Dulhan Ajit

Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India

OBJECTIVEnNaked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugols iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India.nnnMETHODSnCytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae.nnnRESULTSnThe sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%.nnnCONCLUSIONnAs a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI.

Accuracy of concurrent visual and cytology screening in detecting cervical cancer precursors in rural India

The high burden of cervical cancer and inadequate/suboptimal cytology screening in developing countries led to the evaluation of visual screening tests, like visual inspection with acetic acid (VIA) and Lugols iodine (VILI). We describe the performance of VIA, VILI and cytology, carried out in a multinational project called “Screening Technologies to Advance Rapid Testing” in 5,519 women aged 30–49 years, in detecting cervical intraepithelial neoplasia (CIN). VIA, VILI and cytology were positive in 16.9%, 15.6% and 6.1% women, respectively. We found 57 cases of CIN2, 55 of CIN3 and 12 of cervical cancer; 90% of CIN3 and 43% CIN2 cases were positive for p16 overexpression and high‐risk HPV infection, indicating a high validity of histological diagnosis. The sensitivity of VIA, VILI and cytology to detect high‐grade CIN were 64.5%, 64.5% and 67.7%, respectively; specificities were 84.2%, 85.5% and 95.4%. A high proportion of p16 positive CIN 3 (93.8%) and 2 (76.9%) were positive on cytology compared with visual tests (68.8% and 53.8%, respectively) indicating a higher sensitivity of cytology to detect p16 positive high‐grade CIN. However, the immediate availability of the results from the visual tests permits diagnosis and/or treatment to be performed in the same sitting, which can potentially reduce loss to follow‐up when women must be recalled following positive cytology. Organizing visual screening services in low‐resource countries may facilitate the gradual building of an infrastructure committed to screening allowing the eventual introduction of more sensitive, highly objective, reproducible and affordable human papillomavirus screening tests in future.

Utility of the thromboplastin-plasma cell-block technique for fine-needle aspiration and serous effusions

(I) To assess the feasibility of thromboplastin‐plasma (TP) method for cell block, (II) to concentrate the minimal cellular material from effusions and needle‐rinses by block preparation and improve visual details, (III) to compare conventional cytological smears with cell blocks for final assessment, and (IV) to assess utility of immunocytochemistry (ICC) for diagnostic accuracy.

Cytology of Ileal Conduit Urine in Bladder Cancer Patients

OBJECTIVE To study the cytomorphology of urine obtained from the ileal conduit and to determine its utility and identify the pitfalls. STUDY DESIGN Urine specimens from 469 cases of suspected or proven bladder cancer received over a period of 5 years were analyzed in the cytology laboratory. In 35 cases, total bladder resection was followed by ileal conduit reconstruction. The follow-up cytologic analysis of these 35 ileal conduit cases formed the basis of this study. RESULTS There was absence of urothelial cells in all but 2 cases. The smear predominantly showed small, scattered intestinal mucosal cells with pyknotic nuclei, extensive karyorrhexis and numerous bacteria. In 2 cases, cytology proved superior to endoscopy and radiology in detecting recurrent disease. We had 2 false negative cases, and the negativity was attributed to sampling errors. There was 1 false positive case in which 3-dimensional clusters of intestinal columnar cells were erroneously diagnosed as adenocarcinoma. CONCLUSION Urine obtained from ileal conduit specimens shows a smear picture that is different from that of specimens from the bladder. Thus, it is imperative to understand the difference between the cytomorphology of bladder urine and ileal conduit urine, to minimize the pitfalls and increase diagnostic utility.

Signet-ring cells--a caveat in the diagnosis of a diffuse peritoneal mesothelioma occurring in a lady presenting with recurrent ascites: an unusual case report.

A diffuse peritoneal mesothelioma is a rare tumor. Exfoliative cytology forms the first step in the diagnosis of mesothelioma, since most of these cases presented with effusion. Despite well established cytomorphological features, a challenge exists in differentiating mesothelial cells, including reactive and malignant types from carcinoma cells and macrophages. Presence of “signet‐ring” cells increases the diagnostic challenge as these can be forms of benign and malignant cells. Ancillary techniques like immunohistochemical (IHC) markers and ultrastructural analysis form useful adjunct in substantiating exact diagnosis. We report an unusual case study of a diffuse peritoneal mesothelioma in a 57‐years‐old lady, with no history of asbestos exposure, presenting with recurrent ascites, diagnosed on ascitic fluid cytology and on histology as an adenocarcinoma, based upon the presence of “signet‐ring” cells. On review, clinicopathological correlation with IHC was helpful in forming correct diagnosis. Diagn. Cytopathol. 2010.

Has Urine Cytology a Role to Play in the Era of Fluorescence in Situ Hybridization

OBJECTIVEnTo determine the efficacy of urine cytology as a diagnostic tool and in follow-up of patients with urinary bladder cancer.nnnSTUDY DESIGNnFrom 951 cases, 1,831 urine specimens were collected in a 5-year period (2000-2004). Six hundred fifty-two cases were suspected to have primary bladder cancer and formed the basis of the study. The final diagnosis was based on histology. When histology was not available, clinical or radiologic findings formed the basis for the final diagnosis.nnnRESULTSnWe had 173 false negative and 6 false positive cases in our series, giving an overall sensitivity of 82% and specificity of 96%. The main reason for false negativity was screening error, noticed in low grade urothelial carcinoma. False positivity was due to inflammatory atypia and polyomaviral cytopathic changes.nnnCONCLUSIONnThe sensitivity and specificity in our study compared well with those in the world literature. Urine cytology can be successfully used as a primary diagnostic tool and also as a follow-up modality as the cystoscopically occult malignancy can be detected easily.

Identification of Atypical Glandular Cells in Pap Smears: Is It a Hit and Miss Scenario?

Objective: Glandular cell abnormality (GCA) in Pap smears is uncommon. Detection is important as the possibility of underlying high-grade lesions is greater in this entity than in atypical squamous cells of undetermined significance. This study was undertaken with an aim to correlate GCA cases with histology, scrutinize its mimics and identify cytologic features to segregate significant lesions from benign. Study Design: A total of 22,618 conventional Pap smears were retrospectively analyzed. In all, 74 GCA cases were identified, correlated with histology and reevaluated using parameters based on architectural pattern, cellular features and background. Results: This study revealed 15 false positives. On review, 11 cases [1 adenocarcinoma, 5 atypical glandular cells (AGC), not otherwise specified, 5 AGC, favor neoplasia (FN)] were recategorized as reactive. Of 9 cases reported as cervical intraepithelial neoplasia on histology, cytodiagnosis in 5 was revised from AGC-FN to high-grade squamous intraepithelial lesion involving glands. Initial overall cytohistology concordance was 79.7%. Reevaluation of the smears, based on stringent cytomorphological criteria, enhanced overall agreement to 94.59%. Conclusions: A diagnosis of AGC has considerable clinical implications. Dissociated atypical cells, nuclear membrane, architecture and chromatin pattern are the key distinguishing features between neoplastic and benign lesions.

Case Report of Renal Cell Carcinoma Diagnosed in Voided Urine Confirmed by CD10 Immunocytochemistry

Background: Preoperative diagnosis of renal cell carcinoma (RCC) by exfoliative urine cytology is difficult, as infiltration of RCC into the pelvicalyceal system is uncommon. The exfoliation of RCC cells in urine is a rare phenomenon and when it does occur, it is likely to be missed. Cytologic examination of the urine coupled with ancillary immunocytochemistry can clinch the diagnosis leading to appropriate clinical management. Case: A 50-year-old man presented with complaints of hematuria and abdominal pain of 6 months’ duration. Ultrasonographic examination of the abdomen and pelvis showed a well-defined mass lesion in the upper pole of the left kidney, suggestive of neoplastic etiology. In the given clinical context of renal mass, urine cytology was suggestive of RCC and biopsy confirmation was suggested. One cytology smear subjected to immunocytochemistry with anti-CD10 antibody which showed strong diffuse cytoplasmic positivity in these cells confirmed the diagnosis of RCC. Subsequently, fine needle aspiration cytology of the kidney mass was reported as RCC. Conclusions: RCC has distinct cytologic features that facilitate a diagnosis in urine in an appropriate clinical and radiological context. Their recognition in the urine smear is important to avoid costly and invasive modalities like image-guided needle biopsy.

Pulmonary non-Hodgkin's lymphoma (NHL) of diffuse large B-cell type with simultaneous humeral involvement in a young lady: an uncommon presentation with cytologic implications.

A bronchogenic carcinoma, almost invariably, presents as a lung mass. Primary pulmonary lymphomas are rare. We report an unusual case of a pulmonary non‐Hodgkins lymphoma (NHL) with simultaneous involvement of the right humerus in a 37 year old lady. Bronchial lavage smears showed atypical cells with irregular nuclear membranes raising a suspicion of a hematolymphoid tumor, over a small cell carcinoma that was the closest differential diagnosis. Biopsy from the lung mass and from the lesion in the humerus showed an identical malignant round cell tumor with prominent apoptosis. On immunohistochemistry (IHC), tumor cells were diffusely positive for leukocyte common antigen (LCA), CD20 and MIB1 (70%), while negative for cytokeratin (CK), epithelial membrane antigen (EMA) synaptophysin, chromogranin, neuron specific enolase (NSE), CD3, and CD10. Diagnosis of a pulmonary NHL of diffuse large B‐cell type with involvement of the humerus was formed.

Cytodiagnostic Problems in Cervicovaginal Smears from Symptomatic Breast Cancer Patients on Tamoxifen Therapy

OBJECTIVEnTo evaluate the effect of tamoxifen on cervicovaginal epithelium, identify tamoxifen-related changes that mimic cancer and detennine the morphologic features differentiating the 2 changes.nnnSTUDY DESIGNnCervicovaginal smears from 153 conventionally treated primary breast cancer patients presenting with gynecologic symptoms were studied.nnnRESULTSnAll 153 patients presented with menorrhagia or irregular periods. Of 4 patients with a cytodiagnosis of atypical glandular changes, 2 had negative histology; 1 each had a uterine leiomyoma and endometrial hyperplasia. Of the 6 cases reported as adenocarcinoma, 3 were histologically confirmed, and the others were false positives. Conversely, 1 false negative case histologically was an endometrioid carcinoma.nnnCONCLUSIONnOur study revealed that reactive glandular cells are a cause of false positive diagnoses. Tamoxifen-associated cellular changes can mimic morphologic features of cancer. To avoid diagnostic errors, cervicovaginal smears should be repeated after discontinuing tamoxifen treatment. Clinical correlation is mandatory. Regular follow-up with cervicovaginal smears from patients on tamoxifen treatment is recommended.