Premalignant / preinvasive lesions
HSIL (CIN II - moderate dysplasia, CIN III - severe dysplasia)

Topic Completed: 1 May 2014

Revised: 27 December 2018, last major update May 2014

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PubMed Search: HSIL cervix [title]

Seema Khutti, M.D.
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Cite this page: Khutti S. HSIL (CIN II - moderate dysplasia, CIN III - severe dysplasia). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixHSILCINIII.html. Accessed October 18th, 2019.
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
  • Also known as CIN II and CIN III
  • Predominantly at transformation zone
  • Acetowhite epithelium or leukoplakia
  • Mosaicism, punctations, atypical vessels secondary to vascular change
Case reports
  • Wide excision of transformation zone
Clinical images

Images hosted on other servers:

Colposcopic image

Microscopic (histologic) description
  • Exhibit atypia in all layers of the epithelium, extent and degree of atypia exceeds the limits of that described in LSIL
    1. Loss of maturation and cytologic atypia in the lower two thirds (CIN II) to full thickness (CIN III) epithelium
    2. Syncytial growth with lack of distinct intercellular borders in basal and parabasal layers
    3. Immature cells with high N/C ratio, irregular nuclear membrane contour, coarse chromatin, and inconspicuous nucleoli
    4. 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:
    1. 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
    2. 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
    3. Immature HSIL with columnar differentiation
      • Now considered to be adenocarcinoma in situ, stratified variant (SMILE)
Microscopic (histologic) images

Images hosted on PathOut server:

Involvement of endocervical glands

Various images

At squamocolumnar junction

LSIL merging into HSIL


Images hosted on other servers:

HSIL - 200×

HSIL - 400×

Tripolar mitosis, endo cervical involvement

Severe dysplasia, 100×

Severe dysplasia, 400×

Severe dysplasia, p16


Full thickness of squamous epithelium

Various images - CIN II

Various images - CIN III

Cdc6, MIB-1 (figures E, F)

Cytology description
Positive stains
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
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