A Rare Case of Primary Signet-Ring Cell Cervical Carcinoma: Early Stage with Independent Bilateral Ovarian Metastases

Figures & data

Figure 1 Primary signet-ring cell carcinoma of the uterine cervix in the biopsy. (A) Colposcope image of the cervical mass. (B) Histopathological findings of the cervical (left) and ovarian (right) lesion (hematoxylin and eosin stain, ×200 magnification).

Figure 2 Ovarian involvement associated with the cervical adenocarcinomatous lesion. (A) Computed tomography depicting the pelvic lesion with a solid-cystic appearance. (B) The cervix and right ovary during surgery.

Figure 3 Immunohistochemical staining and polymerase chain reaction results of the cervical lesion. (A) Tumor cell nuclei were negative for estrogen receptor. (B) The presence of human type 18 papillomavirus in cervical and ovarian tissue.

Table 1 Summary of Cases of Primary Signet-Ring Cell Carcinoma of the Cervix, Modified from Giordano, Sal, Hamada et al

Authors	Number	Age(Yrs)	PresentingSymptoms	Type	FIGO Stage	Metastasis	HPV	ER/PR	Immunohistochemical Studies Other Than ER and PR
MOLL (1990)	1	50	Postcoital vaginal bleeding,menometrorrhagia	NA	III	NA	NA	NA	NA
Mayorga (1997)	1	68	Postcoital bleeding	NA	IB2	NA	NA	NA	NA
	2	74	Postmenopausal bleeding	NA	IB1	NA	NA	NA	NA
Haswani (1998)	1	33	Asymptomatic (AGUS on a routine vaginal smear)	NA	IIIB	NA	18+	NA	NA
	2	38	Postcoital vaginal bleeding	NA	IB	NA	NA	NA	NA
Cardosi (1999)	1	53	Abnormal perimenopausal bleeding	Endophytic	IB	–	NA	ER+,PR+	NA
Moritani (2004)	1	29	Abnormal vaginal bleeding	Endophytic	IIIB	–	–	ER-,PR-	Positive for CK, MUC5AC
									Negative for vimentin, MUC2, MUC6
Suarez (2007)	1	80	Postmenopausal bleeding	Exophytic	IIIB	–	NA	ER-,PR-	Positive for CK,AE1-AE3, CK 20, CEA, chromogranin A, synaptophysin.
									Negative for vimentin, S-100 protein, HMB-45, adrenocorticotropic hormone, prolactin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, growth hormone, GCDFP 15
Insabato (2007)	1	46	Abnormal vaginal bleeding	NA	IB1	NA	NA	NA	NA
McCluggage (2007)	1	NA	NA	NA	NA	NA	NA	NA	Positive for CK 7 and CK 16
	2								Negative for CK 20 and CDX2
Versas (2009)	1	36	Thromboembolic events	NA	IV	Multiple distant metastasis	+	ER-,PR-	Positive for p16 and CK 7
									Negative for CK 20, CDX2 and Dpc4.
	2	43	Metastases of lung and lymph nodes	NA	IV	Multiple distant metastasis		ER-,PR-	Positive for p16 and CK
									Negative for CK 20, CDX2 and mammaglobin
Lowery (2009)	1	60	Post-menopausal bleeding	Endophytic	IB1	–	NA	NA	NA
Balci (2010)	1	53	Postmenopausal hemorrhage	Endophytic	IIB	–	18+	ER-,PR-	Positive for CK, p16, CEA, MUC1, and MUC5.
									Negative for CK 20, GCDFP15, MUC2, chromogranine, synaptophysin, PGP 9.5, CD56, vimentin, CDX-2, TTF-1, and mammaglobin
Yoon (2011)	1	47	Postcoital vaginal bleeding	Endophytic	IB1	–	16+, 18+	NA	Positive for p53 and Rb
Giordano (2012)^Citation6	1	45	Vaginal discharge	Exophytic	IIB	Sigmoid,right ovary	18+	NA	Positive for CK 7, CA-125, CEA and p16
									Negative for vimentin
Kaidar-person (2013)	1	37	Post-coital bleeding	NA	IIB2	NA	NA	NA	Negative for chromogranin, synaptosin, CEA.
Washimi (2015)	1	31	Abnormal uterine bleeding	Endophytic	IB1	–	18+	ER-,PR-	Positive for MUC2, CDX2, CEA, CK7.
									Negative for MUC1, MUC5AC, MUC6, p53, CK20, TTF-1, GCDFP-1, mammaglobin, chromogranin-1, p16, HIK1083
Cracchiolo (2016)	1	64	Abdominal fullness	Endophytic	IVB	–	–	ER+,PR+	Positive of cytokeratin 7, (CEA).P16
									Negative of S-100 protein synaptophysin, (SMA), CDX-2, colon carcinoma and Cytokeratin 20
Sal (2016)^Citation14	1	48	Postcoital vaginal bleeding	Endophytic	IB1	–	18+	ER-,PR-	Positivity for p16, CDX-2, MUC1, MUC2 and MUC5AC.
									Negativity for synaptophysin,chromogranin A and CK20
Doghri (2017)	1	48	Abnormal vaginal bleeding	Endophytic and exophytic	IB2	Liver, lombo-aortic adenopathy	18+	ER-,PR-	Positive for p16, Cytokeratin 7 and carcinoembryonic antigen
									Negative cytokeratin 20, chromogranin A, synaptophysin, vimentin
Hamada (2019)^Citation15	1	40	Abnormal vaginal bleeding	NA	IB2	Ureteral wall	NA	NA	NA
	2	44	NA	NA	IB1	–	NA	NA	NA
Kawai (2019)^Citation16	1	40	Abnormal cervical cytology	Endophytic	NA	–	16+	NA	Positive for p16,CA125, CK7, MIB1, and MUC5AC
									Negative for p53, TTF1, CDX-2, CK20, E-cadherin, and beta-catenin, GCDFP15, MUC2, MUC6
Present case	1	35	Postcoital vaginal bleeding	Endophytic	IB1	Bilateral ovaries	18+	ER-,PR-	Positive for CK7, p16, CEA, D2-40,Ki-67, CK20, CDX-2, MUC2,MUC6
									Negative for AFP,p53,CK17, CK5/6, Inhibin-a, Vimentin

Abbreviations: CK, cytokeratin; MUC, mucin; TTF, thyroid transcription factor; GCDFP, gross cystic disease fluid protein; ER, estrogen receptor; PR, progesterone receptor; NA, not available; Yrs, years; CEA, carcinoembryonic antigen; CDX-2, caudal-type homeobox 2; SMA, smooth muscle actin; PGP, protein gene product; TTF, thyroid transcription factor 1.

Table 2 Key Points of Primary Signet-Ring Cell Carcinoma of the Uterine Cervix (PSRCCC) with Ovarian Involvement

PSRCCC, as a HPV-associated (HPVA) type of endocervical adenocarcinomas (ECAs), is exceptionally rare with about 25 reported cases

PSRCCC with independent bilateral ovarian metastases has no case reported in the literature to date.

The same expression of HPV18, no distant tumor find and negative of ER and PR support that cervix is the primary site

There are at least four possible pathways of spread for cervical carcinoma to the ovary, we would prefer the probable route is tumor cell exfoliation and transtubal spread.

The indolence exfoliative cells (seeds) site in ovary (congenial soil) selectively.

Mounting evidence suggests that the transtubal spread is typically limited to the ovaries and associated with a relatively favorable prognosis

Conservative management of HPVA type’s ECAs with independent ovarian metastases should take into account in therapy.

Giordano G, Pizzi S, Berretta R, et al. A new case of primary signet-ring cell carcinoma of the cervix with prominent endometrial and myometrial involvement: immunohistochemical and molecular studies and review of the literature. World J Surg Oncol. 2012;10:7. doi:10.1186/1477-7819-10-7

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Sal V, Kahramanoglu I, Turan H, et al. Primary signet ring cell carcinoma of the cervix: a case report and review of the literature. Int J Surg Case Rep. 2016;21:1–5. doi:10.1016/j.ijscr.2016.02.007

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Hamada K, Baba T, Takaori A, et al. Primary signet ring cell carcinoma of uterine cervix and related disease: two case reports and a review. Int Cancer Conf J. 2019;8:157–163. doi:10.1007/s13691-019-00375-5

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Kawai S, Torii Y, Kukimoto I, et al. A case of primary signet-ring cell carcinoma of the cervix containing full genome of human papillomavirus 16. Indian J Pathol Microbiol. 2019;62:146–148. doi:10.4103/IJPM.IJPM_507_17

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