syndrome, which may demonstrate clinical similarities but require different treatment.

Pharmacogenomics in dermatology: from susceptibility genes to personalized therapy

Abstract:  A significant proportion of patients with skin disease do not respond to treatment and adverse drug reactions are a common problem. Genetic factors are important determinants for both drug efficacy and toxicity. The fields of pharmacogenetics and pharmacogenomics examine inter‐individual variations in the DNA sequence that are related to drug efficacy and toxicity. Here, we present pharmacogenomic data relevant to dermatology and explore the role of dermatologists in identifying patients who may respond to treatment or experience adverse drug reactions.

Hypoxia-Inducible Factor-1α and CD271 inversely correlate with melanoma invasiveness.

Melanoma is characterized, among other features, by microenvironmental factors and by an altered apoptotic machinery. Melanoma cell response to a hypoxic environment is transcriptionally regulated by the Hypoxia‐Inducible Factor (HIF)‐1α. p75 neurotrophin receptor (p75NTR), also called CD271, mediates apoptosis in several cell systems. The purpose of this study was to analyze the expression of HIF‐1α and CD271 in melanomas at different phases of progression, as evaluated by histology and reflectance confocal microscopy (RCM). By RCM, 41.67% tumors were characterized by the presence of a population of dendritic and pleomorphic cells (D+P), corresponding to in situ melanoma; 25% exhibited a predominantly round‐cell (RN) proliferation with histologic features of superficial melanoma, and 33.33% showed the presence of cells aggregated in nests (DN), typical of invasive melanoma. HIF‐1α was scarcely detected in D+P and in RN melanomas, while it was highly expressed in DN tumors. By contrast, CD271 positive cells were mostly detected in D+P population, and barely observed in the other subtypes. This work demonstrates that CD271 expression inversely correlates with hypoxia in melanoma, and that the two markers may be used in the future as diagnostic/prognostic tools for this neoplasm.

Glomuvenous malformations with smooth muscle and eccrine glands: unusual histopathologic features in a familial setting

Glomuvenous malformations (OMIM 138000) are hamartomas presenting in childhood as multiple, bluish papules and nodules in the skin, which are characterized histopathologically by irregular vascular spaces surrounded by typical glomus cells. Glomuvenous malformations are caused by autosomal dominant mutations of the GLMN gene. A 34‐year‐old woman and her 16‐year‐old son presented with bluish papules and nodules since childhood. Biopsy specimens from both patients showed histopathologic features of glomuvenous malformations, unusually in consistent and close association with smooth muscle, hair follicles and eccrine glands. Sequencing of the GLMN gene revealed the p.C36X (c.108C>A) mutation in germline DNA from both patients. This is probably the first report describing the hamartomatous features of familial glomuvenous malformations consistently associated with a prominent smooth muscle component and eccrine glands.

Pharmacogenetics and Pharmacogenomics I: Linking Diagnostic Classification to Therapeutic Decisions

Innovations in medical therapy have been associated with increasing life expectancy, improved quality of life, and with a decreasing need for hospitalizations and surgery. However, these benefits are not achieved without significant drawbacks. Medications are not completely safe and effective for everyone. Spear et al. [1] analyzed the efficacy of major drugs used to treat several important diseases. The heterogeneity of therapeutic responses was evident, ranging from a low of 25% (for cancer chemotherapeutics) to a high of 80% (for COX-2 inhibitors), with response rates for most drugs falling in the range of 50–75% [1]. Adverse drug reactions (ADRs) represent another important problem, leading to ∼6% of hospitalizations (>2 million per year) and annual health care costs estimated at

Genetic counselling and high-penetrance susceptibility gene analysis reveal the novel CDKN2A p.D84V (c.251A>T) mutation in melanoma-prone families from Italy.

1.5–

Effectiveness of photodynamic therapy in refractory plaque‐stage mycosis fungoides associated with Bowen's disease

4 billion in the United States [2–4]. ADRs are now the fourth leading cause of mortality in the United States, resulting in >100,000 deaths per year [2–4]. Drug efficacy and toxicity are affected by a number of factors, including patient age, sex, hepatic and renal function, drug–drug interactions, diet, lifestyle, and comorbidities. Many drugs also have narrow therapeutic indices (i.e., the therapeutic dose is close to the toxic dose). In addition, DNA sequence variations are known to play a major role in the inter-individual variability of drug response and ADRs [1]. Pharmacogenomic testing could facilitate a more targeted approach to treatment, by predicting which patients are more likely to respond to a drug, as well as those at increased risk for developing an ADR [1]. The tailoring of drug therapy to the individual patient (“personalized medicine”) is an exciting possibility for clinicians.

Usefulness of in vivo photodiagnosis for the identification of tumor margins in recurrent basal cell carcinoma of the face

Genetic susceptibility to primary cutaneous melanoma (PCM) may account for up to 12% of PCMs, presenting as the familial atypical mole/multiple melanoma syndrome (FAMMM), an autosomal dominant condition with incomplete penetrance and variable expressivity, characterized by PCM in at least two relatives and/or more than one PCMs in the same patient. To identify individuals at high genetic risk of PCM, from 1 January 2012 to 31 December 2015, we offered genetic counselling and molecular analysis of the two high-penetrance FAMMM susceptibility genes, cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase 4 (CDK4), to 92 consecutive, unrelated patients with FAMMM. Age at diagnosis and number of PCMs were obtained from medical records; the number of PCMs and affected relatives were recorded for each family. The diagnostic work-up consisted of genetic counselling and cascade genetic testing in patients and further extension to relatives of those identified as mutation carriers. All exons and exon/intron boundaries of CDKN2A and CDK4 genes were screened by direct bidirectional sequencing. We identified CDKN2A mutations in 19 of the 92 unrelated patients (20.6%) and in 14 additional, clinically healthy relatives. Eleven of these latter subsequently underwent excision of dysplastic nevi, but none developed PCM during a median follow-up of 37.3 months. In three patients from unrelated families, the novel CDKN2A p.D84V (c.251A>T) mutation was observed, associated with PCM in each pedigree. Genetic screening of FAMMM patients and their relatives can contribute towards specific primary and secondary prevention programmes for individuals at high genetic risk of PCM. The novel CDKN2A p.D84V (c.251A>T) mutation adds to the known mutations associated with FAMMM.

The skin neurotrophic network in health and disease.

Dear Editor, Bowen’s disease (BD) is a form of squamous cell carcinoma in situ that can develop into invasive carcinoma if not treated, clinically characterized by an erythematous and scaly plaque that can occur both on sunexposed and non-exposed areas of the skin (Idriss, Misri, & B€ oer-Auer, 2016). Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), and it is characterized by erythematous patches distributed in not-sun exposed areas, which can evolve to