J Pathol Transl Med.  2022 Sep;56(5):260-269. 10.4132/jptm.2022.07.05.

Cytopathologic features of human papillomavirus–independent, gastric-type endocervical adenocarcinoma

• Yeo MK
• Bae GE
• Kim DH
• Seong IO
• Suh KS

• KMID: 2533702
• DOI: http://doi.org/10.4132/jptm.2022.07.05

Abstract

Background
Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.
Methods
Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.
Results
Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.
Conclusions
Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.

Keyword

Cervix uteri; Gastric type adenocarcinoma; Cytology; Papanicolaou smear

Figure

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  Fig. 1 Human papillomavirus-independent gastric-type endocervical adenocarcinoma. Irregular angulated glands invading the cervical stroma (A). Tumor cells show negative immunohistochemical reactions for p16 (B), aberrant nuclear overexpression for p53 (C), and positivity for MUC6 (D). Atypical glands with voluminous clear cytoplasm and distinct cell borders (E). The cytoplasm contains neutral mucins that stain pale pinkish-red on Alcian blue/periodic acid–Schiff special staining in contrast to the dark purple of acid mucins of the normal endocervix (inset) (F).

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  Fig. 2 Human papillomavirus–associated usual-type endocervical adenocarcinoma. Irregular confluent glands composed of mucin-depleted cells with pseudostratified, hyperchromatic nuclei (A). Tumor cells show a block-type immunohistochemical reaction for p16 (B).

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  Fig. 3 Human papillomavirus–independent gastric-type endocervical adenocarcinoma. Monolayered honeycomb-like sheets of atypical endocervical cells in a mucinous background (open arrowhead) (A, conventional smear; B, liquid-based preparation). Usual-type endocervical adenocarcinoma. Three-dimensional clusters of hyperchromatic nuclei (C, conventional smear), feathering clusters (empty arrow), and occasional intranuclear cytoplasmic pseudoinclusions (inset, arrow) (D, conventional smear).

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  Fig. 4 Human papillomavirus-independent gastric-type endocervical adenocarcinoma. Vesicular nuclei showing nuclear grooves (open arrowhead) (A, liquid-based preparation [LBP]). Atypical tumor cells having abundant vacuolar cytoplasm with golden-brown mucin (open arrowhead) in contrast with pink normal endocervical-type mucin (arrow) (B, conventional smear). Abundant foamy cytoplasm with distinct cell borders and golden-brown mucin (open arrowhead) (C, LBP) and intracytoplasmic neutrophils (arrow) (D, LBP).

Reference

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