Premalignant / preinvasive lesions - H&E

Topic Completed: 1 January 2014

Minor changes: 25 March 2021

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PubMed search: LSIL / CIN I / low grade dysplasia

Seema Khutti, M.D.
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Cite this page: Khutti S. LSIL / CIN I. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixLSIL.html. Accessed May 15th, 2021.
Definition / general
  • Cervical precursor lesion associated with both low and high risk HPV subtypes
  • This category includes:
    • Flat mature LSIL (flat condyloma or CIN-I)
    • Mature Exophytic LSIL (exophytic condyloma, condyloma acuminatum)
    • Extensive Exophytic LSIL (giant condyloma)
    • Immature Exophytic LSIL (immature condyloma, squamous papilloma, papillary immature metaplasia)
    • Immature Flat Metaplastic LSIL
  • HPV16+ LSIL or ASC have higher risk for HSIL than HPV16- LSIL/ASC (J Natl Cancer Inst 2005;97:1066)
  • The recommended terminology for HPV associated squamous lesions of the lower anogenital tract is Low Grade Squamous Intraepithelial Lesion (LSIL) and High Grade Squamous Intraepithelial Lesion (HSIL), which may be further classified by the applicable intraepithelial neoplasia (IN) subcategorization (Int J Gynecol Pathol 2013;32:76)
  • Reproductive age women
  • Up to 3.0% of Pap smears reported as SIL but true prevalence unknown
Clinical features
  • Asymptomatic
  • Leukoplakia / acetowhite epithelium or cerebriform / papillary raised lesion with prominent vasculature (condyloma acuminatum)
  • Guidelines were revised based on consensus conference, recommendations reflect the acceptance of treatment based on the two tiered system
Case reports
Gross description
  • Often no gross abnormality
  • May appear as tanish white cerebriform lesion (condyloma acuminata) or uncommonly as white irregular plaque
Microscopic (histologic) description
  • Features of LSIL in mature squamous epithelium:
    • Conspicuous superficial cell atypia with binucleation, two fold nuclear enlargement and variable nuclear hyperchromasia
    • Low N/C ratio in maturing epithelial cells with preserved cytoplasmic differentiation
    • Subtle expansion of lower third of epithelium, signifying a mild delay in epithelial cell maturation
    • Range of nuclear features in lower third of epithelium includes euchromasia to uniform hyperchromasia, with minimal variation in nuclear size and shape
    • Well preserved polarity with uniform transition to mature epithelium
  • Features of LSIL in immature squamous epithelium:
    • Increased nuclear density in the upper epithelial layer
    • Preserved cytoplasmic maturation with minimal nuclear overlap
    • Minimal nuclear hyperchromasia with uniform nuclear chromatin
    • Low mitotic index
  • Flat mature LSIL (Flat condyloma or CIN-I):
    • Similar to condyloma acuminata but lacks the exophytic or papillary growth pattern
    • Degree of epithelial maturation and koilocytosis may vary but there is minimal nuclear hyerperchromasia and pleomorphism in the lower third of the epithelium
    • Associated with intermediate and high risk HPV, hence exhibits diffuse immunostaining with p16
  • Mature Exophytic LSIL (exophytic condyloma, condyloma acuminatum): see condyloma
  • Extensive Exophytic LSIL (giant condyloma): see condyloma
  • Immature Exophytic LSIL (immature condyloma, squamous papilloma, papillary Immature metaplasia: see condyloma
  • Immature flat Metaplastic LSIL:
    • Also known as eosinophilic dysplasia (see Am J Surg Pathol 2004;28:1474)
    • Uniform populations of immature metaplastic epithelial cells that maintain a mildly increased nuclear density throughout the epithelium and a mild degree of anisokaryosis
Microscopic (histologic) images

AFIP images

LSIL merging into HSIL

Koilocytosis with markedly enlarged bizarre nuclei

  • Biomarkers are used to identifying SILs that are greater risk for progressing to invasive carcinoma
  • It is less important for sorting out minor epithelial abnormalities for which a precise diagnosis of LSIL is not going to alter the patient management
  • Ki67:
    • Generic cell cycle proliferation marker, normally confined to suprabasal cells of epithelium, positive cells in upper epithelial layers is characteristic of HPV related SIL but denuded inflamed epithelium also stain the same
    • Therefore its use is reserved for occasional distinction of atrophy from HSIL
  • p16:
    • Most reliable marker
    • Intense continuous staining characterizes SIL
    • Intermediate / high risk HPV: strong expression
    • Low risk HPV (HPV 6/11) / low grade lesions: weak / focal staining, which is less specific
      • Have different staining pattern than high risk, with concentration in superficial cell
    • Endocervical columnar epithelium, including microglandular change, often stains focally and intensely for p16, hence requires cautious interpretation
  • Current recommendations are against the use of p16 IHC as a routine adjunct to histologic assessment of biopsy specimens with morphologic interpretations of negative, IN 1, and IN 3
  • Special circumstance:
Cytology description
Electron microscopy description
  • Perinuclear cytoplasmic necrosis with cytoplasmic fibrils condensed along cell periphery
  • Viral particles are present in nuclear crystalline array
Differential diagnosis
  • Cytoplasmic vacuolization due to glycogen of normal squamous epithelium:
    • Usually diffuse, normal epithelial maturation, no nuclear atypia
  • Filiform mucosal excrescences of the vagina:
    • No prominent acanthosis, no nuclear atypia, no atypical parakeratosis
  • HSIL:
    • Nuclear enlargement and atypia throughout full thickness of epithelium
  • Postmenopausal squamous atypia:
    • Pseudo koilocytosis with uniform / round halos with central nuclei, slightly hyperchromatic, occasional grooves, occasional binucleation; associated with urothelial metaplasia and atrophy
    • NOT associated with HPV (Mod Pathol 1995;8:408)
  • Reactive epithelial changes (non specific):
    • Absence of variation, in either cell size or staining intensity, in the cell population
    • Binucleated cell may or may be present but usually is inconspicuous
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