The elusive Luminal B breast cancer and the mysterious chemokines.

PURPOSE: Invasive ductal breast cancer (IDC) is heterogeneous. Staging and immunohistochemistry (IH) allow for effective therapy but are not yet ideal. Women with Luminal B tumors show an erratic response to treatment. This prospective study with 81 women with breast cancer aims to improve the prognostic stratification of Luminal B patients. METHODS: This is a prospective translational study with 81 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry, for survival analysis, and their correlations with the chemokines. Serum measurements of 13 chemokines were performed, including 7 CC chemokines [CCL2(MCP1), CCL3(MIP1α), CCL4(MIP1ß), CCL5(Rantes), CCL11(Eotaxin), CCL17(TARC), CCL20(MIP3α)], 6 CXC chemokines [CXCL1(GroAlpha), CXCL5(ENA78), CCXCL8(IL-8), CXCL9(MIG), CXCL10(IP10), CXCL11(ITAC)]. RESULTS: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with a median follow-up time the 32.87 months (3.67-65.63 months). There were age correlations with IP10/CXCL10 chemokines (r = 0.4360; p = 0.0079) and TARC/CCL17 (Spearman + 0.2648; p = 0.0360). An inverse correlation was found between body weight and the chemokines Rantes/CCL5 (r = - 0.3098; p = 0.0169) and Eotaxin/CCL11 (r = - 0.2575; p = 0.0470). Smokers had a higher concentration of MIP3α/CCL20 (Spearman + 0.3344; p = 0.0267). Luminal B subtype patients who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and higher expression of MIP1ß/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) had a higher risk of metastases. CONCLUSION: Patients with Luminal B breast tumors can be better stratified by serum chemokine expression, suggesting that prognosis is dependent on biomarkers other than TNM and IH.

Epidermal growth factor receptor (EGFR) expression in the serum of patients with triple-negative breast carcinoma: prognostic value of this biomarker.

Background: Epidermal growth factor receptor (EGFR) overexpression has been considered a poor prognostic factor in breast cancer. Methodology: A prospective study of 206 women with breast cancer analysed by stages (I, II, III and IV) and by immunohistochemical subtype (Luminal A, Luminal B, HER2+ and triple-negative (TN)); 89 healthy controls with normal recent mammography were included. The EGFR measured in the serum (sEGFR) was detected by the Enzyme-Linked Immunosorbent Assay (ELISA) method (R&D Systems kit DY231) collected by blood before any treatment in patients. Kaplan-Meier method and Cox regression were carried out to obtain the prognostic value, considering significance if p < 0.05. Results: With a median follow-up of 36.6 months, 47 deaths occurred. Multivariable Cox regression showed difference of overall survival (OS) associated with sEGFR levels (sEGFR ≤ or > 47.8 ng/mL) in patients with TN cancers, but not of Luminal A, Luminal B or HER2+ subtypes; adjusted by stage, the death risk increased by approximately 415% [hazard ratio (HR): 5.149 (1.900-13.955), p = 0.001] for patients with sEGFR > 47.8 ng/mL compared to patients with a lower sEGFR value. There was no significant correlation of sEGFR with staging, histological tumour grade (G1/G2/G3), Ki67 (< or ≥14%) or body mass index. Conclusions: Increased sEGFR expression in patients with TN tumours is a significant predictor of lower OS and its quantification is inexpensive and straightforward.

Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy).

Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p < 0.05); 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy)

ABSTRACT Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p < 0.05); 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study.

Involvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS) is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV) and the importance of these lesions to death. Of these, 90 (96.8%) patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5%) cases. The most common infections were candidiasis (42%), cytomegalovirus (29%), histoplasmosis (11.8%), toxoplasmosis (9.7%) and mycobacterial infection (9.7%). Malignancies were rare, present in four (4.3%) cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma). All segments showed lesions: tongue (48.6%), esophagus (44.8%), stomach (44.7%), colon (43.2%) and small intestine (28.9%). The lesions found were immediate cause of death in five (5.4%) cases. In another 36 (38.7%) cases the basic disease was systemic and also compromised the digestive system.

Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study / Alterações morfológicas no sistema digestivo de 93 pacientes infectados pelo vírus da imunodeficiência humana: um estudo de autopsias

Involvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS) is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV) and the importance of these lesions to death. Of these, 90 (96.8%) patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5%) cases. The most common infections were candidiasis (42%), cytomegalovirus (29%), histoplasmosis (11.8%), toxoplasmosis (9.7%) and mycobacterial infection (9.7%). Malignancies were rare, present in four (4.3%) cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma). All segments showed lesions: tongue (48.6%), esophagus (44.8%), stomach (44.7%), colon (43.2%) and small intestine (28.9%). The lesions found were immediate cause of death in five (5.4%) cases. In another 36 (38.7%) cases the basic disease was systemic and also compromised the digestive system.

Envolvimento do sistema digestório em pacientes com síndrome da imunodeficiência adquirida (AIDS) é frequente e muitas alterações nesses pacientes são diagnosticadas apenas à autopsia. Há escassos estudos de autopsia com análise detalhada desse sistema e apenas um deles foi realizado no Brasil. Neste estudo avaliamos cada segmento do sistema digestório em 93 autopsias consecutivas de indivíduos infectados pelo vírus da imunodeficiência humana (HIV) e a importância dessas lesões para o óbito. Desses, 90 (96,8%) pacientes apresentavam AIDS. Revisamos prontuários médicos, relatórios de autopsias e cortes histológicos da língua ao reto corados pela técnica de hematoxilina-eosina. Quando necessário, analisamos colorações especiais e imuno-histoquímica para pesquisar infecções. Havia lesões no sistema digestório em 73 (78,5%) casos. As alterações mais comuns foram infecciosas: candidíase (42%), citomegalovirose (29%), histoplasmose (11,8%), toxoplasmose (9,7%) e infecção por micobactérias (9,7%). Neoplasias malignas foram raras, presentes em quatro (4,3%) casos (dois sarcomas de Kaposi, um adenocarcinoma gástrico e um carcinoma embrionário metastático). Todos os segmentos apresentaram lesões: língua (48,6%), esôfago (44,8%), estômago (44,7%), intestino grosso (43,2%) e intestino delgado (28,9%). As lesões encontradas foram causa imediata do óbito em cinco (5,4%) casos. Em outros 36 (38,7%) casos a doença básica era sistêmica comprometendo, também, o sistema digestório.

Neuropathology of AIDS: An Autopsy Review of 284 Cases from Brazil Comparing the Findings Pre- and Post-HAART (Highly Active Antiretroviral Therapy) and Pre- and Postmortem Correlation.

A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies.

Benign and malignant neoplasias in 261 necropsies for HIV-positive patients in the period of 1989 to 2008.

Considering that there are some studies with autopsies from AIDS describing only malignant neoplasias and that changes can occur after the introduction of Highly Active Antiretroviral Therapy (HAART), our objectives were to analyze the frequency of benign and malignant neoplasms in AIDS patients in the periods of both pre- and post-HAART. This is a retrospective study with 261 autopsies of HIV-positive patients between 1989 and 2008 in Uberaba, Brazil. Sixty-six neoplasms were found (39 benign, 21 malignant and six premalignant) in 58 patients. The most frequent malignant neoplasms were lymphoid, in 2.7% (four Non-Hodgkin lymphoma, one Hodgkin, one multiple myeloma and one plasmablastic plasmacytoma), and Kaposi's Sarcoma, in 2.3% (six cases). The most frequent benign neoplasms were hepatic hemangiomas in 11 (4.2%) of 261 cases and uterine leiomyoma in 11 (15.7%) of 70 woman. In the pre-HAART period eight (9.8%) benign neoplasias and four (4.9%) malignant occurred in 82 patients; in the post-HAART period, 29 (16.2%) benign and 17 (9.5%) malignant were present; however, the differences were not significant. We conclude that the introduction of HAART in our region doesn't look to have modified the frequency of neoplasms occurring in patients with HIV.

Benign and malignant neoplasias in 261 necropsies for HIV-positive patients in the period of 1989 to 2008 / Neoplasias benignas e malignas em 261 necropsias de pacientes HIV positivos no período de 1989 a 2008

Considering that there are some studies with autopsies from AIDS describing only malignant neoplasias and that changes can occur after the introduction of Highly Active Antiretroviral Therapy (HAART), our objectives were to analyze the frequency of benign and malignant neoplasms in AIDS patients in the periods of both pre- and post-HAART. This is a retrospective study with 261 autopsies of HIV-positive patients between 1989 and 2008 in Uberaba, Brazil. Sixty-six neoplasms were found (39 benign, 21 malignant and six premalignant) in 58 patients. The most frequent malignant neoplasms were lymphoid, in 2.7 percent (four Non-Hodgkin lymphoma, one Hodgkin, one multiple myeloma and one plasmablastic plasmacytoma), and Kaposi's Sarcoma, in 2.3 percent (six cases). The most frequent benign neoplasms were hepatic hemangiomas in 11 (4.2 percent) of 261 cases and uterine leiomyoma in 11 (15.7 percent) of 70 woman. In the pre-HAART period eight (9.8 percent) benign neoplasias and four (4.9 percent) malignant occurred in 82 patients; in the post-HAART period, 29 (16.2 percent) benign and 17 (9.5 percent) malignant were present; however, the differences were not significant. We conclude that the introduction of HAART in our region doesn't look to have modified the frequency of neoplasms occurring in patients with HIV.

Tendo em vista que trabalhos sobre necropsias de AIDS analisam apenas neoplasias malignas e que ocorreram alterações após a terapia antiretroviral altamente eficaz (HAART), este estudo foi feito com objetivo de avaliar a frequência de neoplasias benignas e malignas nos períodos pré e pós-HAART. Estudo retrospectivo de 261 necropsias de HIV positivos entre 1989 e 2008 em Uberaba - Brasil. Foram encontradas 66 neoplasias (39 benignas, 21 malignas e seis lesões pré-invasivas) em 58 pacientes. As neoplasias malignas mais frequentes foram linfóides, em 2,7 por cento (quatro linfomas não Hodgkin, um Hodgkin, um mieloma múltiplo e um plasmocitoma plasmoblástico) e, sarcoma de Kaposi, em 2,3 por cento (seis casos). As benignas mais frequentes foram hemangiomas hepáticos em 11 (4,2 por cento) dos 261 casos e leiomiomas uterinos em 11 (15,7 por cento) das 70 mulheres. No período pré-HAART ocorreram oito (9,8 por cento) neoplasias benignas e quatro (4,9 por cento) malignas em 82 pacientes; no pós-HAART, 29 (16,2 por cento) benignas e 17 (9,5 por cento) malignas; entretanto, essas diferenças não foram estatisticamente significantes. Concluímos que a introdução da HAART em nossa região não parece ainda ter alterado a frequência de neoplasias em pacientes HIV.

Concordância entre diagnósticos neuropatológicos premortem e postmortem em 90 pacientes com síndrome da imunodeficiência adquirida, submetidos à necrópsia em um hospital de ensino no Brasil / Agreement between premortem e postmortem neuropathological diagnoses in 90 patients with acquired immune deficiency syndrome, submitted to autopsy at a teaching hospital in Brazil

Objetivo: Estudar as lesões anatomopatológicas no SNC, analisando se contribuíram para o óbito des s es pacientes e avaliar a concordância entr e os diagnósticos neuropatológ icos premortem e postmortem. Método: Estudo retrospectivo com análise de 90 necrópsias sequenciais de SIDA, realizadas entre 1989 e 1996, além de busca de dados epidemiológicos/clínicos e comparação com a suspeita clínica para avaliar concordância entre diagnóstico pre e postmortem. Resultados: Idade média 34 ± 11 anos; 81,1% do sexo masculino; todos apresentavam alguma alteração no SNC, sendo relevantes para o óbito em 54 (60%) casos. Apenas em 15 (27,8%) desses 54 casos houve s uspeita clínica da le s ão. As lesões encontr adas no SNC for am: toxoplasmos e (34,4%), c r i ptococo s e (12,2%), c itomega lovi r o s e (4,4%), encefa lite nodul a r m ic r og li a l (3,3%), mening ite bacter iana (2,2%), infecção pelo vír us JC (2,2%), tuberculos e/micobacter ios e (2,2%), histoplasmose (1,1%) e paracoccidioidomicose (1,1%). As alterações não relacionadas ao óbito (40%) for am: g lios e, fibros e meníngea focal, infar to antigo, calcificações e edema . Este estudo confirma que existem diversas alterações no SNC de pacientes com SIDA, sobretudo infecções oportunistas, frequentemente não suspeitadas clinicamente, evidenciando a importância da necrópsia. Esses achados sugerem que investigação minuciosa deveria ser feita no SNC de pacientes com SIDA, particularmente naqueles com diagnóstico tardio ou que não estão respondendo ao tratamento.

Agreement between premortem e postmortem neuropathological diagnoses in 90 patients with acquired immune deficiency syndrome, submitted to autopsy at a teaching hospital in Brazil. Objective: The aim was to study the anatomopathological lesions in CNS, analyzing if they have contributed to the death of those patients, and to evaluate the agreement between premortem and postmortem neuropathological diagnoses. Method: Retrospective study on 90 necropsies on patients with AIDS, performed between 1989 and 1996, besides having been performed the search for clinical and epidemiologycals datas, was done a comparison with the clinical suspicion, to analyze the concordance between premortem and postmortem diagnoses. Results: The patients? mean age was 34 ± 11 years, 81.1% were male. CNS lesions were found in all of the cases. In 54 (60%) cases, CNS lesions of relevance to the death were found, but there had only been clinical suspicion of such lesions in 15 (27.8%) of them. The lesions consisted of toxoplasmosis (34.4%), cryptococcosis (12.2%), cytomegalovirosis (4.4%), microglial nodular encephalitis (3.3%), bacterial meningitis (2.2%), JC virus infection (2.2%), tuberculosis/mycobacteriosis (2.2%), histoplasmosis (1.1%) and paracoccidioidomycosis (1.1%). The unrelated lesions with the death (40%) were: gliosis, meningeal fibrosis, old infarct, calcifications and edema. Conclusion: This study confirms that several changes occurred in the CNS of patients with AIDS, especially opportunistic infections, that frequently are not suspected clinically. These findings suggest that detailed investigation should be conducted on CNS of patients with AIDS, particularly those who are not responding to treatment or with late diagnoses.

Granulomatose linfomatóide-relato de caso / Lymphomatoid granulomatosis -case report

Objetivo: descrever um caso com manifestaçõs clínicas e achados histopatológicos de Granulomatose Linromatóide (GL), uma rara doença linfoproliferativa das células B, angiocêntrica e angiodestrutiva associada ao vírus Epstein-Barr (EBV). A apresentação clínica mais comum é no pulmão, podendo acometer qualquer órgão, sendo os achados extra-pulmonares as principais manifestações nestes casos. Relato do caso: mulher de 65, com lesão cutânea vulvar e que evoluiu com quadro neurológico associado a lesão expansiva envolvendo parênquima cerebelar, sem alterações pulmonares. Considerações Finais: pelo seu prognóstico e capacidade de ser confundida com outras vasculites a GL impõe-se como um importante diagnóstico diferencial dessas doenças.

lntroduction: this report describe a case of Lymphomatoid Granulomatosis (LG,s a rare linfoproliferative disorder of B cell showing angiocentric growth and destructive behaviour caused by Epstain-Barr virus (EBV). The predominant clinical presentations are confined to the pumonary system, however ; extra-pumonary manifestations can sometimes be the main feature of the dieseses. Method: here we report a 65 year old female, with a skin vulvar lesion, and another in cerebelus, without pulmonary disease. Conclusion: the LG can mimics systemic vasculits and is a diagnostic challenge.

Disseminated Balamuthia mandrillaris amoeba infection in an AIDS patient from Brazil.

This report describes a 32-year-old male AIDS patient. He presented with a clinical picture characterized by severe headache, blurred vision, and fever that had lasted for 10 days. At admission, no remarkable neurologic abnormalities were observed. Cranial tomography showed a ring-enhanced lesion with edema and a mass effect in the right occipital lobe. The initial diagnosis was toxoplasmosis, and treatment of this was administered. However, 5 days later, the patient's clinical status worsened and he died. The necropsy showed necrotizing and hemorrhagic encephalitis, with trophozoites similar to an amoeba species. Furthermore, the kidneys, adrenal glands, thyroid gland, and liver were also involved. The amoeba Balamuthia mandrillaris was identified by an immunofluorescence test.

Cellular angiofibroma of the vulva: case report with clinicopathological and immunohistochemistry study.

CONTEXT: Cellular angiofibroma of the vulva is a rare tumor that was first described in 1997. It occurs in middle-aged women (average age: 47 years), has small size (< 3 cm) and well-circumscribed margins. CASE REPORT: We describe a case in a 51-year-old woman whose preoperative diagnosis was confounded with Bartholin's glandular cyst. The neoplasia was well delimited and made up of three characteristic components: fusiform cells forming small fascicles, numerous blood vessels and adipose tissue interspersed between the fusiform cells. The stroma cells were positive for vimentin and negative for CD34, protein S-100, actin and desmin. The differential diagnoses for this tumor include aggressive angiomyxoma, angiomyofibroblastoma, lipoma of fusiform cells, solitary fibrous tumor, perineurioma and leiomyoma.

Cellular angiofibroma of the vulva: case report with clinicopathological and immunohistochemistry study

CONTEXTO: O angiofibroma celular da vulva é um tumor raro que foi inicialmente descrito em 1997. Ocorre em mulheres de meia-idade (média de idade: 47 anos), apresentar pequeno tamanho (< 3 cm) e margem bem circunscrita. RELATO DE CASO: Descrevemos um caso em mulher de 51 anos de idade cujo diagnóstico pré-operatório foi confundido com cisto de glândula de Bartholin. A neoplasia era bem delimitada e constituída por três componentes característicos: células fusiformes formando pequenos fascículos, numerosos vasos sangüíneos e tecido adiposo entremeado às células fusiformes. As células do estroma eram positivas para vimentina e negativas para CD34, proteína S-100, actina e desmina. O diagnóstico diferencial deste distinto tumor inclui angiomixoma agressivo, angiomiofibroblastoma, lipoma, tumor fibroso solitário, perineurioma, e leiomioma.