PubMed Health⌕ Search

Biomedical subjects

Daniela Massi

Publications and source records attributed to Daniela Massi.

At least 19 recordsLinked to original sources
PubMed2026

primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma.

PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC. METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint. RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo. CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.

Adult↗
PubMed2007

Primary cutaneous osteosarcoma of the scalp: a case report and review of the literature.

We report on an 84-year-old man with a solitary, nodular lesion on the scalp. The patient had been previously submitted to electrodessications of the scalp due to multiple solar keratoses. Histopathologically, the lesion showed features of a high-grade conventional osteoblastic osteosarcoma involving the dermis. Computed tomography showed no involvement of the underlying bone tissues. Clinical examination and extensive total body radiologic workup revealed absence of bone lesions in any body site, thus suggesting a final diagnosis of primary cutaneous extraskeletal osteosarcoma. The clinico-pathological features of the case are discussed in light of the rare cases previously described in the literature.

Aged, 80 and over↗
PubMed2006

Expression of p16 in sinonasal malignant melanoma.

The aim of this study was to investigate the expression of p16 in relation with the histopathologic features and the clinical course in patients with sinonasal melanoma. Thirty-seven sinonasal melanomas were immunostained for p16. Seventeen tumours were investigated for loss of the 9p21 region using interphase fluorescence in situ hybridization (FISH). Twenty-seven melanomas (72.9%) showed loss of p16 expression. All cases with spindle or mixed cytology showed loss of p16, whereas this was present in 50% of epithelioid tumours (p=0.01). Loss of p16 expression was more frequently seen in melanomas with alveolar architecture (87.5%) than in tumours with diffuse architecture (68.9%) (p=0.4). There was no correlation between p16 expression and presence of lymph node or distant metastases (p=0.57 and 0.24, respectively). In addition, p16 status did not influence overall survival (p=0.2). The FISH results were in good agreement with immunohistochemistry: 11 tumours out of 17 showed deletion of the 9p21 region and 10 of these showed loss of protein expression. Loss of p16 expression is a frequent event in sinonasal melanoma and it is mainly related to deletion of 9p21 region. At variance from cutaneous melanoma, loss of p16 is not correlated with the prognosis of patients affected by sinonasal melanoma.

Aged↗
PubMed2006

Dermoscopy improves accuracy of primary care physicians to triage lesions suggestive of skin cancer.

PURPOSE: Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer. PATIENTS AND METHODS: PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists. RESULTS: Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002). CONCLUSION: The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.

Adolescent↗
PubMed2006

Inducible nitric oxide synthase activity correlates with lymphangiogenesis and vascular endothelial growth factor-C expression in head and neck squamous cell carcinoma.

Nitric oxide (NO) is a diatomic free radical molecule that has been implicated in tumour angiogenesis and progression of head and neck squamous cell carcinoma (HNSCC). However, the mechanism underlying the effect of NO on tumour spread remains largely unknown. Tumour lymphangiogenesis has recently received considerable attention and there is increasing evidence that it is relevant for metastasis to lymph nodes in HNSCC. Here, we study the correlation between inducible NOS synthase (iNOS) activity and lymphangiogenesis in a series of 60 HNSCCs and the possible involvement of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. HNSCC presenting with lymph node metastasis had a significantly higher lymphatic vessel density in both the tumour mass and the peritumour area (p = 0.006 and p = 0.001, respectively). Similarly, tumours with lymph node metastasis showed greater lymphatic vessel area than tumours with no lymph node involvement (p = 0.001 for intratumour lymphatics and p < 0.001 for peritumour lymphatics). iNOS activity measured in specimens from the tumour periphery correlated strongly with both lymphatic vessel density and lymphatic vessel area (p = 0.01, rs = 0.45 and p < 0.001, rs = 0.725, respectively). Conversely, these correlations were not observed in specimens from the tumour core. In addition, VEGF-C mRNA expression was significantly elevated in tumours with high iNOS activity (p = 0.008, rs = 0.563), and VEGF-C expression correlated positively with the presence of lymph node metastases (p = 0.03). In vitro, in the A431 human squamous carcinoma cell line, exogenous and endogenous stimulation of the iNOS pathway led to up-regulation of VEGF-C, which was blocked by the NOS inhibitor L-NNA. Taken together, our results indicate that iNOS activity may promote lymphangiogenesis and spread to lymph nodes in HNSCC, with the possible involvement of VEGF-C.

Aged↗
PubMed2006

Diagnosis of Anderson-Fabry's disease in over seventy-year-old women: description of two cases.

Anderson-Fabry's disease (AFD) is a rare inborn X-linked sphingolipid storage disorder. Deficient activity of the lysosomal enzyme alpha-galactosidase A (alpha-GAL-A) leads to progressive accumulation of glycosphingolipids within most visceral tissues and body fluids of affected patients, provoking a clinical syndrome that includes nervous system, renal, cardiac, ophthalmologic and cutaneous manifestations. Also heterozygous women, who had been considered as healthy carriers until recently, often demonstrate clinical signs of multi-organ involvement. In older women these manifestations are frequently attributed to other more common conditions of older age, and a genetic disorder is rarely hypothesized. We report the cases of two elderly women, who had been diagnosed with AFD at the ages of 70 and 74. Although it is a rare disease, AFD should be considered as a diagnostic hypothesis in women with a clinical history of cardiomyopathy and vascular encephalopathy, appearing at ages 40-50 without identification of major vascular risk factors.

Age Factors↗
PubMed2006

Dermoscopy for "true" amelanotic melanoma: a clinical dermoscopic-pathologic case study.

Completely amelanotic melanomas are rare and therefore often misclassified, with tragic consequences for patients. The use of dermoscopy for these lesions has not been validated yet because of the lack of studies that are based on large series. The analysis of the vascular pattern, which is often the only dermoscopic parameter to be seen, is therefore essential for a correct diagnosis. We present a case of "true" amelanotic melanoma on the forehead of an 89-year-old man, which clinically mimicked squamous cell carcinoma. The patient was investigated both clinically and by focusing on his dermoscopic features and their pathologic correlates. The dermoscopic diagnostic algorithms routinely used for pigmented lesions are not helpful in diagnosing amelanotic melanoma because they are based on specific parameters not normally seen in amelanotic lesions. In the light of our experience, pattern analysis is the most reliable method for diagnosing these particular lesions correctly because it allows in-depth morphologic analysis of the few parameters found.

Aged↗
PubMed2006

Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma.

The Notch signaling has been implicated in the regulation of self-renewal of adult stem cells and differentiation of precursors along a specific cell lineage, in normal embryonic development and organogenesis. There is also evidence that signaling through Notch receptors regulate cell proliferation and cell survival in several types of cancer, with opposing results depending on tissue context. No data are available in the literature concerning modulation of the expression of Notch receptors, and their ligands, in human cutaneous malignant melanoma. Here, we have investigated, for the first time, the expression of Notch-1, Notch-2, Jagged-1, Jagged-2 and Delta-like 1 proteins, by immunohistochemistry, in a series of benign and malignant human melanocytic lesions: five common melanocytic nevi, five 'dysplastic nevi' and 20 melanomas (five in situ, five T1-T2, five T3-T4 and five metastatic melanomas). We found that the expression of Notch-1 and Notch-2, as well as Notch ligands, was upregulated in 'dysplastic nevi' and melanomas as compared with common melanocytic nevi. These results indicate that the activation of Notch may represent an early event in melanocytic tumor growth and upregulation of Notch signaling may sustain tumor progression.

Adult↗
PubMed2006

Features of regression in dermoscopic diagnosis: a confounding factor? Two clinical, dermoscopic-pathologic case studies.

BACKGROUND: In dermoscopy, the presence of regression areas is generally associated with melanocytic lesions and is often considered a clue of malignancy. However, some lesions included in the differential diagnosis of melanoma may show dermoscopic regression parameters. Regression may indeed be one of the most confounding dermoscopic parameters because it tends to cover, or rather to destroy, other parameters, thus often hindering a correct diagnosis. OBJECTIVE: We propose to raise the issue of the actual diagnostic role of this parameter. METHODS: We discuss two clinical cases (melanoma and basal cell carcinoma) with major dermoscopic regression features. CONCLUSION: Dermoscopic regression parameters should not be regarded as almost pathognomonic signs of melanocytic lesions. Rather, they should be taken into account only after having considered other dermoscopic parameters of greater diagnostic significance and just as signs that may better typify the lesion.

Aged↗
PubMed2006

Macrophage migration inhibitory factor protein and mRNA expression in cutaneous melanocytic tumours.

Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in various biological processes. Although MIF's functions in cancer have not been completely elucidated, its expression has usually been correlated with tumour progression and aggressiveness, and it is currently discussed as a new promising target for novel therapies. Recent studies seem to confirm its active role in melanoma pathobiology; however, its expression has not yet been extensively studied in melanocytic tumours. We evaluated MIF protein expression in 126 skin lesions, including benign and atypical nevi, melanoma and melanoma metastases. In 55 cases, we also assessed MIF mRNA expression by real-time RT-PCR. Benign nevi were subdivided into nevocytic and Spitz/blue types; and melanomas into the radial, and vertical growth phase. A strong cytoplasmic MIF positivity was found in most samples, although it was more heterogeneous in malignant tumours; MIF nuclear expression characterized Spitz/blue nevi, atypical nevi, melanomas and metastases. All samples expressed MIF mRNA but it was significantly lower in benign nevi vs atypical nevi, melanomas and metastases (p=0.001; p<0.0001; p=0.002, respectively). Our study shows a widespread distribution of MIF among melanocytic tumours. Whereas we observed a trend towards higher expression levels of mRNA in atypical and malignant tumours, MIF protein was highly expressed in all lesions, although limited to the cytoplasm in most benign nevi. These observations suggest differences in MIF protein storage, subcellular location and properties in most benign nevi vs atypical and malignant tumours that should be confirmed by further investigation and correlation with clinical outcome.

Cell Nucleus↗
PubMed2005

Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma.

Protease-activated receptors (PARs) are members of the G protein-coupled receptor superfamily that are activated by the proteolytic cleavage of their amino terminal domain. PAR-1 activation by thrombin results in several biologic effects, including platelet adhesion to other cells or extracellular matrix, fibroblast, and endothelial cell growth, whereas PAR-2, activated by trypsin, has mainly a proinflammmatory and angiogenetic role. PAR-1 and PAR-2 modulate cell proliferation in physiopathologic cell invasion processes, suggesting that they may play a role in the setting of cancer growth and metastasis. Here, we have investigated the expression of PAR-1 and PAR-2 proteins by immunohistochemistry in a series of benign and malignant melanocytic lesions: 20 melanocytic lesions (10 common melanocytic nevi and 10 atypical or "dysplastic" melanocytic nevi) and 50 melanomas (10 in situ melanomas, 10 melanomas T1, 10 melanomas T2, 10 melanomas T3 to T4, and 10 metastatic melanomas). PAR-1 was significantly overexpressed in atypical nevi and melanomas in comparison with common melanocytic nevi. PAR-2 was strongly and diffusely expressed by immunohistochemistry in all melanocytic lesions, with no statistically significant differences between nevi and melanomas. Because we found a differential expression in PAR-1 protein, but not in PAR-2, we next investigated the expression of PAR-1 messenger RNA (mRNA) by ribonuclease protection assay in paraffin-embedded tissues using a paraffin block RNA isolation procedure. Similarly to immunohistochemical results, PAR-1 mRNA expression was significantly higher in atypical nevi and melanomas in comparison with common nevi and controls. Overexpression of PAR-1 in atypical nevi and melanomas supports a role for PAR-1 in the initial phases of melanoma development as well as in tumor progression and metastasis. Conversely, the significance of PAR-2 up-regulation in both benign and malignant melanocytic lesions requires further research.

Adult↗
PubMed2005

Vulvar basal cell carcinoma: retrospective study and review of literature.

OBJECTIVES: Basal Cell Carcinoma (BCC) is the most common human malignant neoplasm. It does not occur only in anatomical areas commonly exposed to sunlight, but also in relatively protected body sites such as the axillae, the groin and buttocks, and in regions which are entirely protected from the sun, like the vulva. The aim of this study is to assess the impact and clinical features of BCCs in the vulva versus other anatomical sites. METHODS: For this purpose, we retrospectively reviewed all the histological diagnoses of BCCs made between 1995 and 2003 in the Department of Human Pathology and Oncology of the University of Florence, Italy. RESULTS: Out of 3604 cases of BCC, 63 were in the vulva. The average age of patients suffering from the latter was 70.35 years. The average size of the vulvar BCCs was 2.1 cm and 18 (28%) were ulcerated at presentation. CONCLUSIONS: Our study shows that vulvar BCC is not a particularly rare occurrence; in fact it should be suspected whenever lesions that we believe to be inflammatory do not respond to usual treatment. In our experience, mucocutaneous examination of this anatomical area should be performed especially in patients with a history of skin cancer. In case of suspicion, a biopsy is recommended to obtain a preoperative confirmatory diagnosis.

Adult↗
PubMed2005

Possible histopathologic correlates of dermoscopic features in pigmented melanocytic lesions identified by means of optical coherence tomography.

Optical coherence tomography (OCT) is a novel non-invasive imaging technique for in vivo histologic characterization of tissues. Besides pure morphology, additional functional parameters of the tissue investigated can be evaluated at the same time, such as the refractive index and the scattering coefficient. The purpose of our study is to correlate in vivo the dermoscopic structures that first appear in the melanocytic pigmented lesion (pigment network and brown globules) using this new method, with the histopathologic correlates, in order to improve their characterization and achieve easier recognition and inter-observer reproducibility. We concentrated in particular on the pigment network and the brown globules, as these are dermoscopic parameters of great diagnostic importance in melanocytic lesions. Moreover, as these parameters are the histopathologic equivalents of structures located at the level of the dermo-epidermal junction, they enable a correct evaluation to be made using OCT, that at present has only a few millimetres penetration power. The results of our trial, performed using the histopathological preparation as an evaluation gold standard, show that in selected cases OCT allows an in vivo correlation to be made between surface dermoscopic parameters and histopathologic correlates, in particular the pigment network and brown globules. The resolution is not high enough to reveal the morphology of the single cells, but it is possible to evaluate the architecture of a lesion.

Adult↗
PubMed2005

Iatrogenic calcinosis cutis following nadroparin injection.

Accumulation of calcium in the skin is usually classified as a group of disorders referred to as calcinosis cutis. We report the case of a patient who developed iatrogenic calcinosis at the site of subcutaneous administration of low-molecular-weight heparins (LMWH) as nadroparin. This is usually used for the prevention of deep venous thrombosis, especially following renal transplantation. The role of calcium content in nadroparin is discussed.

Aged↗