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Biomedical subjects

Vera Luiza Capelozzi

Publications and source records attributed to Vera Luiza Capelozzi.

At least 19 recordsLinked to original sources

Inflammatory cell phenotyping of the pulmonary interstitium in idiopathic interstitial pneumonia.

BACKGROUND: Several studies have implicated the role of inflammation in the pathogenesis of lung damage in idiopathic interstitial pneumonias (IIPs). Investigations of inflammatory cells in IIP have show that eosinophils, neutrophils and T cells may be associated with a poorer prognosis. OBJECTIVES: The aim of our study was to map, by quantitative analysis, the number of inflammatory cells in the lung tissue of patients with non-specific interstitial pneumonia/non-specific interstitial pneumonia (NSIP/NSIP), acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) and to correlate them with lung function tests and survival. METHODS: After immunohistochemical staining, we quantified the content of inflammatory cells [macrophages, neutrophils (elastase+), plasma cells, and CD3, CD4 and CD8 T lymphocytes (TLs)] in 20 NSIP, 20 DAD and 20 UIP surgical lung biopsies. RESULTS: The total density of inflammatory cells was significantly increased in DAD and NSIP when compared to UIP (p = 0.04). TLs were increased in DAD and NSIP when compared to UlP lungs (p < 0.05). The density of inflammatory cells in UIP showed significant differences in normal, intervening and dense fibrosis areas (p < 0.05). The most numerous cells infiltrating the mural fibrosis and honeycombing areas were plasma cells, neutrophils (elastase+), CD20+, CD3+, CD4+ and CD8+ (p < 0.05). In UIP, CD3+ TLs were directly correlated with forced expiratory volume in 1 s/forced vital capacity ratio x 100 (p = 0.05). CD68+ cells presented a significant positive correlation with the forced expiratory volume in 1 s (p = 0.04); neutrophil (elastase+) cells significantly correlated with residual volume (p = 0.02), residual volume/total lung capacity (p = 0.04) and carbon monoxide transfer factor (p = 0.03). The most important predictor of survival in UIP was CD3+ TLs (p = 0.05). CONCLUSION: The total density of inflammatory cells and lymphocytes presents a different distribution within the pulmonary parenchyma in AIP/DAD, NSIP/NSIP and IPF/UIP evolutionary adapted responses to injury. There is a localized distribution of inflammation in the normal, intervening and dense fibrosis areas of UIP for CD3+, associated with a lethal deterioration of the pulmonary function and poor survival. Our findings provide further evidence of the importance of inflammation in the pathophysiology of IIPs.

Adult↗

Interstitial and vascular type V collagen morphologic disorganization in usual interstitial pneumonia.

Recent evidence suggests that type V collagen plays a role in organizing collagen fibrils, thus maintaining fibril size and spatial organization uniform. In this study we sought to characterize the importance of type V collagen morphological disorganization and to study the relationship between type V collagen, active remodeling of the pulmonary vascular/parenchyma (fibroblastic foci), and other collagen types in usual interstitial pneumonia (UIP). We examined type V collagen and several other collagens in 24 open lung biopsies with histological pattern of UIP from patients with idiopathic pulmonary fibrosis (IPF). We used immunofluorescence, morphometry, and three-dimensional reconstruction to evaluate the amount of collagen V and its interaction with the active remodeling progression in UIP, as well as types I and III collagen fibers. Active remodeling progression was significantly related to type V collagen density (p<0.05), showing a gradual and direct increase to minimal, moderate, and severe fibrosis degree in UIP and in the three different areas: normal, intervening, and mural-organizing fibrosis in UIP. Parenchymal changes were characterized by morphological disorganization of fibrillar collagen with diverse disarray and thickness when observed by three-dimensional reconstruction. We concluded that in the different temporal stages of UIP, vascular/parenchyma collagen type V is increased, in disarray, and is the most important predictor of survival.

Biopsy↗

Neuroendocrine gastric carcinoma expressing somatostatin: a highly malignant, rare tumor.

Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.

Aged↗

Scleroderma-like remodeling induced by type V collagen.

Recently, we discovered that New Zealand rabbits immunized with human type V collagen plus Freund's adjuvant present fibrosis and vasculitis of organs usually affected by systemic sclerosis. In this way, we studied the fibrillogenesis process to identify possible factors involved in altered remodeling observed in this scleroderma-like model. Additionally, we have done a very preliminary comparison with human skins obtained from scleroderma patients (n=3). Female New Zealand rabbits (n=10) were immunized subcutaneously with two doses of 1 mg collagen V (COL V) plus complete Freund's adjuvant for a 30-day interval, followed by two additional intramuscular booster immunizations in incomplete Freund's adjuvant for a 15-day interval. Animals from control group (n=10), were only inoculated with complete and incomplete Freund's adjuvant given at same conditions of COL V. Histological analysis of skins from animals and patients were done by Masson's trichrome staining, and immunofluorescence method to detect collagen fibers and interactions of types I, III and V collagen in the remodeling process. The analysis of animal skins showed collagen fibril deposits in the dermis after 7 days of sensibilization and an increase in these deposits after 75 and 120 days, respectively. Skin thickness and atrophy of sebaceous and sweat glands were progressively more intense in late sacrificed animals and correlated with increased amount of collagen deposition. Surprisingly, type V collagen was overexpressed both in animals and patients, forming dense and atypical collagen fibers in the dermis. We suggest that this anomalous expression of morphologically different type V collagen could justify the remodeling observed in scleroderma plaque.

Adult↗

Immunohistochemistry quantification by a digital computer-assisted method compared to semiquantitative analysis.

PURPOSE: To compare immunostaining quantification obtained by a digital computer-assisted method with the well-established semiquantitative analysis. METHODS: Cytoplasmic staining of galectin-3 was obtained by standard immunohistochemical reactions in 25 cases of well-differentiated thyroid carcinoma. The expression index that associates the conventional area fraction of labeled cells with the immunostaining intensity score based on visual qualitative observation was used as the semiquantitative analysis. A digital computer-assisted method is described based on the use of an image processing program (ImageLab). Three parameters were obtained: (1) percentage of labeled cells; (2) digital immunostaining intensity, and (3) digital expression index. The proposed method allows numerical analysis of the immunostaining intensity. RESULTS: There was a strong correlation between the immunostaining intensity obtained by the two methods (Pearson correlation coefficient, r = 0.71, P = 0.0001). The same was observed between expression indexes (Pearson correlation coefficient, r = 0.66, P = 0.0001). CONCLUSION: Results obtained with our proposed digital computer-assisted method for immunoexpression analysis were concordant with the semiquantitative analysis. In addition, digital values can also resolve disagreement among different observers about the quality of staining intensity because the digital method does not classify the results into groups, but rather provides a numerical value for each individual case; thus, it increases the diagnostic and, more importantly, the prognostic sensitivity of the immunohistochemical analysis.

Analysis of Variance↗

Correlation between surgical lung biopsy and autopsy findings and clinical data in patients with diffuse pulmonary infiltrates and acute respiratory failure.

INTRODUCTION: Surgical lung biopsy is an invasive procedure performed when other procedures have failed to provide an urgent and specific diagnosis, but there may be reluctance to perform it in critically ill patients with diffuse pulmonary infiltrates. PURPOSE: To evaluate the diagnostic accuracy, the changes in therapy and survival of patients with diffuse lung infiltrates, mostly presenting acute respiratory failure, who underwent surgical biopsy. METHODS: We retrospectively examined medical records and surgical lung biopsies from 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates. Clinical diagnoses were compared to histopathological ones, from biopsies and autopsies. Laboratory and epidemiological data were evaluated, and their relationship to hospital survival was analyzed. RESULTS: All histological specimens exhibited abnormalities, mostly presenting benign/inflammatory etiologies. Fifteen patients had an etiologic factor determined in biopsy, most commonly Mycobacterium tuberculosis. The preoperative diagnosis was rectified in 37 patients. Autopsies were obtained in 25 patients and confirmed biopsy results in 72% of cases. Therapy was changed for 65% of patients based on biopsy results. Forty-nine percent of patients survived to be discharged from the hospital. Characteristics that differed significantly between survivors and nonsurvivors included sex (P = 0.05), presence of comorbidity (P = 0.05), SpO2 (P = 0.05), and presence of diffuse alveolar damage in the biopsy (P = 0.004). CONCLUSION: Surgical lung biopsy provided a specific, accurate etiologic diagnosis in many patients with diffuse pulmonary infiltrates when clinical improvement did not occur after standard treatment. Surgical lung biopsy may reveal a specific diagnosis that requires distinct treatment, and it would probably have an impact in lowering the mortality of these patients.

Acute Disease↗

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage.

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (alpha-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65% +/- 3.24%), while extrapulmonary diffuse alveolar damage (9.52% +/- 3.64%) and idiopathic diffuse alveolar damage (7.34% +/- 2.11%) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36% +/- 3.12%), extrapulmonary (16.12% +/- 4.58%), and idiopathic (13.74 +/- 4.20%) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12% +/- 6.25%) than extrapulmonary diffuse alveolar damage (3.93% +/- 2.86%), with this difference being statistically significant (P < 0.001). Equally significant was the difference for progressive decrease of cytokeratin AE1/AE3 immunostaining in hyaline membranes present in the extrapulmonary diffuse alveolar damage (5.42% +/- 2.80%) and idiopathic diffuse alveolar damage (0.47% +/- 0.81%) groups (P < 0.001). None of the groups stained for cytokeratin CK-7, CK-8, vimentin, or a anti-smooth muscle actin. CONCLUSIONS: This study showed that only the epithelial/endothelial components (SP-A, factor VIII, and AE1/AE3) of the alveolar/capillary barrier are present in hyaline membranes formation in the 3 groups of patients with diffuse alveolar damage. The significant difference in the expression of factor VIII-related antigen and cytokeratin AE1/AE3 in the expDA versus iDAD groups as well as the significant difference in the amount of hyaline membranes present in the pDAD versus iDAD groups are suggestive of a local and specific lesion with different pathways (direct, indirect, or idiopathic), depending on the type of diffuse alveolar damage.

Analysis of Variance↗

Angiogenesis as an indicator of metastatic potential in papillary thyroid carcinoma.

UNLABELLED: Angiogenesis is new blood vessel formation, a process that can lead to tumor development. Microvessel count has been correlated to metastasis in some neoplasias. PURPOSE: To determine if measurement of microvessel density is useful in predicting metastasis to the cervical lymph node and prognosis in patients with papillary thyroid carcinoma. METHODS: A retrospective analysis was performed in 30 patients that had undergone total thyroidectomy. They were divided in 2 groups of 15 patients--with and without metastatic disease. Immunohistochemistry was used to detect expression of CD34 in archival paraffin-embedded papillary thyroid tumors, and microvessel density was calculated based on it. Association between microvessel density and the presence of metastasis, according to histological subtype, disease recurrence, and AMES prognostic index groups was determined through statistical analysis. RESULTS: The median microvessel density for the patient group without metastasis (200.0 microvessels/mm2) was apparently, but not significantly, less than that observed among metastatic disease patients (254.4 microvessels/mm2) (P=.20). When papillary carcinoma subtypes were analyzed, this difference became significant (P=02). The follicular variant exhibited a greater microvessel density than the other subtypes, independent of metastasis presence. There was an apparent, but not significant, tendency for a larger median microvessel density in the group of patients that presented recurrence (294.4 microvessels/mm2 vs 249.6 microvessels/mm2, P=.11). There was no relationship between risk level and microvessel density: in the low- and high-risk groups, the median MVD was 304.0 microvessels/mm2 and 229.6 microvessels/mm2, respectively (P=.27). CONCLUSIONS: The results suggest that angiogenesis is more intense among metastatic tumors in the classic and the tall cell variants, indicating that microvessel count can be an indicator of the potential for metastasis in these subtypes of papillary thyroid carcinoma. Patients that developed recurrent disease had a tendency to exhibit higher angiogenesis; however, there was no association between microvessel density and the AMES prognostic index.

Adolescent↗

Immunohistochemical and in situ detection of cytomegalovirus in lung autopsies of children immunocompromised by secondary interstitial pneumonia.

Secondary interstitial pneumonia (SIP), a disease affecting patients immunocompromised by primary underlying diseases during their treatment in hospital, is frequently associated with cytomegalovirus (CMV) infection, a potentially treatable condition. However, in many cases, no infectious agent can be determined, and this clinical disease rapidly progresses to death. Theoretically, SIP could be caused by CMV, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect the virus. To test the hypothesis that immunohistochemistry (IH) and in situ detection by hybridization (ISH) provides more accurate results than the mere histological demonstration of CMV inclusions, these methods were applied to 37 autopsied lung sections obtained from children immunocompromised by primary underlying diseases and who died of SIP. As a result, the cases were subdivided into three groups: (1) children with SIP CMV inclusions (Diffuse alveolar damage-DAD-related) (n = 7); (2) children with SIP without classical viral inclusions (CMV-DAD-related) (n = 3); (3) children with SIP exhibiting nuclear cytopathic effect (not CMV-NSIP-related) (n = 27). In the first group, all three techniques yielded clearly positive results, whereas IH and ISH indicated that three of the children of the second group had CMV-related DAD without histological demonstration of CMV inclusions. In the third group, there were no positive CMV signals. These data indicate that DAD-related CMV infection is an important cause of SIP and of death in children immunosuppressed by primary underlying diseases, and that IH and in situ detection were more sensitive than the histological demonstration of CMV inclusions. A direct involvement of CMV in SIP exhibiting DAD is likely, but not in the non-specific interstitial pneumonia (NSIP) pattern. We conclude that all children with primary underlying diseases should be investigated for CMV SIP using sensitive IH and in situ tests in conjunction with histological routine procedures.

Autopsy↗

Nuclear markers (star volume, mitotic index, AgNOR and Ki-67) of the primary tumor and its metastasis in non-small cell lung carcinomas.

Although tumor growth is controlled by growth rate and cell cycle, it is also likely that the proliferative activity of tumor cells can influence the growth rate of the primary cancer and account for their aggressiveness. Variations in growth rate, cell cycle control and proliferative activity could, in part, explain differences in invasive and metastatic properties among non-small cell lung carcinomas (NSLC). The purpose of this report is to: (1) evaluate growth rate by using growth- and cell cycle-regulating markers (mitotic count, nuclear star volume, AgNOR, and Ki-67) as reflections of growth rate and (2) compare the indices of primary NSLC with the indices of their metastasis in a series of patients with advanced disease. Thirty-three patients with non-small cell lung cancer and hematogenous metastases were retrospectively studied by histochemical, immunohistochemical, and morphometrical investigations. Clinical variables were examined for differences in the frequency of histological subtypes, nuclear star volume, mitotic index, AgNOR area, and Ki-67 immunohistochemistry indices of expression in subgroups of patients stratified by primary tumor and hematogenic metastasis. The impact of these factors on overall follow-up was analyzed. In the samples available in this study, consisting of primary-met paired tumors, which are unique and rarely available for studies of lung cancer, we found that nuclear star volume and mitotic index in metastatic tumors were significantly higher than in the primary tumors. Although there was no significant difference between the Ki-67 index of metastatic and primary tumors, the Ki-67 index in metastatic brain tumors was significantly higher than in the corresponding primary tumors. Examination of Kaplan-Meier survival curves demonstrated that patients with metastatic tumors showing AgNOR area higher than 10.82 microm2 and nuclear star volume lower than 559.50 microm3 had approximately the same odds ratio (log rank of 4.16 and 3.25, p = 0.04 and 0.01, respectively) for survival with a median survival time equal to 17 months for both groups. Analysis of the remaining marker correlation had no impact on survival. We conclude that these results offer future possibilities for more complex studies, including the results of additional immunohistochemical analysis using molecular markers that are known to be important in regulating cell proliferation, e.g., cyclin D1, p27, and cyclin E. These would influence clinical decisions or different therapeutic approaches in advanced stage disease of non-small cell lung cancer.

Adult↗

Nuclear and environment morphometric profile in tumor size and nodal metastasis of resected typical pulmonary carcinoid.

As the biologic behavior in lung tumors with neuroendocrine differentiation is highly dependent on cell death (apoptosis) and extracellular matrix invasion, Bcl2 and extracellular matrix density have been targeted as potentially useful tumor markers. In this study, we sought to validate the importance of Bcl2 and ECM density and to study the relationships of Bcl2 and ECM density with clinical factors and other tumor or stromal markers. We examined Bcl2 and several other markers in tumor tissues from 55 patients with surgically excised pulmonary typical carcinoid. We used histochemistry, immunohistochemistry, and morphometry to evaluate the amount of tumor staining for Bcl2 and ECM; the surrogate markers for aggressive potential for our study were tumor size and lymph node metastasis determined at diagnosis. Multivariate logistic model analysis demonstrated that after surgical excision control, tumor size was significantly related to nodal metastasis (P = 0.01), but quantitative staining of the tumor for Bcl2 and ECM added prognostic information and was as strongly prognostic as tumor size (P<0.01). Cutpoints at the median staining of 3.1% and 9.8 microm2 for Bcl2 and ECM, respectively, divided patients into two groups with distinctive risk for nodal metastasis. Those with Bcl2 > 3.1% and ECM <9.8 microm2 had high risk for nodal metastasis. We concluded that tumor staining for Bcl2 and ECM in resected PTC is strongly related to tumor size and nodal metastasis. Patients with > 3.1% and <9.8 microm2 staining in their tumors comprise a subset with a high hazard for nodal metastasis and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.

Adolescent↗

Pulmonary and mediastinal "sarcoidosis" following surgical resection of cancer.

Previous reports indicate that enlarged hilar and mediastinal lymph nodes caused by sarcoid-like reactions may develop after curative resection of cancer, and their presence does not necessarily denote neoplastic recurrence. Reports further suggest that coexisting pulmonary infiltrates in this setting may be related to sarcoidosis. In this study, we describe two patients who had resected lung and gastric cancer and who later developed pulmonary interstitial infiltrate, concurrent with progressive mediastinal lymphadenopathy initially thought to be caused by intrathoracic dissemination of their cancer. These changes were shown by open lung biopsy to be a benign, granulomatous reaction interpreted as sarcoidosis. Thus, it is important to recognize this clinical pattern when pulmonary infiltrates develop after complete treatment of cancer in an otherwise relapse-free patient and to encourage lung or lymph node biopsy in these particular settings in order to confirm a sarcoid-like reaction, thereby avoiding unnecessary chemotherapy for presumed tumor recurrence.

Aged↗

Quantitation of conventional histologic parameters and biologic factors in prostatic needle biopsy are useful to distinguish paramalignant from malignant disease.

The scope of this work was to determine the potential use of prostatic conventional histologic parameters and biologic factors in distinguishing between paramalignant and malignant prostatic disease, taking into account benign fragments of biopsies obtained from patients with prostatic cancer or from patients suspected to have cancer. Each prostate sample was semi-quantified for macronucleoli, mucin, crystalloid, collagen micronodules, and quantified for glands, stroma, AgNOR, and p53. The database covered 185 biopsy specimens from 136 patients: 56 samples from the same number of patients in whom all the biopsies were benign; 49 samples from patients whose biopsies showed malignant features, and 80 malignant samples. Discriminant analysis of the results showed statistical differences for four parameters: macronucleoli, mucin, gland volume, and AgNOR, allowing us to identify three patterns of prostate involvement: normal, paramalignant, and malignant. The discriminant function permitted an adequate classification of the three patterns in 84% of the cases. Normal areas showed glands with a mean volume of 38.93 microm3, inconspicuous nucleoli, low mucin production, and a mean AgNOR area of 1.26 microm2. Prostatic biopsies with prominent nucleoli and the presence of mucin (60%), gland volume of 22.31 microm3, and AgNOR area of 2.14 microm2 characterized the paramalignant condition. Malignant areas were characterized by mean glands with a volume of 8.11 microm3, prominent nucleoli, high mucin secretion (100%), and AgNOR area of 4.47 microm2. We concluded that modifications in prostate histoarquitecture and function, such as the presence of macronucleoli, volume of glands, abnormal secretion of acid mucin and AgNOR expression, represent important parameters that must be incorporated in the pathologist's evaluation of prostate biopsies to the purpose of indicating a subsequent biopsy, particulary in those patients with clinical suspicion of malignancy, and whose prostate biopsy specimen showed paramalignant areas.

Adenocarcinoma↗

Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adenocarcinoma of the lung.

PURPOSE: Recently, several matrix metalloproteinases (MMPs) have shown promise as prognosticators in non-small cell lung cancer. In this study, we sought to validate the importance of MMP-9 and to study the relationships between MMP-9 and several other tumor or stromal markers. EXPERIMENTAL DESIGN: We examined MMP-9 and several other markers in tumor tissues from 152 patients with surgically excised adenocarcinomas of the lung. Their preoperative clinical stages were T(1-4)N(0)M(0); however, pathological exam of their resected tissues demonstrated that 33 were stage II, and 64 were stage III. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for MMP-9, and the outcome for our study was survival time until death from recurrent lung cancer. RESULTS: Multivariate Cox model analysis demonstrated that pathological stage was significantly related to survival time (P < 0.01), but quantitative staining of the tumor for MMP-9 added prognostic information (P < 3.0 x10(-16)) and was more strongly prognostic than pathological stage. In the subset of pathological stage I patients, staining for MMP-9 was also significantly associated with survival (P < 1.0 x10(-6)), and a cutpoint at the median staining of 11.2% for MMP-9 divided them into two groups with distinctive survival times. Those with MMP-9 > 11.2% had a median survival time of just 11 months. Those with MMP-9 < 11.2% had not reached a median survival and had a mean survival time of >62 months. CONCLUSIONS: Tumor staining for MMP-9 in resected adenocarcinoma of the lung is strongly related to survival. Patients with >11.2% staining in their tumors comprise a subset with a high hazard for dying of lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.

Adenocarcinoma↗

Autopsy-proven determinants of death in HIV-infected patients treated for pulmonary tuberculosis in Sao Paulo, Brazil.

The aim of this work is to describe and compare pulmonary pathology and proven causes of death in HIV-infected and non-HIV patients treated for tuberculosis, to identify the presence and extension of the lesions, and to suggest appropriate interventions based on the results. Of 246 adult patients (aged > 15) autopsied with tuberculosis and tested for HIV infection at Hospital das Clinicas, School of Medicine, São Paulo University, from January 1994 to December 1996, 100 HIV-infected patients were matched with 44 non-HIV-infected patients. Demographic determinants influencing patients' death were as follows: 1. Age and sex were not found to be important for the histological outcome, but do seem to correlate with HIV infection. Older patients with tuberculosis are less likely to be HIV-infected; 2. Previous tuberculosis and its treatment had no influence on the course of secondary or reinfection tuberculosis; 3. The efficiency of the diagnostic criteria used at the time of death was very low (59.2%); 4. Tuberculosis was more frequently investigated in HIV-infected than in non-HIV-infected patients; 5. Only 79 (56%) of the patients received first line agents for treatment; 6. Patients presented with advanced disease; 7. Their mortality is high, and death occurs early. Morphological determinants with influence on patient's death were related to differences in the spectrum of tuberculosis presentation and time of treatment. Noncaseating generalized multibacillary tuberculosis was likely to be the primary cause of death in HIV-infected patients who died during therapy, whereas deaths of patients occurring after the second course of treatment because of recurrence or incomplete treatment were increased for other manifestations of HIV disease (pyogenic pneumonia, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, wasting syndrome). In these patients, dimorphic tuberculosis, an intermediate reactive spectrum form of presentation, was the predominant histological finding. In the opposite spectrum, paucibacillary tuberculosis, a reactive form of tuberculosis presentation, was equally regarded in non-HIV-infected patients as the primary cause of death after four months of therapy. In the same spectrum, non-HIV-infected patients with tuberculosis, who completed all or most of their treatment, died of associated diseases after therapy (alcoholism, cancer, diabetes mellitus). Autopsy-proven determinants of death were associated with HIV status, the spectrum of tuberculosis presentation, and time of treatment. Early treatment for tuberculosis and associated diseases can improve survival and the quality of life even of highly immunosuppressed patients.

AIDS-Related Opportunistic Infections↗

Centrilobular fibrosis: a novel histological pattern of idiopathic interstitial pneumonia.

The classification of idiopathic interstitial pneumonias (IIP) is still under debate. In this context, we observed in some of our patients with a clinical and radiological diagnosis of IIP a different histological picture with an aggressive centrilobular scarring centered in the bronchiolar epithelia, but involving the surrounding parenchyma, which underwent extensive remodeling. We hypothesized that this pattern is a form of IIP that could be separated out histologically from the previously described patterns, in particular from usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Forty-nine patients with clinical and radiological diagnosis of IIP and open-lung biopsies were retrospectively selected from 1982 to 1998. The biopsies were reviewed according to the following criteria: derangement of lobular architecture, temporal homogeneity and subpleural or bronchocentric distribution of the lesions, fibroblast foci, bronchial epithelium necrosis and regeneration, exposure of the basal membrane, squamous metaplasia, basophilic intraluminal contents, and foreign bodies within the remodeling airspaces. Three groups were found: UIP (24 patients), NSIP (13), and a third that we named centrilobular fibrosis (CLF) (12). All histological parameters were significantly different among the three groups (p < 0.001). CLF is a specific, homogeneous, and recognizable histological pattern of IIP, and can be isolated from UIP and NSIP.

Aged↗