ICAM-1 expression on immune cells in chronic villitis.

INTRODUCTION: ICAM-1 expression on the villous syncytiotrophoblast (ST) is believed to participate in migration of maternal cells into the inflamed villi regardless of villitis etiology. However, its expression on immune cells in chronic villitis (CV) has yet to be analyzed. ICAM-1 induces cell-cell adhesion allowing intercellular communication, T cell-mediated defense mechanism, and inflammatory response. MATERIAL AND METHODS: 21 cases of CV (all without an identifiable etiologic agent) and 3 control placentas were analyzed using ICAM-1, and for immune cells CD45, CD3 and CD68. These cells were subdivided according to their location in inflamed villi: a) within the inflamed villi and b) outside forming perivillous aggregates. RESULTS: Large amounts of CD45, CD3 and CD68 were found within the inflamed villi and forming perivillous aggregates attached to areas of trophoblastic loss. Inflamed villi usually showed ICAM-1+ ST. The majority of immune cells surrounding areas of trophoblastic rupture presented marked expression of ICAM-1. In contrast, a small number of immune cells within the inflamed villi exhibited ICAM-1 expression. Only some (<5%) inflamed villi without trophoblastic rupture and with ICAM-1+ ST presented adherence of immune cells. DISCUSSION: In inflamed villi of chronic villitis, the level of ICAM-1 expression on immune cells depends on their location: high in number of cells in the perivillous region and low within the villi. The strongest expression of ICAM-1 on immune cells attached to areas of trophoblastic rupture suggests that the loss of trophoblast can lead to an amplification of the inflammatory response.

Carcinoma ex pleomorphic adenoma in a Brazilian population: clinico-pathological analysis of 38 cases.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare tumour, with different prevalence rates reported among studies. Epidemiological studies of large series of CXPAs in developing countries are scarce. The aim of the present study was to describe Brazilian patients with CXPA; this was a retrospective study of 38 patients. Demographic and clinico-pathological features were evaluated. No preferential gender was found, and the mean age at diagnosis was 57.6 years. The most commonly involved site was the parotid, followed by the submandibular and the minor salivary glands. A prevalence of clinical stages III and IV was observed at diagnosis. The most common histological subtypes were salivary duct carcinoma, adenocarcinoma not otherwise specified, myoepithelial carcinoma, and epithelial-myoepithelial carcinoma. Moreover, by invasive phase, most were frankly invasive carcinoma. Recurrence was observed in seven out of 24 patients with outcome information available, and all were invasive cases. All seven patients died of causes related to the disease. The distributions of cases according to age, gender, tumour location, and clinical stage were similar to those reported in the literature. Frankly invasive cases presented a worse prognosis. More information is needed to further our understanding of the clinico-pathological aspects of CXPA.

ICAM-1 is overexpressed by villous trophoblasts in placentitis.

Although an in vitro study has hypothesized that expression of ICAM-1 by villous trophoblasts could be important for the influx of maternal immune cells in villitis, it remains to be shown whether the same phenomenon occurs in human villitis. To investigate the expression of ICAM-1 by villous trophoblasts, its relationship with rupture of the trophoblastic barrier and influx of immune cells into the villi, we analysed 18 paraffin-embedded placentas with placentitis (5 by Toxoplasma gondii, 3 by Trypanosoma cruzi, 2 by Paracoccidioides brasiliensis and 8 of unknown aetiology - VUE) and 8 control placentas for detection of ICAM-1 by immunohistochemistry. All cases but one of placentitis showed trophoblast overexpression of ICAM-1 in the inflamed villi, located almost exclusively next to the areas of trophoblastic rupture. The villitis cases (caused by T. cruzi, T. gondii and VUE) presented leukocyte adherence in the areas of trophoblastic rupture. When the inflammatory reaction was situated in the intervillous space (placentitis by P. brasiliensis), in spite of the trophoblastic rupture and ICAM-1 overexpression there was no leukocyte influx into villi. None of the control placentas showed ICAM-1 expression by the trophoblast. We concluded that overexpression of ICAM-1 by villous trophoblasts occurs during placentitis characterized by accumulation of leukocytes in the villous or intervillous space and probably plays an important role in the rupture of the trophoblastic barrier. The influx of immune cells into the villi appears to be mediated by ICAM-1 but the location of the antigen within villous stroma is certainly a crucial factor for its occurrence.

Immunohistochemical characterization of the inflammatory infiltrate in placental Chagas' disease: a qualitative and quantitative analysis.

Chagas' disease, a systemic illness endemic to some regions of South America, is caused by the protozoan Trypanosoma cruzi. Transplacental infection may occur during any phase and cause fetal death. This study is the first to characterize the inflammatory cells in chagasic villitis by immunohistochemistry. Paraffin sections of 8 placentas with villitis by T. cruzi (4 live births and 4 stillbirths), as well as 8 control placentas without inflammation, were stained with hematoxylin and eosin, monoclonal antibodies for CD45RO, CD20, CD45RO/OPD4, CD8, HNKI, CD15, MAC387, and CD68 proteins, and a polyclonal antibody for S-100 protein. Quantification of positive cells was performed in 3 different high-power fields. In all cases of chagasic villitis, the inflammatory infiltrate was composed mainly of CD68+ macrophages, T lymphocytes, and a few natural killer cells. Among T cells, CD8+ cells outnumbered CD4+ cells in all placentas (CD4+:CD8+ ratios ranged from 0.04 to 0.38). B cells were absent or rare. In stillbirths, villitis was diffuse and severe with numerous T. cruzi, while in live births it was focal with few parasites. Other features that characterized villitis in stillbirths were 1) frequent trophoblastic necrosis, 2) presence of MAC387+ macrophages and CD15+ granulocytes attached to the sites of trophoblastic necrosis, 3) low CD4+: CD8+ ratios in most cases, 4) increased numbers of S-100 positive cells in the villous stroma. In conclusion, CD68+ macrophages and CD8+ T lymphocytes were the major cell population in villitis caused by T. cruzi. However, the pattern of inflammatory reaction differed between stillbirths and live births and was probably related to the number of parasites in the placental villi.

Quantitative analysis of modes of invasion and lymph node metastases in oral squamous cell carcinoma.

The mode of tumor invasion has been suggested to have a relationship to the occurrence of cervical metastasis and to prognosis in oral squamous cell carcinoma (OSCC). However, a tumor usually does not have a single mode of invasion, and the importance, if any, of the relative proportions of different modes for metastatic potential has not been studied. Forty two cases of OSCC resected with cervical lymph nodes were selected, 20 of which had nodal metastases and 22 which had not. The mode of invasion in the tumor-host interface was classified as: I - pushing borders, II - bands, III - thin cords, IV - single cells and analyzed in 20 consecutive medium power fields. Also studied were other morphological parameters: perineural and angiolymphatic invasion, tissue eosinophilia, mitosis and intensity of inflammatory infiltrate at the tumor-host interface. The majority of the cases (95.2%) showed two or more modes of invasion. Modes I, II and III occurred with similar frequency in cases with and without metastases. Mode II was the commonest and most extensive in both groups. No mode of invasion was significantly associated with metastases, independent of its extension. The other morphological parameters were neither significantly associated with cervical metastasis. In conclusion, OSCC usually shows two or more modes of tumor invasion if a large extension of tumor-host interface is analyzed. However, the relative proportions of the modes have no correlation with the metastatic potential.

[Kaposiform hemangioendothelioma associated with Kasabach-Merritt syndrome] / Hemangioendotelioma kaposiforme associado à síndrome de Kasabach-Merritt.

OBJECTIVE: To describe a case of kaposiform hemangioendothelioma, the only malignant tumor of vascular origin specific of childhood.METHODS: We report a case of a 40-days-old girl who presented with a giant hemangioma of the face. Rapid enlargement of the tumor lead to laryngeal compression with severe respiratory distress. She had also a consumptive thrombocytopenic coagulopathy (Kasabach-Merritt syndrome).RESULTS: She was admitted to the pediatric intensive care unit of the Hospital das Clínicas da Universidade Estadual de Campinas and mechanical ventilation was introduced. A ten day course of dexamethasone was only partially effective. We then started alpha-2a interferon at a dose of 1.8 million units/m(2)/day by subcutaneous route, but she died four days after the onset of this therapy. The microscopic features showed a kaposiform hemangioendothelioma.CONCLUSION: We discuss this unusual fatal evolution of a rapidly growing hemangioma and its hematological complications.

Mesotelioma maligno de pleura com associaçäo etiológica a asbesto: a propósito de três casos clínicos / Malign mesothelioma of pleura with etiological association to asbestos: apropos of 3 clinical cases

O mesotelioma maligno de pleura (MM) é tumor de ocorrência rara e nosso meio e tem-se mostrado, quando em elevada incidência, relacionado à exposiçäo pregressa a asbesto ou amianto nas séries descritas em outros países. OBJETIVO. A partir de casos clínicos atendidos no Hospital de Clínicas da UNICAMP, procurou-se evidenciar tal associaçäo epidemiológica, visando alertar profissionais médicos quanto à possível elevaçäo da incidência de tal tumor nesta década e, futuramente, por características próprias da história natural desse tipo de tumor. MÉTODOS. Säo descritos três casos de MM de pleura ocorridos na regiäo de Campinas, SP, num período de dois anos, dos pontos de vista clínico, laboratoriais complementares e anatomopatológico, incluindo minuciosa investigaçäo anamnésica ocupacional e ambiental. RESULTADOS. Todos os casos foram confirmados do ponto de vista anatomopatológico, incluindo microscopia eletrônica, como casos de MM. Os três casos mostraram relaçäo epidemiológica, comprovada por meio de história ocupacional, com exposiçäo a asbesto no passado. Um dos casos teve exposiçäo ocupacional pregressa de curta duraçäo (cerca de um ano); outro teve exposiçäo doméstica a partir de asbesto trazido do ambiente de trabalho por seu pai, durante sua infância, e o terceiro caso com contaminaçäo ocupacional indireta. CONCLUSÃO. A ocorrência de MM de pleura relacionada à exposiçäo a asbesto, no passado, parece ser realidade em nosso meio, como mostram estes três casos clínicos. Destaca-se a necessidade da anamnese ocupacional e ambiental detalhadas na abordagem desses casos, alertando-se para maior atençäo no diagnóstico dos tumores primários da pleura e do peritônio, nos próximos anos, em funçäo de provável aparecimento de novos casos relacionados a exposiçäo a asbesto pregressa, tendo em vista o intervalo de tempo entre o início da manipulaçäo do asbesto em nosso país e o aparecimento destes primeiros casos coincidir com o tempo de latência médio esperado para a ocorrência de MM. Destacam-se, ainda, as necessidades de definiçäo precisa de critérios diagnósticos, para esse tipo de tumor, e criaçäo de registro centralizado de casos.

[Malignant mesothelioma of the pleura with etiological association to asbestos: report of 3 clinical cases]. / Mesotelioma maligno de pleura com associação etiológica a asbesto: a propósito de três casos clínicos.

UNLABELLED: Diffuse Malign Mesotheliomas (DMM) has a low background prevalence. High incidences of this tumor have been related to asbestos exposure in the past. PURPOSE: To describe and discuss three clinical cases treated in our hospital, in which precise histopathologic diagnosis was made, and detailed occupational and environmental histories were taken, trying to identify in their past some kind of asbestos exposure. METHODS: Three cases of DMM are described. Diagnosis was confirmed by histochemical analysis and electronmicroscopy. Detailed occupational and environmental histories were taken from subjects and their families, searching for past contact with asbestos. RESULTS: The cases were diagnosed in a short period of time (two years), in a region of the country where many asbestos cement plants are located since the mid sixties. Skillful histological procedures were used. From these cases we found out that one had a twelve months period of exposure, 24 years before, in one of those plants. Another patient had an exposure for three years, as a bystander, in the same plant (also 24 years before) and a third patient was contaminated by asbestos brought home by his father in the 1950s (latency period of 30 years). All cases were histochemically studied and diagnosis confirmed by the presence of microvilli at electronmicroscopic examination. CONCLUSIONS: These three cases seem to confirm the existence of the epidemiologic association with asbestos exposure in our country. Definition of diagnosis criteria, centralization of cases registry and the necessity of more attention to this kind of asbestos related disease are discussed and stressed, as many new cases like those described are thought to occur in the near future, as the latency period of the disease seems to match with that of industrial asbestos manipulation in Brazil.

Eosinophilic angiocentric fibrosis of the nasal cavity.

Eosinophilic angiocentric fibrosis (EAF) is a rare condition of unknown etiology that causes stenosis of the upper respiratory tract. We report one case in which immunohistochemical studies were performed that involved the mucosa of the lateral nasal wall and septum of a 54-year-old woman. The lesion showed areas with vascular proliferation, small-vessel vasculitis, and dense inflammatory infiltrate consisting of T lymphocytes, macrophages, polyclonal plasma cells, and numerous eosinophils and neutrophils. Other areas were hypocellular and fibrotic, and in those, the collagen bundles showed perivascular onion-skin whorling. The clinical and histologic similarities between our case and those previously described, in addition to the immunohistochemical findings, support the hypothesis that eosinophilic angiocentric fibrosis is a chronic inflammatory condition with a peculiar and striking stromal response.

Nucleolar organizer region (NORs) in pseudocarcinomatous hyperplasia and squamous cell carcinoma of the oral mucosa.

Counts of nucleolar regions (NORs) demonstrated by a silver staining technique in paraffin sections, have been used to distinguish benign from malignant lesions. AgNORs were studied in 24 biopsies from oral cavity (5 cases of normal oral mucosa, 5 of pseudocarcinomatous hyperplasia and 14 of squamous cell carcinoma, subdivided according to degree of differentiation: 5 grade 1, 5 grade 2 and 4 grade 3) to find whether they were helpful in distinguishing pseudocarcinomatous hyperplasia due to chronic parasitic infections from squamous cell carcinoma. Two methods of counting AgNORs were used: (A) a simpler one which counts nucleolar clusters (AgNU) and satellite AgNORs and the other (B) counting all individual AgNORs, including those within AgNUs. In both methods the lowest mean values were observed for grade 3 carcinoma, while the highest belonged to grade 2 carcinoma. The simpler method (A) was the most useful because AgNU counts showed significant difference when pseudocarcinomatous hyperplasia was compared with grade 1 and 2 carcinomas, which are the most difficult to discriminate from it. However the overlapping of values render the technique of limited use in individual cases.

Hemorrhagic endovasculitis of the placenta. A clinical-pathological study in Brazil.

Hemorrhagic endovasculitis (HEV) of the placenta involves damage to or destruction of chorionic vessels and fetal erythrocytes. We evaluated the frequency and extension of the HEV and clinical events and morphologic changes associated with it in placentas from liveborn and stillborn infants. Two hundred sixty four placentas were examined: 214 from livebirths and 50 from stillbirths. The livebirths were subdivided according to the time of intrauterine retention (IUR). HEV occurred in 8.8% of placentas from livebirths and in 32% from stillbirths. In the livebirths the lesion affected small number of villi, was frequently associated with villitis (73.6% of the cases), but there was no significant association with maternal disease or birth weight. In the stillbirths, HEV was strongly associated with the time of IUR. In stillbirths with 1 day of IUR, HEV occurred in frequency similar to the livebirths (9.5%), but in stillbirths with 2-7 days of IUR the frequency was high (71.4%) and numerous vessels were involved. In those over 7 days the lesion was less extensive and frequent (20%) and it had the appearance of end stage of organization. We conclude that HEV, in livebirths and fresh stillbirths is frequently a small lesion of little significance, while in macerated stillbirths it is an artifact of maceration.

Nucleolar organizer regions (NORs)

Counts of nucleolar regions (NORs) demonstrated by a silver staining technique in paraffin sections, have been used to distinguish between benign and malignant lesions. AgNORs were studied in 24 biopsies from oral cavity (5 cases of normal oral mucosa, 5 of pseudocarcinomatous hyperplasia and 14 of squamous cell carcinoma, subdivided according to degree of differentiation: 5 grade 1, 5 grade 2 and 4 grade 3) to find whether they were helpful in distinguishing pseudocarcinomatous hyperplasia due to chronic parasitic infections from squamous cell carcinoma. Two methods of counting AgNORs were used: (A) a simpler one which counts nucleolar clusters (AgNU) and satellite AgNORs and the other (B) counting all individual AgNORs, including those within AgNUs. In both methods the lowest mean values were observed for grade 3 carcinoma, while the highest belonged to grade 2 carcinoma. The simpler method (A) was the most useful because AgNU counts showed significant difference when pseudocarcinomatous hyperplasia was compared with grade 1 and 2 carcinomas, which are the most difficult to discriminate from it. However the overlapping of values render the technique of limited use in individual cases.

[Nasal rhinosporidiosis in children]. / Rinosporidiose nasal na infância.

Rhinosporidiosis is a rare fungal disease resulting from infection by Rhinosporidium seeberi. There seems to be a relationship between the disease and agriculture, suggesting that Rhinosporidium lives in soil, and many authors agree that water is a necessary medium of transmission. The sites of infection are the nose (most common), eye, nasopharynx, penile urethra and external ear. Nasal cases generally present obstruction, epistaxis, watery or mucopurulent discharge, presence of tumoral pedunculated polypoid mass, generally with septal implantation. Histological examination presents characteristic sporangia in large numbers and in the submucosa a granulomatous host response. The treatment is by surgical excision (recurrence occurs in 10% of cases), and medical treatment used diaminodiphenylsulfone or Amphotericin B to avoid recurrent cases. We present a case of Rhinosporidiosis in a 10 years-old child, female, with 3 months history of nasal obstruction, epistaxis and presence of nasal mass in left nasal cavity that was submitted to surgical excision.

Granulocytic sarcoma of the larynx preceding chronic myeloid leukemia.

The authors report one case of granulocytic sarcoma infiltrating the larynx and cervical lymph nodes in a 50-year-old smoking patient. At the time of diagnosis there was no clinical and laboratory evidence of acute myeloid leukemia or chronic myeloproliferative disease. Four months after diagnosis, bone marrow morphology was consistent with chronic myeloid leukemia, accelerated phase. Cytogenetic abnormalities (Ph 1 chromosome, t(1; 12) (p36; p13), and trisomy of chromosome 20) were also found in hemopoetic cells. Granulocytic sarcoma preceding installation of chronic myeloid leukemia, as described here, seems to be a rare clinical event.

Placental involvement in paracoccidioidomycosis.

A case of juvenile-type paracoccidioidomycosis in a pregnant woman is reported. The disease pre-dated pregnancy and antifungal treatment was being administered when she became pregnant. A premature male infant was delivered with no evidence of infection. Microscopic examination of the placenta showed numerous Paracoccidioides brasiliensis yeast forms in the intervillous space, enmeshed in a macrophagic-phagocytic reaction, with damage of the trophoblastic layer. Placental transfer of specific P. brasiliensis antibodies was demonstrated.

Immunohistochemical study of the inflammatory infiltrate in villitis of unknown etiology. A qualitative and quantitative analysis.

Villitis is characterized by an inflammatory infiltrate within the substance of the chorionic villi. Quantitative and qualitative analyses of the mononuclear infiltrate in areas of villitis were performed in placentas with villitis of unknown etiology (VUE). We used a panel of monoclonal antibodies and immunoperoxidase technique in paraffin sections from 17 placentas with VUE and 8 without VUE. Macrophages followed by T lymphocytes were the predominant inflammatory cells in areas of villitis in virtually all cases. B lymphocytes were not observed and monocytes were present usually in small number in 58 per cent of the cases. Mononuclear cells which expressed HLA-DR antigens were found in 75 per cent of the cases. In areas of villitis with trophoblastic necrosis, we found monocytes and some T lymphocytes adhered to them. These cells apparently had migrated from the maternal circulation. We suggest that in areas of villitis with destruction of the trophoblast and its basal membrane the inflammatory infiltrate might have a mixture of fetal and maternal cells. The maternal monocytes and T lymphocytes might be attracted to these sites of trophoblastic necrosis and activated due to exposure to fetal MHC antigens of the villous stroma.

Immunological studies in placentas with villitis of unknown etiology: complement components and immunoglobulins in chorionic villi.

Villitis of unknown etiology (VUE) is a common placental lesion and complement-fixing immune complexes is one of the mechanisms proposed for its development. We examined 16 placentas with VUE and 16 without VUE by immunofluorescence in order to compare the distribution and amount of C1q, C3d, IgG and IgM in the chorionic villi between the two groups. We found both in cases with and without VUE a distribution of the complement components and immunoglobulins similar to that described in normal placentas. The amount of deposit was also not significantly different in the two groups. Only the inflamed villi showed an abnormal distribution of C1q which was present diffusely in the stroma of these villi.

Cord IgM levels in placentas with villitis of unknown etiology.

Villitis of unknown etiology (VUE) is the largest category of the placental villitides and its incidence varies in different countries. The possibility that a higher incidence of intrauterine infection could explain the high frequency of VUE in developing countries led us to determine the incidence of raised IgM levels (a non-specific monitor to intrauterine infections) in cord serum of placentas with VUE. Eighty-six placentas were studied. Of these 67 were from infants with adequate weight for their gestational age (AGA) and 19 from infants small for their gestational age (SGA). IgM level in the cord serum was measured on radial immunodiffusion plates. VUE was found in 36 placentas (41.8%) and it predominated in the SGA group. Raised IgM levels were found in only 13.8% of the placentas with VUE. In spite of our frequency of VUE being high, our incidence of raised IgM levels in placentas with VUE was low and similar to that reported by authors who have low incidence of VUE in their series. We conclude that determination of cord IgM did not help significantly in the investigation of the cause of the high frequency of VUE in our series.