Histopathological classification of endocervical adenocarcinoma

The purpose of this website is to provide training in performing histopathological classification of endocervical adenocarcinoma. This is done by diagnosis of one of the histotypes of endocervical adenocarcinoma, using the criteria below:

• ~85% of all endocervical adenocarcinomas in an international series
• Easily identified apical mitotic figures and karyorrhexis (apoptotic bodies) at 40X magnification
• Confirmation of HPV status is optional; it can be performed with HR-HPV mRNA-ISH, HPV-PCR or p16.  mRNA-ISH test has superior sensitivity and specificity.  p16 immunostaining is a good surrogate marker provided one is cognizant of its imperfect specificity.
• Morphologic variants include:
  • Usual
    • Glandular, cystic, cribriforming, papillary, microglandular, solid patterns
    • Extravasated mucin may be seen
    • Pseudostratified, enlarged, elongated, and hyperchromatic nuclei
    • Conspicuous apical mitoses and apoptotic bodies at scanning magnification
    • Apical amphophilic to eosinophilic cytoplasm with < 50% of tumor cells containing intracytoplasmic mucin (“mucin depleted”)
  • Papillary (including villoglandular)
    • Exophytic growth with long, slender papillae
    • One or several layers of tall mucin-poor endocervical or intestinal-type epithelium
    • Mild cytologic atypia and variable mitotic activity
    • Fibrovascular cores contain spindle cells and frequent acute and chronic inflammatory cells
  • Mucinous
    • NOS:
      • ≥ 50% of tumor cells with intracytoplasmic mucin in a background of usual endocervical type adenocarcinoma
      • No specific features of gastric, intestinal, or signet ring cell morphology
    • Intestinal (with goblet cells, sometimes with neuroendocrine differentiation):
      • ≥ 50% of cells with goblet morphology in a background of usual endocervical type adenocarcinoma
      • It may have argentaffin and Paneth cells
    • Signet ring cell:
      • ≥ 50% of cell with signet ring cell morphology in a background of usual endocervical type adenocarcinoma
      • Diffuse, trabecular, glandular, and cord-like growths
    • Invasive stratified mucinous carcinoma:
      • Invasive nests or trabeculae of pseudostratified pale columnar cells with peripheral palisading and variable intracytoplasmic mucin (closely resembling morphologically SMILE-in situ counterpart-)
      • Intracytoplasmic mucin/microlumens but no well-formed lumens or glands
      • Moderate cytologic atypia, brisk mitoses and apoptotic bodies
      • Brisk acute inflammatory infiltrate common
      • Often confused with adenosquamous carcinoma
  • Mixed
    • Not infrequently a mixture of HPVA related subtypes is seen
  • HPV-Associated, Not otherwise specified
    • Doesn’t fit into any other of the above categories but it is confirmed to be HPVA related
  • Note that more than one variant may coexist in a tumor

• Gastric-type endocervical adenocarcinoma, ~10% of all endocervical adenocarcinomas in an international series
  • NO easily identified apical mitotic figures and karyorrhexis at 40X magnification
  • Glands lined by large, columnar cells, frequently containing pink-to-clear mucin, with crisp cytoplasmic borders (“plant-like”) and atypical nuclei
  • Range of differentiation, from well-formed glands without obvious desmoplasia (“minimal deviation” mucinous adenocarcinoma), to those containing goblet cells and neuroendocrine-type granules, and those showing poor differentiation in the form of fragmented glands and single cells with obvious desmoplasia
  • Confirmation of HPV-negativity may be sought, as described above
• Clear cell carcinoma, ~3% of all endocervical adenocarcinoma in an international series
  • NO easily identified apical mitotic figures and karyorrhexis at 40X magnification
  • Typical clear cell carcinoma morphology
  • Confirmation of HPV-negativity may be sought, as described above
• Mesonephric carcinoma, < 3% of all endocervical adenocarcinoma, in an international series
  • NO easily identified apical mitotic figures and karyorrhexis at 40X magnification
  • Mixture of patterns (microglandular, glandular, papillary, glomeruloid, spindled), typical of mesonephric carcinoma
  • Confirmation of HPV-negativity may be sought, as described above
• Endometrioid carcinoma, <2% of all endocervical adenocarcinoma in an international series
  • NO easily identified apical mitotic figures and karyorrhexis at 40X magnification
  • Endometrioid-associated features present:  endometriosis, low-grade endometrioid glands, squamous differentiation, secretory change, frequently ER/PR positive
  • EXCLUDE extension from lower uterine segment and uterine corpus
  • Confirmation of HPV-negativity may be sought, as described above
• Non-HPV-Associated, Not otherwise specified
  • Doesn’t fit into any other of the above categories but it is confirmed to be non-HPV related

You will be asked to place each tumor into one of the following categories, from a drop down menu:

1. HPV-associated (HPVA) related patterns:
   1. Usual
   2. Papillary (including villoglandular)
   3. Mucinous
      1. NOS
      2. Intestinal (with goblet cells, sometimes with neuroendocrine differentiation)
      3. Signet ring
      4. Invasive stratified mucinous carcinoma
   4. Mixed
   5. Not otherwise specified (confirm HPVA, but doesn’t fit into any other category)
2. Non-HPV-associated (NHPVA):
   1. Gastric-type
   2. Clear Cell
   3. Mesonephric
   4. Endometrioid
   5. Not otherwise specified (confirm Non-HPVA, but doesn’t fit into any other category)

There are 56 cases and they are divided into 25 cases as a TRAINING SET; for each of these cases, please review the slide and choose the most appropriate histopathological classification, as per the guidelines above, and click on the result button to immediately see the classification assigned by the study pathologists.

There are also 31 cases in the TEST SET; for this series of 31 scanned slide images, please choose a histopathological classification for each image, and when you have completed all 31 slides, you will be given your results for the series, compared to the classification assigned by the study pathologists.

To start, click on the TRAINING SET link, below. After reviewing the training set cases, please proceed to the TEST SET.

TRAINING SET (25 cases)

TEST SET (31 cases)