Linee guida per il trattamento per pazienti con strisci atipici

• Le linee guida internazionali per il trattamento delle donne con strusci citologici atipici sono state preparate con l'aiuto del Programma Europeo Contro il Cancro nel 1993 (European J of Cancer vol 29A supp 4)
• Le linee guida sono state pubblicate con la chiara intenzione che le decisioni sul trattamento erano interamente materia di un giudizio clinico e sotto l'indicazione della citologia
• Comunque qualche clinico apprezza la presenza all'interno del referto di qualche commento o giudizio.
• Le linee guida presentate qua sono state preparate in collaborazione con un gruppo internazionale di ginecologi e sono basate sul corrente concetto della patogenesi del carcinoma cervicale e del potenziale maligno delle varie lesioni CIN.
• Deve essere poi ricordato che la diagnosi citologica è una diagnosi presuntiva. La colposcopia e la biopsia sono essenziali in tutti i casi dove è stata proposta una diagnosi citologica di neoplasia al fine di ottenere una diagnosi definitiva prima che il trattamento venga iniziato.
• Il test per la valutazione dei ceppi da alto rischio di HPV DNA è un sistema alternative per il trattamento dell' ' ASC-US quando può essere fatto anche in associazione con la ripetizione della citologia: il Trattamento raccomandato per ASC-H (che rappresenta una categoria di refertazione usata da qualche citologo) è la colposcopia.

Cytological diagnosis	Management guidance
LSIL (incorporating ASCUS and CIN1/mild dysplasia (with and without HPV changes)	Repeat smear in 6 months. If  the  repeat smear  is also reported as LSIL refer for  colposcopy.
HSIL (incorporating moderate and  severe dysplasia, carcinoma in situ CIN2  and CIN3)	Colposcopy advised
Suspicious of invasive  squamous carcinoma	Colposcopy advised
Invasive Squamous carcinoma	Colposcopy advised
Endocervical adenocarcinoma in situ ; endocervical adenocarcinoma	Colposcopy advised
Atypical glandular cells (endocervical or  endometrial or not otherwise specified)	Referral for gynaecological opinion
Other malignant lesions	Referral for gynaecological opinion

Colposcopy

The colposcope is an instrument which permits examination of the uterine cervix, vagina and vulva at high magnification. It consists of a microscope mounted on a mobile stand which has   a light source and video camera attached.  It was first described by Hinselmann in 1925 and was widely used by gynaecologists as a diagnostic tool for invasive cervical cancer in Germany for many years before it was used to complement Citologia Cervicale for the detection of preinvasive and early invasive cervical cancer.

With the introduction of Citologia Cervicale, the colposcope has become an indispensable tool for the identification and location of lesions in the cervix which give rise to abnormal smear reports.  It should be remembered that cervical cancer at its earliest preinvasive stage is rarely detectable to the naked eye and a cytological diagnosis of CIN is at best a presumptive diagnosis. The magnification afforded by the colposcope enlarges the field of view up to x 40 normal size. The magnified images of the cervix enable the colposcopist to do the following:

1. Identify abnormal areas in the cervical epithelium and subepithelial angio architecture which are not be visible on normal inspection.
2. Precisely locate the lesions and define their limits.
3. target areas for biopsy
4. carry out histological examination of the biopsy material and obtain a tissue diagnosis
5. exclude invasion
6. define an appropriate treatment  scheme for each woman
7.  confirm  the cytological findings

 

The process of colposcopy requires that the patient is placed in a modified lithotomy position and the cervix exposed using a bivalve speculum. A repeat cervical smear is often   taken at this stage taking care to minimise the risk of bleeding which could subsequently interfere with the field of view. The cervix is then swabbed gently with a cotton swab soaked in saline and inspected. A dilute solution of acetic acid (3% or 5%) is gently applied with the swab and left for approximately five seconds. The acetic acid renders abnormal epithelium visible to the naked eye. Abnormal areas appear as a white usually sharply defined area (aceto white) on the ectocervix. The effect of the dilute acetic acid on the epithelium is believed to be achieved by coagulation of nuclear protein. Because of the high density of nuclear protein in areas of CIN and the changes in angio architecture associated with neoplasia, the areas appear more opaque than the surrounding normal epithelium.

.Colposcope; fine focus knob (A) zoom focus (B), and green filter (C): "Colposcopy: principles and practice"; Apgar, Brotzman, Spitzer 2002

Indications for referral for colposcopy

Before the introduction of colposcopy, women who had abnormal smears or whose cervix looked suspicious were frequently treated by hysterectomy or cone biopsy.  Once colposcopy became the routine first step in the investigation of women with abnormal smears, the need for surgical intervention was dictated by the extent, location and type of lesion and the individual preferences of the patient. At present, colposcopy is usually recommended for women who have a smear pattern suggestive of a high grade lesion i.e. CIN2or 3, or CGIN.    
Colposcopy is not usually recommended the first time a woman has a smear report suggestive of a low grade lesion (ASCUS or borderline or even LSIL) as these lesions are often transitory. However if a repeat smear indicates that the lesion has persisted for 6 months or more, referral for colposcopy is advisable. Colposcopy is also essential for women who have symptoms or signs of invasive cancer (e.g. intermenstrual or post coital or post menopausal bleeding) even in the presence of a “Negative” smear report.

Biopsy for the confirmation of cytologic and colposcopic findings

It is worth remembering that neither cytology nor colposcopy are able to provide a definitive diagnosis of neoplastic changes in the cervix. The evidence of CIN from a Pap smear or colposcopic examination of   aceto white areas is at best presumptive.
A definitive diagnosis of CIN can only be provided by tissue biopsy and the demonstration of histological changes of CIN in the cervix.
For this reason one or more colposcopically directed punch biopsies should always be taken when an area of aceto white is detected in the cervix. The biopsies should be taken from the most abnormal looking areas of the cervix using a specially designed biopsy forceps with the aim of excluding invasion.

Once a histological diagnosis has been obtained, appropriate treatment can be applied. Ablative techniques such as radical electrocoagulation diathermy, cryocautery, laser vaporisation, and cold coagulation are currently used for the treatment of CIN.

It should be remembered that colposcopic biopsies are generally small and not easy to target so that the most severe pathological changes lesion in the cervix may occasionally be missed on punch biopsy. Large loop excision of the transformation zone (LLETZ) provides a satisfactory solution to this problem   as it combines diagnostic biopsy with treatment. The whole lesion is excised by a single sweep of the diathermy loop and all the tissue removed can be processed for histological examination.

Cone biopsy (cold knife or laser) are often reserved for those cases where the lesion appears to be intraepithelial in nature but extend outside the range of colposcopic appraisal or where the   cytology suggests a   more serious condition than that seen at colposcopy. Cone biopsy is also recommended if the cytology suggests glandular neoplasia as colposcopy can be uninformative in   cases of Aden carcinoma in situ or early invasive cervical adenocarcinoma.