Francisco Dário Rocha Filho

Orbital metastasis as primary clinical manifestation of thyroid carcinoma: case report and literature review

Capillary thyroid carcinoma (PTC) is the most common neoplasm of thyroid. It usually grows slowly and is clinically indolent; although rare, its aggressive forms with local invasion or distant metastases can occur. Metastatic thyroid carcinoma rarely involves the orbit. We reported an uncommon case of orbital metastasis of PTC. A 66-years-old woman presented proptosis of the right eye. The biopsy of the tumor in orbit revealed metastatic thyroid carcinoma. The ultrasensitive TSH level was 1,34 mUI/L and free T4 level was 1,65 ng/dL. A total thyroidectomy was performed and histopathological analysis of the nodule revealed follicular variant of papillary thyroid carcinoma. Currently, the patient has been receiving palliative chemotherapy with Clodronate Disodium. The importance of the case is due to its unusual presentation, which emerged as a primary clinical manifestation. Although rare, thyroid carcinoma should be suspected in orbit metastasis.

Bone marrow fibrosis (pseudo-myelofibrosis) in human kala-azar

Thirty cases of human kala-azar were diagnosed by iliac crest biopsy and myeloculture. Histological analysis of 12 patients showed diffuse thickening of reticulin fibers. To the best of our knowledge, this is the third report describing secondary bone marrow fibrosis (myelofibrosis-like) associated with kala-azar. Patients with positive bone marrow fibrosis (pbmf = 12) were compared to patients without detectable bone marrow fibrosis (wbmf = 18). There were no significant differences in clinical and blood parameters following treatment. All patients showed regression of hepatosplenomegaly. Our findings suggest that associated bone marrow fibrosis is transient and did not interfere in the evolution of treated patients.

Tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome

Background At the time of diagnosis, more than 50% of patients with myelodysplastic syndrome have a normal karyotype and are classified as having a favorable prognosis. However, these patients often show very variable clinical outcomes. Furthermore, current diagnostic tools lack the ability to look at genetic factors beyond karyotyping in order to determine the cause of this variability. Objective To evaluate the impact of p53 protein expression at diagnosis in patients with low-risk myelodysplastic syndrome. Methods This study enrolled 38 patients diagnosed with low-risk myelodysplastic syndrome. Clinical data were collected by reviewing medical records, and immunohistochemical p53 staining was performed on bone marrow biopsies. Results Of the 38 participants, 13 (34.21%) showed p53 expression in their bone marrow. At diagnosis, this group of patients also presented clinical features characteristic of a poor prognosis more often than patients who did not express p53. Furthermore, patients expressing p53 had a shorter median survival time compared to those without p53 expression. Conclusion This study shows that the expression of p53 at diagnosis is a useful indicator of distinct clinical characteristics and laboratory profiles found in low-risk myelodysplastic syndrome patients. These data indicate that the immunohistochemical analysis of p53 may be a prognostic tool for myelodysplastic syndrome and should be used as an auxiliary test to help determine the best therapeutic choice.

Primary non-Hodgkin lymphoma of bone: an unusual presentation.

Primary lymphoma of bone (PLB) is an extremely rare condition that is usually confused with other primary injuries of the bone. It is characterized by the involvement of one or more bone locations, with or without involvement of regional lymph nodes and viscera. PLB constitutes 3-7% of all malignant bone tumors and approximately 3% of all extranodal lymphomas. It is found at all ages, being most frequently seen in adult life. Any part of the skeleton can be involved, but a trend exists in favor of bones with persistent bone marrow. We report a case of PLB with an unusual presentation: involvement of the proximal phalanx of the thumb. Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide established complete remission. Consolidation with radiotherapy of the femur and phalanx was performed. There was no evidence of recurrence at the 14 th month follow-up.

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome

Aims To study the immunoexpression of proteins related to the mitotic checkpoint (cell division cycle 20 (CDC20), mitotic arrest deficient 2 (MAD2)) and the mitotic spindle (Aurora-B) in patients with myelodysplastic syndrome (MDS). Methods Protein expression was analysed in bone marrow tissue samples from 40 patients with MDS using immunohistochemistry. Prognostic markers (transfusion dependency, depth of cytopenias, chromosomal abnormalities and survival) were also studied. Results Higher MAD2 expression was observed among patients with platelets <50×109/L than among patients with platelets ≥50×109/L (42.6±22.8% vs 22.7±19.1%, respectively). Higher CDC20 expression was identified among patients with three dysplasias compared with patients who presented with one or two dysplasias (33.9±24.1% vs 10.5±5.7% vs 12.8±7.8%, respectively), among patients who exhibited a complex versus non-complex karyotype (50.0±30.2% vs 18.4±14%, respectively) and among patients with platelets <50×109/L vs platelets ≥50×109/L (38.2±26.2% vs 16.1±12.4%, respectively). Higher Aurora-B expression was found in patients with an abnormal versus normal karyotype (21.2±13.2% vs 7.5±5.0%, respectively). High expression of MAD2 and CDC20 (≥50%) was associated with severe thrombocytopenia. We also found statistically significant differences in the overall survival rate when comparing different degrees of CDC20, MAD2 and Aurora-B protein expression. Conclusions To the best of our knowledge, this is the first report to demonstrate that these proteins are associated with chromosomal abnormalities and poor prognosis in patients with MDS.

Células de Langerhans no epitélio da prega vocal humana: estudo imunoistoquímico

Langerhans Cells (LC) are a type of dendritic cells that have functions which involves antigen presentation and the stimulation of a T cell response. They represent about 4% of the laryngeal epithelial cells. AIM: The aim of this study was to identify the presence of LC in the epithelium of the vocal folds, to compare their subpopulations, as well as to compare the capacity of four immunohistochemistry markers. STUDY DESIGN: Experimental. MATERIAL AND METHOD: Six cadavers, 3 men and 3 women, were studied. Analysis of vocal folds and skin paraffin blocks stained with commercially available polyclonal S-100, vimentin, CD-68 and fascin were done. After histological analysis, Student t test and Analysis of Variance (ANOVA) were accomplished in the statistical study. RESULTS AND CONCLUSIONS: It was possible to identify the presence of LC in the epithelium of the human vocal folds in no smokers of both sexes. Fascin, vimentin and CD-68 were superior markers of LC than S-100 polyclonal antibody in vocal folds (p=0,01) and in the skin (p=0,02). It was also possible to identify three different subpopulations of LC in the vocal folds and skin. However, just in the skin it was observed larger amount in the basal layer of the epithelium statistically significant.

Hematogônias: distinção com blastos da leucemia linfóide aguda de células B por citometria de fluxo

Hematogones are normal B-lineage cell precursors with morphologic and sometimes immunophenotypic, similarities to neoplastic lymphoblasts. The aim of this work is to compare using flow cytometry sub-populations of B-lineage cells: normal bone marrow precursors (hematogones) and lymphoblasts. Normal bone marrow from patients with hematogones observed by optical microscopy and new cases of acute lymphoblastic leukemia of B-cell precursors were included in the study. Antibodies directed against CD19, CD10, CD45, CD34, IgM and CD22 were used. Analysis of hematogones, using CD10 x CD45 fluorescence intensity as a parameter, showed three sub-populations: immature, intermediary and mature marker expressions. CD34, IgM, TdT and CD22 marker expressions reinforced these results. The leukemic blasts cells formed a single population with positive expression for only immature antigens. In conclusion, hematogones and blast cells demonstrated different immunophenotypic profiles. Hematogones exhibit a broad spectrum of immature, intermediary and mature cells in one sample and blast cells have essentially immature features.

Nódulos linfóides medulares

Bone marrow trephine biopsies are an integral part of the diagnosis, staging and follow-up of patients with haematologic disorders. Lymphoid nodules are a common finding, usually reported in association with chronic inflammatory syndromes, infection haemolysis, myeloproliferative disorders and autoimmune diseases. They are usually considered to be a reactional feature. As bone marrow is the most common site of extranodal involvement of follicular lymphoma, the most important differential diagnosis is represented by bone marrow involvement by malignant lymphoma. From a practical point of view bone marrow lymphoid infiltrates are easy to diagnose on a histological basis. Benign aggregates are typically smaller, well distinguishable, contain a mixed population of cells and are nonparatrabecular. Neoplastic aggregates involving bone marrow as a paratrabecular infiltrate composed of cleaved cells. Immunophenotyping using a panel of monoclonal antibodies is capable of determining the lineage, subset and stage of differentiation of neoplastic lymphoid cells and may therefore contribute to confirm diagnosis. Especially in controversial cases, immunogenotypic analysis of the lymphoid proliferation may be helpful. Monoclonality may be detected by monotypic expressions of immunoglobulins or clonal rearrangements in the immunoglobulin heavy chain or T cell receptor genes. Ideally, the results of immunogenotypic analysis should be interpreted only in conjunction with the results of morphologic evaluation and immunophenotypic analysis. Morphology is still the gold standard in evaluating bone marrow infiltration by follicular lymphoma and immunophenotypic and immunogenotypic analysis should be considered as useful complementary investigations.

Apresentação incomum de sarcoma granulocítico mamário

O termo sarcoma granulocitico (SG) designa um raro tumor solido composto de agregados de precursores granulociticos imaturos em sitios extramedulares. A lesao geralmente ocorre durante o curso natural da leucemia mieloide aguda (LMA) ou apos sua remissao. O SG primario manifesta-se mais comumente na pele e linfonodos, portanto, quando se apresenta na mama, o erro diagnostico de linfoma nao Hodgkin, carcinoma lobular, sarcoma e melanoma maligno e um problema comum. A mama tem sido relatada como um local incomum de SG. Relata-se um caso raro de SG bilateral em mamas concomitante com LMA numa mulher de 47 anos. A paciente foi admitida em nosso hospital devido a manifestacoes neurologicas e descobrimos, durante a investigacao, tumoracoes nas mamas. A histopatologia das lesoes sugeriu linfoma nao Hodgkin, sendo iniciada quimioterapia esquema CHOP. No entanto, o mielograma mostrou hiperplasia das series granulociticas, e a imuno-histoquimica revelou mieloperoxidase e CD68 positivos, confirmando o diagnostico de SG primario em mamas. A citogenetica nao detectou anomalias. A revisao da microscopia e a analise do liquor confirmaram a presenca de infiltracao no parenquima mamario e no sistema nervoso central por leucemia monoblastica aguda (LMA-M5a). O protocolo de inducao da remissao foi iniciado com daunorrubicina, arabinosideo-C e quimioterapia intratecal com metotrexate, arabinosideo-C e dexametasona (MADIT). Um mes depois, a paciente recusou a continuacao do tratamento, depois de ter feito pedido de alta.

Células dendríticas foliculares: imunofenotipagem no linfoma de Hodgkin clássico esclerose nodular

O linfoma de Hodgkin classico esclerose nodular (LHCEN), de origem linfoide da celula B do centro germinativo (CG), apresenta agregados de celulas dendriticas foliculares (CDF), celula Hodgkin/Reed Sternberg e variantes, celulas B formando complexos relacionados ao CG, sugerindo uma associacao entre esclerose nodular e formacao do centro germinativo. O objetivo desse estudo foi avaliar a celula dendritica folicular, por imunofenotipagem com o anticorpo fascina, em biopsia de linfonodo periferico ou massa do mediastino de pacientes com LHCEN previamente diagnosticados, procurando identificar criterios como fatores prognosticos. Foram selecionados 38 pacientes, 55,2% do sexo masculino com relacao M:F de 1,23: 1 e a idade com media de 29,3 anos; 52,6% em estadios clinicos I-II, sendo 68,4% com sintomas B. Foram analisados 38 especimes de biopsias, sendo 57,9% do subtipo esclerose nodular II. O estudo imuno-histoquimico mostrou 100% de positividade para o CD30 e 68,4% para o CD15. As CDFs foram identificadas pelo anticorpo fascina, considerado padrao-ouro, atraves da tecnica imunoenzimatica indireta peroxidase-anti-peroxidase estreptavidina-avidina-biotina (PAP-Strept ABC), realizada em lâminas pre-tratadas do material de biopsia incluido em blocos de parafina. Foi evidenciado padrao CDF1 em 7,9%, CDF2 em 47,4% e CDF3 em 44,7%. Nao houve relacao entre a presenca da CDF e sexo, idade, estadio clinico e resposta ao tratamento, mas foi demonstrada uma tendencia para associacao (p=0,056) entre CDF os subtipos LHCEN. Os pacientes com presenca de celula dendritica folicular foram acompanhados por maior periodo, com media de 32,9 meses, com associacao estatisticamente significativa (p=0,001).