Neoplasia folicular in situ y neoplasia de células del manto in situincidencia y significado clínico

  1. BERMÚDEZ PINARGOTE, GLENDA MARIUXI
Dirixida por:
  1. Miguel Ángel Piris Pinilla Director
  2. Santiago Montes Moreno Director

Universidade de defensa: Universidad de Cantabria

Fecha de defensa: 29 de xuño de 2017

Tribunal:
  1. Eulogio Conde García Presidente/a
  2. Carlos Montalbán Sanz Secretario/a
  3. Máximo F. Fraga Rodríguez Vogal

Tipo: Tese

Teseo: 485221 DIALNET lock_openUCrea editor

Resumo

Follicular lymphoma (FL) is one of the most common non-Hodgkin lymphomas in adults, for about 20% of all lymphomas, with an incidence of 2.6 per 100,000 people/yr.), with a median age in the 6th decade and slight predominance in European women. In two thirds of cases it is usually diagnosed in stage III and IV. It is characterized by chromosome translocation t(14; 18) (q32; q21). Mantle cell lymphoma (MCL) comprises approximately 3% to 10% of non-Hodgkin's lymphomas. It occurs in individuals with a median age over 60 years with predominance in men. Most patients are diagnosed with stage III or IV disease, with lymphadenopathy, hepatosplenomegaly, involvement of bone marrow and peripheral blood. It is characterized by chromosome translocation t(11;14)(q13;q32). The therapeutic success obtained with the early detection of a malignant neoplasm and / or its preneoplastic state explains scientific interest in determination of precursor lesions. Therefore, the importance of precursor lesions in FL and MCL because both are diagnosed in advanced stages, which has a negative impact on prognosis and survival. Actually, in situ follicular neoplasia” (ISFN) and in situ mantle cell neoplasia (ISMCN) are considered as potential precursors. In situ, because B cells with t(14; 18) or t(11; 14) are restricted to a tissue compartment normally occupied by its physiological counterpart. In situ follicular neoplasia” (ISFN) and in situ mantle cell neoplasia (ISMCN) are histopathologic findings of undetermined clinical significance. The objective of this study was to establish incidence of "incidental" ISFN and ISMCN in systematic and retrospective sampling of lymphadenectomy specimens from patients diagnosed with colorectal (201 cases) and breast (140 cases) adenocarcinoma during 3 consecutive years (1998-2000) and establish the risk of progression to FL and overt MCL after a minimum follow-up of 13 years. Also, to make a comparison between the consecutive series of 3 years with a different series of cases of ISFN or ISMCN from Hematopathology consultation files. The laboratory techniques used are staining methods, hematoxylin eosin and immunostaining BCL2, CD10, cyclin D1. In addition, FISH was performed. Incidental and isolated ISFN was identified in 11/341 patients (3.23%), whereas incidental and isolated ISMCN was found in 2/341 patients (0.59%). None of these 13 cases in this series developed overt lymphoma during the follow-up period (range 7-192 months). In the second series of 17 cases of ISFN (16 cases) and ISMCN (1 case) from consultation files, five cases had incidental and isolated ISFN and none progressed to manifest lymphoma. Overall, none of the 16 cases with incidental and isolated ISFN in both series developed overt FL after a median follow-up of 54 months (range 7 to 187 months). However, the 12 cases with clinical suspicion of lymphoproliferative disease showed association (in different lymph nodes) or combination (in the same sample) of ISFN or ISMCN with other lymphoid neoplasms (LF, splenic marginal zone lymphoma, nodal marginal zone lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia / small cell lymphocytic lymphoma, multiple myeloma). In conclusion, the clinical relevance of ISFN and ISMCN seems to strictly depend on the clinical context. In the retrospective sampling series, isolated and incidental ISFN or ISMCN had zero risk of transformation to FL or MCL respectively. However, when ISFN or ISMCN are diagnosed in the context of a clinical suspicion of lymphoproliferative disorder this finding is more frequent than expected, suggesting a basic disorder that facilitates the emergence of clonal B cells populations and should lead to a rigorous clinical study.