Primary cutaneous B-cell lymphoma: narrative review of the literature.

Primary cutaneous B-cell lymphomas comprehend a group of lymphoproliferative disorders characterized by being monoclonal proliferations of B-cell primarily involving the skin. Despite being recognized as autonomous and distinct clinico-pathologic entities since the late 80s, their classification is still an ongoing matter of debate. At the moment, WHO classification recognizes three disorders: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma and primary cutaneous diffuse large b-cell lymphoma (leg type). Primary cutaneous diffuse large b-cell lymphoma (other) has been used to define rare cases which show histologically an infiltrate with diffuse pattern composed by large b-cell, but not fitting with criteria for follicle center lymphoma nor for primary cutaneous diffuse large b-cell lymphoma (leg type). Aim of this review was to briefly describe all recognized and provisional entities included in the primary cutaneous b-cell lymphomas and to discuss recent acquisitions that may influence their future classifications.

Rituximab plus liposomal pegylated doxorubicin in the treatment of primary cutaneous B-cell lymphomas.

BACKGROUND: In primary cutaneous B-cell lymphomas (PCBCL), radiotherapy - or surgery in a minority of cases - is the first-line treatment in follicle center lymphoma (PCFCL) and marginal zone B-cell lymphoma (PCMZL). Conversely, patients with multifocal skin involvement or relapsed/refractory disease deserve a systemic chemotherapy. In diffuse large B-cell lymphoma, leg type (PCLBCL-LT), due its poorer outcome, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimens are the most commonly used frontline, although hard to propose in elderly patients. In this regard, the association of rituximab (R) and pegylated liposomal doxorubicin (PLD) can be considered a promising, alternative approach. AIMS: Based on the favorable results reported with R and PLD in several recent trials, we decided to test efficacy and safety of this combination. METHODS: Twelve patients with PCBCL were treated with R plus PLD, and 7 had relapsed disease. Treatment plan consisted of 2 monthly cycles of R 375 mg/m(2) and PLD 20 mg/m(2) day 1;15, followed (in responders) by two cycles given only at day 1. All patients received prophylactic pyridoxine to prevent palmar-plantar erythrodysesthesia (PPE). RESULTS: Ten of 12 patients had a response (eight complete; two partial), remarkably 2/3 with PCLBCL-LT. Two patients did not respond (one progressive disease, PD, and one stable disease). Three patients died after a median follow-up of 56 months, two patients due to PD, and 1 due to a second neoplasm. Two out of 10 responders relapsed after 31 and 32 months, respectively. Hematological toxicity was negligible (one case of grade 2 neutropenia), as well as extra-hematological toxicity (two cases of grade 2 PPE). CONCLUSIONS: These preliminary data suggest that R-PLD is effective and well tolerated in all subsets of PCBCL and may be offered frontline in indolent cases unsuitable for radiotherapy or surgery as well as in more aggressive cases with contraindications to CHOP-like regimens.

Role of bexarotene in the treatment of cutaneous T-cell lymphoma: the clinical and immunological sides.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoid neoplasms. The incidence of CTCLs has risen over the last three decades. The most common CTCLs are mycosis fungoides and Sèzary syndrome. Therapies for CTCLs are various and range from skin-directed therapy to chemotherapy. Retinoids have been used in CTCL treatment since the 1980s with good results. Bexarotene is the first retinoid approved by the US FDA for CTCL therapy. Since then, numerous experiences of both its efficacy and mechanism of action have been reported. The aim of this paper is to review bexarotene action on CTCLs, as well as to highlight its immunological targets.

Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy.

AIMS: Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well-documented complication in the setting of breast-conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation-induced AVL and angiosarcomas (AS). METHODS AND RESULTS: Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon. CONCLUSIONS: The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation-associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.

Tolerability and safety of biological therapies for psoriasis in daily clinical practice: a study of 103 Italian patients.

Studies comparing the safety and tolerability of biological therapies for psoriasis in the long-term and in daily clinical practice are lacking. Most published studies are of selected patients with short-term (3-6 months) follow-up. We performed a retrospective cohort study of 103 patients in order to describe the frequency and the clinical features of adverse events, and to evaluate and compare the tolerability and safety of efalizumab, etanercept, infliximab, and adalimumab in clinical practice. A total of 136 courses of biological therapies were administered, with a mean duration of 16 months/patient; 55 patients received efalizumab, 45 etanercept, 33 infliximab, and 3 adalimumab. Infliximab had an incidence rate ratio of suspension due to severe adverse events 5.9 times (95% confidence interval (95% CI) 1.9-18, p < 0.001) higher than etanercept and 9.8 times (95% CI 3.2-30.1, p < 0.001) higher than efalizumab. Safety profiles for efalizumab and etanercept were more favourable than for infliximab. Concerning tolerability, we found that more patients responded to infliximab, but long-term tolerability was higher for both efalizumab and etanercept due to the better safety profile and a higher compliance to therapy.

Papules arising after radiotherapy for rhabdomyosarcoma.

Radiation therapy, even at low doses, can induce a wide spectrum of vascular skin proliferations ranging from nonmalignant ones, such as benign lymphangiomatous papules (BLAP), to frankly malignant pathologies, such as angiosarcoma. We describe a 50-year-old Caucasian woman with a past history of uterine rhabdomyosarcoma, treated 22 years prior with surgical excision, chemotherapy, and radiotherapy. She presented with a few skin-colored papules and a clear discharge located in the previously irradiated area (right inguinal region). Histopathology showed a proliferation of irregular, interanastomosing vascular channels, thin walled and lined by prominent endothelial cells with focally hobnail features. Cytological atypia of endothelial cells, mitotic figures, hemorrhagic areas, and necrosis were not observed. The endothelial cells expressed D2-40 and CD31. A diagnosis of BLAP following radiotherapy for uterine rhabdomyosarcoma was made. The patient was treated with complete excision using electrodessication. At the 20-month follow-up visit the patient was still free of recurrence.