Squamous Cell Carcinoma In situ of the Cervix with Superficial Intraepithelial Extension to the Endometrium of Lower Uterine Segment: A Rare Presentation.

Carcinoma of the cervix is the most common malignancy in women in India. Squamous cell carcinoma accounts for more than 70% of the cervical malignancies. Carcinoma of the cervix generally invades the uterine wall by direct extension with or without parametrial involvement, however, rarely can spread superficially to the inner surface of the uterus replacing the endometrium. It is an uncommon phenomenon for an in situ lesion of the cervix to have contiguous superficial spread to the endometrium. We report a case of cervical in situ squamous cell carcinoma in a 45-year-old female with contiguous extension to the endometrium of the lower uterine segment.

Introduction

Carcinoma of cervix is the most common gynecological malignancy caused by persistent infection with carcinogenic types of human papilloma virus (HPV). The proportion with squamous histology is around 70%. Cervical squamous cell carcinoma can directly invade the uterine wall with or without parametrial involvement or by lymphatic invasion. Direct extension to the endometrium replacing it without myometrial invasion is very uncommon.[1] A case of carcinoma in situ of cervix with contiguous extension to the endometrium of the lower uterine segment is reported hereby with emphasis on immunohistochemistry.

Case Report

A 45-year-old female (para three, live three) presented with lower abdominal pain and excessive bleeding per vaginam. She got married at the age of 18 years and has three full-term spontaneous vaginal deliveries. Her first child was born at the age of 20 years. There was no significant past medical or surgical history. She has not undergone cervical smear examination until now. Pelvic examination revealed a firm cervix. Ultrasound imaging revealed a small myoma in the anterior wall. With the provisional clinical diagnosis of myoma uterus, total abdominal hysterectomy with bilateral salpingectomy was performed. On gross examination, the uterus and cervix measured 9 cm × 5 cm × 4 cm with granular appearance of ectocervix. The endometrial surface was thin and smooth.

Microscopically, the ectocervix was lined by squamous epithelium with full thickness dysplasia with nuclear atypia, loss of polarity, and hyperchromasia [Figure 1a]. Basement membrane was lost in some foci. Invasion into the stroma beneath or stromal desmoplasia was not seen. There was contiguous extension of the dysplastic squamous epithelium into the lower uterine segment replacing the endometrium [Figure 1b]. There was no myometrial invasion. Endometrium lining the uterine body, and the fallopian tubes were free of tumor spread. Leiomyoma was identified in the anterior myometrium.

Figure 1

(a) Cervical intraepithelial neoplasia III of the uterine cervix with nuclear atypia (×100). (b) In situ tumor sweeps over the endometrium of the lower uterine segment (×40). (c) Strong expression of CD138 in the cervix in situ tumor (×40). (d) strong expression of CD138 in the in situ tumor in the lower uterine segment (×40)

Immunohistochemical analysis with CD138 revealed strong and diffuse expression in the dysplastic squamous epithelium in the cervix [Figure 1c] and in the lower uterine segment [Figure 1d] in its full thickness including the basal layers.

Discussion

Squamous cell carcinoma of cervix is the most common tumor of the female genital tract, accounting for about 70% of the cervical malignancies.[2] Cervical carcinoma spreads generally upward to the parametrium and through lymphatic invasion to the uterine wall. The presence of squamous cell carcinoma in situ of the cervix with squamous carcinoma in situ of the endometrium of the lower uterine segment suggests a superficial spread of carcinoma cells originating from the cervical mucosa. Although initial studies cited the role of radiation in pathogenesis,[3] the present studies found monoclonal neoplasia originating from the cervical mucosa with loss of heterozygosity analysis.[4] The superficial spread of cancer to the endometrium may be evident on gross examination as “cake icing” or “Zukerguss” where the tumor sweeps over to replace the endometrium.[1]

The clinicopathological features of the previously described cases of superficial spreading carcinoma of cervix revealed older age at presentation with various predisposing factors, such as early marriage, early first sexual intercourse, multiparity, and HPV infection. Few of these factors were seen in our patient as well.

The histology of the cervical neoplasia in the previously reported cases was ranging from squamous cell carcinoma in situ, microinvasive squamous cell carcinoma, invasive squamous cell carcinoma to adenosquamous carcinoma. Although contiguous spread of tumor was restricted to the endometrium, few studies reported spread of tumor to the fallopian tube and or ovaries as well.[156] Moreover, the pattern of tumor spread in the endometrium was either in situ as in our case or with invasive component in contiguous with the cervical malignancy.

In our case, the age at presentation was 5 years earlier to those described in literature with early marriage, early first sexual intercourse, and multiparity. Ishida and Okabe demonstrated strong expression of CD138 in carcinoma cells that participate in superficial spreading by regulating cell to cell interactions while cells in the invasive focus lack CD138 expression.[7] CD138 in our case also showed intense expression of the in situ component in the cervix and lower uterine segment without loss of expression in the deeper layers of the epithelium.

Conclusion

The superficial spread of squamous cell carcinoma in situ of cervix to the endometrium is a rare event, with few cases reported in the literature. The International Federation of Gynaecology and Obstetrics staging has not included such an entity in the staging of cancer cervix. The World Health Organization in its classification of tumors of the cervix has not described such a phenomenon. The prognostic significance and management guidelines for such type of unusual spread of carcinoma cervix are also lacking. It is hoped that the increase in reporting of such rare phenomenon will help in recognition of this entity with etiopathogenesis and formulating the management guidelines.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.