Cytomorphological Features of Hyperchromatic Crowded Groups in Liquid-Based Cervicovaginal Cytology: A Single Institutional Experience

Abstract

Background: Hyperchromatic crowed groups (HCGs) are defined as three-dimensional aggregates of crowded cells with hyperchromatic nuclei, and are frequently encountered in cervicovaginal liquid-based cytology (LBC). Here, we aimed to examine the prevalence of HCGs in cervicovaginal LBC and the cytomorphological characteristics of various epithelial cell clusters presenting as HCGs. Methods:We first examined the prevalence of HCGs in a "routine cohort" of LBC cytology (n = 331), consisting of all cervicovaginal LBCs accessioned over 3 days from outpatient clinics (n = 179) and the screening population (n = 152). Then we examined a second "high-grade epithelial cell abnormalities (H-ECA) cohort" (n = 69) of LBCs diagnosed as high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC), or adenocarcinoma during 1 year. Results: HCGs was observed in 34.4% of the routine cohort and were significantly more frequent in the epithelial cell abnormality category compared to the non-neoplastic category (p = .003). The majority of HCGs represented atrophy (70%). Of the 69 histologically confirmed H-ECA cases, all contained HCGs. The majority of cases were HSIL (62%), followed by SCC (16%). Individually scattered neoplastic cells outside the HCGs were significantly more frequent in SCCs compared to glandular neoplasia (p = .002). Despite the obscuring thick nature of the HCGs, examining the edges and the different focal planes of the HCGs and the background were helpful in defining the nature of the HCGs. Conclusions: HCGs were frequently observed in cervicovaginal LBC and were mostly non-neoplastic; however, neoplastic HCGs were mostly high-grade lesions. Being aware of the cytomorphological features of different HCGs is important in order to avoid potential false-negative cytology interpretation.

The association of atypical squamous cells, cannot exclude a high grade squamous intraepithelial lesion, hyperchromatic crowded groups and high grade squamous intraepithelial lesions involving endocervical glands

“…Although the nuclear features can overlap, cigar shaped nuclei are a feature of endocervical AIS and not HSIL involving endocervical glands. 17 Similar findings were reported by Lee et al 22…”

“…Although the nuclear features can overlap, cigar shaped nuclei are a feature of endocervical AIS and not HSIL involving endocervical glands 17 . Similar findings were reported by Lee et al 22 HCGs were present on ThinPrep Pap tests from all 69 histologically confirmed cases of high grade epithelial cell abnormalities; the majority of which were squamous.…”

Atypical glandular cells (AGC): Cytology of glandular lesions of the uterine cervix

“…Under low-power HCGs are seen as spheres of small groups of cells and may resemble exodus of three-dimensional cluster of endometrial cells with high N/C ratio. [ 18 ] The individual nuclei appear larger than the normal endometrial nuclei. On high power, the nuclei are hyperchromatic, with occasional small nucleoli.…”

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

“…In a reparative process, sheets of atypical endocervical cells have enlarged nuclei with increased nuclear to cytoplasmic ratios, sometimes multiple nucleoli, and mitotic activity. A regular honeycomb arrangement of reactive endocervical cells is also a cytologic feature of non-neoplastic HCGs [ 19 ]. Endocervical or endometrial cells presenting as HCGs may mimic glandular high-grade precancers.…”