—  SPECIALTY CONFERENCE  —

Gynecologic Pathology

Case 2 - Uterine Serous Carcinoma Arising in an Adenofibroma

W. Glenn McCluggage
Royal Group of Hospitals Trust
Belfast, Northern Ireland


Click on each slide thumbnail image for an enlarged view
Clinical History:
A 61 year old postmenopausal woman, para 0, presented with irregular vaginal bleeding. She had been taking continuous combined hormone replacement therapy for six years. Hysteroscopy and endometrial biopsy was performed. At hysteroscopy a polypoid endometrial lesion was seen. She then underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy.


Case 2 - Figure 1 - Low power of the lesion showing a pronounced papillary pattern.
Case 2 - Figure 2 - The cores of the papillary processes are cellular and contain spindle-shaped cells. The papillary processes are lined by a single layer of bland epithelial cells.


Case 2 - Figure 3 - Focally the papillae are lined by bland epithelial cells but in areas the epithelial cells are enlarged with pleomorphic nuclei containing prominent nucleoli.
Case 2 - Figure 4 - In areas there is invasion of the stromal cores of the papillae by cells with enlarged pleomorphic nuclei.

Pathological Findings
The uterus contained a broad based endometrial polypoid lesion measuring 1 cm in maximum dimension which protruded into the endometrial cavity. The remaining pelvic organs were grossly and histologically unremarkable. Histology showed the polypoid lesion to be composed of papillary processes largely lined by cuboidal to low columnar endometrial type epithelial cells. The stromal cores of the papillae were cellular and composed of spindle shaped fibroblast-like cells. Largely the epithelial lining was bland without cytological atypia or mitotic figures. However, focally the epithelial lining of the polypoid lesion was composed of cells with enlarged hyperchromatic pleomorphic nuclei, often with prominent nucleoli. In these areas mitotic figures were identified. In small areas these pleomorphic cells infiltrated the stromal cores of the polypoid lesion. Beneath the polypoid lesion glandular structures lined by pleomorphic cells infiltrated the inner half of the myometrium. There was also focal involvement of the endocervical glandular surface. The large pleomorphic cells were positive with DO7 (anti-p53) and exhibited a high proliferation index with MIB1. They were negative with oestrogen receptor (ER). The bland nuclei lining the papillary lesion were positive with ER, negative with DO7 and exhibited a low proliferation index with MIB1.

Differential Diagnosis

  • Uterine adenofibroma with focal atypia
  • Endometrial polyp with focal atypia
  • Uterine adenofibroma with uterine serous carcinoma
  • Endometrial polyp with uterine serous carcinoma
  • Uterine carcinofibroma
  • Adenosarcoma

Diagnosis: Uterine serous carcinoma arising in an adenofibroma

Discussion

Uterine adenofibroma is a variant of mixed Mullerian or mixed mesodermal tumour in which both the epithelial and mesenchymal elements are histologically benign1. They are very rare uterine neoplasms and much less common than adenosarcoma from which they should be differentiated2. The polypoid lesion in this case was regarded as an adenofibroma rather than an adenosarcoma due to the absence of the following features:- a broad leaf like growth pattern, stromal nuclear atypia, stromal mitotic activity and a cambium layer.

Adenofibromas generally occur in postmenopausal women and present with abnormal uterine bleeding. Superficial myometrial infiltration, invasion of myometrial blood vessels and local recurrence following simple excision may rarely be seen1,3,4. As far as I am aware, there have been only two previous reports of an adenocarcinoma involving a uterine adenofibroma5,6. These both appear to have been endometrioid in type. I interpret this lesion as a uterine serous carcinoma (USC) arising in an adenofibroma. In the present case the endometrium away from the adenofibroma contained no USC or endometrial intraepithelial carcinoma (EIC)7,8 (the precursor lesion of USC) but the USC invaded the inner half of the myometrium and also focally involved the endocervical glands (stage 2A).

An alternative diagnostic consideration in this case was a carcinofibroma. These are extremely rare uterine neoplasms composed of a malignant epithelial and a benign mesenchymal component9,10. Only a few cases have been reported9,10. The polypoid lesion does not correspond to a carcinofibroma but rather a carcinoma arising in an adenofibroma. In carcinofibroma the carcinoma is associated with a fibroblastic stroma which may represent a stromal reaction to the tumour.

There are no pre-existing benign glandular elements as an integral part of the tumour. In the present case there was an obvious benign glandular component to the pre-existing lesion.

USC is the prototype of type II endometrial carcinoma11,12. These tumours are usually aggressive, often with extrauterine spread at presentation. They are not oestrogen responsive, are negative with ER and usually exhibit strong diffuse nuclear positivity with anti-p53 antibodies13, as in this case. They are often associated with p53 mutations14 and arise in an atrophic endometrium. In contrast, type I endometrial carcinomas (the prototype of which is endometrioid adenocarcinoma) are usually low stage neoplasms which arise in a hyperplastic endometrium. They are usually ER positive and p53 negative. The immunophenotype in this case is characteristic of, but not pathognomonic of, USC. Diffuse positive staining with p53 may also be found in a proportion of endometrioid adenocarcinomas, especially of high grade15. In the present case a diagnosis of USC was made on the morphology, supported by immunohistochemistry. Strong p53 immunoreactivity of the scanty preoperative endometrial biopsy resulted in strong suspicion of a USC.

USC and EIC have a known propensity to arise in or involve otherwise benign endometrial polyps16-19. The pre-existing polypoid lesion in this case had well-defined papillary projections and a cellular fibroblastic stroma. It lacked the cystic glands and thick-walled blood vessels characteristic of an ordinary endometrial polyp. I consider this to represent an adenofibroma. As far as I can ascertain, the phenomenon of USC arising in a uterine adenofibroma has not been described previously.

USC arising in atrophic non-polypoid endometrium and USC arising in endometrial polyps have been described in association with tamoxifen therapy16,17,20, as have occasional cases of uterine adenofibroma21,22. There was no history of tamoxifen therapy in this case.

In summary, this is a case of USC and EIC arising in a uterine adenofibroma.

References

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