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The development of the Papanicolaou smear test by Dr. George Nicholas Papanicolaou (1883-1962) is one of the most significant achievements in screening for disease and cancer prevention in history. The Papanicolaou smear has been used for screening of cervical cancer since the 1950s. The test is technically straightforward and practical and based on a simple scientific observation: malignant cells have an aberrant nuclear morphology that can be distinguished from benign cells. Here, we review the scientific understanding that has been achieved and continues to be made on the causes and consequences of abnormal nuclear morphology, the basis of Dr. Papanicolaou's invention. The deformed nuclear shape is caused by the loss of lamina and nuclear envelope structural proteins. The consequences of a nuclear envelope defect include chromosomal numerical instability, altered chromatin organization and gene expression, and increased cell mobility because of a malleable nuclear envelope. HPV (Human Papilloma Virus) infection is recognized as the key etiology in the development of cervical cancer. Persistent HPV infection causes disruption of the nuclear lamina, which presents as a change in nuclear morphology detectable by a Papanicolaou smear. Thus, the causes and consequences of nuclear deformation are now linked to the mechanisms of viral carcinogenesis, and are still undergoing active investigation to reveal the details. Recently a statue was installed in front of the Papanicolaou's Cancer Research Building to honor the inventor. Remarkably, the invention nearly 60 years ago by Dr. Papanicolaou still exerts clinical impacts and inspires scientific inquiries.

The discovery of occult invasive and intra-epithelial tubal carcinomas in BRCA1 mutation carriers undergoing prophylactic surgery has implicated the fallopian tube epithelium as the source of serous cancer. However, little is known of the early molecular events of serous oncogenesis, or why cancers in BRCA1 mutation carriers are found preferentially in tissues which are responsive to reproductive hormones. We hypothesize that molecular alterations present in morphologically normal tubal epithelium from BRCA1 heterozygotes reflect the earliest events in serous carcinogenesis and may be markers of increased cancer risk as well as targets for risk reduction. Genetic profiling of microdissected tubal epithelium from histologically normal BRCA1 mutation carriers and controls was performed. We sought to define a signature which differentiated BRCA1 mutant tubal epithelium from women with low risk of developing ovarian cancer. Molecular differences between the follicular and luteal phases were prominent and, by using filtering techniques and a two-way ANOVA without a False Discovery Rate correction, we identified 440 probe sets with a more than two-fold change in gene expression related to BRCA1 mutation status. Using gene ontology and known associations to cancer pathways, we selected five genes for further analysis by qPCR and immunohistochemistry, and were able to demonstrate statistically significant differentiation of BRCA1 and control cases in an independent set of cases. The altered expression profiles in histologically normal tubal epithelium from BRCA1 heterozygotes suggest that these cells may respond differently to microenvironmental stresses. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The pathologist forms a very important part of the clinical team in the management of pediatric intra-abdominal masses in giving a rapid, accurate diagnosis for these potentially curable tumors. Fine-needle aspiration cytology (FNAC) is an invaluable tool in this regard when interpreted with clinicoradiologic parameters. With this in mind, we decided to evaluate the role of FNAC in pediatric abdominal masses in our institution. A total of 83 of 105 FNAC accessioned in the pathology department over 5 years (2003-2007) were studied. These included only cases where a diagnosis could be offered on cytology. Detailed clinicoradiological features were obtained from hospital records. Cytomorphological features examined included cellularity, architectural pattern, background, key cellular details. Immunocytochemistry were done where necessary. Lesions diagnosed on FNAC included Wilms' tumor (19), lymphoma (10), neuroblastoma (6), hepatoblastoma (5), PNET (5), rhabdomyosarcoma (2), DSRCT (2), germ cell tumor (6), and miscellaneous tumors (7). Definite diagnosis could be offered on cytomorphology in 74.7% (62) cases, while in 25.3% (21) cases only a diagnosis of round cell tumor could be offered. Concordance with final histopathology and biochemical parameters was subsequently obtained in 79/83 (95.5%) of cases. A clinically relevant classification is possible on FNAC in pediatric abdominal tumors when interpreted with clinicoradiologic parameters. This obviates the need for a more time-consuming biopsy procedure in critical situations and in stage II nephroblastoma where it is contraindicated.