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Biomedical subjects

A M Borges

Publications and source records attributed to A M Borges.

At least 19 recordsLinked to original sources

Papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma: treatment outcome and prognosis.

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is one of the extremely rare variants of papillary thyroid carcinoma. To date, the majority of reported cases have been published in the surgical pathology and cytopathology literature, addressing the diagnostic difficulties posed by the condition's extensive, reactive stromal proliferation. Because of the rarity of PTC-NFS among papillary thyroid carcinoma variants, it has been unexplored from a clinical viewpoint. A MEDLINE search on the clinical course, role of radioiodine, treatment outcome and long term follow up of this disease yielded no result.We report the clinicoradiologic and histopathologic profile, together with post-treatment long term follow up, in a 35-year-old woman harbouring this rare entity. To the best of our knowledge, this is the first report of a five-year follow up of this rare variant of PTC following total thyroidectomy and radioiodine treatment. Our follow-up findings reiterate the disease's favourable clinical course when managed in the same manner as a classical, differentiated papillary carcinoma of the thyroid, akin to that predicted by the pathologists, and emphasize the importance of differentiating PTC-NFS as a separate entity from the papillary carcinoma variants with aggressive histology. Given the rarity of this condition, the experience gained from the present case is a useful addition to the current knowledge on disease prognostication and management.A systematic review of the existing literature on PTC-NFS, including the case reported in the present paper, is also carried out, aiming to explore the patient characteristics and clinical behaviour pattern of this rare entity and to make appropriate recommendations on management strategy. The age of presentation ranges from 20 to 82 years, with a mean of 44.5 years. Female preponderance was observed, with a female to male ratio of 3ratio1. No racial predilection was observed. Tumour size varied from 2 to 9 cm along its greatest diameter (mean = 4.3 cm). Metastasis to lymph nodes at presentation occurred in 25 per cent of cases. Metastasis to surrounding structures (e.g. parathyroid and skeletal muscle) was observed in 12.5 per cent. There have been no reports of pulmonary or skeletal metastasis at presentation.

Adult↗

Genital lesions associated with visceral leishmaniasis and shedding of Leishmania sp. in the semen of naturally infected dogs.

Although visceral leishmaniasis is primarily transmitted by a biological invertebrate vector, transmission in the absence of the vector has been reported, including venereal transmission in humans. Considering the possibility of venereal transmission, we studied genital lesions in dogs naturally infected with visceral leishmaniasis and shedding of Leishmania sp. in the semen. Approximately 200 dogs were serologically tested for anti-Leishmania antibodies and divided into three groups: 1) serologically negative dogs (n = 20), 2) asymptomatic serologically positive dogs (n = 20), and 3) symptomatic serologically positive dogs (n = 20). Samples from both testes, all segments of both epididymes, prostate gland, glans penis, and prepuce were histologically evaluated and processed for immunodetection of Leishmania sp. Semen samples were obtained from 22 symptomatic serologically positive dogs and processed for detecting Leishmania DNA by polymerase chain reaction. A significantly higher frequency of inflammation was observed in the epididymes, glans penis, and prepuce of dogs with visceral leishmaniasis, which was associated with a high frequency of immunohistochemically positive tissues (up to 95% of tissues from symptomatic dogs were positive by immunohistochemistry). Leishmania DNA was detected in eight of 22 semen samples from symptomatic dogs. Together these findings indicate that genital lesions and shedding of Leishmania sp. (donovani complex) in the semen are associated with visceral leishmaniasis. Additional studies should address the possibility of venereal transmission of the disease in the dog.

Animals↗

Apoptosis index is a predictor of metastatic phenotype in patients with early stage squamous carcinoma of the tongue: a hypothesis to support this paradoxical association.

BACKGROUND: Patients with squamous carcinoma of the oral tongue in clinical stages TIN0M0 and T2N0M0 with a tumor thickness < or = 3 mm usually do not have lymph node (LN) metastasis. However, factors that are useful in predicting LN metastasis in thicker tumors (> 3 mm thick) need to be identified. The authors investigated the clinical relevance of the apoptotic index (AI), the proliferation index, and tumor grade in relation to LN metastasis in patients with early stage squamous carcinoma of the oral tongue. METHODS: Twenty-three patients with squamous carcinoma of the anterior two-thirds of the tongue measuring < 2 cm in height and > 3 mm in thickness were evaluated for tumor grade, AI (by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique), and proliferation index (by proliferating cell nuclear antigen [PCNA] expression). RESULTS: The mean AI value was significantly higher in LN positive patients compared with LN negative patients (P = 0.012). The LN positive and LN negative subgroups did not differ in the mean PCNA index, and there was no significant difference in the distributions of tumor grade between LN positive and LN negative subsets. Four of 12 tumors with an AI < or = 5% and 10 of 11 tumors with an AI > 5% had LN metastasis (P = 0.009; risk ratio, 20). The AI maintained its significance with respect to LN metastasis in the multivariate analysis (P = 0.003). The 4-year recurrence free survival was significantly better in patients with tumors that had an AI value < or = 5% compared with patients with tumors that had an AI > 5% (92% vs. 32%) (P = 0.033). However, the AI lost its impact on recurrence free survival within a Cox proportional hazards model (P = 0.068). CONCLUSIONS: A higher AI value is a predictor of LN metastasis and may serve as a prognostic factor in patients with early stage squamous carcinoma of the oral tongue. The authors present a hypothesis to explain this rather surprising finding.

Apoptosis↗

Angiogenesis is redundant for tumour growth in lymph node metastases.

AIMS: Angiogenesis is essential for the growth of solid tumours. As the role of angiogenesis is unclear in the pathogenesis of primary lymph node (LN) tumours, we wondered whether neoangiogenesis was important in supporting and promoting the growth of tumours in LNs. METHODS AND RESULTS: We investigated 16 cases of squamous carcinoma involving oral cavity (n=9) and larynx/pyriform fossa (n=7), all of whom had lymph node metastases. Sections of the primary tumour, uninvolved mucosa, metastatic LN and nonmetastatic LN were double-immunostained with factor VIII-related antigen and MIB-1. Proliferating blood vessels, i.e. neoangiogenesis, was identified by coexpression of factor VIII-related antigen-stained blood vessels and MIB-1 staining of the endothelial cell nuclei. Counts were performed in an area of 4 mm2. Primary tumours (127-188.7), uninvolved mucosa (54-84.5) and metastatic LNs (123.5-167) had significantly lower vessel counts than nonmetastatic LNs (194-253.9) (P=0.003; P < 0.001; P < 0.001, respectively). With regard to neoangiogenesis, primary tumours (1.7-5) had significantly higher counts than uninvolved mucosa (0-0.4), nonmetastatic LNs (0-0.4) and metastatic LNs (0.9-2.4) (P < 0.001; P < 0.001; P=0.047, respectively). CONCLUSIONS: Our data suggest that because of the rich native vascularity of lymph nodes, neoangiogenesis is redundant for the growth of metastatic tumour.

Blood Vessels↗

Hodgkin's disease involving Waldeyer's ring: a study of four cases.

We report four cases of Hodgkin's disease who presented with involvement of Waldeyer's ring. Their clinical, morphological and immunohistochemical features are discussed. The patients were immuno-competent, were between 17 and 65 years of age and presented with symptoms related to swelling in the nasopharynx or oropharynx and cervical lymphadenopathy. The nasopharyngeal biopsy and the cervical lymph node in all four cases showed features of classical Hodgkin's disease. The Reed Sternberg cells expressed CD15 and CD30, and in three cases, CD20 and Epstein-Barr virus--latent membrane protein -1 (EBV-LMP-1). Extranodal involvement by Hodgkin's disease which is not in continuity with nodal disease is rare in immunocompetent patients. Morphologically, such extranodal lesions, especially in locations like the oropharynx and nasopharynx, should be differentiated from EBV-associated lymphoproliferations.

Adolescent↗

Primary extranodal mucosa associated lymphoid tissue (MALT) lymphoma of the prostate.

Low-grade B-cell mucosa associated lymphoid tissue (MALT) lymphoma can rarely present primarily in extranodal sites other than stomach, which is the most common site for it. Until now only four cases of primary prostatic MALTomas have been described in the literature and we report the fifth. We describe a case of primary prostatic MALToma in a 67-year-old man and the diagnosis was made on the trans-urethral resection specimen of the prostate. As the disease was limited to prostate (stage IEA), the patient was treated with external beam radiation therapy to a total dose of 4400cGy in 22 fractions. The patient achieved completed remission and has remained free of disease in the following 36 months.

Disease-Free Survival↗

Intermediate histological effect markers for breast cancer.

The evidence that ductal carcinoma of the breast (DCIS) is an obligate precursor of invasive breast cancer and thus qualifies as an intermediate effect marker in chemoprevention research is reviewed. Much of the evidence on the natural history of DCIS has been derived from the era before the introduction of mammographic screening. Thus it may not be applicable in the present situation when women are likely to be under mammographic surveillance in chemoprevention trials. Further, the data that are becoming available from breast screening trials suggest that at least over follow-up periods now exceeding a decade, detection and treatment of DCIS has no impact on subsequent incidence of breast cancer. Although there are some indications that other biomarkers of malignancy are expressed similarly in DCIS and invasive cancer of similar grade, this evidence may not be sufficient to allow exclusive reliance on DCIS as an intermediate-effect marker in chemoprevention research.

Biomarkers, Tumor↗

Cytokeratin expression in human fetal tongue and buccal mucosa.

Expression of cytokeratins (CK), a subset of intermediate filament (IF) proteins in epithelia, is developmentally regulated. CK expression may also change after malignant transformation. Our earlier studies on CK expression in human oral tumours and pre-cancerous lesions have shown specific changes in CK expression. We analysed CK expression in human tongue and buccal mucosa (BM) in fetuses in the embryonic age group of 16 to 27 weeks using biochemical and immunohistochemical techniques to find out whether there is any similarity in CK expression in human oral squamous cell carcinomas (SCC) and fetal oral tissues. CK 1, 8 and 18 were detected in a majority of samples using both techniques. Our earlier studies had shown aberrant expression of CK 1 and 18 in many of the oral SCC and leukoplakias. Studies by immunohistochemistry showed that these different CK antigens were expressed in different cell layers. CK 1(2) were present in the stratified epithelial layers whereas CK 8 and 18 were restricted to glandular epithelium. Till 27 weeks of gestation, both tongue and BM expressed CK 1, 8 and 18 along with CK 6 and 16. Thus, fetal tissues showed some similarities in CK pattern with their respective SCC.

Electrophoresis, Gel, Two-Dimensional↗

Scrape cell-block technique for fine needle aspiration cytology smears.

An inconclusive diagnosis on fine needle aspiration cytology (FNAC) may be due to poor spreading and presence of thick tissue fragments despite aspiration of adequate material. Repeat aspiration may not be possible especially when aspirates of deep seated organs have been obtained by image guided techniques. We have resorted to a 'scrape cell-block' (SCB) technique in such cases. In this technique the cellular material on the slides which had already been fixed and stained, was carefully removed by scraping following destaining and then processed as a cell block. SCB interpretation was then compared with the smear diagnosis and histological diagnosis, wherever available. A total of 27 cases were studied. In 12 cases SCB slides added information to the FNAC smears. In 14 cases SCB did not offer any additional information. SCB was inconclusive in one case. Final histological correlation was available in eight cases and the SCB diagnosis was confirmed in six cases, whereas in two cases SCB failed to identify the tumour. Immunocytochemistry (ICC) was done in one case. SCB is a useful technique to make the best use of the available material when reaspiration is difficult.

Adenocarcinoma↗

Long-term carcinogenicity of pan masala in Swiss mice.

Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the long-term animal bio-assay 6- to 7-week old male and female S/RVCri mice were divided randomly into intermediate and lifetime exposure groups and fed normal diet without pan masala-(zero dose) or diet containing 2.5% and 5% pan masala. Animals in the intermediate-exposure group (n = 10/gender/dose group) were killed after 6, 12 or 18 months of treatment, while those in the lifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopathological observations of tissues from control animals did not reveal any neoplastic alterations. However, lifetime feeding of pan masala induced adenoma of the liver, stomach, prostate and sebaceous glands, also forestomach papilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forestomach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neoplastic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lung (n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 animals in the lifetime-exposure group. Statistical analysis of tumor-induction data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major target tissue for the carcinogenic action of pan masala.

Animals↗

MALT lymphoma of nasal mucosa treated with antibiotics.

Mucosa associated lymphoid tissue (MALT) lymphomas occur in sites other than the gastrointestinal tract and in the early stages respond to treatment with antibiotics. We report a rare case of nasal mucosal MALT lymphoma which responded to treatment with antibiotics and has since then remained in remission.

Adult↗

p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India.

The inactivation of p53 tumour suppressor gene vis-á-vis point mutation, overexpression and degradation due to Human Papilloma virus (HPV) 16/18 infection, was examined in chewing tobacco-associated oral cancers and oral leukoplakias from India. The analysis of mutations was assessed by polymerase chain reaction (PCR) with single strand conformation polymorphism (PCR-SSCP) of exons 5-9 on DNA from 83 oral cancer cases, and the mutations confirmed by direct nucleotide sequencing of the PCR products. p53 protein expression was evaluated by immunohistochemical analysis on paraffin-embedded sections of 62 representative oral cancer biopsies and 22 leukoplakias, using p53-specific monoclonal antibody DO-7. The presence of HPV16/18 was detected in the 83 oral cancer cases by PCR analysis using HPV L1 consensus sequences, followed by Southern hybridization with type-specific oligonucleotide probes. Forty-six per cent (38/83) of oral cancer tumours showed p53 alterations, with 17% (14/83) showing point mutations, 37% (23/62) with overexpression and 25% (21/83) with presence of HPV16 wherein the E6 HPV16 protein degrades p53. HPV18 was not detected in any of the samples. Ninety-two per cent concordance was observed between missense point mutations and overexpression of p53 protein. A significant correlation was not observed between p53 alterations in oral cancer and clinico-pathological profile of the patients. Twenty-seven per cent (6/22) of oral leukoplakias showed p53 overexpression. The overall p53 alterations in oral cancer tissues and oral lesions are comparable to data from the oral cancers reported in the Western countries with smoking and alcohol-associated oral cancers, and suggest a critical role for p53 gene in a significant proportion of oral cancers from India. The overexpression of p53 protein in leukoplakias may serve as a valuable biomarker for identifying individuals at high risk of transformation to malignant phenotype.

Adult↗

Evaluation of carcinogenic/co-carcinogenic activity of a common chewing product, pan masala, in mouse skin, stomach and esophagus.

Pan masala, a dry powdered mixture of areca nut, catechu, lime, unspecified spices and flavoring agents, has gained widespread popularity as a chewing substitute in India. In this study, the carcinogenic and tumor-promoting potential of an ethanolic pan masala extract (EPME) was determined using skin of S/RVCri-ba mice and forestomach and esophagus of ICRC mice as the target tissues. Carcinogenic activity of pan masala was tested by painting the mouse skin for 40 weeks with EPME or by gavage feeding for 6 months. Following initiation with 9,10-dimethylbenz(a)anthracene (DMBA), carcinogenesis of mouse skin was promoted with different doses of EPME, while gastric- and esophageal-tumor-promoting activity was determined by administering EPME by gavage to animals initiated with diethylnitrosamine (DEN). The ability of EPME to effect progression of skin papilloma to carcinoma and cutaneous alterations after a single or multiple EPME treatment were also evaluated. EPME at 25 mg per dose promoted skin-papilloma formation between 30 and 40 weeks of treatment and enhanced the rate of conversion of papilloma to carcinoma. Induction of mild epidermal hyperplasia, dermal edema, increase in epidermal mitotic activity and the rate of epidermal and dermal DNA synthesis by EPME correlated well with its skin-tumor-promoting potential. In ICRC mice, EPME was inactive as a complete carcinogen, but effectively promoted the development of forestomach and esophageal papilloma and carcinoma in a concentration-dependent manner. The tumor incidence at 25 mg EPME per dose was comparable with that obtained in the 12-O-tetradecanoylphorbol-13 acetate(TPA)-treated group. The findings indicate that habitual pan-masala use may exert carcinogenic and co-carcinogenic influence.

9,10-Dimethyl-1,2-benzanthracene↗

Teratocarcinosarcoma of the paranasal sinuses: a clinicopathologic and immunohistochemical study.

We report four cases of sinonasal teratocarcinosarcoma (SNTCS), a rare malignant tumor that displays combined features of an immature or malignant teratoma and a carcinosarcoma. The patients, three men and one woman, were all adults ranging in age from 21 to 69 years who presented with nasal obstruction and epistaxis. The tumors were typically composed of round cells and short spindle cells with neuroectodermal/rosette-like structures. Also seen were foci of fetal-like squamous epithelium, glandular epithelium, immature mesenchyme, immature cartilage, and neuronal differentiation. Immunohistochemistry performed in three cases showed expression of vimentin, CD99 (MIC2), and neuron-specific enolase in most cells, and focal expression of cytokeratin, epithelial membrane antigen, alpha fetoprotein, glial fibrillary acidic protein, chromogranin, and synaptophysin. The tumors were consistently negative for beta human chorionic gonadotrophin, neurofilament protein, and leukocyte common antigen. The entities considered in the differential diagnosis were poorly differentiated carcinomas, sarcomas, and olfactory neuroblastoma. We suggest that these neoplasms arise from a primitive cell capable of organized divergent differentiation.

12E7 Antigen↗