CERVICO VAGINAL CYTOLOGY - CLASSIFICATION WITH A MATHEMATICAL MODEL

César  T.  VELA-VELASQUEZ
1996

To the Editors:  
 
The ideal point of the cytologic diagnosis is that it is identical to the hystologic diagnosis, that is to say, with the participation of cytology or histology we reach the same diagnosis, but in regard to the cytologic diagnosis we only rely on cellular morphology; however, we have not taken into consideration important pieces of information such as: the behavior of the cell with relation to its same tissue, its behavior with other neighboring hystologic structures. 
Acording to this, we observe in the daily practice that the cytologic diagnosis has an "indeterminate area" in relation to the hystologic diagnosis, it is for that reason that we believe that for the cytologic diagnosis we have to accept "area of indeterminant cells". 
The main objective of the cervical-vaginal cytology is the detection of neoplastic cells, in which the specification of dysplasia or carcinoma is considered to be important, since the first one reflects reversible chromosomal changes or potentially reversible changes; on the other hand, in the cancerous cells the chromosomal changes are irreversible and they acquire infiltration properties and cellular destruction concomitantly. 
In the routine work we frequently have the doubt that the cellular changes which we observe are due to reactive changes or if they are dysplasia or cancer; for this reason, we think that in these 3 categories the problem of identification of the cellular alterations is located in the cervical-vaginal cytology. Therefore, it is important to schematize the universe of the cytologic diagnosis using a mathematical diagram of the group theory in the following way: 

Where: 
U:  It represents the universe of all of the cytologic diagnoses. 
Group R: All cells in this group have characteristics consistent with reactive cells.
Group D: All cells in this group have characteristics consistent with cellular dysplasia. 
Group C: All cells in this group have characteristics consistent with carcinoma. 
Area R1: Cells whose characteristics are undoubtedly of reactive cells. 
Area D1: Cells whose characteristics are undoubtedly of cellular dysplasia. 
Area C1: Cells whose characteristics are undoubtedly of carcinoma. 
.............The intersection areas represent "area of indeterminant cells", that is, they can
.............correspond to any of the implied groups, as explained below:
Area RD: Cells with some characteristics of reactive cells or dysplasia; 
Area DC: Cells with some characteristics of dysplasia or carcinoma; 
Area RC: Cells with some characteristics of reactive cells or carcinoma; and 
Area RDC: Cells with some characteristics of reactive cells or dysplasia or carcinoma. 

Finally, the shady area represents the rest of the cytologic diagnoses. 
The size of the morphologic "area of indeterminant cells" varies according to the population, that is to say, in some of them it will be small and in others it will be big, but the important thing is to conceive these areas because we have the opinion that they will always exist, since if in the near future many of these cells will be classified in the correct category with genetic methods, then it is possible that the cellular indeterminacy will reside in finer molecular changes, that is, we want to stress that there will always be "area of indeterminant cells" until, at any moment in the future, the evolution of  cytology will be such that these "area of indeterminant cells" will be equal to zero. 
 
In the cytologic report, we have to get to the ideal point of balance between our cytologic diagnosis and the message that has to be given to the patient appropriately, that is, to make it in such a way that we harm the patient neither physically nor psychologically, especially when we refer to these "area of indeterminant cells"; therefore, we have to transfer our message in such a way that the patient does not neglect her treatment nor does she feel unquiet (for example as we will see later, we suggest labeling the area RD "indeterminant (squamous or glandular) cell with dyskaryosis", since all dysplastic cells have dyskaryosis, but not all cells with dyskaryosis are dysplastic; the same happens to area RC and area RDC, where we only use the word "neoplasm" and not "malignant  neoplasm", since it is likely to be a reactive change only).  
 
Consequently, we consider the following terminology appropriate for the "area of indeterminant cells": 

Area RD: Indeterminant (squamous or glandular) cell with dyskaryosis. 
Area RC: Indeterminant (squamous or glandular) cell of low grade of suspicion of neoplasm. 
Area RDC: Indeterminant (squamous or glandular) cell of high grade of suspicion of neoplasm.  
Area DC: Indeterminant neoplasic (squamous or glandular) cell. 
 
 
In relation to dysplasia, we believe that it is important to remember that the exocervical epithelium is the product of the maturation of the basal cells, and the strange agent that can produce dysplasia is probably present already from the basal layer, but the morphologic manifestation is in the other layers (the more superficial the squamous cell is, the more nuclear physiologic mechanisms are lost, that is to say, the more superficial the cell is, the more sensitive it becomes, and therefore it may get attacked easily by strange agents, which can cause chromosomal imbalance), that is, if we find a superficial cell with  dyskaryosis of dysplasia we speak of mild dysplasia. If it is an intermediate cell, then it is moderate dysplasia. And finally, if the dyskaryosis of dysplasia is also in parabasal cells, we speak of severe dysplasia. 
 
 
A lot of information on the human papillomavirus (HPV) has come about; the article written by Richart et al. (1) is very interesting and complete; we think that if it is true that the gene of the HPV is already acting molecularly in the nucleus of the guest cell, while there is no dyskaryosis evidence it should not be spoken of dysplasia, since while there is no morphologic manifestation of nuclear alteration it means that the mechanisms of genetic protection and the working of the virus is in a point of balance that makes  the cell stay physiologically normal, but it requires the patient's strict medical care. The same previous reasoning can be applied in the future for any element " X " (given by the cytologic investigation) that can lead to dysplasia or cancer, that is, if there is no morphologic evidence of dyskaryosis it should not be spoken of dysplasia. 
 
We believe that the contribution of the Bethesda System (2), regarding the approach of adecuacy of the sample and the use of appropriate recommendations in the cytologic report, is significant; we also believe that the cytologic report should keep a scientific format, that is, to give the most comprehensive information with the minimum number of words. 
 

1- NEGATIVE CYTOLOGY FOR NEOPLASTIC CELL

1.1- Without significant cellular changes

1.2- With inflammatory pathology 

1.2.1- Bacterial cervical-vagintis (3)
1.2.2- Trichomoniasis
1.2.3- Candidiasis

1.2.4- Cervical infections by Chlamydia (4)
1.2.5- Viral infections (not included the HPV nor the genital Herpes) 
1.2.6- Other inflammatory agents 

1.3- With reactive epithelial changes (squamous metaplastic cells, repair cells, etc.; in generalin association with inflammatory pathology)

1.4- Cytology with the presence of high-risk agents (HPV, genital Herpes, other agents given in the future by the cytologic investigation)

1.5- Hormonal evaluation (the same as the Bethesda System)

2- CYTOLOGY WITH INDETERMINANT EPITHELIAL CELLULAR CHANGES:

2.1- Indeterminant (squamous or glandular) cell with dyskaryosis. 
2.2- Indeterminant (squamous or glandular) cell of low grade of neoplasm suspicion. 

2.3- Indeterminant (squamous or glandular) cell of high grade of neoplasm suspición (for example cell of "atypical parakeratosis" [5]).
 

2.4- Indeterminant neoplasic (squamous or glandular) cell.

3- NEOPLASIC CYTOLOGY:

3.1- Epithelial cell with cellular dysplasia: 

3.1.1- Mild dysplasia of squamous cell 
3.1.2- Moderate dysplasia of squamous cell 
3.1.3- Severe dysplasia of squamous cell 
3.1.4- Dysplasia of glandular cell 

3.2- Cells of malignant neoplasms: 

3.2.1-Carcinoma of squamous cells: Optional categories for differentiations in:

3.2.1.1- Carcinoma in situ
3.2.1.2- Microinvasive carcinoma
3.2.1.3- Invasive carcinoma

3.2.2- Adenocarcinoma

3.2.2.1- Adenocarcinoma of endocervix
3.2.2.2- Adenocarcinoma of endometrium

3.2.3- Other malignant neoplasm: Specify

 
 
Finally, we are convinced that the present article will contribute in the discussion and classification of the cervical-vaginal cytology. 

REFERENCES

1.Richart RM, Masood S, Syrjänen KJ, Vassilakos P, Kaufman RH, Meisels A, Olszewski WT, Sakamoto A, Stoler MH, Vooijs P, Wilbur DC: Human Papillomavirus. IAC Task Force Summary.

Acta Cytol 1998; 42: 50-58

2.The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses.

Acta Cytol 1993; 37: 115-124

3.Vela CT, Mendoza N: Diagnóstico citológico y gram de la vaginosis bacteriana.

Rev Med IPSS 1995; 4: 53-58

4.Vela CT: Cytologic Diagnosis of Chlamydia in Cervical-vaginal Secretions. Use of a Papanicolaou Stain Modification with Buffered Wright Solution.

Acta Cytol 1998; 42: 954-958

5.Vela CT: "Atypical Parakeratosis" Cells in Cervical Carcinoma Cytology.

Acta Cytol 1997; 41: 614-616

Acknowlegements: My gratitude to Mr. Felipe A. Vela-Izquierdo for his assistance in the translation of the present manuscript.