Giovanni Borroni

CD30/Ki-1-positive lymphoproliferative disorders of the skin - Clinicopathologic correlation and statistical analysis of 86 cases: A multicentric study from the European organization for research and treatment of cancer cutaneous lymphoma project group

PURPOSE Recently, it has been shown that CD30 antigen expression is associated with a relatively favorable prognosis in primary cutaneous large-cell lymphomas (CLCLs). However, prognostic subsets within the CD30+ group have been difficult to identify due to lack of uniform clinicopathologic and immunophenotypic criteria, limited clinical information, and the inclusion of relatively few patients for statistical analysis in prior studies. To address these problems, we formed a multicentric study group of pathologists and dermatologists to classify and evaluate 92 cases of CD30+ cutaneous lymphoproliferative disorders. PATIENTS AND METHODS An expert panel established consensus diagnoses for 86 CD30+ cutaneous lymphomas. Cases, clinically and histologically classified as lymphomatoid papulosis (LyP), anaplastic large-cell lymphoma (ALCL), nonanaplastic lymphoma, and borderline histology between LyP and ALCL, were then analyzed statistically by univariate, multivariate, and Cox regression model analysis of potential prognostic features. RESULTS Spontaneous regression and age less than 60 years were associated with a favorable prognosis, while extracutaneous disease and age greater than 60 had a poor prognosis. Patients with LyP had the best prognosis, followed by those with primary CD30+ lymphomas, regardless of cytologic type (anaplastic or nonanaplastic). Borderline cases, morphologically indistinguishable from LyP and CD30+ ALCL, had a favorable prognosis, similar to LyP. CONCLUSION Our findings indicate that CD30+ cutaneous lymphoproliferative disorders comprise a spectrum of closely related skin lesions, which can be assigned a relatively favorable or unfavorable prognosis by a combined clinical and pathologic analysis.

Prognostic Factors in Primary Cutaneous B-Cell Lymphoma: The Italian Study Group for Cutaneous Lymphomas

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% and 85%, respectively. Compared with FCL/MZL, DLBCL, leg type, was characterized by statistically significant lower complete response rates, higher incidence of multiple cutaneous relapses and extracutaneous spreading, shorter time to progression, and shorter OS rates. The only variable with independent prognostic significance on the OS was the clinicopathologic diagnosis according to the WHO-EORTC classification (DLBCL, leg-type, showed a significantly worse prognosis v FCL and MZL; P < .001), whereas the only variable with independent prognostic significance on disease-free survival was the presence of a single cutaneous lesion (P = .001). CONCLUSION Our study identifies a possible PCBCL subclassification and the extent of cutaneous involvement as the two most relevant prognostic factors in PCBCL. These data can be considered reasonably as the clinical background for an appropriate management strategy.

Hypopigmented mycosis fungoides in Caucasian patients: A clinicopathologic study of 7 cases

BACKGROUND Hypopigmented mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma. It is more frequent in dark-skinned or Asian patients, particularly children. Only 9 cases in Caucasian patients have been reported in the literature so far. OBSERVATION We describe 7 Caucasian patients (2 children and 5 adults) with hypopigmented MF. Histologic examination confirmed the diagnosis in all cases. The phenotype of neoplastic lymphocytes was T helper in 4 cases and T suppressor in 3 (2 of them children). Monoclonality of the T lymphocytes could be detected in hypopigmented lesions in all 7 cases with the use of a polymerase chain reaction technique. In 4 patients, polymerase chain reaction analysis of T-cell receptor-gene rearrangement after laser-based microdissection of the specimen revealed that the monoclonal population of T lymphocytes was confined mainly to the epidermis. CONCLUSION Hypopigmented lesions of MF can be observed in Caucasian patients. Children affected by MF often present with this rare clinical variant of the disease. Persistent or unusual hypopigmented lesions should be subjected to biopsy to avoid delay in the diagnosis of MF, especially in children.

Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia

Hydroxyurea is an antimetabolite agent used in the treatment of myeloproliferative disorders and sickle cell anaemia. Although hydroxyurea is relatively well tolerated, adverse effects often involve skin and mucous membrane during long‐term therapy. A group of 510 patients affected by chronic myeloid leukaemia from 1977 to 1998 has been considered. Only 158 patients were treated with hydroxyurea and fulfilled inclusion/exclusion criteria of this study. A spectrum of severe cutaneous and mucosal changes (inflammatory and neoplastic) was seen in about 13% of patients (21 patients out of 158) and was studied in detail. Cutaneous and mucosal atrophy were observed in all 21 patients. Skin atrophy was often characterized by numerous telangiectases, especially on legs and on sun‐exposed sites (16/21). Cutaneous, mucosal and nail hyperpigmentation was evident, albeit with variable extent, in 10 of the 21 patients. Severe stomatitis and glossitis with flattening of papillae were another common finding. Five patients, who received a particularly long treatment with hydroxyurea, developed squamous‐cell neoplasms on sun‐exposed sites (both squamous‐cell carcinomas and keratoacanthomas). Acral changes were characteristic and constant, including acral erythema (21/21), dermatomyositis‐like changes on the dorsa of hands (7/21), ulcers localized on acral areas of legs, on genitalia and oral mucosae (20/21). The frequency and the variety of these muco‐cutaneous changes are reported and the mechanisms by which hydroxyurea may induce this muco‐cutaneous syndrome‐like group of changes, are proposed.

Paederus fuscipes dermatitis: A histopathological study

Paederus fuscipes (PF) dermatitis is a self-healing blistering disorder of the skin caused by a small insect belonging to genus Paederus, family Staphylinidae, order Coleoptera. Crushing PF on the skin causes acute dermatitis within 24 hours, corresponding in shape and dimensions to the area affected by the substance released (pederin). The acute vesicular lesions become crusted and scaly within a few days and heal completely in 10–12 days, with a transitory postinflammatory hypercromic patch. Twenty consecutive cases of PF dermatitis at different stages were studied histologically by routine light microscopy. The pederin causes a spectrum of histopathologic changes ranging from acute epidermal necrosis and blistering in acute stages, to marked acanthosis with mitotic figures in the late stages. PF dermatitis is an entomological model of irritant contact dermatitis, having histopathologic features of intraepidermal and subepidermal blistering, epidermal necrosis and acantholysis. The presence of some acantholytic foci, relatively far from the foci of clinically involved skin, in four of the cases considered suggests a possible role of pederin in inducing acantholysis indirectly. Acantholysis is probably caused by the release of epidermal proteases.

Critical evaluation of the variants influencing the clinical response of vitiligo: study of 60 cases treated with ultraviolet B narrow‐band phototherapy

Background  The treatment of vitiligo is still a challenge, but ultraviolet B narrow‐band (UVB‐NB) therapy has been recently reported to be an effective and safe therapeutic option in patients with vitiligo.

Prevalence, severity and clinical features of psoriasis in fingernails and toenails in adult patients: Italian experience.

Background  Psoriasis is a chronic inflammatory skin disease affecting 2.0–6.5% of the European population. Although the most striking clinical features of psoriasis involve the skin, other organs including nails and joints may be affected in a substantial proportion of patients. Literature reports nail involvement in 10–56% of psoriatic patients, with common physical and social impairment. However, the precise prevalence of specific clinical features of nail psoriasis is somewhat under‐reported.

Useful treatment of vitiligo in 10 children with UV-B narrowband (311 nm).

Abstract:  We report our experience with UV‐B narrowband (UV‐B–NB) therapy in children affected by vitiligo. We studied 10 Caucasian Italian children (six boys, four girls, mean age 9.7 years ± 2.67). Treatment mean term was 5.6 months; frequency was three times a week on nonconsecutive days or only twice a week, because of school or family duties. The percentage of repigmentation was evaluated by comparing photographs taken before, during, and after the treatment, and showed a repigmentation level higher than 75% in five patients (5/10, 50%) and between 26% and 75% in three patients (3/10, 30%). Of our patients, 80% had a satisfactory response to phototherapy. Adverse events were limited and transient. No significant relationships between repigmentation grades and variables such as skin type, positive family history, and disease extension were observed. Some areas responded better than others; the best results were shown on the face and neck. Perhaps we studied too few patients to be conclusive, but the results obtained so far seem to indicate that children affected by recent vitiligo have a better response to the therapy. We feel that UV‐B–NB therapy is a valuable and safe option for the treatment of pediatric vitiligo, and should be started as soon as possible.

Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience

In the last years, several tyrosine kinase inhibitors (TKIs) have been developed and approved for human cancer treatment. Imatinib mesylate was the first of this novel family of drugs that target cancer‐specific molecules and signalling pathways. The appearance of imatinib resistances led to the introduction of second‐generation TKIs with higher potency and selectivity, such as dasatinib and nilotinib. However, the range of activity of these agents is not simply directed at tumour cells. Patients and their clinicians are indeed frequently confronted with the cutaneous side‐effects associated with the employ of these drugs, which represent the most common non‐hematological adverse reactions. For this reason, a systematic dermatological survey of patients receiving these therapies is highly important, and an early and appropriate dermatological treatment is required. In this review, we analyse the clinical and pathological characteristics of the most commonly reported adverse skin events associated with first‐ and second‐generation tyrosine kinase inhibitors, with a particular emphasis on our clinical experience.

Cutaneous CD30+ lymphoproliferative disorders: expression of bcl-2 and proteins of the tumor necrosis factor receptor superfamily

The spectrum of CD30+ cutaneous lymphoproliferative disorders is characterized by the histology of a high-grade lymphoma but frequent clinical regression of skin lesions in lymphomatoid papulosis (LyP) and occasional regression in CD30+ large cell lymphomas (LCLs). A recent study shows that apoptosis may be a significant mechanism of regression of LyP (Arch Dermatol 133:828-833, 1997). Therefore, we studied expression of proteins that induce apoptosis, including CD27, CD40, CD95, and nerve growth factor receptor (NGF-R), as well as anti-apoptotic protein bcl-2 in skin lesions from 25 patients within the spectrum of CD30+ cutaneous lymphoma. Our results show consistent expression of CD95 (APO-1/Fas), but rare or absent expression of CD27, CD40, and NGF-R on tumor cells from both regressing LyP lesions and nonregressing CD30+ lymphomas. Bcl-2 was expressed at low levels in LyP and at high levels in pleomorphic CD30+ lymphomas. These results indicate that, in addition to CD30, CD95 expression is preferentially expressed at high levels in all cutaneous CD30+ lymphomas and suggest that CD95 may play a role in the regression of CD30+ skin lesions. Expression of bcl-2 appears to protect tumor cells from apoptosis in CD30+ lymphoproliferative disorders.