Positive sentinel node biopsy in a 30-month-old boy with atypical Spitz tumour (Spitzoid melanoma).
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Antigens, Neoplasm↗
Biomedical subjects
L Borgognoni
Publications and source records attributed to L Borgognoni.
[Sentinel lymph nodes in cutaneous melanoma: the experience in the Florence area].
In the period 1997-2001, 466 sentinel lymph nodes from 342 lymphatic basins in 322 melanoma patients were examined at the Health Unit of Florence. The lymphatic mapping was performed through pre-operative lymphoscintigraphy using technetium-labelled nano-colloid, intradermal injections of vital blue dye and intra-operative gamma-probe. The examined patients were 182 females and 140 males. Sentinel lymph node was one in 65.2% of cases; two sentinel lymph nodes were detected in 27% of cases and more than 2 sentinel nodes were detected in 7.8% of cases. Melanoma metastases in one or more sentinel lymph nodes were found in 61/322 patients (18.9%). Lymphatic basins resulted to be involved by melanoma metastases were 64/342 (18.7%); sentinel lymph nodes containing metastatic melanoma deposits were 73/466 (15.6%). No metastasis was found in patients with melanoma thickness < or = 1 mm. One or more positive sentinel lymph nodes were found in 7.5% of patients with melanoma thickness > 1.00 and < or = 1.50 mm, in 27.7% of patients with melanoma > 1.50 and < or = 3.00 mm, in 38.2% of patients with melanoma > 3.00 and < or = 4.00, and in 60.7% of patients with melanoma > 4.00 mm. Frozen section analysis of sentinel lymph nodes, performed in 59/61 patients with nodal metastases, detected nodal involvement in 21 patients (35.6%). Metastases were identified by routine hematoxylin-eosin staining in 57/64 positive lymphatic basins; in 7 cases (11%) metastases were detected by immunohistochemical stainings (S100 and HMB-45). A nodal nevus was found in 3/466 sentinel lymph nodes (0.6%). Our data are analyzed and compared to previously data of the literature. The value of frozen section analysis and the major problems in the diagnosis of melanoma micrometastases in sentinel lymph nodes are discussed. The importance of the sentinel node biopsy for the detection of occult metastases and for the correct staging of melanoma patients are stressed, according to the new TNM melanoma classification.
Adolescent↗
Microsatellite analysis in cutaneous malignant melanoma.
The status and relevance of repetitive nucleotide sequences or microsatellite alterations in sporadic cutaneous melanoma has not been fully clarified. In this study we evaluated the presence of microsatellite alterations in a series of sporadic primary and metastatic melanomas in order to discover which genetic events may have a pathogenetic role in the development of this disease. Tumour samples were obtained from 21 patients with sporadic cutaneous melanoma, and from eight corresponding positive sentinel lymph nodes and one corresponding in-transit metastasis. In each specimen, selected neoplastic cells were procured by laser-assisted microdissection. Polymerase chain reaction-based microsatellite analysis was performed using a panel of 11 microsatellite markers, located at chromosome 2p, 4q, 9p, 16q, 17p and 21q. Overall, we found microsatellite alterations in five (23.8%) melanomas. Of these, one case showed alteration at marker D2S2182 and one at marker D17S261, whereas in another case alterations at three loci, D2S2182, D2S2291 and D9S171, were found. The fourth patient demonstrated an alteration at locus D9S171 both in the primary tumour and in the histologically positive sentinel lymph node. The fifth case was characterized by alterations at D2S2182 and at D17S250, whereas the corresponding in-transit metastasis showed the same alterations as the primary tumour and an additional alteration at IFN alpha. In conclusion, our study confirms previous observations that cutaneous melanomas demonstrate microsatellite alterations, although such instability occurs at a lower frequency than specific mismatch repair defects. Genetic analysis of metastatic lesions revealed that the same microsatellite alterations as in the primary tumour are seen, but additional genetic changes may develop during disease progression.
Adult↗
Inducible nitric oxide synthase expression in benign and malignant cutaneous melanocytic lesions.
Nitric oxide (NO) is synthesized by nitric oxide synthases (NOS) and plays an important role in tumour growth. In this study, inducible NOS (iNOS) expression was evaluated by immunohistochemistry in 34 melanocytic naevi (13 common melanocytic naevi, six Spitz naevi, and 15 so-called 'dysplastic naevi'), ten cutaneous melanomas in situ, 50 stage I invasive melanomas, and eight subcutaneous metastases of melanoma. In addition, four samples of melanocytic naevi and four samples of invasive melanomas were collected in order to perform western blot and northern blot analysis. By immunohistochemistry, melanocytic naevi never expressed iNOS. Among cases of melanoma in situ, two were negative, seven displayed staining in less than 20% of melanoma cells, and positivity was observed in 21-50% of melanoma cells in only one case. iNOS expression was detected in 46 out of 50 invasive melanomas (92%). Among these cases, 18 showed positivity in less than 20% of melanoma cells, 18 showed positivity in 21-50% of melanoma cells, and ten showed iNOS expression in more than 50% of cells. Statistical analysis revealed a significant difference in iNOS expression between melanocytic naevi and cutaneous melanomas (p<0.001). In addition, iNOS expression was significantly higher in invasive melanomas than in melanomas in situ (p=0.01). Among primary cutaneous melanomas, no significant correlation was found between iNOS expression and histopathological parameters (histotype, level, thickness and presence of regression/inflammatory infiltrate) and disease-specific survival. In subcutaneous melanoma metastases, iNOS expression was diffuse in more than 50% of cells. Statistical analysis revealed that subcutaneous melanoma metastases showed greater iNOS immunoreactivity than invasive melanomas (p=0.02). Molecular analyses confirmed that iNOS mRNA and protein were highly expressed in melanoma samples. In conclusion, iNOS was constantly absent in melanocytic naevi, whereas it was frequently expressed in melanomas, with up-regulation of the enzyme paralleling tumour progression. These data suggest that iNOS may play a role in the malignant transformation of melanocytes and in tumour growth. In addition, iNOS may be useful as an immunohistochemical marker for malignant melanocytic lesions.
Adult↗
Keloids and hypertrophic scars of Caucasians show distinctive morphologic and immunophenotypic profiles.
The aim of this study was to identify possible morpho-phenotypic differences between keloids (K) and hypertrophic scars (HS) in a Caucasian population. Young HS (< or =1 year of age) presented a high number of diffusely distributed spindle-shaped cells (alpha-smooth-muscle actin+ and fibronectin+). Fully developed HS (> 1 year of age and <3 years of age) were characterized by the frequent presence of distinct collagenous cellular nodules (cells: alpha-smooth-muscle actin+ and fibronectin+). Old HS (> or =3 years of age) showed widespread collagenization phenomena. The histological profile of K was not related to the age of the lesion and was characterized by the almost constant presence of abnormally thick, hyalinized collagen fibers, the presence of collagenous cellular nodules, and variable--albeit lower than in HS-- expression of alpha-smooth-muscle actin and fibronectin. Ultrastructurally, myofibroblasts were the predominant cell type in young and fully developed HS and in K. The immune-cell infiltrate was composed of CD3+, CD45RO+, CD4+, human lymphocyte antigen (HLA)-DR+, and lymphocyte function associated antigen (LFA)-1+ T lymphocytes, strictly associated with CD1a+/ CD36+, HLA-DR+, and intercellular adhesion molecule (ICAM)-1+ dendritic cells, both in HS and K. However, different amounts of immune cells were observed in relation to the type and age of the lesion, and these findings support the hypothesis that cell-mediated, major histocompatibility complex (MHC)-class II-restricted immune responses play an important role in the development of HS and K.
Actins↗
Thick cutaneous malignant melanoma: a reappraisal of prognostic factors.
The prognosis of patients with thick (>3 mm) cutaneous malignant melanomas is generally poor; however, some cases survive far longer than expected. Thus tumour thickness cannot serve as the only predictor of disease course in the individual patient. The aims of the current study were to evaluate the clinical outcome of patients with thick (>3 mm) cutaneous melanoma and test the prognostic value of a series of clinicopathological parameters on disease-free and cause-specific survival. We retrospectively evaluated 140 patients with stage I cutaneous melanoma >3 mm in thickness. Disease-free and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on prognosis. The overall 5-year and 10-year disease-free survival rates were 35.5% and 29.3%, respectively, whereas the overall 5-year and 10-year cause-specific survival rates were 55.3% and 47.7%, respectively. In the univariate analysis, the following factors were found to be significantly associated with the disease-free and cause-specific survival: tumour thickness, mitotic rate/mm2, type of invasive front, ulceration, thickness of the nodular component and predominant cell type. In addition, the presence of vascular invasion was significantly correlated with the risk of metastases but not with survival. In the multivariate analysis (Cox proportional hazards model), only tumour thickness (both as a continuous variable and >7.5 mm), infiltrating invasive front, presence of ulceration and mitotic rate/mm2 (both as a continuous variable and >10 mitoses/mm2) were significant independent predictors of poorer clinical outcome.
Adult↗
Thin cutaneous malignant melanomas (< or =1.5 mm): identification of risk factors indicative of progression.
BACKGROUND: Although thin cutaneous melanomas generally have a favorable prognosis, in some cases they may undergo progression. The current study was undertaken to identify variables that may predict a more aggressive clinical outcome in these patients. In addition to classic clinicopathologic features, the authors tested the prognostic impact of three new morphometric quantitative parameters: 1) tumor thickness plus regression thickness (T+R), 2) percentage of skin thickness infiltrated by tumor cells (T/S ratio), and 3) percentage of skin thickness infiltrated by tumor cells and regression ([T+R]/S ratio). METHODS: The authors retrospectively evaluated 287 patients with invasive cutaneous melanoma < or = 1.5 mm in thickness. Disease free survival rates (Kaplan-Meier method) were compared by using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on progression. Progression was defined as any documented cutaneous local and/or distant metastasis. RESULTS: Thirty-two of the 287 patients (11.1%) underwent disease progression. The overall 5-year and 10-year disease free survival rates were 89.3% and 84.6%, respectively. In the univariate analysis, the following factors were found to be significant predictors of progression: male gender (P = 0.01), acral-lentiginous histotype (P = 0.02), tumor thickness (P = 0.005), T+R (P = 0.001), T/S ratio > or = 50% (P = 0.03), (T+R)/S ratio > or = 50% (P = 0.006), vertical growth phase (P = 0.04), and absence of inflammatory response (P < 0.0001). Conversely, age, site, and Clark's level did not affect the risk of recurrences and/or metastases significantly. In the multivariate analysis, only T+R (P = 0.009) and inflammatory response (P < 0.0001) were found to be independent predictors of progression. Five-year disease free survival rates according to presence versus absence of inflammatory response were 93.4% and 63.8%, respectively (P < 0.0001). CONCLUSIONS: In the current study, peritumoral and intratumoral inflammatory infiltrate and T+R were found to be strong independent predictors of progression in thin cutaneous melanomas.
Adult↗
Osteonectin expression correlates with clinical outcome in thin cutaneous malignant melanomas.
Osteonectin, also termed BM40 or SPARC (secreted protein, acidic and rich in cysteine) is a multifunctional glycoprotein involved in tissue mineralization, cell-extracellular matrix interactions as well as angiogenesis. It has been suggested that osteonectin may play a key role in the process of tumoral invasion and metastasis in certain malignancies. In this study, we reviewed the clinical records and the histopathologic slides of 188 thin cutaneous malignant melanomas (< or = 0.75 mm). Among them, 12 cases underwent progression and were selected for the study. Osteonectin expression was investigated by immunohistochemistry in these 12 patients and 24 matched controls who did not undergo progression. Osteonectin staining was correlated with clinical outcome and other clinicopathologic parameters. Progression-free and disease-specific survival rates were calculated with the Kaplan-Meier method and their differences were evaluated by the log rank test. Overall, immunoreactivity for osteonectin was found in 23 (63.8%) cases. Eighteen cases (50%) displayed staining in 1% to 50% of neoplastic cells whereas five cases (13.8%) showed a diffuse positivity in more than 50% of the tumor cells. Osteonectin expression was significantly correlated with risk of progression (P = .01), incidence of distant metastases (P = .005) and survival (P = .03). There was a higher incidence of osteonectin-positive tumors in cases that did experience regional lymph node metastases versus those cases that did not, but that difference did not reach statistical significance (P = .06). No significant correlation was found between osteonectin expression and other clinicopathologic features, including age, sex, site, histotype, Clark's level, presence of regression, presence of inflammatory response, and tumor growth phase. Our data showed that osteonectin expression is a predictor of clinical outcome in thin cutaneous melanomas.
Adult↗
Comparison of two dressings in the management of partial-thickness donor sites.
This study evaluated and compared the performance of an adhesive hydro-cellular dressing with that of a paraffin gauze dressing in the treatment of partial-thickness skin-graft donor site wounds. Fifty patients were included in the study, each acting as his/her own control. Donor site area ranged from 20 cm2 to 71 cm2; half the area of each patient's donor site was treated with the trial dressing, the other half with paraffin gauze. Outcome measures assessed were: time to complete epithelialisation; ease of dressing removal; pain on removal; and appearance of the wound bed. The trial dressing demonstrated a significantly faster healing time (p < 10(-6)) and enhanced patient comfort.
Adolescent↗
Malignant melanoma associated with human immunodeficiency virus infection: a case report and review of the literature.
A case of malignant melanoma arising in a young patient suffering from human immunodeficiency virus (HIV) infection is reported, along with a review of the literature. The neoplasm was characterized by aggressive clinical behaviour and, histopathologically, by a peculiar retiform pattern of growth with neoplastic cells interspersed among collagen bundles in the dermis without evident fibroplastic stromal reaction. In addition, a complete absence of host inflammatory cell infiltrate was noted. We hypothesize that this unusual histopathological pattern of growth, which has never been reported in this clinical setting, might be associated to HIV disease, immunosuppression and poor clinical outcome.
Adult↗
Infusion of in vitro expanded tumour-infiltrating lymphocytes and recombinant interleukin-2 in patients with surgically resected lymph node metastases of malignant melanoma: a pilot study.
A pilot study was set up in order to evaluate the feasibility and safety of infusing in vitro expanded tumour-infiltrating lymphocytes (TILs) and recombinant interleukin-2 (rIL-2) in a group of patients with advanced melanoma after radical resection of lymph node metastases. Twenty-four patients were eligible for the study and proliferating TILs were collected in 16. These patients were infused with TILs and then treated with rIL-2 and alpha-interferon. Short-term toxic effects (such as fever) were in general controlled by symptomatic drugs, whereas chronic toxicities were absent. The median follow-up period was 19 months; at present, 13 patients are alive and disease free, one patient is in progression and two patients have died. The approach was feasible and safe and the clinical results observed are comparable to those obtained by long-term treatment with other biological response modifiers.
Adult↗
Intralesional hyaluronic acid treatment of pathological scars.
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Administration, Topical↗
Incidence of cutaneous melanoma in the centre of Italy: anatomic site distribution, histologic types and thickness of tumour invasion in a registry-based study.
The majority of epidemiological data on cutaneous melanoma (CM) derives from studies carried out in a predominantly fair-skinned population. On the contrary, little is known of the epidemiological figures (including incidence data) in mediterranean populations. The aim of this study was to investigate the incidence rates of CM in a geographically-defined area of the centre of Italy, with particular attention to anatomic site distribution, histologic types and thickness of tumour invasion. After revision of the data base of the Tuscany Cancer Registry concerning the period 1985 to 1987, 282 incident cases of invasive CM (135 males, 147 females) were found in a resident population of 1,174,121 inhabitants. The mean annual age-standardized rates were 6.7/100,000 for males and 7.0/100,000 for females. Site-specific incidence rates showed an almost three-fold higher incidence of CM of the trunk in males than females (3.7/100,000 vs 1.4/100,000). Conversely, a four-fold higher incidence in females than in males was observed for the lesions of lower limb (2.1/100,000 vs 0.5/100,000). A statistically significant difference of incidence rates was also observed for the thigh (females 1.1/100,000, males 0.2/100,000), a normally sun-exposed area. Concerning histologic types of CM, the incidence of the nodular type was higher in males than in females (1.8/100,000 vs 1.3/100,000), even if the difference was not statistically significant in any class of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Reconstruction of a medial canthus defect with a myocutaneous flap.
Defects in the inner canthal area are generally repaired by full-thickness skin grafts, V-Y advancement flap, or frontal flap. Each of these techniques may give some problems in restoring the functional or aesthetic features of that region, or both. To avoid these inconveniences, we performed the reconstruction of the medial canthal area after tumor excision by using a myocutaneous rotation flap from the upper lid joined to a rotation flap from the lower lid and cheek. No scar resulted inside the aesthetic unit and a fine result was achieved from both the functional and the aesthetic point of view.
Aged↗
CD36(OKM5)+ dendritic cells in the oral mucosa of HIV- and HIV+ subjects.
In this study, we have investigated by light and electron microscopy the presence, distribution, and inner structure of CD36(OKM5)+ dendritic cells (DC) in the lamina propria and epithelium of the oral mucosa of HIV- and HIV+ subjects; in the latter, both clinically healthy areas and areas of hairy leukoplakia (HL) were studied. Perivascular CD36+ DC were present in the lamina propria of all the specimens studied. They were also found in small numbers in the epithelium of clinically healthy mucosa of HIV- and HIV+ subjects, but were practically absent from the epithelium of HL. CD36+ DC seemed to be regularly HLA-DR+ in HIV-subjects; this positivity was recognized only in some cells in the clinically healthy mucosa of HIV+ subjects, and practically never in HL. Because the only perivascular cells observed in the clinically healthy areas of HIV+ subjects were CD36+, we investigated the ultrastructure of perivascular DC in these same areas. These cells were characterized by the presence of a prominent Golgi apparatus, many lysosomes, and focal adhesions to the extracellular matrix. It may be concluded that 1) CD36+ DC are physiologic components of the oral mucosa, 2) they share some ultrastructural features with macrophages, 3) no differences in numbers were found between HIV+ and HIV- subjects, and 4) these cells are affected in their expression of HLA-DR antigens during HIV infection, particularly in areas of HL. This may be a hint that the antigen-presenting function of these cells in the oral mucosa is negatively affected during HIV infection.
Adult↗
Morphology and membrane antigens of nonlymphoid accessory cells in oral hairy leukoplakia.
We have investigated the features and distribution of accessory cells (ACs) and the relationship of these cells to each other and to lymphocytes in the epithelium and lamina propria of oral hairy leukoplakia (HL), with the objective of better defining the differentiation and mutual interactions of immune-response cells within HL as a preliminary step to understanding the onset and significance of this lesion during human immunodeficiency virus (HIV) infection. Twenty-four HIV-infected patients with HL, two asymptomatic HIV-positive subjects, and three HIV-negative subjects were studied by immunohistochemistry; five HIV-positive patients with HL and three asymptomatic HIV-positive subjects were studied by electron microscopy. In both the epithelium and the lamina propria of HL, we found cells with the immunohistochemical and ultrastructural features of variably differentiated ACs; differences were found between the epithelium and lamina propria. In the lamina propria, ACs were characterized by dendritic shape, multiple contacts with lymphocytes, expression of CD1a antigen, and ultrastructural features of fully differentiated ACs. Conversely, in the epithelium ACs showed bluntly dendritic shape, low expression of CD1a, absent expression of HLA-DR, constant expression of CD11c and CD14 antigens, only occasional contacts with lymphocytes, and ultrastructural features of variably, but always incompletely, differentiated cells of monocyte-dendritic lineage. Seventy-nanometer wide intracisternal particles, closely resembling A particles described in retroviral infections, were found in the intraepithelial ACs in two patients with HL. The defective differentiation of ACs in the epithelium of HL--possibly influenced by the perturbation of the epithelial microenvironment induced by Epstein-Barr virus, and following the direct HIV infection of these cells--and the exceptional finding of close contacts with lymphocytes suggest that the lesional epithelium of HL may constitute a pathway for the entry of foreign antigens which circumvent monitoring by ACs and can induce immune tolerance. The impairment of the local immune response in HL may contribute to the development of full blown, systemic immunodeficiency.
Acquired Immunodeficiency Syndrome↗
HLA-DR and 96-K antigens and intratumoral lymphocytic infiltrate in primary cutaneous melanoma as markers of tumor progression.
It was recently demonstrated that HLA-DR antigens in primary melanomas are correlated with 96-K antigen expression and with the presence of an intratumoral lymphocytic infiltrate (ILI). As HLA-DR antigens are known to be associated with advanced phases of tumor progression in melanocytic lesions, we investigated whether primary melanomas in different progression phases could be distinguished on the basis of the expression of HLA-DR and 96-K antigens and of the presence of an ILI. A concordant presence of the two antigens and of an ILI was frequent both in vertical growth pattern melanomas and in melanomas thicker than 1 mm. On the contrary, both antigens and the ILI were frequently absent both in thin melanomas (less than 1 mm) and in radial growth pattern melanomas. These observations suggest that a joint study of HLA-DR and 96-K antigens and of the ILI is useful to define the phase of progression of primary melanomas.
Antibodies, Monoclonal↗
[Cultured epidermis in the treatment of leg ulcer: "edge effect" and correlation with keratinocyte proliferation index].
Cultured keratinocyte grafting (KG) of chronic leg ulcers produces an impressive stimulation of host epithelization by an effect on the edge of the ulcer, which starts to grow in rapidly ("edge effect"). In 5 patients with chronic leg ulcers treated by KG, we have studied the proliferation index of the epidermis of the edge and of the graft area and that of secondary culture keratinocytes. The aim of the study was to correlate this parameter with the clinical evolution of the treated lesions. We found a significant correlation between the proliferation index of the edge epidermis and the clinical evidence of "edge effect".
Aged↗