Low-grade squamous intraepithelial lesion

Terminology and classification

Traditionally, initial changes in the structure of the cervical epithelium were termed "mild dysplasia". Today in global medical practice, including cytologic screening, the Bethesda System (TBS) is universally applied. It divides all lesions into two broad categories:

• LSIL (Low-grade squamous intraepithelial lesions): low-grade squamous lesions. These include mild dysplasia (CIN I), condylomas, and koilocytosis.
• HSIL (High-grade squamous intraepithelial lesions): high-grade lesions classified as obligate precancer (moderate and severe dysplasia, as well as carcinoma in situ).

In the modern WHO histological classification (2020), a similar division into SIL groups is used. From the perspective of general oncomorphology, any intraepithelial neoplasia (CIN) represents structural and cellular atypia. This process disrupts normal maturation, differentiation, and stratification of the epithelium, while tumor cells strictly do not involve the basement membrane.

Morphological pattern and cellular atypia

In low-grade squamous intraepithelial lesions, the disruption of cell proliferation begins in the basal and parabasal layers.

Main morphological manifestations of the pathology:

1. Limited lesion: undifferentiated immature cells are located exclusively in the lower 1/3 of the epithelial layer.
2. Maturation of upper layers: cells of the upper two-thirds of the layer remain mature, although various degenerative changes may be detected in them.
3. Signs of cellular atypia: this is a key symptom of neoplasia. Microscopic examination reveals an increased nuclear-cytoplasmic ratio, nuclear hyperchromasia and polymorphism, and uneven chromatin distribution.
4. Proliferation: mitotic activity is increased, atypical mitoses may occur, and cell polarity is lost.

For clarity, here is the gradation of neoplasia severity depending on the depth of penetration of immature cells:

Role of HPV and the phenomenon of koilocytosis

Precancer and invasive cervical cancer share common pathogenetic mechanisms and a single etiology—papillomavirus infection. Viral genetic material is detected in 98% of dysplasia cases.

There are two variants of the virus presence within the cell:

• Episomal form: viral particles assemble inside the cell without affecting its genome.
• Integrative form: viral DNA integrates into the epitheliocyte genome, which triggers true tumor transformation.

For LSIL, a specific cytopathic effect of the virus is highly characteristic, manifested by the formation of koilocytes. It is important to note that even isolated koilocytosis without pronounced signs of parabasal layer proliferation is classified as CIN I.

Morphology of a typical koilocyte:

• Large hyperchromatic nucleus containing coarse clumps of chromatin.
• Thickened, irregularly shaped nuclear membrane.
• Perinuclear halo—a wide rim of cleared cytoplasm surrounding the nucleus.

Clinically important nuance: as the infection progresses and HPV transitions into the integrative form, signs of koilocytosis completely disappear.

Principles of screening and diagnostics

In the overwhelming majority of patients, low-grade neoplasia is completely asymptomatic. Only in rare cases may "contact" spotting occur. In 90% of cases, the pathology develops against the background of prior cervical conditions.

Since the progression of CIN to invasive cancer is a lengthy process taking up to 10 years or more, regular screening takes precedence.

Screening rules:

• Target group: women aged 21–65 (may be performed in patients under 21 with a sexual history of over 3 years).
• Examination interval: every 3 years.
• Sampling: the smear must be taken from the ectocervix and endocervix (unless canal atresia is present).

Traditional and liquid-based cytology are used for the study. Liquid-based cytology is considered more effective for detecting LSIL and HSIL: it has higher sensitivity (72.9%) and specificity (90.3%), and most importantly, it dramatically reduces the percentage of inadequate smears, which is about 10% with the traditional method.

If an abnormal smear is obtained, reviewing the primary slide is advisable. Taking a repeat smear in 1.5–2 months is not recommended, as such studies have low reproducibility. The diagnosis is verified exclusively by pathomorphological examination of biopsy material obtained during colposcopy.

Class and exam questions

What else to study on this topic

• High-grade squamous intraepithelial lesion (HSIL) and morphology of obligate precancer
• Specific cytologic criteria for smear evaluation according to the Bethesda system
• Mechanisms of tumor transformation in the integrative form of HPV
• Colposcopic pattern and visual assessment after acetic acid application (VIA)
• Morphological characteristics of preinvasive cancer (carcinoma in situ)

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.