CERVICAL CYTOLOGY REPORTING

Abnormal Findings

The term” dyskaryosis” meaning’ abnormal nucleus’ is used to describe cells with nuclear abnormalities and maturity of cytoplasm and is still used in UK. The term” dysplasia” is also used to describe the same, mainly in USA. Both these terms can be used interchangeably.

Dysplastic (Dyskoryotic) Cells

Dysplastic (dyskaryotic) cells show slight to moderate nuclear abnormalities (enlargement and hyperchro- masia) in well differentiated squamous or glandular
lesions. More advanced lesions show nuclear enlarge- ment, hyperchromasia, along with high N:C ratio, coarse chromatin and thickened nuclear membrane.

Dysplastic squamous cells are of 3 types:

1. Intermediate dysplastic cells seen in LGSIL.

2. Parabasal dysplastic cells resemble closely parabasal or metaplastic cells in size and shape but have atypical nuclei. Cells lie singly or in clusters or strings or files. These cells are seen in HGSIL or cancer.
3. Small parabasal and basal dysplastic cells. These cells indicate more aggressive lesion. Cells lie scattered loose or in loose clusters or in syncitia.

Dysplastic Endocervical Cells

Dysplastic endocervical cells are uncommon and difficult to recognize. They may be seen in HGSIL or early adenocarcinoma, and are seen as columnar cells with enlarged hyperchromatic or pale nuclei and large nucleoli.

Koilocytes

Koilocytes are mature squamous cells of intermediate type with abnormal enlarged hyperchromatic nuclei that are smudged, homogenous, and are surrounded

by sharply demarcated perinuclear halo. Sometimes binucleation/multinucleation may be seen. Koilocytes are characteristic of HPV infection and are seen with
both low-risk and high-risk types of HPV infection and form the criteria for the diagnosis of LGSIL.

Leukoplakia

White discoloration or abnormal keratinization of cervical surface is called leukoplakia. This is because of keratinization of superficial cells which are seen as anucleate, olygonal, transparent cells with pink or yellow cytoplasm. Brown cytoplasmic granules may be present and ghost nuclei are seen.

Parakeratosis/Pseudoparakeratosis

Also presents as white patch clinically. Small nucleated squmaous cells present in sheets. Cause is not known. But such cells can be seen in HPV infection, low grade and high-grade squamous lesions.

CERVICAL CYTOLOGY REPORTING

Terminologies/Classifications Papanicolaou, the founder of contemporary diagnostic cytology, proposed a classification in 1943 (Table 16.1), but it did not reflect current understanding of cervical neoplasia, classes had no equivalents in histopathologic terminology, and did not reliably communicate clinically relevant information. Over the years, different systems and terminologies evolved to overcome the deficiencies of the previous ones. WHO and CIN classifications had the drawbacks of lack of reproduci- bility in assigning lesions to different categories and the biological behavior of the lesions did not correspond with the cytological categories. Terminology for reporting cervicovaginal smears was further standar- dized by The Bethesda System (TBS) in 1988. Since the goal of any screening program is to detect the precursor lesions and treat them early in order to halt their progress to frank cancer, it is of utmost importance for the clinicians and the pathologists to be familiar with the terminology, morphology and management protocols of the precancerous lesions.

Table 16.1: Evolution of reporting system precancerous
lesions of cervix

Papanicolaou!s classification

Class I: Absence of atypical or abnormal cells

Class II: Atypical cytology but no evidence of malignancy

Class III: Cytology suggestive of but not conclusive for malignancy

Class IV: Cytology strongly suggestive of malignancy

Class V: Cytology conclusive for malignancy

WHO classification proposed by Reagen and Patten in 1962:

Mild dysplasia
Moderate dysplasia
Severe dysplasia
Carcinoma in situ
CIN classification: Proposed by Richart in 1967 to further
improve upon the concept of disease continuum.

CINI
CIN II
CINIII
The Bethesda system: Standardized in 1988, revised twice there
after current system developed in 2001

CYTOLOGY- NORMAL PAP SMEAR

Normal Pap Smear

In child bearing age, predominantly superficial cells and intermediate cells are seen (Fig. 16.13). Parabasal cells are seen only occasionally in normal smears but are seen in certain situations which will be described later. Basal cells are seen rarely. Endocervical cells form an important constituent of the Pap smear. Neutrophils may be present.

In menopausal women, cytology findings are affected by withdrawal of estrogenic activity. In early meno-pause, estrogen deficiency is mild. There is reduction in the number of superficial and predominance of intermedia te cells and some large parabasal cells (Fig. 16.14). As estrogen deficiency increases, thick crowded and large clusters of intermediate large parabasal cells are seen. Some cells may resemble navicular cells. In advanced stage of menopause, estrogen levels are markedly low. Yield of cellular material is poor due to dryness of genital tract. Dominant cell is para basal type; there is enhanced eosinophilia of the cytoplasm and pyknosis of nuclei, nuclear breakup and marked variation in cell size. Sometimes there is enlargement of nuclei of parabasal cells and such cells may be mistaken for dysplastic cells. Occasionally sheets of spindle cells may be seen which may be mistaken for malignant cells. Endocervical cells are few or absent.

It is now almost established that carcinoma cervix is preceded by cellular abnormality of surface epithelium. Most high grade lesions start de novo though some low grade lesions may develop into cancer. Transformation zone is the site of initiation in most cases.

CYTOLOGY-EDUCATIONAL NOTES

INVASIVE ENDOCERVICAL ADENOCARCINOMA
Columnar cells possess cytoplasmic vacuoles, nuclear enlargement, eccentric nuclei, large eosinophilic nucleoli, multiple nucleoli and papillary spherical clusters. There is overlapping of nuclei and clusters may have a lumen (rosette or glands). Such cells are seen in adenocarcinoma, squamous cell carcinoma and HGSIL.

It is difficult to differentiate between dysplastic and malignant endocervical cells. However, in adenocar- cinoma, smear shows necrotic and bloody background.

Signet ring cells may be present. Mitotic figures and apoptotic nuclei are present. A few dysplastic squamous cells may be seen (Fig. 16.38).

OTHER
This category is created for reporting normal or abnormal endometrial cells in women who are 40 years or older, as the presence of even benign-appearing endometrial cells on cervical cytology in women who are at least 45 years of age is more often associated with endometrial adenocarcinoma and endometrial hyper- plasia than with benign endometrium. However, since cervical cytology is primarily a screening test for squamous epithelial lesions and squamous cancer, it is not reliable for detection of endometrial lesions.

ANCILLARY TESTING AND EDUCATIONAL NOTES
If slides are scanned by automated computer systems, the type of system used should be reported with the result. Ancillary testing such as HPV DNA is performed, if appropriate, and reported with the cytology results.

Written comments regarding the interpretation of a cytologic specimen are optional and may be conveyed to the clinician by the pathologist as a means of clarification and information

DIGISCAN HAS LAUNCHED A VERY AMBITIOUS ON LINE DERMATOPATHOLOGY LECTURE SERIES

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In this lectures series eminent, distinguished speakers and faculty of highly acclaimed institutions of the country will be giving lectures on various important topics. It is planned to have 24 lectures to cover most of the topics. These lectures will be highly valuable for post-graduate students and residents of Dermatoloy as well as Pathology.
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Dermatopathology set for postgraduate students and residents in pathology & young practicing pathologists consists of large number of lesions including all the topics of dermatopathology . Digital slides have been annotated for ease of understanding and self study.
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It is now a common practice in radio diagnosis to provide DVD of the images and interpretation of images to the patient providing them freedom to seek opinion from other experts globally. This practice is lacking in pathology laboratories so far but time has come when pathology laboratories also will have to adopt new technologies and will have to offer solutions to their problems of seeking second opinion from the expert pathologists of their choice globally.

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CYTOLOGY-BETHESDA SYSTEM

BETHESDA SYSTEM (2011) FOR REPORTING CERVICAL CYTOLOGIC DIAGNOSIS
establish an effective communication with the referring Bethesda system (Table 16.2) considered cervico- vaginal smear as a medical consultation and stressed it to be reported in clear, unambiguous language so as to consultant and facilitate cyto-histologic correlation.

Table 16.2: The 2001 Bethesda system for reporting cervical cytologic diagnosis

I. Specimen type

Indicate conventional smear (Pap smear) vs. liquid-based

II. Specimen adequacy

Satisfactory for evaluation

(presence/absence of endocervical/transformation zone component and any other quality indicators, e.g. partially

obscuring blood and inflammation)

Unsatisfactory for evaluation … (specify reason)

Specimen rejected/not processed (specify reason)
Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality (specify reason)
III. General categorization (optional)

Negative for intraepitheliallesion or malignancy-see interpretation/result

Epithelial cell abnormality (specify ‘squamous’ / ‘glandular’)-see interpretation/result
Other (e.g. endometrial cells in a woman> 40 years of age)-see interpretation/result

IV. Interpretationlresult

Negative for intraepithelial lesion or malignancy

(State whether or not there are organisms or other non-neoplastic findings)

Organisms:

Trichomonas vaginal is
Fungal organisms morphologically consistent with Candida spp
Shift in flora suggestive of bacterial vaginosis
Bacteria morphologically consistent with Actinomyces spp.
Cellular changes consistent with herpes simplex virus
Other non-neoplastic findings (optional to report):

Reactive cellular changes associated with inflammation (includes typical repair) radiation intrauterine contraceptive
device (IUD)
Glandular cells status post-hysterectomy
Atrophy
Epithelial cell abnormalities
Squamous cell
Atypical squamous cells (ASC):

ASC of undetermined significance (ASC-US)
ASC-cannot exclude HSIL (ASC-H)
Low grade squamous intraepitheliallesion (LGSIL)
Encompassing: HPV, mild dysplasia, and CIN 1
High grade squamous intraepitheliallesion (HGSIL)

Encompassing: Moderate and severe dysplasia, CIS, CIN 2, and CIN 3

Squamous cell carcinoma

Glandular cell

Atypical glandular cells (AGC)

Specify endocervical, endometrial, or gladular cells not otherwise specified
Atypical glandular cells, favor neoplastic

Specify endocervical cell or not otherwise specified
Endocervical adenocarcinoma in situ (AIS)
Adenocarcinoma

Other:

Endometrial cells (in a woman> 40 years of age-specify if ‘negative for squamous intraepitheliallesion’)

Automated review and ancillary testing (include if appropriate)

Educational notes and suggestions (optional)

CYTOLOGY-EDUCATIONAL NOTES

INVASIVE ENDOCERVICAL ADENOCARCINOMA

Columnar cells possess cytoplasmic vacuoles, nuclear enlargement, eccentric nuclei, large eosinophilic nucleoli, multiple nucleoli and papillary spherical clusters. There is overlapping of nuclei and clusters may have a lumen (rosette or glands). Such cells are seen in adenocarcinoma, squamous cell carcinoma and HGSIL.

It is difficult to differentiate between dysplastic and malignant endocervical cells. However, in adenocar- cinoma, smear shows necrotic and bloody background.

Signet ring cells may be present. Mitotic figures and apoptotic nuclei are present. A few dysplastic squamous cells may be seen (Fig. 16.38).

OTHER

This category is created for reporting normal or abnormal endometrial cells in women who are 40 years or older, as the presence of even benign-appearing endometrial cells on cervical cytology in women who are at least 45 years of age is more often associated with endometrial adenocarcinoma and endometrial hyper- plasia than with benign endometrium. However, since cervical cytology is primarily a screening test for squamous epithelial lesions and squamous cancer, it is not reliable for detection of endometrial lesions.

ANCILLARY TESTING AND EDUCATIONAL NOTES

If slides are scanned by automated computer systems, the type of system used should be reported with the result. Ancillary testing such as HPV DNA is performed, if appropriate, and reported with the cytology results.

Written comments regarding the interpretation of a cytologic specimen are optional and may be conveyed to the clinician by the pathologist as a means of clarification and information.

CYTOLOGY-SPECIMEN ADEQUACY

SATISFACTORY FOR EVALUATION

Cervicovaginal smear should be representative of epithelia of ectocervix, endocervix and should include transformation zone as aim of cervical smear examination is detection of abnormal cells which generally arise in the transformation zone. Therefore, ideally the smear should contain squamous cells, metaplastic cells (TZ) and/ or endocervical cells, and should not be obscured by the presence of blood/ inflammation, etc. However, since the absence of endocervical cells/presence of partially obscuring factors have not shown to increase the risk of a false negative report; TBS 2001 considers such specimens to be reported as “satisfactory for evaluation”, but the comments about the TZ components/ partially obscuring factors are placed in the narrative report which should be read carefully by the clinician to note that the trans- formation zone was not sampled and to improve the specimen adequacy henceforth. In conventional Pap smears, cervical mucus itself is evidence of smear adequacy in absence of endocervical cells. However, in liquid-based preparations, this valuable resource is lost. Since only a part of sample aliquot is used in smear preparation, 5000 well preserved squamous cells per smear and 10 endocervical cells form the basis of adequacy. In older women, TZ may be situated within endocervix canal and is much more difficult to sample and presence of endocervical cells or mucus is not necessary for adequacy. Any smear containing abnormal cells is considered satisfactory for evaluation irrespective of the number of cells present.

UNSATISFACTORY FOR EVALUATION

When the smear does not contain adequate cellular material for reliable interpretation, it is reported as “unsatisfactory for evaluation”. The report would specify, whether the specimen was rejected and not processed (with reason); or whether it was processed and examined, but found unsatisfactory for evaluation of epithelial abnormalities. The causes of unsatisfactory smears could be:

  1. Heavy inflammation obscuring cells (Fig. 16.14)
  2. Air drying artifact (Fig. 16.15)
  3. Excessive cytolysis (Fig. 16.16)
  4. Bloody smear with only few cells
  5. Uniformly thick smear
  6. Scanty cellular material
  7. Lubricant contaminant
  8. Inadequate fixation
  9. Unrepresentative material
  10. Menstrual cells