Octavio Servitje

PURPOSE: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. PATIENTS AND METHODS: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). RESULTS: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). CONCLUSION: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients.

BACKGROUND: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging. OBJECTIVES: To develop a prognostic index for MF. METHODS: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. RESULTS: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. CONCLUSIONS: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

OBJECTIVE: To analyze risk factors for systemic involvement and long-term course in leukocytoclastic vasculitis. DESIGN: A clinicopathological study of 160 patients with leukocytoclastic vasculitis followed up for at least 3 years. Univariate and multivariate analysis were conducted by logistic regression methods. SETTING: The Bellvitge Hospital, a referral center in Barcelona, Spain. PATIENTS: One hundred sixty patients with cutaneous leukocytoclastic vasculitis. Patients in the categories cutaneous/systemic vasculitis and acute/chronic cutaneous vasculitis were selected for comparative analysis. MAIN OUTCOME MEASURES: Clinical, laboratory, and histopathological findings. RESULTS: Of 89 females and 71 males, aged 14 to 89 years, systemic involvement was documented in 20% of cases. Perinuclear-staining antineutrophil cytoplasmic autoantibodies were found in 21% of patients and cryoglobulins in 25.4%. Of the patients, 1.9% died of systemic vasculitis. The average duration of cutaneous lesions was 27.9 months. In 67.2%, a cause or associated condition was identified. Of the skin specimens, 59.6% showed vasculitis limited to superficial dermal vessels. Direct immunofluorescence was positive in 84.3% of cases. In the multivariate analysis, paresthesia, fever, and absence of painful lesions were found to be risk factors for systemic involvement. Cryoglobulins, arthralgia, and normal temperature were risk factors for chronic cutaneous disease. CONCLUSION: Our results identify prognostic factors in leukocytoclastic vasculitis and may provide some aid in the management of this heterogeneous group of patients.

BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (MZCL) has recently been described. Differentiation from follicular centre cell lymphomas and lymphocytomas is often difficult due to insufficient experience and a lack of large series of patients. OBJECTIVES: To characterize primary cutaneous MZCL better, we report clinical, histopathological, immunophenotypic and molecular genetics features in a series of 22 patients. METHODS: All patients were treated and followed up at the same institution. Diagnosis of MZCL was based on the World Health Organization classification criteria. All samples were routinely tested with a wide panel of monoclonal antibodies. DNA was extracted from every sample following standard methods. IgH rearrangement and t(14;18)(q32;q21) studies were performed in all samples. RESULTS: Twenty-two patients (20 men, two women; mean age 50 years, range 24-77) were included. The mean follow-up was 43 months. Seventy per cent of patients presented with characteristic skin lesions on the trunk or extremities, consisting of deep red to violaceous infiltrated plaques, nodules or tumours frequently surrounded by diffuse or annular erythema. Four patients presented with lesions on the head and neck area. Two patients had disseminated skin lesions. The main histopathological features were non-epidermotropic, dense lymphocytic infiltrates mainly distributed in a nodular pattern. Adnexal involvement was usually present, with eventual formation of lymphoepithelial complexes. Cytologically, the infiltrate was polymorphous with marginal zone B cells and B-monocytoid cells. Blastoid CD30+ cells were often observed. Colonized reactive germinal centres and lymphoplasmocytoid differentiation were frequently present. Neoplastic cells were CD20+, CD79a+, CD5- and CD10-. Monotypic expression of light chains was observed in 18 cases (13 kappa; five lambda). Clonal IgH rearrangements were detected in 14 cases. The bcl-2 mutation t(14;18)(q32;q21) was demonstrated in two cases. Most patients were treated with local radiotherapy. Complete response rate with this approach was 100%. Six patients (27%) had skin recurrences from 6 months to 8 years after first treatment. Five patients (23%) had extracutaneous involvement. Two of them had a large cell transformation and one died of lymphoma. Three of four patients with head and neck presentation developed extracutaneous disease. CONCLUSIONS: MZCL appears to be a well recognizable entity, clinically, histologically and immunophenotypically. Although prognosis is generally good, the disease has potential for skin as well as extracutaneous recurrences. Large cell transformation and head and neck presentation may be associated with a worse prognosis.