By definition, The Bethesda System (TBS) is a system which is used in Pap Smear in reporting cervical cytological abnormalities or cervical cancer. (Apgar BS.,et al.; 2003). For squamous epithelial lesion (SIL), it generally describe the precancerous changes of the cervical cells. Based on the American Family Physician Journal (2003),SIL is abnormal non-invasive cervical cells which include condyloma, dysplasia and CIN.
TBS was initially recommended in 1988 before subsequently reviewed based on proper management in reporting cervical cancer cases. Apgar BS. also stated that the 2001 Bethesda System is actually an evaluation of terminology as compared to the 1988 and 1991 Bethesda System. In evidence, she cited that the 2001 system introduced more uniform terminology for cytological report in which whether an individual specimen is sufficient to satisfy for an evaluation. This is necessary for the cytological laboratory to notify any possibility of invasion rather than validating a definite invasion or cancer. In comparison with the 1991 Bethesda System, the 2001 system specified mainly on the specimen adequacy, cytological categorization and interpretation of results. (Apgar BS.,et.al; 2003)
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As for High Squamous Intraepithelial Cell (HSIL), it refers to abnormal and immature cervical cells which are prescribed as precancerous (BD Worldwide, 2010). Even though invasive cancer is not likely to occur in HSIL, but the lesion itself has a significant outcome. In this case , if it is left untreated or not removed the lesion may progress to invasive cancer.
Atypical Squamous Cells-"cannot exclude HSIL" (ASC-H) is a new terminology introduced into 2001 Bethesda System. (Solomon D, Davey et al., 2002). As referred to Solomon D., positive value for HSIL in ASC-H is greater than those in ASC-US but not sufficient enough to conclude as HSIL even though it shows almost similar value to HSIL.
CHARACTERISTICS OF HSIL
In cytology, the cells usually have their own features that differentiate between low or high grade squamous intraepithelial lesions (SIL). Even though some borderline cases occur, the cytological morphology features usually can used for the classifying either Low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesions (HSIL). Morphology that favor a high-grade lesion includes higher nuclear/cytoplasmic ratios (N/C), irregularities in the outline of nuclear membrane, coarsening of chromatin and chromatin clumping.
According to Leung et al. (2008)in the journal entitled Characteristics of false-negative ThinPrep cervical smears in women with HSIL, the chromatin morphology in nucleus usually shows fine or also known as pale dyskaryosis, small, and evenly distributed. The general morphology for HSIL can see through its aggregation. The cells often occur in sheets or in syncytial-like aggregation. The size of the nucleus usually enlarged two times or more from the normal intermediate cell nuclei (Leung et al., 2008). The nucleus shapes tend to be round to oval. The chromasia or known as colour for HSIL nucleus is hyperchromasia (Leung et al., 2008). Hyperchromasia here defined as darker staining and the nucleus will stain dark blue in colour compared to intermediate cell in the same smear (Leung et al., 2008). The predictive value in diagnosis HSIL is based on the nuclear membrane. The nuclear membrane will shown thickening and no present of nucleoli.
In laboratory finding, HSIL is characterized by dysplastic cells with dense, round-oval cytoplasm and increased nuclear-cytoplasmic ratio. In general, the cytoplasmic characteristics of HSIL are those of metaplastic cells, except in keratinizing dysplasia in which the categorization is based upon nuclear/cytoplasmic ratio. Moreover in severe dysplasia HSIL, the cell size is small when is comparable to parabasal cells and the nuclear-cytoplasmic ratio is exaggerated with the nucleus enlargement occupying greater than half of the cytoplasmic diameter. Cell of an HSIL have a more immature types of cytoplasm which can either lacy and delicate or dense metaplastics with rounded cell border. In overall, cell size is smaller in HSIL as compared with LSIL. HSIL cells with larger amounts of dense cytoplasm are categorized as moderate dysplasia. (Rosemary E Zuna1 R. A., 2004)
Normally, tumour diathesis is absent in HSIL. Tumour diathesis usually associated with invasive carcinoma. Tumour diathesis will not present if the invasive squamous cell carcinoma less than 5mm. For liquid based (Thin-Prep and Sure-Prep), squamous cell carcinoma may have clinging diathesis contain of necrotic material at periphery of cell groups or reduced cellularity (Clark SB, 2002).
IMPLEMENTATION OF ASC-H IN THE BETHESDA SYSTEM 2001
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ASC-H is a new category that had been included in the Bethesda Classification 2001 under the epithelial cell abnormalities. From the several journals that we had read, Selvaggi et al reported 68% of high-grade dysplasia in follow-up cervical biopsies in cases with ASC-H. (SM., 2003). Ali et al reported 48% CIN-1 and 51% CIN 2-3 out of 257 cervical smears with ASC-H, of which 72 had follow-up biopsies (Ali et al., 2003). In another study Raab et al reported 26% of high-grade dysplasia detected in the follow-up biopsies of all the cervical smears with ASC-H (Raab et al., 2003). The variation in cytohisto correlation pattern reported by different studies may be due to many factors including interpret the cytomorphological features as ASC-H or HSIL in a particular lab. These studies further emphasize the challenges due to lack of well-defined cytomorphological criteria for ASC-H interpretation (Chivukula et al., 2006).
This suggests a need for well defined specific cytomorphological criteria to help categorize such cervical smears as ASC-H. Our purpose in this journal is to study the cytomorphology of all the smears interpreted as ASC-H and HSIL to get a better understanding of the various patterns associated with them (Chivukula et al., 2006).
The ASC-H category includes 2 cytological patterns. The first is atypical immature squamous metaplastic cells with a high N/C ratio and/or tissue fragments/disorganized groups of hyperchromatic cells. Most authors agree that ASC classified as ASC-H resembles metaplastic squamous cells with increased N/C ratios, mild irregular nuclear membrane, and mild hyperchromasia. In our study, the cells of ASC-H were more likely to present as isolated single cells and appear more achromatic in liquid-based preparations. It is difficult to distinguish the morphologic features of atypical squamous metaplasia from HSIL (Reda et al., 2006).
ALGORITHM FOR MANAGEMENT OF ASC-H AND HSIL
Further management of woman with positive HSIL or ASC-H is important to alert any possibility of invasion cancer (Annekathryn Goodman,2009). The smear with abnormal cell HSIL or ASC-H should be follow up with the best suggestion because untreated patient or the lesion itself has a great potency to develop into a cancerous stage. Therefore, an algorithm for both ASC-H and HSIL are used in every cytological laboratory as a reference and to guide the patient for further management.
Table 1 : The algorithm for ASC-H and HSIL management.
Based on the diagram (British Journal of Cancer, 2003), after the ASC-H and HSIL is classified based on their morphology of cells present on the smear, appropriate measure will be performed.
Women with positive ASC-H and HSIL will be follow-up with the colposcopy and biopsy for affirmative diagnosis in (PAP) test. (Vassilakos P, 2002). Positive value for HSIL is most likely to associate with (HPV) infection. The positive HSIL with or without HPV infection should be follow-up with colposcopy and biopsy. As for negative value for ASC-H and HSIL, individual is required to follow-up another PAP test within a year or as scheduled by physician. Colposcopy is crucial for adequate evaluation in diagnosing ASC-H and HSIL as treatment could not be done prior to biopsy.
Goodman (2009) defined colposcopy as a medical method that the doctor or clinician can observe the condition of cervix of patient in a clear view while the patient is lying horizontal position on an special examination table. The colposcopy is performed after the cell of patient is detected as abnormal on Pap smear.
According to Elsheikh TM (2006), The Bethesda System 2001 (TBS 2001) is developed with incremental change of terminology as compared to previous revised system. Consequently, it introduced more improvised method for reporting cervical cytology diagnosis in Pap Smear.
ASC-H terminology is introduced as to define abnormalities which is suggestive of HSIL but reluctantly to report as HSIL due to inadequate properties of HSIL itself. Even though the positive predictive value does not represent a clinical significant as HSIL, but it's highly recommended for cytology laboratory to report out in any case. This would assist the clinician and client to proceed with appropriate measurement in overcoming any progression to HSIL and eventually invasive carcinoma.
In conclusion, early cervical cytological detection and treatment for both ASC-H and HSIL are crucial to prevent future development of invasive cervical cancer. (Elsheikh TM, 2006). Therefore, we must orderly transformed knowledge attitudes and practices in cervical cancer screening and even Pap Smear test among nationwide women to prohibit greater increment of cervical cancer.
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