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Immunoglobulin Kappa light chain gene (IGK) rearrangements are important complementary PCR targets for clonality assessment in mature B-cell proliferations in which detection of clonal VH-JH gene rearrangements fails. Failure to amplify VH-JH rearrangements is mainly attributable to somatic hypermutation. Detection of clonal IGK rearrangements is most relevant in the diagnosis of germinal center (GC) and post-GC B-cell lymphomas that are under a heavy somatic mutation process. Here we present three cases in which histology and immunophenotype of the tissue samples at time of diagnosis were inconclusive. PCR-based B-cell clonality assessment was performed using the standardized BIOMED-2 multiplex PCR protocols and Genescan analysis. No clonal VH-JH rearrangements were observed. Detection of a clonal IGK product in each of the three suspected cases supported the clonal origin of the B-cell proliferations. Interestingly, only rearrangements involving the Kde element were detected. Based in the clonal IGK-PCR result, a definitive diagnosis of follicular lymphoma (case 1 and 3) and extranodal marginal zone lymphoma (case 2) was established.

We report the case of an 86-year-old female who presented with lymphadenopathy, lymphocytosis, and thrombocytopenia. Peripheral blood immunophenotypic analysis identified two lymphoid B cell populations that differ in CD23, CD200, and CD43 expression and in the intensity of CD5, CD20, CD79b, and kappa light chain. By fluorescence in situ hybridization (FISH) analysis, approximately 30% of the mononuclear cells were positive for the t(11;14)(q13;q32) and 40% for trisomy 12; analysis of the two populations separated by fluorescence activated cell sorting showed that t(11;14) occurs exclusively in CD23−/CD200−/CD43− cells and trisomy 12 in the CD23+/CD200+/CD43+ population. Lymph node biopsy showed a typical small lymphocytic lymphoma morphology, with an effaced architecture and a predominantly diffuse proliferation of small to medium-sized lymphoid cells and pseudo-follicles with the characteristic features of proliferation centers. In addition, a different type of randomly dispersed nodules was present, composed of cells slightly larger than the monomorphic lymphocytic proliferation that occupied most of the lymph node. Staining for Cyclin D1 and FISH for CCND1 showed protein expression and gene breaks restricted to these areas. Conventional cytogenetic analysis revealed two separate clones, one with trisomy 12 and the other with t(11;14)(q13;q32), both as unique clonal abnormalities. IGH analysis supports the presence of two populations with a different clonal origin. Taken together, these results provide strong evidence for the presence of a composite small lymphocytic lymphoma/chronic lymphocytic leukemia and mantle cell lymphoma. This association has been described in very rare cases that we briefly review.

Dissertação de mestrado integrado em Arquitectura, Universidade Lusíada de Lisboa, 2011. Exame público realizado em 24 de Janeiro de 2012. O início do século XIX foi marcado pela introdução do Liberalismo, defensor dos modelos culturais da Revolução Francesa, o qual contribuiu para uma profunda alteração na forma de pensar a cidade. Na 1.ª metade do século XIX, não há significativa alteração da malha urbana, continuando a cidade a caber nos espaços herdados do período pós-terramoto. Em meados do século XIX, com o fomento da indústria e do comércio, verifica-se um crescimento urbanístico para Norte. A construção da Avenida da Liberdade é o projecto urbanístico que melhor representa o momento de ruptura entre uma Lisboa romântica a Lisboa progressista, que ansiava uma modernização urbanística e que culminaria com o início da construção das Avenidas Novas. As Avenidas Novas foram o projecto que consolidou a ideia do desenvolvimento urbano que fez avançar a cidade de Lisboa para Norte, na primeira metade do século XX. Surgem novos bairros com imóveis de rendimento, ocupados por uma classe média em crescimento. Nesta fase, surgem os autores da chamada "Primeira Arquitectura Moderna", introduzindo-a até certo ponto na sociedade da época. Contudo, verifica-se que, por outro lado, renunciam-na nos termos dos limites inseridos pelos propósitos do Estado Novo. Esta geração nasce limitada por duas personagens, através da determinada "política de espírito", habilmente conduzida por António Ferro e Duarte Pacheco. Com o Bairro de Alvalade, projectado por Faria da Costa, põe-se termo aos bairros com características rurais, pensando-se, pela primeira vez, numa solução para o problema da habitação social, dentro da cidade. É um bairro pioneiro dentro da história da cidade, pois é a primeira manifestação de urbanismo moderno na capital, caracterizado por linhas direitas e espaços verdes. O Bairro de Alvalade começou a ser construído a seguir à 2.ª Guerra Mundial. Entre as suas construções destaca-se o Bairro das Estacas, nome derivado dos pilares que sustentam os edifícios. Era o início de uma verdadeira revolução na arquitectura em Portugal, seguindo-se de forma inovadora os princípios da "Carta de Atenas". A par do Bairro de Alvalade, surge o plano do Bairro do Areeiro. Este plano integra-se no extenso programa de construção de frentes urbanas lançadas por Duarte Pacheco, então Ministro das Obras Públicas e Presidente da Câmara Municipal de Lisboa. Um dos grandes reflexos de todo este processo é a criação Praça do Areeiro, que representa fielmente as políticas urbanas desta fase. Em 1948, verificou-se o I Congresso Nacional de Arquitectura, patrocinado pelo governo, onde os arquitectos se reuniram para discutir o significado do seu trabalho. As conclusões mais importantes do Congresso foram a clara manifestação de que a arquitectura deveria exprimir-se numa linguagem internacional, assim como a defesa de uma arquitectura e urbanismo modernos, criada com o objectivo de resolver problemas de habitação. Neste contexto, surgiam novos bairros municipais, no nordeste periférico, a mando de Duarte Pacheco: Olivais Sul, Olivais Norte e Chelas, projectos modernos caracterizados por experiências, resultantes de uma distribuição na encomenda dos projectos e enquadramento no contexto de revisão da produção arquitectónica que caracterizou os anos 50.

Although the skin is the second most common site of involvement for extranodal lymphomas, only 20% of cutaneous NHL are of B cell origin. A wide range of B cell lymphomas can occur as primary cutaneous tumors and their clinical course can not always be predicted by histology alone. The incidence and significance of the presence of clonal B cell populations in the BM of affected patients at the time of diagnosis are presently unknown. On another hand, the BIOMED II primers were shown to have a high sensitivity for the detection of clonality in B cell lymphoproliferative disorders. We sought to determine the incidence of occult BM involvement in a series of twelve patients (3 women and 9 men, median age 54.5, 28 to 77 years old) diagnosed with primary cutaneous B cell lymphoma between August 2000 and May 2004, for whom skin biopsies, BM trephine biopsies and aspirates and clinical data were available for review. For that, we investigated the presence of clonal B cell populations in the BM aspirates obtained as part of the initial staging procedures by PCR (employing heteroduplex and GeneScanning analysis), using the BIOMED II primers for the immunoglobulin k light chain (IGK) and the immunoglobulin heavy chain complete and incomplete (IGH) rearrangements. At the same time, a set of amplified gene fragments of known sizes was run as a control of the DNA integrity. Patients’ diagnoses, according to the WHO classification, were marginal zone B cell lymphoma (5 cases), diffuse large B cell lymphoma (5 cases), follicular lymphoma (1 case) and NHL NOS (1 case). In all cases clinical evaluation, CT scans from the thorax, abdomen and pelvis as well as BM trephine biopsies failed to demonstrate extracutaneous involvement by NHL. Moreover, a maximum of 6% of policlonal CD19+ B cells were present in the BM aspirates as evaluated by flow cytometry. In three out of 12 cases (25%) a B cell clonal population was present in the BM, as demonstrated by the presence of an IGH clonal rearrangement detected by heteroduplex and/or GeneScanning analysis; they corresponded to two diffuse large B cell NHL cases and one marginal zone B cell lymphoma. Two of these patients are still under treatment and one (with diffuse large B cell lymphoma) remains in complete remission 9 months after first line therapy. In this small series of patients the detection of clonal B cell rearrangements in the BM analyzed at the time of diagnosis was uncommon; the clinical course of the positive cases did not differ from the whole series. Further follow-up studies are needed to define the significance and prognostic impact of those BM clones in cutaneous B cell NHL patients.