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. 2022 Jun 1;46(6):765-773.
doi: 10.1097/PAS.0000000000001863. Epub 2022 Jan 5.

Clear Cell Carcinoma (CCC) of the Cervix Is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome: A Comprehensive Analysis of 58 Cases

Simona Stolnicu  1 , Georgia Karpathiou  2 , Esther Guerra  3 , Claudia Mateoiu  4 , Armando Reques  5 , Angel Garcia  5 , Joost Bart  6 , Ana Felix  7 , Daniela Fanni  8 , Joao Gama  9 , David Hardisson  10   11   12 , Jennifer A Bennett  13 , Carlos Parra-Herran  14 , Esther Oliva  15 , Nadeem Abu-Rustum  16 , Robert A Soslow  17 , Kay J Park  17
Affiliations

Clear Cell Carcinoma (CCC) of the Cervix Is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome: A Comprehensive Analysis of 58 Cases

Simona Stolnicu et al. Am J Surg Pathol. .

Erratum in

Abstract

Cervical clear cell carcinoma (CCC) is a rare human papillomavirus-independent adenocarcinoma. While recent studies have focused on gastric-type endocervical adenocarcinoma (GTA), little is known about CCC. A total of 58 (CCCs) were collected from 14 international institutions and retrospectively analyzed using univariable and multivariable methods and compared with 36 gastric-type adenocarcinomas and 173 human papillomavirus-associated (HPVA) endocervical adenocarcinoma (ECA) regarding overall survival (OS) and recurrence-free survival (RFS). Most cases were FIGO stage I (72.4%), with Silva C pattern of invasion (77.6%), and the majority were treated with radical surgery (84.5%) and adjuvant therapy (55.2%). Lymphovascular invasion was present in 31%, while lymph node metastasis was seen in 24.1%; 10.3% were associated with abdominopelvic metastases at the time of diagnosis; 32.8% had recurrences, and 19% died of disease. We did not find statistically significant differences in OS and RFS between CCC and GTA at 5 and 10 years (P=0.313 and 0.508, respectively), but there were significant differences in both OS and RFS between CCC and HPVA ECA (P=0.003 and 0.032, respectively). Also, OS and RFS in stage I clear cell and GTA were similar (P=0.632 and 0.692, respectively). Multivariate analysis showed that OS is influenced by the presence of recurrence (P=0.009), while RFS is influenced by the FIGO stage (P=0.025). Cervical CCC has poorer outcomes than HPVA ECA and similar outcomes to human papillomavirus-independent GTA. Oncologic treatment significantly influences RFS in univariate analysis but is not an independent prognostic factor in multivariate analysis suggesting that alternative therapies should be investigated.

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Conflict of interest statement

Conflicts of Interest and Source of Funding: Funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 (R.A.S., K.J.P., N.A.-R.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Figures

Figure 1:
Figure 1:
Clear cell carcinoma: tubular structures lined by atypical tumor cells with abundant clear, glycogen-rich cytoplasm (A); oxyphilic variant of clear cell carcinoma with tumor cells presenting with abundant eosinophilic cytoplasm (B); clear cell carcinoma with hobnail-type tumor cells (C) and with signet-ring tumor cells (D)
Figure 2:
Figure 2:
Low- and high-power of Silva A (A, B), Silva B (C, D) and Silva C (E, F) pattern of invasion
Figure 3:
Figure 3:
Kaplan Meier analysis: OS in Clear Cell Carcinomas versus Gastric type ECA (A); RFS in Clear Cell Carcinomas versus Gastric type ECA (B)
Figure 4:
Figure 4:
Kaplan Meier analysis: OS in CCC versus HPVA related ECA (A); RFS in CCC versus HPVA related ECA (B)
Figure 5:
Figure 5:
Kaplan Meier analysis in FIGO stage I CCC versus stage I Gastric type ECA (A); FIGO stage I CCC versus stage I Gastric type ECA (B)
Figure 6:
Figure 6:
Kaplan Meier analysis: OS in CCC stage I versus CCC stage II-IV (A); RFS in CCC stage I versus CCC stage II-IV (B)
See this image and copyright information in PMC

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