Decoy cells in the urine cytology of a renal transplant recipient: an immunohistochemical study.

Human polyoma virus causes renal dysfunction and graft loss as a result of tubulo-interstial nephritis in renal transplant recipients after reactivation of latent virus in renal epithelium. The infected cells in the urinary sediments are characterized by large homogenous inclusions, which may cause diagnostic error in urine cytology. The epithelial cells with polyoma viral inclusions in urine cytology specimens are termed Decoy cells to caution pathologists not to misdiagnose these cells as cancer cells. We present a case of polyoma viral changes detected the first time in our laboratory in the urine of a 46year old male who underwent renal transplantation six months back and followed by immunotherapy. Urine cytological examination showed decoy cells and subsequently revealed on histopathology. Immunoperoxidase staining for SV-40 LT antigen (LT ag), expression of proliferating cell nuclear antigen (PCNA), p53 and Rb genes were also studied in the tissue sections for further observation. The expression of SV40 LT ag was negative, while PCNA showed strong positivity; p53 and Rb were expressed moderately in the nuclei of cells in the tubules. The report of a case of decoy cells in the urine of a patient with renal transplantation focuses the importance of cytologic analysis of urine as a diagnostic tool for screening renal transplant recipients at risk of polyoma viral infection.

Hereditary breast/ovarian cancer: clinicopathological characteristics and survival of BRCA2 positive and negative cases.

The clinical and pathological characteristics and prognostic outcome of patients with hereditary breast/ovarian cancer and BRCA2 mutations are poorly known. Hence, the present study aimed to correlate the BRCA2 mutation status with clinical characteristics and overall survival of 102 breast/ovarian cancer patients in Kerala, South India. All the coding regions of BRCA2 genes were PCR amplified and analyzed for mutations employing Conformation Sensitive Gel Electrophoresis and characterized by sequencing. The ORs with 95% Cls was computed to assess the association between BRCA2 gene mutation status and clinicopathologic characteristics of breast cancer patients. Survival curves were generated according to Kaplan-Meier method using Log Rank test and Cox proportional hazards regression method. Out of the 102 breast/ovarian cancer patients with known BRCA2 status, 19 were BRCA2 mutation positive. In survival analysis, BRCA2 gene mutation status (P = 0.02) and clinicopathologic parameters such as tumour size (p = 0.01), metastasis (P = 0.01), disease stage (P = 0.03) and laterality (P = 0.02) were significantly associated with poor prognosis of breast cancer patients. Patients with hereditary breast/ovarian cancer resulting from a BRCA2 mutation have been conclusively shown to have a worse survival prognosis compared to the non mutated group of patients.

Mucinous carcinoma of breast with abundant psammoma bodies in fine-needle aspiration cytology: a case report.

Fine-needle aspiration (FNA) cytology plays an important role in the diagnosis of various pathologic conditions in the breast. Microcalcification can be observed in benign and malignant breast lesions, but psammoma bodies (PBs) are rarely reported in breast lesions and are a feature of papillary neoplasms. However, we have observed PBs in large numbers in a mucinous carcinoma of breast, which is not previously reported in FNA of breast lesions. A 65-yr-old postmenopausal woman underwent FNA of a palpable mass. The aspirate revealed mucinous carcinoma cells associated with plenty of PBs. This case report of mucinous carcinoma of the breast with abundant PBs highlights the cytodiagnostic pattern of the lesion and formation of PBs.

Determination of zinc diethyldithiocarbamate released into artificial sweat from natural rubber latex vulcanizates by HPLC.

A simple high-performance liquid chromatography method is adopted in order to quantitate the amount of zinc diethyldithiocarbamate (ZDEC) released into artificial sweat from natural rubber latex vulcanizates. The artificial sweat is extracted with dichloromethane, and the residue is recovered and re-dissolved in a known quantity of dichloromethane. ZDEC is quantitated as its copper complex by reacting with copper(II) sulphate. A reversed-phase C18 column and detection wavelength of 435 nm are used to measure the copper-dithiocarbamate complex. The procedure is repeated with cobalt(II) chloride, and the amount of ZDEC obtained by both the methods is compared. It is found that the recovery of ZDEC from the artificial sweat is high when copper(II) sulphate is used, indicating that the copper(II) sulphate is a better complexing agent than cobalt(II) chloride under the conditions used in the present study. The limits of detection and the quantitation of ZDEC are found to be 0.25 and 0.86 microg/mL, respectively. The present method, based on precolumn derivatization using copper(II) sulphate, facilitates the quantitation of ZDEC in latex products.

Carcinoma of tongue and the buccal mucosa represent different biological subentities of the oral carcinoma.

PURPOSE: Clinico-epidemiological studies show that the behaviour of the tongue cancer is different from the cancer originating at other sites of the oral cavity. However, studies identifying the reason for such difference are lacking in the literature. METHODS: In the present study, we have attempted to see whether any difference existed in the cell cycle regulatory mechanism of these tumours by comparing immunohistochemically the expression of major cell cycle regulatory proteins in 147 buccal and 94 tongue carcinoma (anterior two-third of tongue) prospectively. RESULTS: On comparison of buccal and tongue carcinoma, expression of p16 and p21 showed significant difference. In combined analysis, simultaneous down regulation of p16 and p21 was seen in 47% of tongue cancer cases as against 28% in buccal carcinoma (P=0.004). In univariate analysis, none of the clinico-biological variables studied showed significant association with survival in tongue carcinoma, whereas, some of the clinico-biological variables associated with survival in buccal carcinoma. Among the biological markers, the overexpression of cyclin D1 (P=0.007) and p53, detected using both the clones of antibodies-DO7 (P=0.008) and PAb240 (P=0.014) and the down regulation of p16 (0.033), showed significant association with shorter disease free survival (DFS) in these cases. Whereas in the case of overall survival (OS), overexpression of p53 [DO7 (P=0.031) and PAb240 (P=0.017)] and cyclin D1 (P=0.001) associated with poor survival. In multivariate analysis, the expression pattern of p53 and p16 protein influences the DFS whereas cyclin D1 expression showed independent association with the OS in buccal carcinoma. CONCLUSIONS: Thus, tongue and buccal cancers represent different biological subentities, and such differences should be considered in oral cancer management.

Significance of silver-stained nucleolar organizer regions in early diagnosis and prognosis of oral squamous cell carcinoma: a multivariate analysis.

Argyrophilic nucleolar organizer regions (AgNORs) appear to be of diagnostic and prognostic significance in different types of human tumour. The present study examined the AgNOR counts in normal, premalignant and malignant oral mucosa to evaluate their potential as a biological marker for tumour progression and a prognostic predictor for treatment outcome in oral carcinomas. The Spearmann's rank correlation analysis between AgNOR counts and various stages of tumour progression in oral mucosa exhibited a highly significant positive coefficient (r(s) = 0.7969; p < or = 0.001), thus indicating the role of AgNORs in the early diagnosis of potentially malignant oral leukoplakia. When analyzing the prognostic significance of AgNOR in oral carcinomas, mean count > 2.8 concurred with poor prognosis in both univariate and multivariate analysis. Along with AgNOR counts, the T-status of disease was also found to be an independent predictor for treatment outcome in multivariate analysis. Thus T3 and T4 tumours, with mean AgNOR counts more than 2.8, are aggressive and may exhibit resistance to current treatment protocols.

Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma.

The two well-defined pathways that are shown to be prominently altered in a variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb genes. The present study is undertaken to find the pathway that is more altered in oral carcinoma at protein level, with special emphasis on its prognostic significance. The expression pattern of key molecules of the Rb and p53 pathways, such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique. The expression index of these molecules and various clinicopathological factors were statistically correlated with treatment end points to assess its prognostic efficacy after following up these patients up to a maximum of 48 months with a median of 23 months. Rb pathway proteins, Rb (P=0.016), cyclin D1 (P=0.0001) and p16 (P=0.012) showed significant association with disease-free survival, and p16 (P=0.041) and cyclin D1 (P=<0.0001) with the overall survival. Among p53 pathway proteins studied, only p53 expression index showed association with both disease-free survival and overall survival. Multivariate analyses confirmed that the biological variables, cyclin D1 and p16 and the clinical variable, 'stage of disease' were independent predictors of disease-free survival and overall survival. Subgrouping of the patients on the basis of p16 and cyclin D1 expression revealed that the subgroup having downregulation of p16 and overexpression of cyclin D1 exhibited the worst disease-free survival and overall survival compared to the other subgroups. The present data showed that disabling of the Rb and p53 pathways were frequent events in oral carcinoma. The study also demonstrated that the Rb pathway proteins are comparatively more important than p53 pathway proteins for the prognostication of oral carcinoma patients. The combined evaluation of p16 and cyclin D1 in oral carcinoma could identify a group of patients with the worst survival who might therefore need alternate or more intense treatment strategies.

Primary sarcoma of the breast.

BACKGROUND AND OBJECTIVES: Primary sarcoma occurring in breast is rare and comprises 0.5-1% of all breast neoplasm. Majority of the series include both stromal and cystosarcoma phyllodes, only a few hundred cases of sarcomas other then cystosarcoma are reported. PATIENTS AND METHODS: We carried out a retrospective analysis of 19 patients with primary sarcoma of the breast treated between 1982 and 2002. RESULTS: Mean age of the patients was 38.6 years (12-70 years). Gradually progressive swelling was the commonest presenting feature. There were eight cases of angiosarcoma, four cases of spindle cell sarcoma, two each of pleomorphic sarcoma and stromal sarcoma, and one each of malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, and sarcoma (NOS). Eight of these were high-grade (42%). Eight patients underwent either radical or modified mastectomy, three underwent wide excisions, and one underwent quadrantectomy. Ten (52.6%) patients received postoperative adjuvant radiation. Two patients received chemotherapy. After a mean follow-up time of 34.5 months (median 25 months), eight patients failed. Failure was local in five, opposite breast in one, and both local and distant in two. The disease free survival at 3-year was 39%. In univariate analysis only the margin of first surgery was found to be a significant predictor of survival (P = 0.05). CONCLUSIONS: Primary sarcomas of the breast are aggressive tumors. Surgical treatment should consist of at least simple mastectomy. All attempts should be made to achieve a negative margin as this appears to be the only factor influencing survival in these patients.

Squamous cell carcinoma in untreated psoriasis: a case report.

Skin cancer developing after treatment for psoriasis is seen more often than expected, however, there has been no report of cutaneous squamous cell carcinoma developing in a case of untreated psoriasis. Here, a case has been reported where an untreated psoriasis lesion progressed on to develop squamous cell carcinoma, with a brief review of literature.

p53, p16 and cyclin D1: molecular determinants of radiotherapy treatment response in oral carcinoma.

Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far. Our study analyses a set of proteins that previously demonstrated radio response influence for their possible prognostic value in decision-making process between the respective fractionation schemes. Expression patterns of regulatory proteins such as p53, cyclin D1, p16, Cdk4, p21, Rb, bcl-2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose. Among these 125 patients, 90 (72%) received altered fractionation, whereas 35 (28%) received conventional fractionation. p53 over-expression correlated with local treatment failure among the patients treated with conventional fractionation whereas cyclin D1 over-expression and p16 underexpression were associated with local treatment failure as well as overall survival in altered fractionation treated cases. Our findings suggest that wild-type p53 status may be an important parameter for achieving high local control in those patients undergoing conventional fractionation, where as intact p16 and cyclin D1 status may be beneficial for effective local control in patients who are treated with altered fractionation. Furthermore, it can be assumed that conventional fractionation employs p53-mediated apoptosis, whereas altered fractionation activates the functional G1 cell-cycle checkpoint for tumor growth suppression.

Placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is an uncommon form of gestational trophoblastic disease (GTD) with variable spectrum of clinical behavior. PSTT can occur after a normal pregnancy, spontaneous abortion, termination of pregnancy, ectopic pregnancy or molar pregnancy. Surgery is the primary treatment. Chemotherapy has an established role in loco-regionally advanced and metastatic disease. Many studies indicate that mitotic index is an important prognostic indicator. This article reviews the literature on this rare disease.

Tuberculosis and metastatic carcinoma coexistence in axillary lymph node: A case report.

BACKGROUND: Coexistence of cancer and tuberculosis in axillary lymph nodes is rare. Only seven cases have been reported in the literature. CASE REPORT: We report here a case of infiltrating ductal carcinoma breast metastasizing to the axillary lymph node along with tubercular granuloma in the same lymph node without primary mammary or pulmonary tuberculosis. CONCLUSION: Primary tuberculosis coexisting with carcinoma is of rare occurrence. A possibility should always be borne in mind especially in patients from endemic areas.

Pleomorphic adenoma of minor salivary gland in the parapharyngeal space.

BACKGROUND: Majority of tumours occurring in minor salivary gland are malignant. Pleomorphic adenoma is of rare occurrence in parapharangeal space. CASE PRESENTATION: A rare case of a minor salivary gland pleomorphic adenoma of the parapharyngeal space is reported. Review of literature, clinical features, pathology, radiological findings and treatment of these tumours are discussed. CONCLUSIONS: Parapharangeal salivary tumours presents as a painless progressive swelling with majority of these being malignant. Pleomorphic adenoma in parapharangeal space is of rare occurrence. Complete surgical excision is the treatment of choice.

Epstein-Barr virus-associated gastric carcinoma in southern India: A comparison with a large-scale Japanese series.

Epidemiological and clinicopathological features of Epstein-Barr virus (EBV) associated gastric carcinoma was compared in India and Japan, two countries differing markedly in gastric cancer incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and 2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases (5%), all males, in the Indian series were EBER-positive. This frequency was similar to that in the Japanese series (6.2%). As was the case with Japanese series, the EBV-associated gastric carcinoma in the Indian series was observed most frequently in the middle part of the stomach (1 in antrum, 4 in middle part, 2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's classification (8 cases) was more common than the intestinal type (2 cases). Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were type D. In either series, there was no significant difference in the frequency of tumors with p53 overexpression between EBER-positive and -negative cases. However, the proportion of cells with p53 overexpression in EBER-negative tumors was significantly higher than that in EBER-positive tumors regardless of histological type in both series. In conclusion, the frequency and major clinicopathological features of EBV-associated gastric carcinoma in south India were similar to those observed in Japanese series although gastric cancer incidence in these two countries differs markedly.