Adenofibroma

Uterus
Stromal tumors
Adenofibroma

Author: Özlem Özen, M.D. (see Authors page)
Editor: Ayse Ayhan, M.D., Ph.D.

Revised: 14 April 2017, last major update March 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed search: adenofibroma uterus

Table of Contents

Cite this page: Adenofibroma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusadenofibroma.html. Accessed July 16th, 2017.

Definition / general

Extremely rare biphasic tumor composed of an admixture of Müllerian epithelium and stroma, both components being benign (WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014)

Essential features

First described by Ober in 1959 as a benign form of mixed mesodermal tumor (Ann N Y Acad Sci 1959;75:568) and detailed in 1973 (Am J Clin Pathol 1973;60:543)
Diagnosis has been historically reserved for polyps composed of glands set in fibromatous mitotically inactive stroma, and unqualified diagnosis is discouraged (Soslow: Uterine Pathology, 1st ed, 2012)
- Zones of histological overlap in adenofibroma-adenosarcoma spectrum
- Classification should be based on the histologically MOST MALIGNANT area
- Most (ALL, by some authorities) of these tumors fall within the spectrum of low grade sarcoma
- However, if they exist, they are clinically benign
Necessitates thorough sampling for correct diagnosis
If still problematic after repeat sampling, evaluate imaging studies especially when fertility preservation is necessary
May be extremely difficult to distinguish from low grade adenosarcoma (Am J Surg Pathol 2009;33:278)

Terminology

Synonyms: Müllerian adenofibroma, papillary adenofibroma

ICD-10 coding

9013/0

Epidemiology

Very rare, accounting for < 5% of tumors in the adenofibroma-adenosarcoma spectrum (Clement: Atlas of Gynecologic Surgical Pathology, 3rd ed, 2013)
Most commonly occurs in perimenopausal or postmenopausal women but can be seen at a younger age (Mutter: Pathology of the Female Reproductive Tract, 3rd ed, 2014, Endometrial Stromal Tumors, Mixed Müllerian Tumors, Adenomyosis, Adenomyomas and Rare Sarcomas, E. Oliva)

Sites

In uterus, mostly endometrial - may also rarely be in endocervical, ovarian, pelvic ligaments

Pathophysiology

Subjective niche between endometrial polyps on one hand and the low end of the spectrum of adenosarcoma on the other

Etiology

Origin is a continued source of debate; may be related to: papillary adenofibroma, cystadenofibroma, lipoadenofibroma and adenomyosis
Occasional cases have been associated with tamoxifen therapy (Int J Clin Exp Pathol 2015;8:15381, J Med Ultrason 2005;32:71, Abdom Imaging 2002;27:592)
Some authors believe that (at least) some of the tumors currently classified as adenofibromas (on the basis of their low mitotic count and lack of significant nuclear atypia) are well differentiated adenosarcomas, they recommend classifying as adenosarcoma of low malignant potential (Am J Surg Pathol 2009;33:278)

Clinical features

Similar to those of adenosarcoma
Most patients present with abnormal vaginal bleeding, discharge or a prolapsing mass (WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014)
Rare cases have been associated with tamoxifen therapy (Int J Clin Exp Pathol 2015;8:15381, J Med Ultrason 2005;32:71, Abdom Imaging 2002;27:592)
May invade myometrium and pelvic veins (Int J Gynecol Pathol 1990;9:363)
Diagnosis difficult based on curettings due to variable cellularity

Diagnosis

Only by histopathology - thorough microscopic examination

Prognostic factors

If strictly defined (diffusely paucicellular stroma with no periglandular cuffing, no stromal atypia and absent or rare mitotic figures < 2 MF/10 HPF), has benign biological behavior (WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014, Mutter: Pathology of the Female Reproductive Tract, 3rd ed, 2014, Endometrial Stromal Tumors, Mixed Müllerian Tumors, Adenomyosis, Adenomyomas and Rare Sarcomas, E. Oliva)
The rare reported cases of myometrial or pelvic vein invasion are probably examples of low grade adenosarcoma (Int J Gynecol Pathol 1990;9:363, Am J Surg Pathol 2009;33:278, WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014)

Case reports

35, 51 and 63 year old patients with endometrial adenofibroma (Arch Gynecol Obstet 2007;275:191)
60 year old woman, endometrial lipoadenofibroma found incidentally during hysterectomy for carcinoma of the cervix (Arch Gynecol Obstet 2008;278:283)
67 year old woman whose tumor contains foci of mature adipose tissue (lipoadenofibroma, Arch Pathol Lab Med 1995;119:274)
68 year old woman with adenofibroma and focal adenocarcinoma (Am J Clin Pathol 1992;97:806)

Treatment

Hysterectomy is the most appropriate treatment and is curative (Kurman: Blaustein's Pathology of the Female Genital Tract, 6th ed, 2011, Mutter: Pathology of the Female Reproductive Tract, 3rd ed, 2014, Endometrial Stromal Tumors, Mixed Müllerian Tumors, Adenomyosis, Adenomyomas and Rare Sarcomas, E. Oliva)
Some tumors initially diagnosed as adenofibromas have been associated with adverse outcome (multiple recurrences or even death of patients) and most likely represented adenosarcomas; thus, adenosarcoma should not be excluded in curettings or biopsy (Kurman: Blaustein's Pathology of the Female Genital Tract, 6th ed, 2011, Mutter: Pathology of the Female Reproductive Tract, 3rd ed, 2014, Endometrial Stromal Tumors, Mixed Müllerian Tumors, Adenomyosis, Adenomyomas and Rare Sarcomas, E. Oliva)

Gross description

Similar to those of adenosarcoma: polypoid masses within the endometrial cavity
May involve lower uterine segment or cervix with similar macroscopy at mucosa
Rarely mural or serosal
Usually solid but a minor cystic component may be seen
Otherwise polypoid, broad based; firm, papillary without necrosis
Reference: WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014

Microscopic (histologic) description

Benign endometrial-type epithelium covering broad papillary fronds of stroma; papillae may be cleft-like and project intraluminally or form small tubular glands; stroma more abundant than epithelial component (WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014)
The epithelial elements may also be ciliated of tubal type, or columnar mucinous of endocervix type and benign in nature (Arch Gynecol Obstet 2007;275:191)
Mesenchymal component composed of benign endometrial stromal or fibroblastic cells (WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014, Reichert: Diagnostic Gynecologic and Obstetric Pathology, 1st ed, 2011)
Cleft-like formation seen usually in adenosarcoma, but may also be seen in adenofibroma
No heterologous elements except for rare cases with foci of fat (Arch Pathol Lab Med 1995;119:274, Arch Gynecol Obstet 2008;278:283)
No periglandular stromal condensation, atypia or mitotic activity (WHO Classification of Tumours of the Female Reproductive Organs, 4th ed, 2014)
Both components are sharply demarcated from the underlying myometrium and adjacent endometrium (Arch Gynecol Obstet 2007;275:191)
No immunohistochemical or molecular tests are contributory to the diagnosis

Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Ayse Ayhan, M.D., Ph.D. and Özlem Özen, M.D.

Top: left side is adenofibroma,
right side is endometriosis
Bottom: magnified endometriosis

Periglandular cuffing is not
prominent, no cleft formation,
no atypia nor mitotic activity,
suggests adenofibroma

Foci of adenofibroma-like growth

Focus of adenofibroma-like growth
(stromal alterations are disturbing)

Focal atypia

Periglandular condensation

Diagnosis: adenosarcoma, based on
periglandular cuffing, atypia and mitoses

Images hosted on other servers:

Various images

Dense fibrous
connective tissue and
glandular spaces

Differential diagnosis

Adenosarcoma: adenofibroma should be diagnosed only if all conditions are met:
- tumor is well sampled and totally removed
- no marked cellularity (including periglandular cuffs of condensed stroma)
- no stromal cell atypia
- < 2 MF/10 HPF
- The presence of any of the above features warrants a diagnosis of adenosarcoma (Clement: Atlas of Gynecologic Surgical Pathology, 3rd ed, 2013, Kurman: Blaustein's Pathology of the Female Genital Tract, 6th ed, 2011, Am J Surg Pathol 2009;33:278)
Benign endometrial polyp: papillary or cleft-like architectural features of the adenofibroma are highly unusual for endometrial polyps (Reichert: Diagnostic Gynecologic and Obstetric Pathology, 1st ed, 2011); the stroma of endomyometrial polyps tends to be more hyaline than that of adenofibroma, although there is considerable overlap (Kurman: Blaustein's Pathology of the Female Genital Tract, 6th ed, 2011)
Endocervical-type adenomyoma: smooth muscle differentiation in stroma; no papillary or cleft-like features; no stromal periglandular accentuation (Nucci: Diagnostic Pathology, 1st ed, 2014)