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Biomedical subjects

D Massi

Publications and source records attributed to D Massi.

At least 19 recordsLinked to original sources

Radiation-induced cutaneous carcinoma of the head and neck: is there an early role for p53 mutations?

BACKGROUND: Little is known about the molecular mechanisms underlying ionizing radiation-induced carcinogenesis of the skin. AIMS: To investigate the possible role of p53 in radiodermatitis and in the development of radiation-induced cutaneous carcinomas. METHODS: The study group comprised six patients affected by cutaneous carcinomas arising in radiodermatitis (one squamous cell carcinoma and five basal cell carcinomas), and seven patients presenting only chronic radiodermatitis. Skin specimens were evaluated for p53 immunohistochemical expression. Using laser-assisted microdissection, areas with different p53 immunoreactivity were separately submitted to DNA isolation and p53 gene analysis. RESULTS: In the majority of cases (9/12, 75%), p53 immunoreactivity was detected in radiation-damaged epidermis. In carcinomas p53 oncoprotein was expressed by several neoplastic cells in one case (16.7%%), or by nearly all neoplastic cells in four (66.7%). SSCP band shifts were detected in 9/25 samples (36%) microdissected from irradiated epidermis and in 3/6 (50%) carcinomas. DNA sequencing demonstrated two repeatedly found mutations: a G deletion at codon 244 and an A-->G transition at codon 205, as well as hallmarks of ultraviolet mutagenic action, including a C-->T transition occurring at a dipyrimidine site and a CC-->TT tandem double-base transition. CONCLUSION: Our data indicate that irradiation induces significant p53 alterations that may be relevant in the modification of epithelial maturation processes and may be responsible for the high risk for development of carcinomas in radiodermatitis.

Base Sequence↗

Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study.

BACKGROUND: Cutaneous melanoma spreads preferentially through the lymphatic route and sentinel lymph node (SLN) status is regarded as the most important predictor of survival. AIMS: To evaluate whether tumour lymphangiogenesis and the expression of vascular endothelial growth factor C (VEGF-C) is related to the risk of SLN metastasis and to clinical outcome in a case-control series of patients with melanoma. METHODS: Forty five invasive melanoma specimens (15 cases and 30 matched controls) were investigated by immunostaining for the lymphatic endothelial marker D2-40 and for VEGF-C. Lymphangiogenesis was measured using computer assisted morphometric analysis. RESULTS: Peritumorous lymphatic vessels were more numerous, had larger average size, and greater relative area than intratumorous lymphatics. The number and area of peritumorous and intratumorous lymphatics was significantly higher in melanomas associated with SLN metastasis than in non-metastatic melanomas. No significant difference in VEGF-C expression by neoplastic cells was shown between metastatic and non-metastatic melanomas. Using logistic regression analysis, intratumorous lymphatic vessel (LV) area was the most significant predictor of SLN metastasis (p = 0.04). Using multivariate analysis, peritumorous LV density was an independent variable affecting overall survival, whereas the intratumorous LV area approached significance (p = 0.07). CONCLUSIONS: This study provides evidence that the presence of high peritumorous and intratumorous lymphatic microvessel density is associated with SLN metastasis and shorter survival. The intratumorous lymphatic vessel area is the most significant factor predicting SLN metastasis. The tumour associated lymphatic network constitutes a potential criterion in the selection of high risk patients for complementary treatment and a new target for antimelanoma therapeutic strategies.

Adult↗

Cutaneous collision tumour (melanocytic naevus, basal cell carcinoma, seborrhoeic keratosis): a clinical, dermoscopic and pathological case report.

The association of contiguous or 'collision' tumours in the same biopsy specimen is not uncommon and is often reported in the literature. The most common association, basal cell carcinoma (BCC) and naevus, is very difficult to diagnose clinically. We describe a 38-year-old woman with a previous history of melanoma, who presented with a modified pigmented lesion of the hip that had begun to change 6 months earlier. Histologically, the lesion was a melanocytic compound naevus and a BCC with a seborrhoeic keratosis. The case was investigated clinically and by focusing on the dermoscopic features and their pathological correlates. Cutaneous collision tumours are extremely difficult to diagnose preoperatively, even with the help of dermoscopy, in particular when one of the lesions is melanocytic.

Adult↗

Pigmented seborrheic keratoses of the vulva clinically mimicking a malignant melanoma: a clinical, dermoscopic-pathologic case study.

The diagnosis of seborrheic keratosis is, in general, a clinical one, but in some cases, the differential diagnosis between pigmented seborrheic keratosis and malignant melanoma is difficult. Dermoscopy may improve the early diagnosis of vulvar melanoma and thus play a role in the preoperative classification of pigmented lesions at this particular site. We report the first case of a pigmented seborrheic keratosis of the vulva clinically mimicking a malignant melanoma, whose dermoscopic features have been investigated together with their pathologic correlates. Dermoscopically our case shows the absence of comedo-like openings and the presence of the pseudo-network. Dermoscopy is therefore a useful method for the differential diagnosis of pigmented lesions even in the vulva.

Aged↗

Subcutaneous alternariosis.

A case of subcutaneous alternariosis caused by Alternaria alternata is reported in a 52-year-old male who underwent kidney transplantation 1 year earlier. The infection manifested as a vegetating mass about 7 cm in diameter on the right forearm. Histological examination with Grocott staining and periodic acid-Schiff diastase revealed fungal spores and hyphae with chronic granulomatous inflammation. Biopsy fragments inoculated on Sabouraud-glucose agar with chloramphenicol produced colonies which were identified as Alternaria alternata on the basis of macroscopic and microscopic characters.

Alternaria↗

CDX-2, cytokeratin 7 and cytokeratin 20 immunohistochemical expression in the differential diagnosis of primary adenocarcinomas of the sinonasal tract.

Because the histopathological features of some primary adenocarcinomas of the sinonasal tract may show considerable overlap, we assessed the diagnostic value of a panel of immunohistochemical markers in the distinction between these malignancies. Paraffin-embedded tumour tissue sections from a series of 39 primary adenocarcinomas of the sinonasal tract, including 25 cases of intestinal-type adenocarcinoma (ITAC), 10 cases of salivary gland-type carcinoma and 4 cases of tubulopapillary low-grade adenocarcinoma were immunostained for CDX-2, cytokeratin 7 and cytokeratin 20. Diffuse nuclear staining for CDX-2 was identified in 80% of ITACs, while all non-ITACs were negative. Staining for cytokeratin 20 was positive in 84% of ITACs, including all cases negative for CDX-2, but negative in all other adenocarcinomas. Cytokeratin 7 was consistently positive in 88% of ITACs and in 100% of non-ITACs. Normal sinonasal epithelia expressed cytokeratin 7, but not CDX-2 and cytokeratin 20. Staining for CDX-2 and cytokeratin 20 has potential use in separating ITACs from other primary malignant glandular neoplasms of the nasal cavities and paranasal sinuses.

Adenocarcinoma↗

Prognostic factors in soft tissue leiomyosarcoma of the extremities: a retrospective analysis of 42 cases.

AIMS: Soft tissue leiomyosarcomas (LMS) are rare tumours which are associated with a poor prognosis. The goals of the present study were to describe the clinico-pathological and prognostic features of 42 patients affected by soft tissue LMS of the extremities. METHODS: The following clinical and pathological parameters were analysed: age, sex, site, size, depth, previous surgical procedures, stage, histological type, nuclear atypia, grade, mitotic activity, necrosis, surgical margins, therapy. Disease-free survival rates were calculated. RESULTS: The overall 2-year and 5-year disease free survival rates were 42.3% and 32.6%, respectively. By univariate analysis, tumour size (< or =10 cm vs. >10 cm; p = 0.01), average mitotic rate (< or =19/10 HPF vs. >19/10 HPF; p = 0.05), type of excision (wide vs. marginal or intralesional; p = 0.001) and adjuvant radiotherapy (none vs. brachytherapy+external beam radiotherapy vs. external beam radiotherapy; p = 0.02) were significantly correlated with disease progression. By multivariate analysis, the only factor that was found to be an independent predictor of disease relapse was type of excision (p = 0.001). CONCLUSIONS: Large tumour size and high mitotic rate resulted adverse prognostic factors. Adjuvant radiation therapy, in combination with wide surgical excision, allowed the best chance of cure.

Adult↗

Histopathological re-classification of extremity pleomorphic soft tissue sarcoma has clinical relevance.

AIMS: The aims were to describe the clinico-pathological features of 65 patients affected by soft tissue pleomorphic sarcomas of the extremities, to evaluate their clinical outcome and to explore the prognostic impact of clinical and pathologic parameters, on disease-free and overall survival. METHODS: Soft tissue pleomorphic sarcomas of the extremities were retrieved to be retrospectively re-evaluated in the current analysis. The following parameters were analysed: age, sex, site, size, stage, histotype, grade, surgical margins, therapy. Disease-free and overall survival rates were calculated according to the Kaplan-Meier method. A multivariate analysis was used to determine which variable had an independent effect on clinical outcome. RESULTS: Sixty-five patients with soft tissue pleomorphic sarcomas of the extremities were included in the study. Upon revision, there were 22 leiomyosarcomas, 13 myxofibrosarcomas, 9 liposarcomas, 10 pleomorphic MFH/undifferentiated high grade pleomorphic sarcomas, and 11 cases were other types of plemorphic sarcomas, including rhabdomyosarcoma (n=4), osteosarcoma (n=2), myofibrosarcoma (n=5). In the whole series, by multivariate analysis, stage was the only factor predictor of disease progression (p=0.001; RR 6.9; 95% CI 1.3-15.6). Considering only localized pleomorphic sarcomas the independent predictors of disease relapse were site (p=0.03; RR 3.6; 95% CI 1.0-12.4) and myogenic differentiation (p=0.04; RR 2.9; 95% CI 0.9-10.0), whereas myogenic differentiation resulted the only independent predictor of overall survival (p=0.03; RR 6.5; 95% CI 1.1-37.9). DISCUSSION: These results indicate that histopathological classification of soft tissue pleomorphic sarcomas is clinically relevant. In our experience, AJCC stage and myogenic differentiation are the factors which independently affect prognosis.

Adolescent↗

Improvement of malignant/benign ratio in excised melanocytic lesions in the 'dermoscopy era': a retrospective study 1997-2001.

BACKGROUND: Because of the many limitations of studies based on the diagnostic setting of excised lesions, the impact of dermoscopy (epiluminescence microscopy, dermatoscopy) in melanoma screening during practice remains to be established. OBJECTIVES: We assumed that effects of the use of dermoscopy on some indicators of diagnostic performance in melanoma screening should be traceable retrospectively; therefore, we analysed the impact of routine dermoscopy use on the malignant/benign ratio in excised melanocytic lesions. METHODS: Preoperative and histological diagnosis of 3053 melanocytic lesions [319 melanomas (10.4%)] consecutively diagnosed and excised at the Department of Dermatology, University of Florence in the period 1997-2001 inclusive were retrieved. Six dermatologists who selected the lesions to excise and who performed preoperative diagnosis were divided into two groups according to their use of dermoscopy in routine activity (n = 2 dermoscopy users and n = 4 nonusers). The study period was divided into a predermoscopy period (1997), a shift phase (1998) and a dermoscopy period (1999-2001). RESULTS: During the study period, the malignant/benign ratio improved in dermoscopy users only (from 1 : 18 to 1 : 4.3, P = 0.037). No significant difference was found for nonusers (from 1 : 11.8 to 1 : 14.4). Dermoscopy users were more likely to have a melanoma diagnosed within a series of excised lesions than nonusers, even taking into account potential confounders such as sex, age and study period by means of multivariate analysis (odds ratio 1.55, 95% confidence interval 1.17-2.01). The percentage of 'problem' naevi (naevi with architectural disorder with or without cytological atypia and Spitz or Reed naevi) over the total number of excised lesions was higher in dermoscopy users than in nonusers (year 2001, 51.6% vs. 40.9%, P = 0.014). Similar findings were obtained after exclusion from the data set of lesions excised for cosmetic reasons. CONCLUSIONS: The adoption of dermoscopy in routine melanoma screening is followed by an improvement of the malignant/benign ratio in excised lesions, suggesting a more appropriate selection of pigmented lesions referred to surgery. Because of the possible limitations of a retrospective study design, future confirmation of this finding by means of a prospective, randomized study is advisable. The introduction of dermoscopy in routine practice may have major implications in large-scale melanoma screening with cost savings and a reduction of the dermosurgery workload.

Female↗

Evaluation of inflammatory infiltrate and fibrogenic cytokines in pseudopelade of Brocq suggests the involvement of T-helper 2 and 3 cytokines.

BACKGROUND: Pseudopelade of Brocq (PB) is an acquired progressive cicatricial alopecia which is characterized by some distinctive clinical features. It may represent either a distinct entity, i.e. an idiopathic primary scarring alopecia, or the end stage of various forms of scarring alopecia such as discoid lupus erythematosus (DLE) or lichen planopilaris (LPP). OBJECTIVES: The aim of the study was to evaluate a set of patients with a clinically defined PB, to ascertain whether their PB was idiopathic or secondary, and then to study the phenotype of the inflammatory infiltrate and the presence of any fibrogenic and antifibrogenic cytokines to identify idiopathic or secondary forms in more detail. METHODS: Twelve female patients with PB were studied by means of histology, direct immunofluorescence (DIF) and immunohistochemistry, by using monoclonal antibodies to cell markers (lymphocyte subtypes, Langerhans cells, macrophages, fibroblasts, mastocytes and activation markers) and fibrogenic and antifibrogenic cytokines. RESULTS: Using histology and DIF, we diagnosed two cases as DLE and three cases as LPP. Seven cases had nonspecific histology or DIF appearances and were classified as noncharacterized pseudopelade (NCPB). Two major phenotypic patterns of dermal infiltrate were identified by immunohistochemistry. These were: (i) a conspicuous infiltrate of CD3+ cells with a high CD4+/CD8+ ratio, variable numbers of macrophages, mast cells and fibroblasts always fewer than lymphocytes; (ii) an infiltrate of CD3+ cells with variable CD4+/CD8+ ratio and conspicuous amounts of macrophages, mast cells and fibroblasts, more numerous than infiltrating lymphocytes. The first pattern was typical of DLE and LPP, the second one was typical of NCPB. Fibrogenic cytokines were observed in all cases, but basic fibroblastic growth factor (bFGF) and transforming growth factor (TGF)-beta were more strongly expressed in NCPB. Interferon (IFN)-gamma was found in LPP. CONCLUSIONS: In our PB patients we identified five of 12 secondary PB and seven of 12 idiopathic PB by means of histology and DIF. The phenotypic pattern of infiltration allowed us to further differentiate secondary (richer in lymphocytes) from idiopathic PB (richer in resident cells). The pattern of cytokine expression showed the presence of fibrogenic molecules (interleukins 4 and 6, bFGF and TGF-beta) in all cases, suggesting the involvement of mechanisms mediated by T-helper 2 and 3 cytokines in PB.

Adult↗

Scarring alopecia in discoid lupus erythematosus: a clinical, histopathologic and immunopathologic study.

Scarring alopecia is a very frequent feature of chronic discoid lupus erythematosus (DLE). So far in the literature, only clinic-pathologic features or histopathologic-immunopathologic traits of DLE scarring alopecia (DLESA) have been reported. We describe the most significant features of clinical morphology, histopathology, serum and tissue immunopathology of 36 DLESA patients (41.9% of all our scarring alopecia patients). Clinically, 33.3% presented a single lesion and 52.7% presented multiple lesions of scarring alopecia, while 13.8% exhibited a picture resembling Pseudopelade of Brocq, with the classic 'footprints in the snow' appearance. The most frequent morphologic features were sclero-atrophy (80.5%) and erythema (63.8%). The main histopathologic aspects appeared to be fibrosis (100%), follicular hyperkeratosis (91.4%), epidermal atrophy (88.5%), lymphocytic infiltrate (88.5%), thickened basement membrane (77.1%) and basal vacuolar degeneration (74.2%). Antinuclear antibodies were present in 42.8% of patients and antigastric mucosa, antithyroid and anticardiolipin antibodies in 17-21% of patients. A positive lupus band test was demonstrated in 81.8% of cases and perivascular deposit in 30.3% of patients. Histopathology alone allowed a correct diagnosis only in 68.5% of cases; in the other cases, the diagnosis was assessed also taking into account immunopathologic findings. Our study defines the clinic, histopathologic and immunopathologic features of DLESA patients and points out that a multiparametric approach is mandatory to assess the diagnosis of DLESA.

Adolescent↗

Cutaneous endometriosis: non-invasive analysis by epiluminescence microscopy.

The clinical appearance of cutaneous endometriosis can share some features with malignant melanoma, thus representing a possible cause for concern in both patient and clinician. In recent years, the use of epiluminescence microscopy (ELM, dermoscopy) has proved useful in improving the accuracy of diagnosis of pigmented skin lesions. The purpose of this study was to analyse the dermoscopic features of cutaneous endometriosis with histopathological correlation. We studied a case which showed homogeneous reddish pigmentation, regularly distributed. Within this typical pigmentation there were small red globular structures, but more defined and of a deeper hue, which we called 'red atolls'. ELM thus revealed a distinctive pattern in cutaneous endometriosis.

Adult↗

Dermoscopic features of naevus-associated melanoma.

Little is currently known about the relationship between melanocytic naevi and melanoma in terms of neoplastic progression. At histological examination, remnants of a pre-existing melanocytic naevus adjoining a melanoma are seen in 20-30% of cases. This study investigated dermoscopic features of 108 naevus-associated melanomas, identified on the basis of histological classification, consecutively observed at a University Department. Because of the risk of misclassification due to destruction of naevus remnants in thick tumours, only lesions of < 1 mm Breslow thickness were considered. We found naevus-associated melanomas showing atypical pigment networks and regression patterns more frequently than de novo melanomas, while irregular blotches and atypical vascular patterns were found less frequently. Dermatologists should be aware that dermoscopic features of melanoma differ according to the histogenesis of the lesion. Atypical pigment networks and regression patterns are the most useful dermoscopic criteria suggested to make a diagnosis of naevus-associated melanoma.

Adult↗

Specific immune therapy-related cutaneous B-cell pseudolymphoma with following dissemination.

We report two cases of cutaneous B-cell pseudolymphoma (PCBCL) induced by intradermal antigen injections for specific immune therapy (SIT). In both cases, the lesions had first developed on the area of injection; years later, new lesions appeared far from the original site. The histological, immunohistochemical, and molecular findings of the lesions showed features consistent with the diagnosis of PCBCL in both cases. In particular, the staining for sIg light chains showed a polyclonal pattern, and the molecular analysis by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot showed a germ-line configuration of the Ig heavy chain genes. While the development of PCBCL related to a specific stimulus is well known and widely reported, the development of histologically and immunohistologically identical lesions far from the injection site is definitely worthy of note. This behaviour might be due to the presence of retained antigens in the injection site. This chronic antigenic stimulation could induce the progressive selection--and subsequent dissemination--of antigen-specific B cell clones.

Adult↗

Multiple pigmented trichoblastomas and syringocystadenoma papilliferum in naevus sebaceous mimicking a malignant melanoma: a clinical dermoscopic-pathological case study.

We report a case of three distinct adnexal neoplasms associated with a naevus sebaceous of the scalp: a nodular pigmented trichoblastoma, a smaller flat pigmented trichoblastoma and a syringocystadenoma papilliferum, and discuss the clinical and histological features of these neoplasms. The clinical manifestation was suggestive of malignant melanoma, a feature that has never been reported before. For the first time in the literature we describe the case also by means of a noninvasive analysis, i.e. epiluminescence microscopy. In our experience, epiluminescence microscopy does not appear to be more diagnostically accurate than simple clinical examination when diagnosing lesions of the scalp, contrary to other regions.

Adenoma, Sweat Gland↗

[Prognostic factors in thin cutaneous malignant melanoma].

An increasing number of thin (< or = 1 mm) cutaneous malignant melanomas are currently diagnosed. The majority of thin lesions is associated with an excellent prognosis, however, some of them may develop local recurrences and/or distant metastases with fatal outcome. Although Breslow thickness is the single most significant prognostic factor in melanoma in general, for thin lesions the identification of other morphological, biological and/or molecular parameters which may have an impact on neoplastic progression is mandatory. At present, Clark's levels and ulceration are regarded as significant prognostic factors. Further studies are needed to confirm the prognostic value of other histopathological parameters, including the evaluation of regression, inflammatory infiltrate and mitotic activity.

Biomarkers, Tumor↗