Cervical Cytology

Cervical cancer: Epidemiology, aetiology, pathogenesis and main histological types

Epidemiology
Clinical presentation
Histological types of cervical cancer
Cervical cancer as a multi stage disease
Histological features of CIN and adenocarcinoma in situ
Risk factors for cervical cancer

 

The concept of cervical cancer as a multi-stage disease

The concept of cervical cancer as a multistage disease originated at the beginning of the 20th century

It is widely accepted that most  invasive squamous cervical cancers are   preceded by an asymptomatic preinvasive stage of the disease  in which  precancerous   cells are confined to the epithelium of the cervix . At this stage, the normal squamous epithelium of the cervix is replaced by an abnormal epithelium composed of neoplastic cells. This is the earliest stage of the disease and is  known as  cervical intraepithelial neoplasia (CIN). If  left undiagnosed and untreated , numerous studies have shown that CIN can progress to invasive cancer. The time span for the progression of CIN to invasive squamous cancer is variable and may be as long as 15 to 20 years. There is strong evidence that invasive cancer can be prevented by the diagnosis and treatment  of preinvasive cancer.

Histological studies of  the cervical epithelium in women with  squamous  cancer of the cervix  have shown that  occasionally an intermediate stage in the development of invasive cancer can be identified .This is termed the microinvasive stage of cervical cancer. At this  stage, individual neoplastic cells or small clusters of neoplastic cells can be seen deep to the basement membrane  confining  the CIN lesion. This is considered to be the earliest evidence of  invasion . As the tumour progresses to the invasive stage , tongues of tumour cells extend from the epithelium of the cervix deep into the underlying stroma.  The tumour may invade quite extensively locally but untimately invades blood vessels and lymphatic channels leading to metastatic spread.

A preinvasive stage  of adenocarcinoma  is also  recognised histologically and is known as adenocarcinoma in situ or cervical glandular intraepithelial neoplasia (CGIN).  The microinvasive stage of adenocarcinoma, although it probably exists, is not a clearly defined histological entity.

Below is a graphic representation of the stages of development of  squamous cervical cancer  cancer and shows the progression from normal epithelium through CIN 1 ,CIN2 and CIN3 to microinvasive and invasive cancer. It is probable that most cancers go through these stages although there are reports of cancers arising de novo  directly from a focus of CIN1.

  • Preinvasive lesions: WHO and CIN terminology

The concept of cervical cancer as a multistage disease originated at the beginning of the 20th century when Rubin (1910) described histological  changes in the cervical epithelium which he believed were precursors of invasive squamous carcinoma. He noted that abnormal cells in the squamous  epithelium of the cervix were similar to the tumour cells found in invasive cancer. These changes were subsequently described as “carcinoma in situ “ to indicate  the malignant potential of these lesions.  Over the next few years, pathologists described  a wide range of squamous  atypia  in the cervical epithelium but there was some uncertainty as to the malignant potential of these changes. The term “dysplasia” was introduced by Reagan et al (1953) to describe the lesser grades of    abnormality.The dysplasias were further classified as mild , moderate or severe according to the proportion of the cervical epithelium occupied by the neoplastic cells.

In 1975 the World Health Organisation (WHO) advised that the term “carcinoma in situ “ be used to describe  those lesions in which  the whole thickness of the epithelium was replaced by undifferentiated neoplastic cells. WHO  also  recommended that the term  “dysplasia” be reserved for neoplastic lesions of the cervix in which only  part of the thickness of the epithelium is replaced by  undifferentiated tumour cells. It was widely assumed at the time that dysplasia was  a pathological condition that was clinically distinct  from carcinoma in situ and had no invasive potential: moreover  dysplasias did not merit treatment . This assumption was challenged by Richart who subsequently introduced the concept that mild , moderate and severe dysplasia and carcinoma in situ are a lesional continuum in which one abnormality merges into to the next. He introduced the term Cervical Intraepithelial Neoplasia  (CIN) as a single descriptive term to embrace all grades of dysplasia including  carcinoma in situ  under a single disease heading.

Three grades of CIN are  now recognised: CIN1 corresponding to mild dysplasia ; CIN2 coresponding to moderate dysplasia  and CIN3  coresponding to severe dysplasia and carcinoma in situ. Prospective studies indicated  that  the risk of progression of CIN to invasive cancer  increases with the grade of the CIN lesion .Thus the likelihood of progression  is greatest in women with CIN3 and least in women with CIN1. 

Both the WHO terminology and the CIN terminology are in current use by histopathologists to describe preinvasive squamous carcinoma .The Bethesda system (TBS) has introduced the terms HSIL and LSIL to describe CIN lesions. These are discussed in the cytology module. The equivalent terminology is shown in Table below.

WHO terminology

CIN terminology

TBS terminology

Mild dysplasia

CIN1

Low grade squamous intraepithelial lesion (LSIL)

Moderate dysplasia

CIN2

High grade squamous intraepithelial lesion (HSIL)

Severe dysplasia

CIN3

Carcinoma in situ

CIN3

Microinvasive squamous carcinoma

Microinvasive squamous carcinoma

 

Invasive squamous carcinoma

Invasive squamous carcinoma

 

 

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