rss
BMJ Case Reports 2013; doi:10.1136/bcr-2012-007868
  • Unusual association of diseases/symptoms

Synchronous papillary cystadenocarcinoma of ovary and squamous cell carcinoma of lower vagina: first report of an unusual chance occurrence

  1. Bal Chander2
  1. 1Department of Obstetrics & Gynecology, Dr RPGMC Tanda, Kangra, Himachal Pradesh, India
  2. 2Department of Pathology, Dr RPGMC Tanda, Kangra, Himachal Pradesh, India
  1. Correspondence to Dr Shashank Shekhar, longshanks28{at}gmail.com

Summary

Synchronously occurring primary gynecological malignancies are rare, and most commonly reported synchronous female genital malignancies are ovarian and endometrial. It is postulated that the extended Mullerian system, comprising the ovarian epithelium, fallopian tube, uterine corpus and cervix, may respond as a single morphological unit to a carcinogenic process, thus producing primary tumours at above-mentioned sites in varying combinations.  We are reporting for the first time, an unusual occurrence of synchronous papillary serous cystadenocarcinoma of the ovary and sqaumous cell carcinoma of lower vagina. Clinical implications of this case along with the multicentric concept of tumourigenesis and diagnosis of synchronous female genital malignancies are briefly discussed. Index case is probably a chance occurrence, as it cannot be explained by the current concepts of muticentric tumourogenesis in the female genital tract. Nonetheless, further research is warranted to explain simultaneous tumourogenesis in embryologically different tissues.

Background

Synchronous primary malignancies of female genital tract are an established yet rare event. Most coexistent multiple cancers are direct extensions or metastatic from one organ. However, it is imperative to distinguish metastatic disease from independently existing primary tumours, as overall survival and treatment differs considerably. Independent primary tumours have been reported at various sites in the upper female genital tract, with primary coexistent tumours of ovary and endometrium being most common.1 However, synchronous primary ovarian and vaginal cancers have never been reported in the literature. We are reporting the first case of unusual coexistence of squamous cell carcinoma of lower vagina and papillary serous cystadenocarcinoma of ovary. Clinical implications of this case along with the multicentric concept of tumourigenesis and diagnosis of synchronous female genital malignancies are briefly discussed.

Case presentation

A 57-year-old third para reported with progressive abdominal distension of 2 weeks. There were no symptoms pertaining to gastrointestinal tract except for recent loss of appetite. The patient had premature menopause at the age of 30 and denied postmenopausal bleeding per vaginum. Family history of malignancy was negative. General physical and breast examinations were unremarkable. Abdomen was grossly distended with evidence of free fluid. External genitalia appeared healthy. Speculum examination revealed a sub-centimetric nodular growth in middle third of lateral vaginal wall, not extending beyond the vagina. Biopsy from the growth later revealed squamous cell carcinoma. Cervix appeared healthy and pap smear revealed atrophic changes. Bimanual examination was largely uninformative because of the presence of large free fluid in abdominal cavity, note was made of multiple hard nodules in the pouch of Douglas. Per rectal examination did not add to the findings. Inguinal lymphadenopathy was absent.

Investigations

Stool examination for occult blood was negative. Grey scale ultrasound pelvis revealed bilaterally enlarged irregular ovaries and normal appearing uterus. Contrast-enhanced computerised tomography of the chest, abdomen and pelvis revealed left pleural effusion, massive ascites and normal appearing upper abdominal organs. Uterus was normal in size and note was made of bilateral complex adnexal masses of heterogenous echotexture measuring 3.1×4.9×4.5 cm and 4.6×4.5×3.5 cm on right and left side respectively. CA-125 was 1928.20 U/ml and CEA was 2.1 ng/ml. Ascitic fluid cytology revealed clusters of cells with features suggestive of adenocarcinoma.

Differential diagnosis

Exploaratory laparotomy was performed 1 week after admission. There was 1 litre of haemorrhagic ascites which was sent for cytology. Right and left ovaries were irregularly enlarged to approximately 5×6 cm and 4×5 cm, respectively, and were buried in the pouch of Douglas, adherent to surrounding structures. Tumour deposits measuring 2–3 cm were seen over utero vesical fold and dome of bladder. Multiple tumour deposits measuring 1–3 cm were present on the following sites: greater omentum, undersurface of the right dome of diaphragm and diagphragmatic surface of the right lobe of the liver. There was no retroperitoneal lymphadenopathy. Final staging of the disease was carcinoma ovary FIGO stage IIIc and vaginal carcinoma stage I.

Treatment

Decision for neoadjuvant chemotherapy was taken. Multiple biopsies were taken and wide excision of vaginal growth was done. Biopsies from the ovaries revealed areas of necrosis along with psammoma bodies, suggestive of papillary serous cystadenocarcinoma (figure 1A). Biopsies from the metastatic deposits revealed tumour cells in solid islands and papillary pattern consistent with metastatic deposits of papillary serous adenocarcinoma (figure 1B). Microscopic examination of the vaginal growth was consistent with squamous cell carcinoma with 0.5 cm tumour-free margins (figure 2A,B). Patient received six cycles of neoadjuvant chemotherapy (paclitaxel+carboplatin). During interval cytoreduction there was no gross evidence of primary or metastatic tumour in the pelvic and abdominal cavity. Total abdominal hysterectomy and bilateral salpingo oophorectomy with pelvic and paraaortic lymphadenectomy was performed. On gross examination uterus measured 6×3×2 cm and cut section revealed atrophic looking endometrium. Ovaries measured 3×2×1.5 cm each. Cervix appeared grossly normal. Microscopic examination of the cut sections of ovaries showed sheets of highly pleomorphic tumour cells with vague gland formation at places. Endometrium was atrophied and cervical epithelium demonstrated squamous metaplasia. Patient received 5500 cGy of radiation brachytherapy of the vagina postoperatively.

Figure 1

(A) Haematoxylin–eosin, ×40, section from an ovarian mass showing psammoma body. (B) Haematoxylin–eosin, ×4, section from omental biopsy showing a tumour composed of highly anaplastic cells in sheets and nests along with mumerous psammoma bodies.

Figure 2

(A) Haematoxylin–eosin ×10, squamous cell carcinoma of the vagina with keratin pearl formation. (B) Haematoxylin–eosin, ×40 view of the keratin pearl.

Outcome and follow-up

Positron emission tomography of the whole body performed 4 weeks later did not find any active malignant disease and CA-125 was 12.5 U/ml. The patient is on a regular follow-up.

Discussion

Two or more primary tumours that occur in a patient simultaneously or closely in time are termed as synchronous tumours.2 It is a well recognised but rare phenomenon in upper female genital tract, with a reported incidence of 0.7–1.8% in patients with gynaecological malignancies.3 Coexistent ovarian and endometrial carcinomas account for 51% of all synchronous gynaecological malignancies, thus being most common.4

Most coexistent multiple cancers are metastatic from one organ; however, it is imperative to distinguish metastatic from independently existing primary tumours, as prognosis and treatment differ considerably. Several pathologists have put forth various clinico-pathological criteria to aid clinicians and pathologists in differentiating metastatic disease from primary coexisting malignancies. These criteria include either different histological types (major criterion) or all of the following minor criteria: (1) both tumours confined to primary sites, (2) no direct extension between tumours, (3) no lymphvascular tumour emboli, (4) no or only superficial myometrial invasion and (5) distant metastasis. It was easier to diagnose coexistent primary tumours in the index case owing to different histology of the tumours.5 ,6

The aetiology of synchronous female genital malignancies is largely speculative, and it has been postulated that the extended Mullerian system comprising the ovarian epithelium, fallopian tube, uterine corpus and cervix may respond as a single morphological unit to a carcinogenic process, thus producing primary tumours at the above-mentioned sites in varying combinations.2 ,6 However, the lower vagina does not share its embryological origin with the upper genital tract, hence coexistent primary malignancy of the lower vagina with that of ovary in the index case cannot be explained by Mullerian field hypothesis. Human papilloma virus (HPV) is strongly associated with vaginal squamous carcinoma, and in rare occurrence has been demonstrated in ovarian squamous intraepithelial neoplasia,7 ,8 although the association is less clear. The ovarian tumour reported in this report is histologically different from those caused by HPV infection. Hormonal ‘field effect’ has also been proposed to explain the simultaneous occurrence of endometroid cancers at two or more sites in the upper female genital tract,9 which also fails to explain the occurrence of histologically distinct tumours in this report.

This is the first documentation of synchronous neoplasm of lower and upper female genital tract, that is, squamous cell carcinoma of the vagina with serous cystadenocarcinoma of the ovary. Given the fact that current concepts of multicentric tumourogenesis are unable to explain synchronous neoplasms in the index case, it seems reasonable to assume that simultaneous occurrence of histologically distinct tumours in embryologically different sites in the female genital tract in the index case is probably a chance occurrence. Nonetheless, pathogenesis of the carcinogenic process involving embryologically different tissues synchronously needs further research and evaluation.

Learning points

  • Synchronous primary malignancies of the female genital tract are a rare phenomenon.

  • It is important to distinguish metastatic disease from multiple primary neoplasms because of the fact that overall survival as well as the treatment varies considerably.

  • These data collected in this report support that synchronous malignancies might occur in embryologically and histologically different tissues in the female genital tract.

  • This unusual first documentation of synchronous lower vaginal and ovarian malignancies cannot be explained by current concepts of muticentric tumourogenesis; hence, further research in this field is warranted.

Footnotes

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review None.

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

References

Register for free content

The full text of all Editor's Choice articles and summaries of every article are free without registration

The full text of Images in ... articles are free to registered users

Only fellows can access the full text of case reports (apart from Editor's Choice) - become a fellow today, or encourage your institution to, so that together we can grow and develop this resource

Don't forget to sign up for content alerts so you keep up to date with all the case reports as they are published, and let us know what you think by commenting on the Editor's blog