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.
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.
- Uterine adenofibroma with focal atypia
- Endometrial polyp with focal atypia
- Uterine adenofibroma with uterine serous carcinoma
- Endometrial polyp with uterine serous carcinoma
- Uterine carcinofibroma
Diagnosis: Uterine serous carcinoma arising in an adenofibroma
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
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.
- Zaloudek CJ, Norris HJ. Adenofibroma and adenosarcoma of the uterus: a clinicopathologic study of
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- Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100
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- Seltzer VL, Levine A, Spiegel G, Rosenfeld D, Coffey EL. Adenofibroma of the uterus: multiple
recurrences following wide local excision. Gynecol Oncol 1990: 37: 427-431.
- Clement PB, Scully RE. Mullerian adenofibroma of the uterus with invasion of myometrium and pelvic
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- Veilos F, Ng ABT, Reagen JW. Papillary adenofibroma of the uterus: a benign mesodermal mixed tumor
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- Miller KN, McClure SP. Papillary adenofibroma of the uterus. Report of a case involved by
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- Ambros RA, Sherman ME, Zahn CM, Bitterman P, Kurman RJ. Endometrial intraepithelial carcinoma:
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- Spiegel GW. Endometrial carcinoma in situ in postmenopausal women. Am J Surg Pathol 1995: 19:
- Peters WW, Wells M, Bryce FC. Mullerian clear cell carcinofibroma of the uterine corpus.
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- Thompson M, Husenmeyer R. Carcinofibroma – a variant of the mixed Mullerian tumour. Case Report. Br
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- Carcangiu ML, Chambers JT. Uterine papillary serous carcinoma: a study of 108 cases with emphasis
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- Zheng W, Khurana R, Farahmand S, Wang Y, Zhang ZF, Felix JC. P53 immunostaining as a significant
adjunct diagnostic method for uterine surface carcinoma: a precursor of uterine papillary serous
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- Matias-Guiu X, Catasus L, Bussaglia E et al. Molecular pathology of endometrial hyperplasia and
carcinoma. Hum Pathol 2001: 32: 569-577.
- Stewart RL, Royds JA, Burton JL et al. Direct sequencing of the p53 gene shows absence of mutations
in endometrioid adenocarcinomas expressing p53 protein. Histopathology 1998: 33: 440-445.
- McCluggage WG, Sumathi VP, McManus DT. Uterine serous carcinoma and endometrial intraepithelial
carcinoma arising in endometrial polyps: report of five cases including two associated with tamoxifen
therapy. Hum Pathol (in press).
- Silva EG, Jenkins R. Serous carcinoma in endometrial polyps. Mod Pathol 1990: 3: 120-128.
- Carcangiu ML, Tom LK, Chambers JT. Stage IA uterine serous carcinoma: a study of 13 cases. Am J
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- Silva EG, Tornos CS, Fullen-Mitchell M. Malignant neoplasms of the uterine corpus in patients treated
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- Huang KT, Chen CA, Cheng WF et al. Sonographic characteristics of adenofibroma of the endometrium
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- Kennedy MM, Baigrie CF, Manek S. Tamoxifen and the endometrium: review of 102 cases and comparison
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