Granulomas piogênicos orais: prevalência, classificação e estudo imunohistoquímico / Oral pyogenic granulomas: prevalence, classification and immunohistochemical study

Granuloma piogênico (GP) é uma lesão de origem inflamatória que ocorre frequentemente em pele e cavidade oral. Existem dois subtipos histológicos: o tipo não lobular (GPNL), que é caracterizado por proliferação vascular semelhante a tecido de granulação, sem padrão de organização; e o tipo lobular (GPL) que se caracteriza pela organização dos vasos em agregados lobulares, separados por feixes de tecido conjuntivo. O objetivo deste estudo foi revisar todos os casos de granulomas piogênicos do nosso serviço de patologia bucal, a partir do ano 2000, reclassificar e correlacionar as características clínicas, microscópicas e imunohistoquímicas com os subtipos da lesão. No levantamento foram encontrados no arquivo 197 casos diagnosticados como granuloma piogênico e hemangioma lobular capilar. Após revisão das lâminas, 9 casos foram reclassificados, e 19 foram excluídos, restando 169 casos, sendo 62 de GPL e 107 de GPNL. Foram coletados ainda dados como sexo, idade, local da lesão, tipo de nódulo, ocorrência de trauma prévio e hipótese diagnóstica clínica. Reações imuno-histoquímicas (GLUT-1, CD34, D2-40, AML e Mast cell) de 22 casos, sendo 11 lobulados e 11 não lobulados. A média de idade de acometimento foi de 38,59 ± 16,96 anos, com 55,62% dos casos ocorrendo em pacientes do sexo feminino (10,12% durante gravidez), com maior acometimento em gengiva (39,64%), 44,97% dos nódulos eram do tipo pediculado e 13,02% relataram trauma mecânico prévio. O GPNL ocorre mais em gengiva, enquanto GPL acomete mais lábio (p < 0,05). O número de microvasos (marcados por CD34), área positiva para AML e ocorrência de atrofia do epitélio são mais prevalentes em GPL (p < 0,05), enquanto o número de mastócitos não teve diferença estatística entre os tipos histológicos. A marcação para GLUT-1 foi negativa em todos os casos. Em conclusão, o GP corresponde a 2,25% das lesões do nosso serviço de patologia, e a maioria é do tipo não lobular. Ocorre mais em indivíduos do sexo feminino, tem predileção por sítios gengivais, e 44% dos nódulos são do tipo pediculado. O GPL ocorre em indivíduos mais jovens do que o GPNL, e em lábios; na maioria das vezes possui epitélio atrófico, não sofre processo de maturação e possui maior vascularização(AU)

Pyogenic granuloma (GP) is an inflammatory lesion that occurs frequently in the skin and oral cavity. There are two histological subtypes: the non-lobular type (NLCH), which is characterized by vascular proliferation similar to granulation tissue, without organization pattern; and lobular capillary hemangioma (LCH) characterized by the organization of vessels in lobular aggregates, separated by bundles of connective tissue. The purpose of this study was to review all cases of pyogenic granulomas of our oral pathology service, from the year 2000, to classify and correlate the clinical, microscopic and immunohistochemical characteristics with the subtypes of the lesion. In the survey, 197 cases diagnosed as pyogenic granuloma and lobular capillary hemangioma were found in our files. After review, 9 cases were reclassified, and 19 were excluded, remaining 169 cases, being 62 LCH and 107 NLCH. Data such as sex, age, site of lesion, type of nodule, previous trauma and clinical diagnostic hypothesis were also collected. Immunohistochemical reactions (GLUT-1, CD34, D2- 40, SMA and Mast cell) of 24 cases, 11 LCH and 11 NLCH. Mean age was 38.59 ± 16.96 years, with 55.62% of cases occurring in female patients (10.12% during pregnancy), with a greater involvement in gingiva (39.64%), 44.97% of the nodules were pedunculated and 13.02% reported previous mechanical trauma. The NLCH occurs more in gingiva, while LCH affects more lips (p < 0,05). The number of microvessels (CD34 positive), SMA positive staining area and occurrence of epithelial atrophy are more prevalent in LCH (p < 0,05), while the number of mast cells had no statistical difference between histological types. In conclusion, PG corresponds to 2.25% of the lesions of our pathology service and most are NLCH. It occurs more in females, has predilection for gingival sites, and 44% of nodules are pedunculated. LCH occurs in younger individuals than the NLCH, and in the lips; most of the time it has atrophic epithelium, it does not undergo maturation process, and has greater vascularization(AU)

[The subpopulation of CD34+ cells and their importance in the healing of grafts in family-related allogenic transplants of peripheral stem cells]. / Subpopulace CD34+ bunek a jejich vyznam pro prihojeni stepu u príbuzenských alogenních transplantací periferních kmenových bunek.

CURRENT STATUS: The determination of concentration of CD34+ cells is the standard method for evaluation of the quality of a bone marrow graft and of peripheral stem cells. Although the relationship between the dose of CD34+ cells and the speed of graft healing in autologous transplants is a proven fact, it may not always be the case in allogenic transplants. PATIENTS AND METHOD: The correlation between the dose of CD34+ cell subpopulations and the speed of healing was monitored in patients indicated for allogenic transplantation of haematopoietic stem cells. The patients were divided according to the type of preparatory regimen they underwent for the purpose of analysis; one group contained those under a myeloablative regimen; a second group contained those under a non-myeloablative regimen. The data was subject to analysis of variance in regression models and non-parametric tests. RESULTS: From among the monitored subpopulations, CD34+36+ cells had the greatest effect on the healing process and were the most significant predictor of the speed of healing in patients under a myeloablative regimen. Nevertheless, a dose ofCD34+ cells continued to be the best healing predictor in patients under a non-myeloablative regimen. Also subpopulations of CD34+38+ and CD34+61+ cells had a significant effect on the speed of healing in both groups. CONCLUSION: Haematopoietic stem cells and progenitor cells defined by co-expression of specific antigens are likely to play a role, through different mechanisms of action, in the process of healing in patients in different pre-transplant regimens. While the dose of CD34+ cells is still the one which correlates best with the speed of healing in patients who underwent transplantation after non-myeloablative regimen, the dose of CD34+36+ cells appears to be a better predictor for the speed of healing after myeloablative regimens.

Na+/H+ exchanger regulatory factor-1 is a hematopoietic ligand for a subset of the CD34 family of stem cell surface proteins.

CD34 and its relatives, podocalyxin and endoglycan, comprise a family of surface sialomucins expressed by hematopoietic stem/progenitor cells and vascular endothelia. Recent data suggest that they serve as either pro- or antiadhesion molecules depending on their cellular context and their post-translational modifications. In addition, their ability to function as blockers of adhesion may be further regulated by their subcellular localization in membrane microdomains via activation-dependent linkage with the actin cytoskeleton. To gain further insights into the function and regulation of CD34-type molecules, we sought to identify the intracellular ligands that govern their localization. Using both genetic and biochemical approaches, we have identified the Na(+)/H(+) exchanger regulatory factor-1 (NHERF-1) as a selective ligand for podocalyxin and endoglycan but not for the closely related CD34. Furthermore, we show that NHERF-1 is expressed by all c-kit(+) /lineage marker(-)/Sca-1(+) cells, which are known to express podocalyxin and have long-term repopulating abilities. Finally, we show that these proteins relocalize and colocalize in response to cytokine signaling. The results suggest that this cytosolic adaptor protein may be important for mobilization of CD34-type proteins in the plasma membrane and may thereby regulate their ability to block or enhance hematopoietic cell adhesion.

Influence of the different CD34+ and CD34- cell subsets infused on clinical outcome after non-myeloablative allogeneic peripheral blood transplantation from human leucocyte antigen-identical sibling donors.

Currently, no information is available regarding the influence of the different CD34+ cell subsets infused on the haematopoietic recovery, following non-myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). We have explored, in a group of 13 patients receiving non-myeloablative allo-PBSCT from human leucocyte antigen-identical sibling donors, the influence of the total dose of CD34+ haematopoietic progenitor cells (HPC) infused, compared with that of the different CD34+ HPC and CD34- leucocyte subsets in the leukapheresis samples, on both engraftment and clinical outcome. The overall numbers of total CD34+ HPC (P = 0.002) and myelomonocytic-committed CD34+ HPC infused (P = 0.0002) were strongly associated with neutrophil recovery (> 1 x 109 neutrophils/l), the latter being the only independent parameter influencing neutrophil recovery. Regarding long-term engraftment, only the number of immature CD34+ HPC infused/kg correlated with the duration of hospitalization in the first 2 years after discharge (r = -0.75, P = 0.005). Both the overall amount of CD34+ HPC and the number of myelomonocytic CD34+ HPC infused showed a significant influence on the risk of graft-versus-host disease (GVHD). Thus, the overall probability of GVHD was 100%vs 25% for patients receiving >/= 5 x 106 CD34+ HPC or >/= 3.5 x 106 of myelomonocytic-committed CD34+ HPC vs lower doses (P = 0.013). None of the other CD34+ and CD34- cell subsets analysed correlated with development of GVHD. In summary, our results suggest that in non-myeloablative allo-PBSCT, high numbers of CD34+ HPC, especially the myelomonocytic-committed CD34+ progenitors, lead to rapid neutrophil engraftment. However, they also strongly impair clinical outcome by increasing the incidence of GVHD.

Identification of endoglycan, a member of the CD34/podocalyxin family of sialomucins.

CD34 and podocalyxin are structurally related sialomucins, which are expressed in multiple tissues including vascular endothelium and hematopoietic progenitors. These glycoproteins have been proposed to be involved in processes as diverse as glomerular filtration, inhibition of stem cell differentiation, and leukocyte-endothelial adhesion. Using homologies present in the cytoplasmic tails of these proteins, we have identified a novel member of this family, which we designate endoglycan. This protein shares a similar overall domain structure with the other family members including a sialomucin domain, but also possesses an extremely acidic amino-terminal region. In addition, endoglycan contains several potential glycosaminoglycan attachment sites and is modified with chondroitin sulfate. Endoglycan mRNA and protein were detected in both endothelial cells and CD34(+) bone marrow cells. Thus, CD34, podocalyxin, and endoglycan comprise a family of sialomucins sharing both structural similarity and sequence homology, which are expressed by both endothelium and multipotent hematopoietic progenitors. While the members of this family may perform overlapping functions at these sites, the unique structural features of endoglycan suggest distinct functions for this molecule.