Cervix
Premalignant / preinvasive lesions - H&E
HSIL / CIN II / CIN III
Author: Seema Khutti, M.D.
Topic Completed: 1 May 2014
Minor changes: 6 July 2020
Copyright: 2003-2020, PathologyOutlines.com, Inc.
PubMed Search: HSIL cervix [title]
Table of Contents
Definition / general | Terminology | Sites | Colposcopy | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Electron microscopy description | Differential diagnosis | Additional referencesCite this page: Khutti S. HSIL / CIN II / CIN III. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixHSILCINIII.html. Accessed August 11th, 2020.
Definition / general
- Asymptomatic precursor lesion to invasive carcinoma associated with high risk HPV subtypes
- If untreated, 22 to 72% develop invasive cancer
- Relatively frequent with incidence up to 31/100,000 women
- Seen in older age group than LSIL, peaks 35 - 39 years
- Lately increasing in younger women secondary to changing sexual practices
Terminology
- Also known as CIN II and CIN III
Sites
- Predominantly at transformation zone
Colposcopy
- Acetowhite epithelium or leukoplakia
- Mosaicism, punctations, atypical vessels secondary to vascular change
Case reports
- 33 year old woman with double cervix with bilateral and synchronous HSIL associated with different high-risk HPV types (Acta Cytol 2004;48:273)
- Squamous cell carcinoma in situ involving mesonephric remnants (Am J Surg Pathol 1994;18:1265)
Treatment
- Wide excision of transformation zone
Clinical images
Images hosted on other servers:
Moderate to dysplasia, carcinoma in situ
Microscopic (histologic) description
- Exhibit atypia in all layers of the epithelium, extent and degree of atypia exceeds the limits of that described in LSIL
- Loss of maturation and cytologic atypia in the lower two thirds (CIN II) to full thickness (CIN III) epithelium
- Syncytial growth with lack of distinct intercellular borders in basal and parabasal layers
- Immature cells with high N/C ratio, irregular nuclear membrane contour, coarse chromatin, and inconspicuous nucleoli
- Superficial layers may show lower nuclear-cytoplasmic ratio and koilocytic change
- Frequent mitosis, including atypical forms:
- CIN II: Mitosis in lower two third of epithelium
- CIN III: Mitosis in all levels of epithelium
- HSIL constitute three overlapping categories:
- Maturing HSIL (Koilocytotic HSIL, CIN II):
- May contain prominent perinuclear halo coexisting with parabasal cell atypia
- In general, koilocytes appear atypical with tightly arranged perinuclear halos and high nuclear density
- Immature HSIL with metaplastic phenotype
- Difficult to recognize on lower magnification
- Characteristic lack of reduction in nuclear density in upper layers
- Has nuclear hyperchromasia, appearance of syncytium of nuclei in superficial epithelium
- Immature HSIL with columnar differentiation
- Now considered to be adenocarcinoma in situ, stratified variant (SMILE)
- Maturing HSIL (Koilocytotic HSIL, CIN II):
Microscopic (histologic) images
Involvement of endocervical glands
Various images
At squamocolumnar junction
LSIL merging into HSIL
H&E
Contributed by Jijgee Munkhdelger, M.D., Ph.D. and Andrey Bychkov, M.D., Ph.D.
CIN 3 p16
HSIL p16
Cytology description
Positive stains
- p16 strong and diffuse positive nuclear and cytoplasmic in at least two thirds of epithelial thickness
- Ki67: positive nuclear Ki67 staining in the upper two thirds of dysplastic epithelium (Int J Gynecol Pathol 2013;32:76)
- Also MUC4 (Hum Pathol 2001;32:1197)
Electron microscopy description
- Loss of intercellular cohesion due to marked reduction in desmosomes, presence of extremely complex cell surface, loss of surface pseudopodia
Differential diagnosis
- Artifacts: uniform nuclear enlargement and hyperchromasia, no anisonucleosis or nuclear crowding
- Atrophy: high N/C ratio, coarse and hyperchromatic nuclei; lacks maturation; uniform sized nuclei, evenly spaced nuclei; absent to rare mitosis
- Immature squamous metaplasia: no cell crowding, minimal variation in nuclear size with fine chromatin and preserved polarity, uniform density throughout the epithelium, lacks abnormal mitosis
- Radiation effect: nuclear enlargement with smudgy chromatin; no increase in N/C ratio; uniform nuclear spacing with minimal crowding; cytoplasmic degeneration with vacuoles
- Reactive / reparative epithelial changes: mild to moderate nuclear enlargement, surface maturation, minimal (anisokaryosis, intercellular edema, prominent nucleoli), Ki67 confined to lower third of epithelium
Additional references
