Premalignant / preinvasive lesions
Adenocarcinoma in situ (AIS)

Topic Completed: 1 February 2015

Revised: 23 December 2019

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Adenocarcinoma in situ [title] cervix

Seema Khutti, M.D.
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Cite this page: Khutti S. Adenocarcinoma in situ (AIS). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixAIS.html. Accessed January 23rd, 2020.
Definition / general
  • An intraepithelial lesion containing malignant appearing glandular epithelium that carries a significant risk of invasive adenocarcinoma if not treated
  • Also known as high grade cervical glandular intraepithelial neoplasia (HGCGIN)
  • AIS is much less common than SIL, represents only 1% of all in situ carcinomas
  • Occurs in reproductive age women (mean 29 years)
  • Transformation zone, frequently unifocal
  • Arises from reserve cells with capacity to undergo columnar differentiation or from columnar epithelium
  • Associated with high risk HPV, particularly types 16 and 18
Clinical features
  • Typically asymptomatic, rarely vaginal bleeding
Case reports
  • Step I:
    • Biopsy / ECC of any visible lesion
  • Step II:
    • Biopsy of proven AIS followed by cold knife conization to evaluate extent of AIS and exclude invasive adenocarcinoma
  • Step III:
    • If fertility is not an issue, hysterectomy is preferred treatment
    • If fertility is desired, and margins are negative on cone biopsy, close follow up with repeat ECC at defined intervals with consideration for hysterectomy following conclusion of child bearing
Gross description
  • No distinctive gross appearance
  • Often multifocal involving multiple quadrants of cervix
  • Often superior to squamocolumnar junction
Microscopic (histologic) description
  • Epithelial cell crowding occurs with or without stratification
  • Variably enlarged nuclei are oval, elongated or irregular
  • Prominent nuclear hyperchromasia with coarse chromatin
  • Mitotic figures are invariably present, easily visualized at luminal pole of cell, but can be as few as one or two per HPF
  • Apoptotic bodies at basal portion of gland in 70% of cases
  • Conspicuous architectural alteration include papillary or cribriform intraglandular growth
  • The stromal interface of the AIS gland maintains the smooth, well demarcated appearance of original benign gland
  • May have abrupt transition to normal epithelium

  • AIS Subtypes:
    • Endocervical type: most common type, columnar cells with mucinous appearing or eosinophilic cytoplasm
    • Endometrial type: more nuclear stratification and less cytoplasm
    • Intestinal type: variable proportion of goblet cells, less nuclear crowding and hyperchromasia
    • Tubal type: this diagnosis should only be made if there are unequivocal nuclear features of AIS including mitotic figures, as most ciliated lesions are nonneoplastic
    • Stratified mucin producing type: resembles SIL on low power but on close inspection, the stratified neoplastic cells contain intracellular mucin; may be a form of adenosquamous carcinoma in situ
Microscopic (histologic) images

Images hosted on PathOut server:
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Endocervical type

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Adenosquamous type

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Contributed by Seema Khutti, M.D.
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Glands with cellular crowding / stratification

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Abundant mitosis and apoptosis

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AIS with adjacent uninvolved glands

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Normal endocervical epithelium with transition to AIS

Cytology description
Positive stains
  • CEA: diffuse cytoplasmic positivity (especially endocervical type)
  • Ki67: high (usually > 30%)
  • p16: strong and diffuse nuclear positivity
Negative stains
  • ER and PR: absent or minimal expression
Differential diagnosis
  • Cervical Arias-Stella reaction: focal, involving only a portion of a gland, a single gland or small number of glands; markedly enlarged cell with hyperchromatic and irregular nuclei, hobnail cells, no mitotic figures, low MIB1 IHC labeling
  • Cervical endometriosis: uniform spacing of glands, less pleomorphism and coarse hyperchromasia, evidence of recent or remote hemorrhage, endometrial stroma
  • Invasive adenocarcinoma: infiltrating glands with budding, desmoplasia, extension of glands beyond normal glandular depth
  • Mesonephric remnants: deep in stroma, bland nuclei, have intraluminal secretions
  • Microglandular hyperplasia: polypoid, smaller and more uniform glands, bland nuclei, no mitotic activity
  • Pseudostratified endocervical mucosa: normal variant - no atypia
  • Radiation and cautery effects: enlarged nuclei with smudged chromatin, preserved N/C ratio; vacuolated cytoplasm, no pseudostratification, no apoptic bodies, no mitotic figures
  • Reparative atypia: preserved N/C ratio, smudgy chromatin; no cellular stratification, rare or absent mitotic figures, no apoptotic bodies
  • Tubal and endometriod metaplasia: nuclear stratification, irregularity, and hyperchromasia is less pronounced than AIS; mitotic figures or apoptotic bodies are rare or absent; does not produce intraglandular papillary and cribriform overgrowth
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