Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, per... more Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, peripheral lymphadenopathies, and circulating atypical cerebriform T-cells. To date, no definite staging system has been developed for these patients. In this retrospective analysis of the archive of the Dermatological Clinic of the University of Turin, Italy, erythrodermic SS patients were classified according to clinical records and photographs into three main presentations: erythematous, infiltrated, or melanodermic. The pattern of erythroderma was found to be associated with disease outcome, as better survivals were recorded in patients with erythematous and infiltrative erythroderma. Patients in the melanodermic group, though less represented in our investigation, seemed to show a worse trend in survival. According to this preliminary evidence, a new prognostic classification, with a revised score specific for Sézary syndrome patients, can be proposed to usefully integrate the current ...
Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TE... more Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TERT promoter mutations have been recently associated with a poor prognosis in stage I-II melanomas. Usually, it is not recommended to perform a mutational test on primary melanoma, as the results do not always reflect the mutational status of metastases. In particular, trunk melanomas have been reported to have an unfavourable prognosis. A series of 105 advanced melanoma patients were analysed by TERT promoter Sanger sequencing. Univariate/multivariate binary logistic regression models were performed using progression to a visceral site as the dependent variable and patient/tumour characteristics as covariates. Performance of the model was assessed in an external independent primary melanoma patients’ dataset. Male gender (odds ratio (OR), 344; 95% CI, 1.12–10.6; p = 0.031), AJCC (American Joint Committee on Cancer) classification (OR, 022; 95% CI, 0.07–0.67; p = 0.008), SLNB (Sentinel Ly...
The American Journal of Tropical Medicine and Hygiene, 2021
Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus endemic in many parts of the worl... more Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus endemic in many parts of the world. Because of migration, cases of HTLV-1 in non-HTLV-1 endemic countries have been increasingly reported. Clinical presentation of HTLV-1 infection is highly variable, with a significant risk of diagnostic delays. Skin can be the first site affected by HTLV-1-related manifestations such as cutaneous involvement of adult T-cell leukemia/lymphoma (ATLL) and infective dermatitis associated with HTLV-1. A 32-year-old Nigerian man was admitted to the infectious disease department for high fever, asthenia, lymphocytosis, and vesicular bullous lesions on both hand palms and lower limbs. After clinical work-up was performed, bacterial superinfected herpes simplex viurs-2 ulcers were the presenting sign of HTLV-1-related chronic type ATLL. Standard treatment based on interferon-α plus zidovudine was started, but it was poorly tolerated; therefore, switching to an off-label dual antiretroviral reg...
The possibility that autocrine or paracrine mechanisms of cytokine production and utilization may... more The possibility that autocrine or paracrine mechanisms of cytokine production and utilization may take place in patients with B-cell chronic lymphocytic leukaemia (B-CLL) is discussed. In particular, evidence is provided for a likely role of interleukin 2 (IL2) on the neoplastic B-cell compartment. Furthermore, the possibility that tumor necrosis factor (TNF) may also be involved is suggested.
Bollettino della Società italiana di biologia sperimentale, Jan 30, 1982
T-lymphocytes express different antigenic determinants which can be recognized using specific ant... more T-lymphocytes express different antigenic determinants which can be recognized using specific anti-T monoclonal antibodies. OK T3 (Ortho Diagnostics, Raritan, N.J.) detects 95% circulating T-lymphocytes, while OK T4 reacts with helper/inducer T-lymphocytes and OK T8 with suppressor/cytotoxic T-lymphocytes. In normal peripheral blood the proportion of mononuclear cells (after "Lymphoprep' separation) positive with the various anti-T monoclonal antibodies is, according to our standards, as follows: OK T3 77 +/- 9.4%, OK T4 51 +/- 7.8%, OK T8 27+/- 6.4%. In this study we have evaluated the positivity with OK T MoAb after activation and proliferation of the T-cell population in a double layer T-lymphocyte colony assay. After 4-5 days of incubation, the proportion of OK T3 + cells had increased to 94 +/- 4.6%, while that of OK T4+ and OK T8+ had raised to 62 +/- 14.1% and 65 +/- 7.1% respectively. These data suggest that T-colony formation gives rise to an increased expression o...
The relationship between the disease course and the prognostic relevance of sequential tyrosinase... more The relationship between the disease course and the prognostic relevance of sequential tyrosinase reverse transcription-PCR assay in the peripheral blood of advanced metastatic melanoma patients was ascertained. The clinical usefulness of tyrosinase in stage IV melanoma patients is still debated, owing to the wide range of variability (positive expression from 30 up to 100% of patients) and the possibility of a transient shedding of melanoma cells into the bloodstream. A total of 200 consecutive stage IV metastatic patients treated at our department were included, 149 with active metastatic disease undergoing systemic therapies (group A), and 51 disease free after surgery (group B). For each patient, a baseline sample was obtained within 3 weeks of either the clinical/radiological demonstration of metastatic disease or the surgical treatment; thereafter, tyrosinase determinations were performed at day 1 of each therapy course before chemotherapy administration or at each follow-up visit. Tyrosinase expression was determined using standard reverse transcription-PCR nested techniques. A baseline positive determination was obtained in 72.5% of the patients with active metastatic disease (group A) but not in any of the patients who were disease free after surgery (group B). Therapy administration induced an early clearance of circulating melanoma cells, from 72.5 to 44.9% at the second down to 29.5% at the third determination. Tyrosinase expression before the third cycle was significantly associated with the clinical response: 56/81 (69.1%) patients with a negative tyrosinase determination obtained a response or a stable disease, whereas 29/34 (85.3%) patients with a positive test developed a progressive disease (P<0.001). A clinical response was observed in all the patients who had a negative tyrosinase at the first three determinations, although all patients whose first three determinations were positive developed a progressive disease. Multivariate analysis showed that baseline tyrosinase status carries an independent prognostic value on both overall survival and time to progression; moreover, tyrosinase results during follow-up were entered as time-dependent covariates in a multivariate analysis and were shown to be the most significant prognostic parameter associated to both overall survival and time to progression. In particular, the presence of a constant positive expression during follow-up was associated with the development of new metastatic sites in 95.6% of patients with active metastatic disease. Our results demonstrate that the discrepancies in the positive tyrosinase rates reported in the literature are related to the disease status at the time of sampling and to chemotherapy administration. Tyrosinase expression in the peripheral blood both at baseline and during follow-up can be considered a reliable prognostic parameter associated with the response to treatment, development of new metastatic sites, time to progression and survival.
Background: Malignant melanoma has an unpredictable biologic behavior and is the neoplasm with th... more Background: Malignant melanoma has an unpredictable biologic behavior and is the neoplasm with the greatest propensity for cardiac involvement. Although relatively frequent at autopsy, cardiac metastases are rarely identified antemortem. Methods: We reviewed 2,810 patients with histologically confirmed malignant melanoma, who were diagnosed and followed up by our clinic. Clinical, histological, and imaging data are presented. Results: Five cases of metastatic melanoma of the heart were identified out of 314 melanoma patients with visceral involvement. One case of a 53-year-old woman, who died unexpectedly during her first chemotherapy course, is described in detail. Postmortem examination determined the cause of death to be the presence of multiple melanoma metastases in the heart, even though the patient had shown no signs of cardiac involvement. Conclusions: The unpredictable biologic behavior of melanoma may lead to unusual metastatic sites, and, therefore, the heart also should be included in routine examinations.
Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emer... more Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emerges within a multiple subclone pattern ("clonal heterogeneity"). PCR analysis has been shown to be useful in the diagnosis of mycosis fungoides (MF) and Sézary Syndrome (SS). Focusing the attention on clonal heterogeneity, the efficacy of the multiplex/heteroduplex (HD) PCR and the GeneScan (GS) capillary electrophoresis analysis was compared in the early diagnosis of MF/SS, using a multiple sample approach. Indeed, GS demonstrated TCRgamma gene rearrangement (GR) in all the 57 SS (100%) and in 123/146 (84%) of the MF samples, whereas the multiplex/HD PCR was less sensitive. An increase in clonality was observed in connection with both a worsening of the cutaneous disease (79% T1/T2; 100% T3/T4) and an increase in the histopathological score (HS < 5, 76%; HS > or = 5, 94%). Clonal heterogeneity with adjunctive reproducible skin TCRgamma-GRs was also observed. "Clonal instability," with different GRs, was present in a small percentage of patients. Therefore, it can be concluded that GS analysis in TCRgamma-GR is able to improve diagnosis in MF/SS patients and the multiple sample approach is helpful for a correct interpretation of clonal patterns in skin lesions, especially in early-stage MF and in SS skin/blood samples.
Purpose Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lym... more Purpose Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lymphomas with few and conflicting data on their prognostic factors. Patients and Methods The study group included 467 patients with PCBCL who were referred, treated, and observed in 11 Italian centers (the Italian Study Group for Cutaneous Lymphomas) during a 24-year period (1980 to 2003). All of the patients were reclassified according to the WHO–European Organisation for Research and Treatment of Cancer (EORTC) classification. Results Follicle center lymphoma (FCL) accounted for 56.7% of occurrences, followed by marginal-zone B-cell lymphoma (MZL; 31.4%); diffuse large B-cell lymphoma (DLBCL), leg type, was reported in 10.9% of patients. Radiotherapy was the first-line treatment in 52.5% of patients and chemotherapy was the first-line treatment in 24.8% of patients. The complete response rate was 91.9% and the relapse rate was 46.7%. The 5- and 10-year overall survival (OS) rates were 94...
Atopic dermatitis (AD) patients present an high susceptibility to infections. The phagocytic acti... more Atopic dermatitis (AD) patients present an high susceptibility to infections. The phagocytic activity of polymorphonuclear granulocytes (PMNs) is mediated by the interactions between Toll-like receptors (TLRs) and pathogen-associated molecular patterns. To investigate functional activity and phenotype of PMNs in AD patients. In vitro PMN phagocytosis and intracellular killing towards Klebsiella pneumoniae were evaluated in 24 AD patients; flow cytometry was applied to analyze PMN phenotype. PMNs from AD patients displayed both reduced phagocytic activity and intracellular killing against K. pneumoniae than healthy subjects (HS). CD11b, CD66b, TLR2, TLR4 and TLR5 median fluorescence intensity (MFI) on PMN membrane were significantly higher in AD patients than in HS. PMN functional impairment in AD patients could represent an additional cause of skin infections, coupled with other known defects in the innate immune system. The increased MFI of adhesion molecules and TLRs is rather a consequence of the increased skin barrier permeability to bacterial molecules capable of stimulating immunological reactions.
CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using im... more CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using immunohistochemical techniques. A sporadic focal CD26 positivity was found in normal skin, whereas increased expression of CD26 was observed both in cutaneous T-cell lymphomas and in inflammatory skin diseases, e.g. psoriasis, lichen planus and spongiotic dermatitis, in the basal and spinous layers. CD26 keratinocyte staining was not specific for a single disease, but seems to be associated with the presence of a reactive or neoplastic infiltrate in the epidermis. We propose that the CD26 molecule may function as a keratinocyte activation antigen.
The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary synd... more The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary syndrome (SS) patients makes it difficult both to ascertain the presence of clonal cells and to quantify the tumour burden in the peripheral blood. In previous reports we showed that the lack of CD26 (dipeptidyl-aminopeptidase IV) is a characteristic feature of circulating Sézary cells (SC). The purpose of this study was to ascertain, by means of high-resolution two-, three- or four-parameter flow cytometry, the relationship between CD26 expression on peripheral blood lymphocytes and peripheral blood involvement in cutaneous T-cell lymphoma patients and to assess its significance in SS diagnosis. The patient population included 52 SS patients, 151 mycosis fungoides (MF) patients at different clinical stages (including 14 with blood involvement, B1-MF), 88 patients with erythrodermic inflammatory skin diseases (EISD) and 72 healthy donors (HD). CD26+ values were available in all cases, whereas CD4+ CD26- level measurement was performed in 23 SS, 141 MF, 71 EISD and 72 HD. CD4+ CD26- percentage values were higher than 30% in all but one B1-MF and higher than 40% in all SS cases, whereas HD, EISD and B0-MF patient values were always lower than 30%. A statistically significant difference was found in both CD26- and CD4+ CD26- percentage and absolute values between SS and HD, EISD and B0-MF patients. The CD26- and CD4+ CD26- percentage values (but not the absolute values) were significantly higher in B1-MF compared with HD, EISD and B0-MF patients (P < 0.001). Moreover, CD26- absolute values and CD4+ CD26- percentage and absolute values were significantly higher in SS than in B1-MF (P < 0.001). A statistically significant direct relationship was found between CD4+ CD26- percentage values and the percentage of circulating SC within the lymphoid population in SS and B1-MF (r = 0.77; P < 0.001). The lack of CD26 was confirmed on phenotypically clonal cells in patients with an expanded circulating TCRvbeta population or a T-cell antigen loss. Sorted CD4+ CD26- cells from both SS patients and HD showed the characteristic cerebriform nuclei of SC. We feel that a CD4+ CD26- percentage value higher than 30% of peripheral blood lymphocytes could correctly identify the presence of peripheral blood involvement in SS and MF patients.
CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion mole... more CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas; the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis; azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR beta-chain gene.
Background: The current COVID-19 pandemic has influenced the modus operandi of all fields of medi... more Background: The current COVID-19 pandemic has influenced the modus operandi of all fields of medicine, significantly impacting patients with oncological diseases and multiple comorbidities. Thus, in recent months, the establishment of melanoma management during the emergency has become a major area of interest. In addition to original articles, case reports and specific guidelines for the period have been developed. Purpose: This article aims to evaluate whether melanoma management has been changed by the outbreak of COVID-19, and if so, what the consequences are. We summarized the main issues concerning the screening of suspicious lesions, the diagnosis of primary melanoma, and the management of early-stage and advanced melanomas during the pandemic. Additionally, we report on the experience of our dermatological clinic in northern Italy. Methods: We performed a literature review evaluating articles on melanomas and COVID-19 published in the last two years on PubMed, as well as con...
Sentinel lymph node biopsy has been demonstrated to be an effective staging procedure since its i... more Sentinel lymph node biopsy has been demonstrated to be an effective staging procedure since its introduction in 1992. The new American Joint Committee on Cancer (AJCC) classification did not consider the lack of information that would result from the less usage of the complete lymph node dissection as for a diagnostic purpose. Thus, this makes it difficult the correct staging and would leave about 20% of the further positive non-sentinel lymph nodes in the lymph node basin. In this paper, we aim to describe a new surgical technique that, combined with single-photon emission computed tomography—computed tomography (SPECT-CT), allows for better staging of melanoma patients. This is a prospective study that includes 104 patients with cutaneous melanoma. Sentinel lymph node biopsy was offered according to the AJCC guideline. Planar lymphoscintigraphy was performed in association with SPECT-CT, identifying and removing all non-biologically “excluded” lymph nodes, guiding the surgeon’s ha...
Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melano... more Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.
Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, per... more Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, peripheral lymphadenopathies, and circulating atypical cerebriform T-cells. To date, no definite staging system has been developed for these patients. In this retrospective analysis of the archive of the Dermatological Clinic of the University of Turin, Italy, erythrodermic SS patients were classified according to clinical records and photographs into three main presentations: erythematous, infiltrated, or melanodermic. The pattern of erythroderma was found to be associated with disease outcome, as better survivals were recorded in patients with erythematous and infiltrative erythroderma. Patients in the melanodermic group, though less represented in our investigation, seemed to show a worse trend in survival. According to this preliminary evidence, a new prognostic classification, with a revised score specific for Sézary syndrome patients, can be proposed to usefully integrate the current ...
Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TE... more Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TERT promoter mutations have been recently associated with a poor prognosis in stage I-II melanomas. Usually, it is not recommended to perform a mutational test on primary melanoma, as the results do not always reflect the mutational status of metastases. In particular, trunk melanomas have been reported to have an unfavourable prognosis. A series of 105 advanced melanoma patients were analysed by TERT promoter Sanger sequencing. Univariate/multivariate binary logistic regression models were performed using progression to a visceral site as the dependent variable and patient/tumour characteristics as covariates. Performance of the model was assessed in an external independent primary melanoma patients’ dataset. Male gender (odds ratio (OR), 344; 95% CI, 1.12–10.6; p = 0.031), AJCC (American Joint Committee on Cancer) classification (OR, 022; 95% CI, 0.07–0.67; p = 0.008), SLNB (Sentinel Ly...
The American Journal of Tropical Medicine and Hygiene, 2021
Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus endemic in many parts of the worl... more Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus endemic in many parts of the world. Because of migration, cases of HTLV-1 in non-HTLV-1 endemic countries have been increasingly reported. Clinical presentation of HTLV-1 infection is highly variable, with a significant risk of diagnostic delays. Skin can be the first site affected by HTLV-1-related manifestations such as cutaneous involvement of adult T-cell leukemia/lymphoma (ATLL) and infective dermatitis associated with HTLV-1. A 32-year-old Nigerian man was admitted to the infectious disease department for high fever, asthenia, lymphocytosis, and vesicular bullous lesions on both hand palms and lower limbs. After clinical work-up was performed, bacterial superinfected herpes simplex viurs-2 ulcers were the presenting sign of HTLV-1-related chronic type ATLL. Standard treatment based on interferon-α plus zidovudine was started, but it was poorly tolerated; therefore, switching to an off-label dual antiretroviral reg...
The possibility that autocrine or paracrine mechanisms of cytokine production and utilization may... more The possibility that autocrine or paracrine mechanisms of cytokine production and utilization may take place in patients with B-cell chronic lymphocytic leukaemia (B-CLL) is discussed. In particular, evidence is provided for a likely role of interleukin 2 (IL2) on the neoplastic B-cell compartment. Furthermore, the possibility that tumor necrosis factor (TNF) may also be involved is suggested.
Bollettino della Società italiana di biologia sperimentale, Jan 30, 1982
T-lymphocytes express different antigenic determinants which can be recognized using specific ant... more T-lymphocytes express different antigenic determinants which can be recognized using specific anti-T monoclonal antibodies. OK T3 (Ortho Diagnostics, Raritan, N.J.) detects 95% circulating T-lymphocytes, while OK T4 reacts with helper/inducer T-lymphocytes and OK T8 with suppressor/cytotoxic T-lymphocytes. In normal peripheral blood the proportion of mononuclear cells (after "Lymphoprep' separation) positive with the various anti-T monoclonal antibodies is, according to our standards, as follows: OK T3 77 +/- 9.4%, OK T4 51 +/- 7.8%, OK T8 27+/- 6.4%. In this study we have evaluated the positivity with OK T MoAb after activation and proliferation of the T-cell population in a double layer T-lymphocyte colony assay. After 4-5 days of incubation, the proportion of OK T3 + cells had increased to 94 +/- 4.6%, while that of OK T4+ and OK T8+ had raised to 62 +/- 14.1% and 65 +/- 7.1% respectively. These data suggest that T-colony formation gives rise to an increased expression o...
The relationship between the disease course and the prognostic relevance of sequential tyrosinase... more The relationship between the disease course and the prognostic relevance of sequential tyrosinase reverse transcription-PCR assay in the peripheral blood of advanced metastatic melanoma patients was ascertained. The clinical usefulness of tyrosinase in stage IV melanoma patients is still debated, owing to the wide range of variability (positive expression from 30 up to 100% of patients) and the possibility of a transient shedding of melanoma cells into the bloodstream. A total of 200 consecutive stage IV metastatic patients treated at our department were included, 149 with active metastatic disease undergoing systemic therapies (group A), and 51 disease free after surgery (group B). For each patient, a baseline sample was obtained within 3 weeks of either the clinical/radiological demonstration of metastatic disease or the surgical treatment; thereafter, tyrosinase determinations were performed at day 1 of each therapy course before chemotherapy administration or at each follow-up visit. Tyrosinase expression was determined using standard reverse transcription-PCR nested techniques. A baseline positive determination was obtained in 72.5% of the patients with active metastatic disease (group A) but not in any of the patients who were disease free after surgery (group B). Therapy administration induced an early clearance of circulating melanoma cells, from 72.5 to 44.9% at the second down to 29.5% at the third determination. Tyrosinase expression before the third cycle was significantly associated with the clinical response: 56/81 (69.1%) patients with a negative tyrosinase determination obtained a response or a stable disease, whereas 29/34 (85.3%) patients with a positive test developed a progressive disease (P<0.001). A clinical response was observed in all the patients who had a negative tyrosinase at the first three determinations, although all patients whose first three determinations were positive developed a progressive disease. Multivariate analysis showed that baseline tyrosinase status carries an independent prognostic value on both overall survival and time to progression; moreover, tyrosinase results during follow-up were entered as time-dependent covariates in a multivariate analysis and were shown to be the most significant prognostic parameter associated to both overall survival and time to progression. In particular, the presence of a constant positive expression during follow-up was associated with the development of new metastatic sites in 95.6% of patients with active metastatic disease. Our results demonstrate that the discrepancies in the positive tyrosinase rates reported in the literature are related to the disease status at the time of sampling and to chemotherapy administration. Tyrosinase expression in the peripheral blood both at baseline and during follow-up can be considered a reliable prognostic parameter associated with the response to treatment, development of new metastatic sites, time to progression and survival.
Background: Malignant melanoma has an unpredictable biologic behavior and is the neoplasm with th... more Background: Malignant melanoma has an unpredictable biologic behavior and is the neoplasm with the greatest propensity for cardiac involvement. Although relatively frequent at autopsy, cardiac metastases are rarely identified antemortem. Methods: We reviewed 2,810 patients with histologically confirmed malignant melanoma, who were diagnosed and followed up by our clinic. Clinical, histological, and imaging data are presented. Results: Five cases of metastatic melanoma of the heart were identified out of 314 melanoma patients with visceral involvement. One case of a 53-year-old woman, who died unexpectedly during her first chemotherapy course, is described in detail. Postmortem examination determined the cause of death to be the presence of multiple melanoma metastases in the heart, even though the patient had shown no signs of cardiac involvement. Conclusions: The unpredictable biologic behavior of melanoma may lead to unusual metastatic sites, and, therefore, the heart also should be included in routine examinations.
Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emer... more Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emerges within a multiple subclone pattern ("clonal heterogeneity"). PCR analysis has been shown to be useful in the diagnosis of mycosis fungoides (MF) and Sézary Syndrome (SS). Focusing the attention on clonal heterogeneity, the efficacy of the multiplex/heteroduplex (HD) PCR and the GeneScan (GS) capillary electrophoresis analysis was compared in the early diagnosis of MF/SS, using a multiple sample approach. Indeed, GS demonstrated TCRgamma gene rearrangement (GR) in all the 57 SS (100%) and in 123/146 (84%) of the MF samples, whereas the multiplex/HD PCR was less sensitive. An increase in clonality was observed in connection with both a worsening of the cutaneous disease (79% T1/T2; 100% T3/T4) and an increase in the histopathological score (HS < 5, 76%; HS > or = 5, 94%). Clonal heterogeneity with adjunctive reproducible skin TCRgamma-GRs was also observed. "Clonal instability," with different GRs, was present in a small percentage of patients. Therefore, it can be concluded that GS analysis in TCRgamma-GR is able to improve diagnosis in MF/SS patients and the multiple sample approach is helpful for a correct interpretation of clonal patterns in skin lesions, especially in early-stage MF and in SS skin/blood samples.
Purpose Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lym... more Purpose Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lymphomas with few and conflicting data on their prognostic factors. Patients and Methods The study group included 467 patients with PCBCL who were referred, treated, and observed in 11 Italian centers (the Italian Study Group for Cutaneous Lymphomas) during a 24-year period (1980 to 2003). All of the patients were reclassified according to the WHO–European Organisation for Research and Treatment of Cancer (EORTC) classification. Results Follicle center lymphoma (FCL) accounted for 56.7% of occurrences, followed by marginal-zone B-cell lymphoma (MZL; 31.4%); diffuse large B-cell lymphoma (DLBCL), leg type, was reported in 10.9% of patients. Radiotherapy was the first-line treatment in 52.5% of patients and chemotherapy was the first-line treatment in 24.8% of patients. The complete response rate was 91.9% and the relapse rate was 46.7%. The 5- and 10-year overall survival (OS) rates were 94...
Atopic dermatitis (AD) patients present an high susceptibility to infections. The phagocytic acti... more Atopic dermatitis (AD) patients present an high susceptibility to infections. The phagocytic activity of polymorphonuclear granulocytes (PMNs) is mediated by the interactions between Toll-like receptors (TLRs) and pathogen-associated molecular patterns. To investigate functional activity and phenotype of PMNs in AD patients. In vitro PMN phagocytosis and intracellular killing towards Klebsiella pneumoniae were evaluated in 24 AD patients; flow cytometry was applied to analyze PMN phenotype. PMNs from AD patients displayed both reduced phagocytic activity and intracellular killing against K. pneumoniae than healthy subjects (HS). CD11b, CD66b, TLR2, TLR4 and TLR5 median fluorescence intensity (MFI) on PMN membrane were significantly higher in AD patients than in HS. PMN functional impairment in AD patients could represent an additional cause of skin infections, coupled with other known defects in the innate immune system. The increased MFI of adhesion molecules and TLRs is rather a consequence of the increased skin barrier permeability to bacterial molecules capable of stimulating immunological reactions.
CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using im... more CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using immunohistochemical techniques. A sporadic focal CD26 positivity was found in normal skin, whereas increased expression of CD26 was observed both in cutaneous T-cell lymphomas and in inflammatory skin diseases, e.g. psoriasis, lichen planus and spongiotic dermatitis, in the basal and spinous layers. CD26 keratinocyte staining was not specific for a single disease, but seems to be associated with the presence of a reactive or neoplastic infiltrate in the epidermis. We propose that the CD26 molecule may function as a keratinocyte activation antigen.
The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary synd... more The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary syndrome (SS) patients makes it difficult both to ascertain the presence of clonal cells and to quantify the tumour burden in the peripheral blood. In previous reports we showed that the lack of CD26 (dipeptidyl-aminopeptidase IV) is a characteristic feature of circulating Sézary cells (SC). The purpose of this study was to ascertain, by means of high-resolution two-, three- or four-parameter flow cytometry, the relationship between CD26 expression on peripheral blood lymphocytes and peripheral blood involvement in cutaneous T-cell lymphoma patients and to assess its significance in SS diagnosis. The patient population included 52 SS patients, 151 mycosis fungoides (MF) patients at different clinical stages (including 14 with blood involvement, B1-MF), 88 patients with erythrodermic inflammatory skin diseases (EISD) and 72 healthy donors (HD). CD26+ values were available in all cases, whereas CD4+ CD26- level measurement was performed in 23 SS, 141 MF, 71 EISD and 72 HD. CD4+ CD26- percentage values were higher than 30% in all but one B1-MF and higher than 40% in all SS cases, whereas HD, EISD and B0-MF patient values were always lower than 30%. A statistically significant difference was found in both CD26- and CD4+ CD26- percentage and absolute values between SS and HD, EISD and B0-MF patients. The CD26- and CD4+ CD26- percentage values (but not the absolute values) were significantly higher in B1-MF compared with HD, EISD and B0-MF patients (P < 0.001). Moreover, CD26- absolute values and CD4+ CD26- percentage and absolute values were significantly higher in SS than in B1-MF (P < 0.001). A statistically significant direct relationship was found between CD4+ CD26- percentage values and the percentage of circulating SC within the lymphoid population in SS and B1-MF (r = 0.77; P < 0.001). The lack of CD26 was confirmed on phenotypically clonal cells in patients with an expanded circulating TCRvbeta population or a T-cell antigen loss. Sorted CD4+ CD26- cells from both SS patients and HD showed the characteristic cerebriform nuclei of SC. We feel that a CD4+ CD26- percentage value higher than 30% of peripheral blood lymphocytes could correctly identify the presence of peripheral blood involvement in SS and MF patients.
CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion mole... more CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas; the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis; azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR beta-chain gene.
Background: The current COVID-19 pandemic has influenced the modus operandi of all fields of medi... more Background: The current COVID-19 pandemic has influenced the modus operandi of all fields of medicine, significantly impacting patients with oncological diseases and multiple comorbidities. Thus, in recent months, the establishment of melanoma management during the emergency has become a major area of interest. In addition to original articles, case reports and specific guidelines for the period have been developed. Purpose: This article aims to evaluate whether melanoma management has been changed by the outbreak of COVID-19, and if so, what the consequences are. We summarized the main issues concerning the screening of suspicious lesions, the diagnosis of primary melanoma, and the management of early-stage and advanced melanomas during the pandemic. Additionally, we report on the experience of our dermatological clinic in northern Italy. Methods: We performed a literature review evaluating articles on melanomas and COVID-19 published in the last two years on PubMed, as well as con...
Sentinel lymph node biopsy has been demonstrated to be an effective staging procedure since its i... more Sentinel lymph node biopsy has been demonstrated to be an effective staging procedure since its introduction in 1992. The new American Joint Committee on Cancer (AJCC) classification did not consider the lack of information that would result from the less usage of the complete lymph node dissection as for a diagnostic purpose. Thus, this makes it difficult the correct staging and would leave about 20% of the further positive non-sentinel lymph nodes in the lymph node basin. In this paper, we aim to describe a new surgical technique that, combined with single-photon emission computed tomography—computed tomography (SPECT-CT), allows for better staging of melanoma patients. This is a prospective study that includes 104 patients with cutaneous melanoma. Sentinel lymph node biopsy was offered according to the AJCC guideline. Planar lymphoscintigraphy was performed in association with SPECT-CT, identifying and removing all non-biologically “excluded” lymph nodes, guiding the surgeon’s ha...
Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melano... more Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.
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Papers by Maria Fierro