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

Abstract

Background: As a rule, endocervical tumours with signet-ring cell are classed as metastatic extra-genital neoplasms. In a patient aged 45 years, we describe primary cervical signet-ring cell carcinoma (PCSRCC) characterized by prominent endometrial and myometrial involvement, simulating primary endometrial adenocarcinoma with cervical extension. In addition, a review was made of the literature to identify the clinical and pathological features of this rare malignancy.

Case presentation: A 45-year-old woman was referred to our Gynaecology Department due to persistent abnormal vaginal bleeding. Transvaginal ultrasonography showed slight endometrial irregularities in the whole uterine cavity suggestive of endometrial neoplasms. Pelvic magnetic resonance imaging revealed diffuse enlargement of the cervix, which had been replaced by a mass. Induration extended to the parametria and sigmoid colon fat.Histological examination of endometrial curettage and a cervical biopsy revealed a neoplasm characterized by neoplastic signet-ring cells and trabecular structures. Immunohistochemical analysis and molecular studies showed certain findings consistent with a cervical neoplasm, such as positivity to CEA, keratin 7, Ca-125 and p16 and the presence of HPV (Human Papilloma Virus) DNA 18.On examination of the hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy, the lesion replacing the cervix, endometrium and myometrium, revealed the same immunohistochemical findings observed on endometrial curettage and cervical biopsy specimens. Metastases were found in an ovarian cystic lesion and the lymph nodes.

Conclusion: With this report the authors have demonstrated that the spread of cervical adenocarcinoma to the uterine corpus, although rare, may be observed, and that in this instance immunohistochemical and molecular studies can provide sufficient information for accurate diagnosis even on small biopsy specimens.

Figure 1

On histological examination both endometrial curettage (A: Haematoxylin-Eosin × 100) and cervical biopsy (B: Haematoxylin-Eosin × 200) specimens revealed the presence of a neoplasm characterized by neoplastic signet-ring cells and trabecular structures.

Figure 2

Immunohistochemical analysis of endometrial neoplasm showed findings consistent with a primary cervical neoplasm, i.e. positivity to Ca-125 (A × 200), CEA (B × 100), and p16 (C × 200) and negativity to Vimentin (D × 200).

Figure 3

Immunohistochemical analysis of cervical neoplasm showed findings consistent with a primary cervical neoplasm, i.e. positivity to Ca-125 (A × 100), CEA (B × 200), p16 (C × 200) and negativity to Vimentin (D × 400).

Figure 4

Results of HPV-PCR amplification using the L1 consensus primers Gp5+/Gp6+ showing strong positivity for HPV-DNA in both endometrial and biopsy specimens: Lanes 1, 2, 3: CL (Cervical neoplastic lesion) DNA at three different dilutions, with strong signal for HPV-DNA. Lanes 4:, 5, 6: EL (Endometrial neoplastic lesion) DNA at three different dilutions, with strong signal for HPV-DNA. M: molecular weight standard; + = HPV positive control; - = HPV negative control.

Figure 5

Sequence alignment illustrating 100% identities between Human papillomavirus type 18 reference sequence (PAVE entry X05015.1) and HPV DNA from both endometrial and cervical specimens. (End: endometrial lesion)

Figure 6

Microscopic examination of hysterectomy specimen revealed the presence of neoplasm with endometrial and myometrial involvement. The endometrial component of the neoplasm was formed by predominant trabecular and glandular structures (A: Haematoxylin-Eosin × 40) In the myometrial part, the tumour was characterized by lakes of mucus in which neoplastic elements floated (B: Haematoxylin-Eosin × 100).