Dermatofibrosarcoma protuberans in childhood: two case reports and review of the literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer with intermediate malignancy, characterized by a progressive local growth and a propensity for local recurrence. DFSP is most frequent in adults; however, in recent years, DFSP in childhood emerged to be more common than previously believed. Unfortunately DFSP in children may be misdiagnosed, leading to a delay in the treatment. The authors report two cases of childhood DFSP with unusual clinical presentation: a congenital nodular variant and an atrophic variant developed at 2 years of age, both with acral localization. They highlight the importance of an early diagnosis by pediatricians and dermatologists to ensure an appropriate complete excision and reduce the risks of recurrences.

[Sentinel lymph nodes in cutaneous melanoma: the experience in the Florence area]. / Linfonodo sentinella nel melanoma cutaneo: l'esperienza nell'area fiorentina.

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.

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.

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.

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.

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.

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.

Adoptive immunotherapy of advanced solid tumors: an eight year clinical experience.

BACKGROUND: Adoptive immunotherapy (AI) of cancer, based upon the injection of in vitro manipulated autologous lymphocytes is still in an experimental phase. Our group started different clinical trials of AI in early 1990, and, at present, some specific targets for this approach seem to have been identified. PATIENTS AND METHODS: 296 patients with solid tumors (melanoma, kidney carcinoma, non-small-cell lung cancer, mesothelioma, neoplastic pleural effusion, and liver cancer) were treated with either locoregional or systemic adoptive immunotherapy (AI) using both LAK and TIL cells in combination with s.c. rIL-2. RESULTS: The surgery/AI combination resulted in good clinical results, characterized by enhanced survival and long lasting disease free periods in a significant number of patients. CONCLUSIONS: AI seems to be efficacious in the treatment of melanoma, lung and hepatic cancers. Further studies will expand the application of the treatment to other malignancies.

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.

Desmoplastic trichoepithelioma.

A 20-year-old male presented with a 4 year history of a solitary nodule, 8 mm in diameter on the left temple. It was covered by normal skin, with a central depression and elevated borders. Histopathology showed numerous horn cysts amidst nests and strands of basaloid cells surrounded by a dense fibrous stroma. The clinical and histopathological features were characteristic of desmoplastic trichoepithelioma.

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.

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.

In situ expression of transforming growth factor beta is associated with melanoma progression and correlates with Ki67, HLA-DR and beta 3 integrin expression.

Transforming growth factor-beta (TGF beta), which is secreted by cultured melanoma cells constitutively, inhibits the proliferation of normal melanocytes and of most melanoma cells in vitro, but some melanoma cells from advanced stages of the disease develop resistance to TGF beta-dependent growth inhibition, without developing any change in TGF beta cell surface binding. In vitro TGF beta also downregulates the expression of HLA-DR molecules on melanoma cells, and upregulates the expression of the beta 3 integrin subunit on some cell lines. Immunohistochemical analysis of 53 melanocytic lesions (12 naevi, 30 primary melanomas and 11 metastases) revealed a trend of increasing expression of TGF beta and TGF beta receptor type III with tumour progression, and a significantly higher expression of both TGF beta (P < 0.0001) and the receptor (P < 0.05) in metastatic and thick (> 1 mm) primary melanomas compared with thin (< 1 mm) primary melanomas. The expression of TGF beta correlated with expression of a marker of proliferation, Ki67, and with HLA-DR and beta 3 integrin subunit expression. Coexpression of the four molecules was observed in all metastases and in most thick primary melanomas. These findings argue against an inhibitory effect of TGF beta on cell proliferation or HLA-DR antigen expression in melanoma, and suggest the upregulation of the beta 3 subunit. TGF beta protein appears to be a biological marker of melanoma progression in situ.

Vessel-wall recovery after diode laser-assisted microvascular anastomosis: clinical and histologic analysis on long-term follow-up.

The authors recently reported an experimental study on diode laser-assisted microvascular anastomosis (LAMA) in the femoral arteries and veins of rats. Good success rates and very promising histologic results obtained in this preliminary phase suggested an extension of the investigation with a larger number of rats and for longer follow-up periods. In the present work, they describe an experimental study with two main goals: 1) improvements of the laser-assisted surgical procedure for reduction in the number of permanent stay sutures, with minimization of bleeding at the end of the intervention, compared with conventional microvascular sutured anastomosis (CMSA); and 2) providing more information on the repair mechanism(s) induced by laser treatment, obtained from clinical and histologic analyses extended up to 3 months of follow-up. In a total of 64 Wistar rats, 46 arterial and 22 venous LAMAs were performed, and 15 arterial and 11 venous CMSAs. The recorded success rates of LAMA in both arteries and veins were fairly high (67/68 at the time of surgery, and 54/55 in the follow-up), and substantially comparable with those of CMSA. Clear evidence of a superior healing process in the LAMAs was provided by histologic examinations. In particular, specific stains and immunohistochemistry analysis indicated that laser irradiation can induce wide proliferation of smooth muscle cells and negligible scar tissue which, together with diminished foreign-body reaction consequent to the reduction of suture material, result in a better restoration of vessel structures.

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)

First recurrence analysis of 840 cutaneous melanomas: a proposal for a follow-up schedule.

AIMS AND BACKGROUND: A correct follow-up schedule for patients who underwent an excision for stage I cutaneous melanoma might allow the early detection of local and distant metastases. At present, there is no general agreement on follow-up protocols. In order to work out a follow-up guide, we have retrospectively evaluated the records of 840 stage I cutaneous melanoma patients surgically treated and followed during the postoperative period in the Division of Plastic Surgery of the University of Florence from 1975 to 1992. METHODS: We evaluated the patients' records by analyzing time, pathway and site of any first recurrence in relation to the main prognostic factors such as patient sex, site, histological type and depth of invasion of each primary melanoma. A statistical analysis was performed. RESULTS: To summarize, the salient results were the following: 80% of relapses occurred in the first 3 years and they occurred significantly earlier when the primary melanoma was localized in the trunk and significantly later when the melanoma was localized in the lower limbs and for < 1.5 mm lesions. The first recurrence occurred earlier by the lymphatic than by the hematic pathway regarding the overall number of patients. The hematic pathway was the most frequent (with respect to the overall percentage of hematic metastases) for the melanomas localized in the head and neck region and for lentigo malignant melanomas, whereas the lymphatic pathway was most frequent for melanomas of the lower limbs and > 3 mm in thickness. CONCLUSIONS: We suggest a follow-up schedule taking into consideration the postoperative behavior of stage I cutaneous melanoma patients (in terms of time and pathway of the first recurrence) in relation to the site and depth of invasion of the tumor.

Sonographic evaluation of dermis and subcutaneous tissue during and after skin expansion.

Soft-tissue thickness modifications were evaluated by high-resolution ultrasound sonography in six patients undergoing skin expansion, with the aim of investigating the possible use of this noninvasive method in the routine monitoring of soft tissues during and after skin expansion. Both during expansion (decrease) and in the postoperative period (increases up to 100 percent or more of the baseline preoperative value), changes in fat thickness occurred faster and were greater in magnitude than those in dermal tissue, overall gradual and limited. In our series, the values of fat thickness ranged between 44 (at full-expansion time) and 140 percent (2 months after expander removal), with a highly significant difference (p = 0.0003), while dermis thickness values ranged between 83 and 114 percent, respectively, showing no significant difference (p = 0.71). Some echo-structural dermal modifications were found by the 20-MHz probe at full skin expansion only. High-resolution ultrasound sonography may be proposed as a noninvasive method in the routine monitoring of soft tissues during and after skin expansion.

Proliferative, phenotypic and functional and molecular characteristics of tumour-infiltrating lymphocytes obtained from unselected patients with malignant melanomas and expanded in vitro in the presence of recombinant interleukin-2.

Tumour-infiltrating lymphocytes (TIL) derived from several histotypes, including melanoma, can be expanded in vitro in the presence of recombinant interleukin-2 (rIL-2) and infused as part of experimental adoptive immunotherapy protocols. Several authors have described the isolation and the expansion of TIL, but little is known about the actual proportion of unselected melanoma biopsies that give rise to 'positive' TIL cultures. We evaluated the proliferative, phenotypic, functional and molecular characteristics of cultured TIL obtained from 26 patients with metastatic melanomas, eligible for inclusion in a protocol of adoptive immunotherapy. Sixteen proliferating cultures were obtained. All TIL belonged to the T cell lineage and were characterized by a wide range of cytolytic activity against autologous and, to a lesser extent, allogeneic melanoma cells. Molecular analysis of the constant region of T cell receptor-beta (TCR-beta) showed an oligoclonal population of TIL in the majority of expanded samples, indicating that a selected subset of lymphocytes present in the tumour site could be expanded in vitro. These features, together with the high number of proliferating samples, make these populations of TIL suitable for infusion into patients with advanced disease.