Large B-cell Lymphoma Leg Type Research Articles

Programmed death‐1 expression in cutaneous B‐cell lymphoma

Numbers of programmed death-1 (PD-1) positive T cells have prognostic significance in some types of nodal B-cell lymphomas, but data on PD-1 expression in cutaneous B-cell lymphoma (CBCL) are few. In this study we determined the expression and distribution of PD-1 on neoplastic B cells and reactive T cells in skin sections from primary CBCLs. By means of immunohistochemical staining, PD-1 expression was investigated in skin biopsies from 10 patients with primary cutaneous marginal zone lymphoma (PCMZL), 18 patients with primary cutaneous follicle center lymphoma (PCFCL) and 12 patients with primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT). Neoplastic B cells were negative for PD-1 in all cases, except for two cases of PCDLBCL-LT. The frequency of PD-1(+) T cells was significantly higher in PCFCL than in PCMZL and PCDLBCL-LT, accounting for 20, 10 and 3% of the total number of infiltrating cells, and 60, 20 and 15% of the total number of CD3(+) T cells, respectively. PD-1 is rarely expressed by the neoplastic B cells in CBCL. High percentages of PD-1(+) T cells, particularly if found outside germinal centers, support a diagnosis of PCFCL.

Primary cutaneous large B-cell lymphoma leg type with CNS metastasis, arising from a filarial limb

Primary cutaneous large B-cell lymphoma leg type with CNS metastasis, arising from a filarial limb

A ‘migrant’ mass of the forehead: Diagnosis and treatment

Primary cutaneous large B-cell lymphoma, leg type, is a rare and aggressive neoplasm as defined by the World Health Organization/European Organisation for Research and Treatment of Cancer classification of cutaneous lymphomas. In some cases this disease may simulate other forms of benign or malignant solid tumours. We present a case of a 74-year-old man showing a quickly 'migrant' mass on his forehead. First skin biopsy, ultrasound and magnetic resonance images were not significant. A deeper biopsy revealed a pathology consistent with a primary cutaneous diffuse large B-cell lymphoma leg type. The patient was successfully treated with only local radiotherapy (total dose: 32.4 Gy). At 1-year follow-up there were no recurrences. To the best of our knowledge, this is the second case of a primary cutaneous diffuse large B-cell lymphoma leg type developed as a quickly 'migrant' lesion. In contrast with the first report, our case developed in a non-leg site. From these two cases, we should bear in mind that aggressive and quickly migrant cutaneous or subcutaneous masses might mask a lymphomatous disease.

Diffuse large B-cell lymphoma leg type secondary to testicular diffuse large cell-B lymphoma

Diffuse large B-cell lymphoma leg type secondary to testicular diffuse large cell-B lymphoma

Primary cutaneous diffuse large B-cell lymphoma leg type presenting with hemophagocytic syndrome

Primary cutaneous diffuse large B-cell lymphoma leg type presenting with hemophagocytic syndrome

Primary Cutaneous Diffuse Large B-Cell Lymphoma (Leg Type) Presenting as Necrotising Fasciitis

Necrotising fasciitis is a rare rapidly progressive, life threatening, soft tissue infection which spreads along fascial planes. We present a patient who was diagnosed with a primary cutaneous Diffuse Large B-Cell Lymphoma (leg type) following initial presentation as probable necrotising fasciitis. Presentation was of a painful swollen leg, septic shock and MRI findings consistent with the clinical signs. Diagnosis of necrotising fasciitis remains challenging and it is often missed in the early stages. Early fascial biopsy and histopathological analysis is useful in cases where the diagnosis is unclear. We feel that this case highlights these important issues and will benefit others in their management of similar cases in the future.

Pegylated Liposomal Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (CBVD) in the Treatment of Advanced Primary Cutaneous Lymphomas.

Abstract 3717Poster Board III-653 IntroductionPrimary cutaneous lymphomas (PCL) present in the majority of histologic variants an indolent behaviour and a good prognosis with a prolonged survival. In a very small number of patients (pts), PCL is aggressive at the onset while in pts who are resistant or have relapsed after repeated topic or systemic therapies an advanced disease is more frequently observed. In these patients no therapy is capable of inducing a stable remission of the disease. The efficacy and low toxicity of Pegylated Liposomal Doxorubicin (PLD) as a single agent in second-line therapy of PCL was recently demonstrated. In our study we tested the safety and efficacy of PLD (Caelyx®) (C) in association with three drugs of proven effectiveness in nodal lymphoprolipherative and other primary cutaneous neoplastic disorders: Bleomycin (B), Vinblastine (B) and Dacarbazine (D) (CBVD). Patients and MethodsFrom February 2003 to December 2008 we observed 37 consecutive pts with advanced PCL: 19 Cutaneous T-Cell Lymphomas (CTCL) and 18 cutaneous B-Cell Lymphomas (CBCL). The CTCL pts were: 15 males and 4 females, with median age 59 (27-86) years, of which 7 pts with Anaplastic Large Cell Lymphoma (ALCL) CD30 positive, 7 pts with transformed Mycosis Fungoides (tMF), 3 pts with CD30 negative ALCL, 1pt with Panniculitis-like (Pl) Lymphoma and 1 pt with transformed Sezary Syndrome (tSS), according to the WHO-EORTC consensus classification. Nine pts presented with a nodal involvement and 10 pts were resistant or relapsed after 1 or more systemic treatments. Among the CBCL pts there were: 8 males and 10 females, with median age 61 (42-84) years, 12 pts had a Follicular Centre Lymphoma (FCL), 3 a Marginal Zone Lymphoma (MZL) and 3 a Diffuse Large B-Cell Lymphoma Leg Type (LT). Five pts presented a nodal involvement and 11 pts had received 1 or more previous systemic therapy. All 37 pts received CBVD therapy at following dosage: C: 20 mg/m2, B: 10 mg/m2, V: 6 mg/m2, D: 325 mg/m2 at days 1 and 15, administered intravenously every 4 weeks for a maximum of 6 cycles. Rituximab (R) at dosage of 375 mg/m2 was administered to CBCL pts at 1st day of each cycle. Before the treatment, pts were submitted to a complete staging of disease including TC-scan, bone marrow biopsy, and immunophenotyping of peripheral blood cells. ResultsIn the CTCL group 4 pts received 4 CBVD cycles, 14 pts received 6 CBVD cycles and 1 pt presented a progressive disease after the 1st cycle. Overall Response Rate (ORR) was 94.7% (18/19 pts). Sixteen out of 18 pts (88.8%) had a Complete Remission (CR) with disappearance of nodal involvement and cutaneous lesions, 2/18 pts obtained a Partial Remission (PR) with disappearance of nodal involvement and 75% of cutaneous lesions. In the CBCL group 3 pts received 2 R-CBVD cycles, 3 pts 4 cycles and 11 pts 6 cycles: ORR was 100% and all pts obtained a CR. The occurrence of palmoplantar erytrodisesthesia in 5 pts and grade 2-3 granulocytopenia in 12 pts did not modify the therapy program. Two CTCL pts (1 tSS, 1Pl) and 1 CBCL (LT) pt in CR after therapy received an allogeneic Hemopoietic Stem Cells (HCS) transplant and 1 CBCL(FCL) pt a syngeneic HCS transplant. In CTCL group 11 (61%) pts maintained their response after a median follow up of 15.5 (9-71) months. Among CBCL pts 14 (77.7%) pts are still in CR after a median follow up of 15 (4-36) months. ConclusionsOur experience demonstrates that the CBVD association is an effective and safe therapy for advanced PCL in inducing an important tumour burden reduction with a high CR rate. The assessment of response duration requires a longer observation. A larger number of patients in a multicentric trial are needed to confirm our promising results. Disclosures:Off Label Use: liposomial doxorubicin has a peculiar cutaneous tropism and low cardiac toxicity compared with other anthracyclines.

Efficacy and safety of pegylated liposomal doxorubicin in primary cutaneous B‐cell lymphomas and comparison with the commonly used therapies

The therapy of advanced, relapsed or refractory primary cutaneous lymphomas is often unsatisfactory. Recent data indicate a favourable pharmacokynetic, pharmacodynamic and toxicity profile of pegylated liposomal doxorubicin (Peg-Doxo) in primary cutaneous T-cell lymphomas, while in primary cutaneous B-cell lymphomas (PCBCLs), the drug efficacy has never been assessed so far. We performed a prospective phase II pilot clinical trial of Peg-Doxo monotherapy (20 mg/m(2)) in PCBCLs. One patient had a marginal zone B-cell lymphoma and four were affected by diffuse large B-cell lymphoma-leg type, all with widespread nodular lesions. All the patients achieved a complete response (CR = 100%) in a short period of time (median 3 months), even when pretreated with radio-chemotherapy. Two experienced a relapse. At follow-up, one patient died for progressive disease; four are in CR after 5, 52, 63 and 69 months. As concerning the toxicity profile, the treatment was well-tolerated, no one decreased or delayed the dose. The haematological toxicity was mild with only one case of grade III neutropenia; a patient showed a grade I neurotoxicity. Dermatological toxicity, in particular the palmar-plantar erythrodysesthesia, did not occurred, probably because of both the low dosages of Peg-Doxo monotherapy and the oral prophylaxis with pyridoxine. In spite of the small number of patients, it emerges that monochemotherapy with Peg-Doxo has a significantly high clinical activity and a good safety profile in PCBCLs, even in aggressive forms, compared with other therapeutic regimens, which are completely reviewed. It suggests the need of further investigations in this field.

Abstract A81: Cutaneous lymphoma incidence patterns in the United States: A population-based study of 3,884cases

Abstract A81 Background Primary cutaneous lymphomas (CL) represent 27 % of all non-Hodgkin lymphoma (NHL) and are a diverse group of lymphoid neoplasms manifesting heterogeneous clinical, histologic, immunophenotypic, cytogenetic, and molecular features. Given their rarity and heterogeneity, cutaneous lymphomas present substantial diagnostic and therapeutic challenges. There have been no prior large population-based descriptive studies focusing on CL in the United States. Methods Using the Surveillance, Epidemiology and End Results (SEER) program, we analyzed CL incidence rates (IR) and patient relative survival rates according to race, gender, and histologic type using the 2005 criteria of the World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification. Age-adjusted (2000 US standard) IR were calculated using the SEER*Stat software public use program version 6.4.4 (Surveillance Research Program); IR were expressed as new cases per 1,000,000 person-years and were analyzed by age, gender, race, ethnicity, and year of diagnosis. Results 3,884 CL were diagnosed in 16 SEER registries during 2001 to 2005. Cutaneous T-cell lymphomas (CTCLs) were the most common group of cutaneous lymphomas (72%), while cutaneous B-cell lymphomas (CBCLs) accounted for 28% of all cutaneous lymphomas. IR for both cell types of CL and their histologic subtypes were all higher among males than females. Overall age-adjusted CL IR were highest among Non-Hispanic Whites and Blacks (11.5/1,000,000 person-years), intermediate in Hispanic Whites (7.9), and lowest among Asian/Pacific Islanders (7.2). CTCL IR were highest among Blacks, whereas the IR of CBCL overall and subtypes were highest among Non-Hispanic Whites and lowest among Blacks. The 5-year relative survival rates for patients with CTCL and CBCL were 87% and 89%, respectively. Patients with primary cutaneous diffuse large B-cell lymphoma-leg type had the poorest survival rates (50%). Conclusion CL incidence rates vary markedly by race, gender, and histological type, supporting the notion that the histologic variants of CL represent distinct clinical entities. Further investigations using large populations and molecular tools are warranted to elucidate the etiology of the diverse spectrum of cutaneous lymphomas. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A81.

Yttrium-90 ibritumomab tiuxetan radioimmunotherapy in primary cutaneous B-cell lymphomas: first results of a prospective, monocentre study

Radioimmunotherapy with Yttrium-90 (90Y) ibritumomab tiuxetan (IT) has been shown to be effective in systemic B-cell lymphomas. We conducted a pilot study to evaluate the outcome and assess complications of 90Y IT therapy in patients with primary cutaneous B-cell lymphomas (PCBCL). Ten patients, all but one, with relapsed PCBCL were included and treated with rituximab (250 mg m−2/body surface) on days 1 and 8 followed by a single dose of 90Y IT (11–15 MBq kg−1). The overall response rate was 100%. The complete response rate was 100%. The median time to relapse was 12 months. Ongoing remissions were achieved in four patients (median follow-up 19 months). Transient and reversible myelosuppression (grade 3–4) was the most frequent adverse event. Radioimmunotherapy with 90Y IT is an effective treatment in relapsed primary cutaneous follicle centre lymphomas and diffuse large B-cell lymphoma leg-type. Further investigations in controlled randomised clinical trials evaluating the role of 90Y IT versus rituximab in PCBCL are needed.