Expressão imuno-histoquímica de metaloproteinase de matriz-9 (MMP-9) e de inibidor tecidual de metaloproteinase-1 (TIMP-1) em neoplasias de glândulas salivares

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

CD10 (Neutral Endopeptidase) expression in myoepithelial cells of salivary neoplasms

CD10 is a cell surface peptidase expressed in a wide variety of normal and neoplastic tissues, including breast myoepithelial cells. In salivary glands, expression of CD10 has only been used to identify neoplastic myoepithelial cells of pleomorphic adenomas and myoepithelial carcinomas. However, its accuracy in other salivary tumors with myoepithelial component has yet to be analyzed. We examined 72 salivary tumors with myoepithelial differentiation using immunohistochemical technique to detect CD10. In salivary glands, CD10 expression was not detected in myoepithelial cells. Only fibrocytes within the intralobular stroma were CD10 positive. In neoplastic myoepithelial cells, CD10 expression was found in 25.71% of benign and 32.43% of malignant neoplasms. When the different groups of tumors were compared, epithelial-myoepithelial carcinomas (EMEC) showed a stark contrast with the others (83.3% of cases with CD10 expression). Surprisingly, adenoid cystic carcinomas and basal cell adenomas were negative in 100% of the cases. Myoepitheliomas, pleomorphic adenomas, and myoepithelial carcinomas were positive in 27.7%, 30.0%, and 40% of the cases, respectively. In conclusion, salivary neoplastic myoepithelial cells gain CD10 expression in relation to their normal counterparts. However, the gain of this protein is not a sensitive marker for detecting myoepithelial cells in the majority of the tumors, except for EMEC. The high expression of CD10 by this carcinoma can be a valuable tool to separate EMEC from the tubular variant of adenoid cystic carcinomas in small incisional biopsies, where the precise diagnosis may be impossible.

Extensive extranodal metastases of basal-like breast cancer with predominant myoepithelial spindle cell differentiation

A differentiation towards myoepithelial cells has been demonstrated in several types of lesions in the breast. These include multifocal myoepitheliomatosis, the rare mixed tumor or pleomorphic adenoma, adenoid cystic carcinoma, adenomyoepithelioma and myoepithelial carcinoma (malignant myoepithelioma). Myoepithelial carcinoma is the only lesion purely composed of myoepithelial cells. All these tumors are benign and/or of low-grade malignancy, with the exception of malignant myoepithelioma. In contrast to the statement of the current World Health Organization (WHO), recent studies have reported that regional and distant metastases may occur in about 50% of pure myoepithelial carcinomas. The presented case of a breast carcinoma with dominant myoepithelial/spindle cell differentiation in a 58-year-old woman is an excellent example to document the highly aggressive biological behavior of this tumor phenotype. Despite an extensive chemotherapy and radiotherapy, the tumor was rapidly progressive, forming a finally exulcerating local tumor relapse and widespread metastases to the myocardium, lungs, liver, kidneys and skin. Similarities in morphology and biological behavior compared to patients with "triple-negative" (hormone receptor and Her2) monophasic sarcomatoid carcinomas and pure spindle cell sarcomas are discussed.

Análise da imunoexpressão de OCT4 e CD44 em neoplasias de glândulas salivares menores e maiores

Salivary gland neoplasms exhibit a wide variety of biological behavior and a high morphological diversity raises the interest in researching these lesions. The stem cells are the main source for the generation and maintenance of cell diversity, disorders in the regulation of these cells can lead to the production of altered stem cells, termed cancer stem cells capable of generate the tumor. Researches on cancer stem cells and associated proteins have been developed in some oral cancers; however, their role in salivary gland neoplasms is not well established. Thus, the aim of this study was to identify the tumor parenchyma cells exhibiting stem cell characteristics, by evaluating the immunoreactivity of OCT4 and CD44, in a number of cases of salivary gland neoplasms. The sample consisted of 20 pleomorphic adenomas, 20 mucoepidermoid carcinomas and 20 adenoid cystic carcinoma located in minor and major salivary glands. The expression of OCT4 and CD44 was evaluated by the percentage of positive cells (PP) and the intensity of expression (IE), it is realized the sum of the scores, resulting in the total score immunostaining (PIT) ranging 0-7. All studied cases showed positive expression of OCT4 and CD44 and higher values than the control groups. It was observed that for OCT4 luminal cells and non-luminal were immunostained in the case of pleomorphic adenomas and adenoid cystic carcinoma. Already the immunoreactivity of CD44 was particularly evident in the non-luminal cells of these lesions. In mucoepidermoid carcinomas for both markers, there was immunoreactivity in squamous and intermediate cells and absence of staining mucous cells. For both markers, a statistically significant higher immunostaining was verified in neoplasms located in the major salivary glands compared with lesions in the minor salivary (p<0.001). At the total sample and in the group of minor salivary glands, malignant neoplasms exhibited higher immunoreactivity for OCT4 than pleomorphic adenoma. However, there was no statistically significant difference between the lesions and between their classifications histomorphologic. Analyzing the correlation between OCT4 and CD44 immunoexpressions, a statistically significant moderate positive correlation (r = 0.444) was observed. The high expression of OCT4 and CD44 may indicate that these proteins play an important role in identifying cancer stem cells, allowing a prediction of biological behavior of salivary gland neoplasms.

DOG1 for the Diagnosis of Gastrointestinal Stromal Tumor (GIST): Comparison Between 2 Different Antibodies

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Discovered on GIST-1 (DOG1) is a recently described protein expressed in GISTs irrespective of mutation status. The aim of this study was to investigate the immunohistochemical expression of DOG1 using 2 different monoclonal antibodies (DOG1.1 and the commercially available K9 antibody) in 668 GIST cases and to compare the results with the expression of KIT. DOG1 and KIT expression also were studied in most human normal tissues and several nonmesenchymal and mesenchymal tumors other than GIST. KIT was expressed in 643 (96.3%) GISTs. DOG1.1 and K9 were positive in 538 (80.5%) and 642 (96.1%) GIST cases, respectively. In 25 (3.7%) KIT-negative GIST cases, DOG1 was expressed in 5 (20.0%) and 19 (76.0%) using DOG1.1 and K9 antibodies, respectively. Only 0.9% of GISTs were negative for KIT, DOG1.1, and K9. Most normal human tissues did not reveal KIT and DOG1 expression. DOG1.1 was positive in only 2 of 57 synovial sarcomas and 1 of 61 soft tissue leiomyosarcomas. K9 was positive in 5 of 57 synovial sarcomas, 1 of 14 angiosarcomas, 1 of 61 soft tissue leiomyosarcomas, 3 of 4 adenoid cystic carcinomas of the head and neck, and in myoepithelial cells of 9 of 11. broadenomas of the breast. In conclusion, the commercially available K9 is of great utility for the diagnosis of most KIT-negative GISTs, and the combination of both KIT and K9 antibody in a panel of immunohistochemistry can define the diagnosis of GIST in more than 99% of cases.

Estudo imuno-histoquímico da co-expressão de citoqueratinas, vimentina e actina em neoplasias de glândula salivar

Human salivary gland tumors originated from intercalated ducts present a broad range of histologic and cytologic patterns, mainly due to the presence of myoepithelial cells. The aim of this study is to verify the differentiation grade of neoplastic cells and a possible relation between myoepithelial cell differentiation and the presence of luminal secretory contents. The expression of vimentin and cytokeratin (CK) intermediate filaments, actin myofilament and epithelial membrane antigen (EMA) was investigated by double labeling immunocytochemical technique, in thirty salivary gland neoplasms: 5 pleomorphic adenomas, 5 myoepitheliomas, 3 basal cell adenomas, 7 adenoid cystic carcinomas (ACC) and 10 polimorphous low grade adenocarcinomas (PLGA). Tumors with intercalated duct differentiation (pleomorphic adenomas, basal cell adenomas and ACC) express CKs 7, 8, 18 and 19 in the luminal cells and coexpress eventually CK14 with these CKs. Some luminal cells stained with anti-EMA antibody, mainly where a secretory content in the lumen was observed. Outer ductal cells and other myoepithelial-like cells express vimentin, sometimes coexpressing actin and/or CK14 with vimentin. Plasmacytoid cells in myoepitheliomas and pleomorphic adenomas express vimentin and rarely CKs 7, 8, 18 and 19, sometimes coexpressing these CKs with CK14 but they are negative for the remaining antigens. Tumors without intercalated duct differentiation (solid basal cell adenoma and PLGA) express vimentin and CKs 7, 8, 14 and 18, sometimes coexpressing CKs 8 and 18 with CK14. In conclusion, in tumors with intercalated duct differentiation, myoepithelial cells express vimentin and sometimes coexpress actin and/or CK14 with vimentin, never coexpressing other CKs with vimentin. CK14 and actin are independently expressed by myoepithelial cells, so their expression is probably induced by different stimulus. However, the secretory function of luminal cells, visualized by EMA staining, ....

Multicystic nephroma in an elderly man. Case report

Multicystic nephroma is a relatively rare tumor of the kidney presenting unclear histological origin. Abdominal mass is a common onset sign in children while abdominal flank pain or abdominal discomfort, hematuria and recurrent urinary tract infections usually affect adults. Preoperative diagnosis is impossible especially in the adult variant of the tumor where clear cells carcinoma with cystic degeneration must always be suspected. We herein report a case of a 77 year old man complaining of flank abdominal pain and recurrent episodes of urinary tract infection due to a right-sided multicystic nephroma successfully treated with nephrectomy.

Carcinoma ex pleomorphic adenoma in a minor salivary gland: report of a case

BACKGROUND: Carcinoma ex pleomorphic adenoma is exceedingly rare in minor salivary glands of the oral cavity. We present a case of carcinoma ex pleomorphic adenoma (CEPA) of the buccal mucosa in a 47-year-old Turkish patient. The buccal mass was of a size of 1.5 cm located in the left cheek. Pleomorphic adenoma was the tentative diagnosis. METHODS: The tumor was removed under local anesthesia. Histopathologic evaluation revealed a preexisting pleomorphic adenoma associated with adenoid tumor component with tubulo-cystic and papillary or pseudopapillary structures; CEPA was diagnosed. Capsular integrity was incomplete with infiltration by islands of metaplastic/dysplastic epithelium. RESULTS: Secondary surgery of the site was performed. No tumor tissue could be detected in the resection specimen. The patient is free of recurrence since 9 months.

Um caso de variante folicular do carcinoma papilar da tiróide num teratoma quístico maduro numa mulher jovem

Malignant transformation of a teratoma occurs in 1-2% of cases, with carcinoma of the thyroid being extremely rare. It is usually diagnosed in the postoperative histopathological exam. We describe a case of thyroid carcinoma in a mature cystic teratoma.

Thyroid carcinoma with papillary and squamous features: report of a case with histogenetic considerations.

We present a case of an 82-year-old female with a painless left latero-cervical swelling, which increased in size over the course of 6 months, compressing adjacent organs. The histopathological examination, following dissection of the left thyroid lobe and ipsilateral cervical lymph nodes, yielded two intermingled morphologically distinct histotypes that included conventional papillary thyroid carcinoma (PTC) and poorly differentiated squamous cell carcinoma (SCC) with cystic features. The clinical presentation, the immunophenotype, and the genotype, especially of the malignant squamous component with partial expression of TTF1, marked expression of p63 and mutation of BRAF, were consistent with the diagnosis of a papillary thyroid carcinoma with squamous component. The possibility of a squamous cell carcinoma of unknown origin metastasizing to a primary papillary thyroid carcinoma cannot be completely ruled out. This particular presentation of thyroid carcinoma carries a poor prognosis in 20% of cases, with high recurrence rates and distant metastasis.

Supervivencia cáncer específica posterior a nefrectomía radical frente a nefrectomía parcial en carcinoma renal t2: revisión sistemática

Introducción: El tratamiento estándar para los tumores renales localizados es la nefrectomía radical, sin embargo debido a la variación el tamaño del tumor renal en el momento del diagnóstico, se ha reemplazado en algunos casos por la nefrectomía parcial. Objetivo: Este estudio busca comparar el resultado oncológico de la nefrectomía parcial en términos de supervivencia cáncer específica, respecto a la nefrectomía radical, en pacientes mayores de 50 años con carcinoma renal estadio II (T2N0M0) Métodos: Se realizó una revisión sistemática de la literatura, con inclusión de estudios de casos y controles, cohortes y experimentos clínicos aleatorizados incluidos en las bases de datos de MEDLINE , EMBASE y CENTRAL Resultados: La búsqueda inicial emitió un total de 101 resultados, 11 artículos fueron preseleccionados y sólo un artículo cumplió con los criterios de selección; éste se clasificó como nivel de evidencia II. Conclusión: No fue posible concluir su equivalencia oncológica de la nefrectomía radical con la nefrectomía parcial, dado que no hay diseños de estudios que permitan llegar a esta conclusión.

Immunohistochemical study of the expression of fatty acid synthase and Ki-67 in salivary gland tumors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Basal expression of the cystic fibrosis transmembrane conductance regulator gene is dependent on protein kinase A activity.

The cystic fibrosis transmembrane conductance regulator (CFTR) functions as a Cl- channel that becomes activated after phosphorylation by cAMP-dependent protein kinase (PKA). We demonstrate that PKA also plays a crucial role in maintaining basal expression of the CFTR gene in the human colon carcinoma cell line T84. Inhibition of PKA activity by expression of a dominant-negative regulatory subunit or treatment with the PKA-selective inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89) caused a complete suppression of CFTR gene expression without affecting other constitutively active genes. Basal expression of a 2.2-kb region of the CFTR promoter linked to a luciferase reporter gene (CFTR-luc) exhibited the same dependence on PKA. The ability of cAMP to induce CFTR over basal levels is cell-type specific. In T84 cells, both the endogenous CFTR gene and CFTR-luc exhibited only a modest inducibility (approximately 2-fold), whereas in the human choriocarcinoma cell line JEG-3, CFTR-luc could be induced at least 4-fold. A variant cAMP-response element is present at position -48 to -41 in the CFTR promoter, and mutation of this sequence blocks basal expression. We conclude that cAMP, acting through PKA, is an essential regulator of basal CFTR gene expression and may mediate an induction of CFTR in responsive cell types.

Congenital cystic adenomatoid malformation of the lung: indications and timing of surgery

We review a single surgeon and surgical centre's experience with congenital cystic adenomatoid malformation of the lung (CCAML) in relation to clinical spectrum, operative experience, and postoperative course. A retrospective hospital record review was done on surgically treated cases of CCAML over a 10-year period, focusing on number with antenatal diagnosis, spectrum of postnatal presentation, type of surgery performed, and outcome. Forty-seven patients from birth to 14 years of age underwent surgery for CCAML. Antenatal diagnosis (ante) was made in 30 cases. Of these, 10 became symptomatic before surgery. Six of the 17 postnatally-diagnosed (pnd) cases were an asymptomatic incidental finding. Overall, 16 were symptomatic in the 1st year of life, and five were symptomatic beyond 1 year of age. Symptoms varied from respiratory distress (seven ante, six pnd) to chronic cough (three, and recurrent chest infection (three ante, two pnd). All preoperative diagnoses were confirmed with chest CT. Most patients (25) were operated on before 3 months of age. Eleven were operated on in the first 2 weeks of life as emergency surgery for respiratory distress. The most common lobe involved was the right upper lobe (16), and lobectomy was performed in 42 cases, segmentectomy in four, and pneumonectomy in one. Seventeen cases were extubated immediately postoperatively; 29 required postoperative ventilation overnight, and nine needed more prolonged ventilation. Early postoperative complications included pneumothorax (two), pleural effusion (one), and chylous effusion (one). Late complications included recurrence in three cases (all segmentectomy), who then subsequently underwent lobectomy. There was one death from respiratory failure. Because there is an increasing trend in the detection of asymptomatic antenatally-diagnosed CCAML, consideration of early surgical excision to prevent complications is suggested by our series. CT scanning is mandatory for postnatal evaluation because chest x-ray could be normal. Safe elective excision after 3 months is supported by our low morbidity and less need for postoperative ventilation. Lobectomy is the procedure of choice to prevent recurrence.

Pancreatic large mucinous cystoadenoma with invasive ductal carcinoma in pregnancy. Case report

Background. Cystic tumour of the pancreas are infrequent and malignancy of the pancreas during pregnancy is extremely rare. Mucinous cystoadenomas is the most frequent cystic pancreatic neoplasm and it is seen mainly in women suggesting a sex hormone influence. Its presentation during pregnancy is extremely rare and entails difficulties in diagnosis and therapy. Case report. A 28 year old woman was referred to our service for abdominal mass. She had given birth to her second child two weeks previously. Ultrasound and CT scan showed a large cystic lesion, with sepitation and inner solid growth portions, involved mainly the left sovramesocolic space. An ultrasound-guided aspiration of the cystic fluid showed high level of CEA and CA. 19-9. The patient underwent laparotomic body-tail pancreatectomy and splenectomy. The histological examination showed mucinous cystoadenoma with associated invasive ductal carcinoma, with ovarian-like stroma and a well delimited fibrous capsule. Hystochemical study revealed a strong positivity for progesterone receptors. Conclusions. To our knowledge this is the eighth case of mucinous cystoadenoma reported in English literature and the forth with an invasive adenocarcinoma associated. This pathological entity should always be kept in mind in case of patient with an hepigastric mass during or soon after pregnancy. Aggressive approach is mandatory.