Alexandre Todorovic Fabro

Vocal Fold Nodules: Morphological and Immunohistochemical Investigations

The objective of this study was to investigate the morphological and immunohistochemical characteristics of vocal fold nodules. The study design was prospective and retrospective. For the histological study, we reviewed 15 slides from the surgical cases of vocal fold nodules, in which we analyzed epithelium, basal membrane (bm), and lamina propria. For the transmission and scanning electron microscopy (TEM, SEM) studies, five new cases on vocal fold nodules were included. Immunohistochemistry study was carried out in the 15 specimens, using antifibronectin, antilaminin, and anticollagen IV antibodies. The main histological alterations were epithelial hyperplasia (73.33%), basement membrane thickening (86.66%), edema, and fibrosis (93.33%). SEM--reduction in mucous lacing and increase in the desquamating cells, without epithelial erosion. TEM--hyperplasia of the epithelium, enlargement of the intercellular junctions, which was filled by fluid, subepithelial thickening of the lamina reticularis, and break points in the basal membrane. Immunohistochemistry--we identified greater immunoexpression of fibronectin on the basal membrane, on the lamina propria, and around the vessels. Antilaminin and anticollagen IV antibodies showed higher pigmentation on the endothelium of the vessels than that on the basal membrane. In vocal fold nodules, combined assessment using light microscopy, electron microscopy, and immunohistochemistry can reveal important morphological details useful in characterizing these lesions.

Is Reinke's Edema a Precancerous Lesion? Histological and Electron Microscopic Aspects

The objectives of this study were to evaluate morphologic alterations and precancerous lesions in Reinkes edema. Patients included were 54 smokers with bilateral Reinkes edema submitted to surgery in the Otolaryngology Department, Botucatu Medical School, São Paulo State University, Brazil, between 2002 and 2006. All specimens were evaluated by light microscopy and five contralateral lesions were also evaluated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The main histological alterations were edema (100%), inflammation (81.48%), basal membrane (bm) thickening (77.77%), and vessel proliferation (75.92%). Epithelium alterations were classified as grade 0 (11.11%), grade 1 (70.37%), grade 2 (14.81%), and grade 3 (3.70%). In the case included in grade 3 classification, microinvasive carcinoma was detected. SEM showed epithelial surface with some cellular desquamation, few microridges, and a polished and impermeable surface aspect. TEM showed epithelial hyperplasia, basal cells with different sizes, widening of the intercellular spaces, abnormal desmosome architecture, thickening of the bm, some electron-dense vesicles, and points of interruption. The morphological alterations presented in this study are not specific to Reinkes edema but this lesion can be the site of different grades of dysplasia and carcinoma, justifying the importance of periodic laryngeal endoscopic exams and meticulous histological analysis.

Achados clínicopatológicos na tromboembolia pulmonar: estudo de 24 anos de autópsias

BACKGROUND: Pulmonary thromboembolism (PTE) is still an enigmatic disorder in many epidemiological and clinical features, remaining one of the most commonly misdiagnosed disorders. OBJECTIVE: To describe the prevalence and pathological findings of PTE in a series of autopsies, to correlate these findings with underlying diseases, and to verify the frequency of PTE clinically suspected before death. METHOD: The reports on 5261 consecutive autopsies performed from 1979 to 2002 in a Brazilian tertiary referral medical school were reviewed for a retrospective study. From the medical records and autopsy reports of the patients found with macroscopically and/or microscopically documented PTE, were gathered data on demographics, underlying diseases, antemortem suspicion of PTE, and probable PTE site of origin. RESULTS: The autopsy rate was 42.0% and PTE was found in 544 patients. In 225 cases, PTE was the main cause of death (fatal PTE). Infections (p=0.0003) were associated with nonfatal PTE and trauma (p=0.007) with fatal PTE. The rate of antemortem unsuspected PTE was 84.6% and 40.0% of these patients presented fatal PTE. Diseases of the circulatory system (p=0.0001), infections (p<0.0001), diseases of the digestive system (p=0.0001), neoplasia (p=0.024) and trauma (p=0.005) were associated with unsuspected PTE. The most frequent PTE site of origin was the lower limbs (48.9%). Probable PTE sites of origin such as right-sided cardiac chambers (p=0.012) and pelvic veins (p=0.015) were associated with fatal PTE. CONCLUSION: A large number of cases do not have antemortem suspicion of PTE. Special attention should be paid to the possibility of PTE in patients with diseases of the circulatory system, infections, diseases of the digestive system, neoplasia, and trauma.

Aspectos clínicos, histológicos e de microscopia eletrônica dos granulomas de intubação das pregas vocais

Granulomas sao lesoes bilaterais e pediculadas das apofises vocais. Etiologias: intubacao, refluxo, traumatismos, fonotraumatismo e idiopatica. OBJETIVO: Analisar aspectos clinicos e morfologicos dos granulomas de intubacao. MATERIAL E METODOS: Estudo retrospectivo dos pacientes submetidos a microcirurgia por granulomas de intubacao, atendidos na Instituicao onde foi realizado, a partir de 2002. Analisaram-se: idade, sexo, indicacao e tempo da intubacao, sintomas, laudos de videolaringoscopia e numero de biopsia. Realizou-se estudo histologico em todos os casos e de microscopia eletronica em tres deles. RESULTADOS: 10 pacientes (7 F e 3 M), idade entre 2 anos e 72 anos e tempo de intubacao entre 4 horas e 21 dias. Rouquidao foi o principal sintoma. A histologia mostrou hiperplasia epitelial, intenso inflamacao importante no corion e proliferacao vascular. Na MEV observou-se epitelio escamoso com escassa descamacao. A MET, juncoes intercelulares alargadas e desmossomos alterados. No corion havia lagos sanguineos, intensa inflamacao, e fibroblastos com alteracoes estruturais como nucleos irregulares e cisternas dilatadas. CONCLUSOES: Granulomas pos-intubacao aparecem em qualquer idade, mesmo em intubacao por curto periodo, e causam rouquidao precocemente. As principais alteracoes morfologicas sao observadas no corion, como proliferacao vascular, inflamacao e alteracoes estruturais em fibroblastos indicando disfuncao e dano celular.

Lupus eritematoso sistêmico: novo fator de risco para aterosclerose?

OBJETIVO: Avaliar a prevalencia de eventos cardiovasculares (ECV) secundarios a aterosclerose em pacientes com lupus eritematoso sistemico (LES) e correlaciona-los aos tradicionais fatores de risco, tempo de doenca e drogas utilizadas na terapia. METODOS: Estudo retrospectivo atraves da coleta e analise dos dados contidos nos prontuarios de pacientes com diagnostico confirmado ha no minimo dois anos e seguidos desde 1992. Foram considerados ECV: angina do peito (AP), IAM e acidente vascular cerebral (AVC) de causa nao relacionada a atividade do LES. Foram computados os fatores de risco para aterosclerose e dados sobre tratamento. RESULTADOS: Foram analisados 71 prontuarios. A media de idade dos pacientes foi de 34,2±12,7 anos; 68 mulheres e tres homens; 58 caucasoides (81,6%). Dez (14,08%) apresentaram ECV. Os pacientes nos quais os eventos cardiovasculares foram observados apresentavam idade mais elevada (42,7 vs 32,8 anos p=0,0021) e maior tempo de doenca (10,8 vs 7,2 anos p=0,011). Os tradicionais fatores de risco, as doses diarias e cumulativas de esteroides, imunossupressores e antimalaricos nao apresentaram diferenca estatistica significante entre pacientes que apresentaram ou nao ECV. CONCLUSAO: A prevalencia de secundarios a aterosclerose no LES foi semelhante ao da literatura, 14,08%. Os tradicionais fatores de risco nao mostraram associacao com a ocorrencia ou nao de ECV no LES. Os pacientes nos quais os eventos cardiovasculares foram observados apresentavam idade mais elevada e maior tempo de doenca. E precoce estabelecer-se que o LES possa ser um fator independente no desenvolvimento da aterosclerose.

Clinical, histological and electron microscopic aspects of vocal fold granulomas

UNLABELLED Granulomas are bilateral and pediculated lesions of the vocal apophysis. Etiologies: intubation, reflux, trauma, vocal abuse, idiopathic origin. AIM To analyze the clinical and morphological aspects of post intubation granulomas. METHODS retrospective study of patients submitted to microsurgery for post intubation laryngeal granulomas seen at our Medical School starting in 2002. We analyzed: age, gender, indication and time of intubation, symptoms, videolaryngoscopic diagnosis and biopsy findings. Light microscopy was performed on all specimens, and electron microscopy on three of them. RESULTS ten patients (7 females and 3 males), between the ages of 2 and 72 years, intubation time between 4h and 21 days. Hoarseness was a frequent symptom, starting in the first week following extubation. Histology shows mild epithelial hyperplasia, severe inflammation and vessel proliferation in the corion. Under SEM, the epithelium presented mild superficial desquamation. Under TEM, intracellular junctions showed widening with structural changes in the desmosomes. In the corion there were vessel proliferations, inflammation and fibroblasts with structural alterations. CONCLUSIONS post intubation granulomas appear in any age and hoarseness is a frequent symptom. Morphological alterations occur in the corion as vessel proliferations, inflammation, and intracytoplasmatic alterations in fibroblasts suggesting cellular dysfunction and damage.

Avaliação da utilização de biópsia transbrônquica em pacientes com suspeita clínica de doença pulmonar intersticial

OBJECTIVE To study the clinical, radiological, and histopathological patterns of transbronchial biopsy (TBB) used in order to confirm the diagnosis in patients with clinical suspicion of interstitial lung disease (ILD) treated at a tertiary-care university hospital. METHODS We reviewed the medical records, radiology reports, and reports of transbronchial biopsies from all patients with suspected ILD who underwent TBB between January of 1999 and December of 2006 at the Hospital das Clínicas de Botucatu, located in the city of Botucatu, Brazil. RESULTS The study included 56 patients. Of those, 11 (19.6%) had a definitive diagnosis of idiopathic pulmonary fibrosis (IPF), the rate of which was significantly higher in the patients in which ILD was a possible diagnosis in comparison with those in which ILD was the prime suspect (p = 0.011), demonstrating the contribution of TBB to the diagnostic confirmation of these diseases. The histopathological examination of the biopsies revealed that 27.3% of the patients with IPF showed a pattern of organizing pneumonia, which suggests greater disease severity. The most common histological pattern was the indeterminate pattern, reflecting the peripheral characteristic of IPF. However, the fibrosis pattern showed high specificity and high negative predictive value. For CT scan patterns suggestive of IPF, the ROC curve showed that the best relationship between sensitivity and specificity occurred when five radiological alterations were present. Honeycombing was found to be strongly suggestive of IPF (p = 0.01). CONCLUSIONS For ILDs, chest CT should always be performed, and TBB should be used in specific situations, according to the suspicion and distribution of lesions.

Edema de Reinke: estudo da imunoexpressão da fibronectina, da laminina e do colágeno IV em 60 casos por meio de técnicas imunoistoquímicas

Reinkes edema is chronic laryngeal disease in which the superficial layer of the lamina propria is expanded by thick mucus, giving it a gelatin aspect. The disease is directly related to smoking and more frequent in women, who end up having a lower tone of voice. Its histological characteristics cannot always distinguish it from other benign lesions of the larynx for which additional histological techniques are necessary. AIM: to study the immunoexpression of fibronectin, collagen IV and laminin in Reinkes edema by immunohistochemical technique. Prospective study. MATERIALS AND METHODS: histological blocks of 60 cases of surgical Reinkes edema were saved, submitted to new cross-sections and to immunohistochemical reactions for fibronectin, laminin and collagen IV by the Avidin-Biotin-Peroxidase method. Fragments of five normal vocal folds were used as control, removed during autopsy. All patients were chronic smokers and adults- 50 women and 10 men. RESULTS: the immunoexpression of fibronectin, collagen IV and laminin was more important in the endothelium of blood vessels (68.33%, 76.66%, 73.33%, respectively) and less relevant in the basement membrane (25.0%, 5.0% and 3.3%, respectively). CONCLUSIONS: the immunoexpression of fibronectin, laminin and of collagen IV in the basal membrane of Reinkes edema was not relevant, with a predominance of these antibodies in the endothelium of blood vessels.

Hyaluronic acid behavior in the lamina propria of the larynx with advancing age.

Objectives To analyze the hyaluronic acid behavior in the lamina propria of the larynx with advancing age. Study Design Prospective study. Setting UNESP-Univ Estadual Paulista, Botucatu Medical School, Brazil. Subjects and Methods Thirty vocal folds were obtained at necropsy from 10 adult males (30–50 years old) and 20 geriatric males (10: 60–75 years old; 10: over 76 years old). Midmembranous vocal fold sections were subjected to immunohistochemical reactions. Digital imaging software (ImageJ) was used to quantify the hyaluronic acid distribution over the lamina propria of vocal folds, from superficial to deep layers. Results Hyaluronic acid distribution was homogeneous for the larynges, at both superficial and deep layers (41.6 and 38.5, respectively). For both 30- to 50-year-old men geriatric age groups, hyaluronic acid level was lower at both layers. Conclusion Hyaluronic acid level in the lamina propria of the larynx of geriatric men decreases with advancing age at both layers of the lamina.

Perfil da atividade de pesquisa publicada nos anais dos congressos brasileiros de pneumologia e tisiologia nos últimos vinte anos

OBJECTIVE: To increase the knowledge base regarding pulmonology research in Brazil. METHODS: A retrospective, observational study of the abstracts published in the Annals of the Brazilian Pulmonology and Phthisiology Conferences held from 1986 to 2004, quantifying the institutions of origin by geographic distribution and type, as well as categorizing the abstracts by study design and topic. RESULTS: A total of 6467 abstracts were published. The institutions of origin were located, variously, in the Southeast (3870 abstracts), South (1309), Northeast (783), Central-West (267) and North (84). There were 94 abstracts originating from foreign institutions, especially from institutions in Portugal (56.3%) and the United States (13.8%). Most of the studies (5825) were conducted in public Brazilian institutions. There were 4234 clinical studies, 1994 case reports and 239 original research articles. A marked, progressive increase was observed in the number of clinical studies and case reports during the period evaluated. Overall, the most common themes were tuberculosis and other infections diseases (25.2%), following by oncology (11.6%), interstitial lung diseases (8.8%) and thoracic surgery (8.5%). Nevertheless, the number of abstracts on each topic varied widely from year to year. CONCLUSION: Public Brazilian institutions are the principal sources of pulmonology research in Brazil. Such research activity is concentrated in the southeastern part of the country. Case reports account for one-third of this activity. Although there was great variability in the subjects addressed, diseases that are highly prevalent in Brazil, such as tuberculosis and other infections diseases, were the most common topics.