Magnetic Resonance Imaging and Flexible Hysterofiberscopic Findings of a Uterine Adenofibroma: Case Report and Literature Review.
Adenofibroma is an extremely rare benign biphasic neoplasm classified as an epithelial and mesenchymal tumor. Only approximately 30 cases have been reported to date (Table 1) [1-18]. Attempts have been made to diagnose these tumors using ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), hysteroscopy, and/or biopsy, but these methods were successful in correctly identifying adenofibroma in only three patients [3,16,17]. To date, only three patients each were assessed using MRI [11, 12,14] and hysteroscopy [5,15,16]. We encountered a patient diagnosed histologically with adenofibroma using MRI and flexible hysterofiberscopy. To our knowledge, this is the first patient with adenofibroma who was assessed using both MRI and hysterofiberscopy. Highly detailed hysterofiberscopic findings in adenofibroma have not been reported previously. This report describes the clinical characteristics of this patient, including findings on MRI and flexible hysterofiberscopy, and provides a literature review of the clinical features of this rare neoplasm.
2. Case Report
A 75-year-old nulliparous woman was referred to our hospital by a private internal medicine clinic for an asymptomatic intrauterine mass. She had been treated for type 2 diabetes mellitus and cholelithiasis for 20 years. The mass was detected on abdominal ultrasonography at the clinic. Transvaginal color Doppler ultrasonography at our hospital revealed a polypoid mass, measuring 3 x 2 cm, in the uterine cavity, and consisting of multiple low echogenic cysts that differed in size without pulsatile blood flow (Figure 1). The patient's serum CA125, CA19-9, CEA, SCC, and LDH concentrations were 11.2 U/mL, 6.7U/mL, 2.7ng/mL, 1.0ng/mL, and 259IU/mL, respectively. MRI also detected an intrauterine tumor, which exhibited punctate heterogeneous hyperintensity or islands of isointense-to-hypointense signals on T2-weighted images (T2WI) (Figures 2(a) and 2(b)). Axial T1-weighted images (T1WI) showed a hypointense signal with focal areas of high signal intensity, suspected of being hemorrhagic foci (Figure 2(c)), whereas axial contrast-enhanced T1WI showed insignificant enhancement (Figure 2(d)). The tumor was well-circumscribed without myometrial invasion, with no high-intensity areas on diffusion-weighted images. Flexible hysterofiberscopy revealed a reddish-pink polyp with a whitish-yellow, cobblestone-like surface (Figure 3(a)), easily deformed by perfusion fluid (Figure 3(b)). Transcervical exeresis was attempted using forceps, but only a small part of the tumor was removed because the cervix was insufficiently dilated. Microscopically, the tumor consisted of a benign biphasic proliferation of epithelial and mesenchymal components (Figure 4(a)). The epithelial elements were endometrial glands of benign appearance. The mesenchymal component was an endometrial stroma containing fibroblasts of benign nuclear features and very low mitotic activity. The mesenchymal part was strongly positive on Masson's trichrome staining, confirming the presence of collagen fibers (Figure 4(b)). Immunohistochemical staining showed that the stromal cells were negative for smooth muscle actin and CD10. These features suggested that the tumor was an adenofibroma. Hysterectomy was recommended, because an adenosarcoma may be present within the residual tumor or an adenofibroma may develop invasive potential and recur [4, 5]. Therefore, total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Macroscopically, the mass in the uterus measured approximately 4 x 2.5 cm and was a gray-semitransparent-edematous necrotic tumor (Figure 5), although the attached area could not be identified. Histological examination revealed that the tumor was completely necrotic and amorphous, such that its origin could not be determined. Residual adenofibroma could not be confirmed in the uterus. One part of the endometrium contained an endometrial polyp, with a pathological morphology that differed completely from the adenofibroma. The postoperative course of the patient was uneventful, and no further treatment was required. Currently, two years after the surgery, the patient remains healthy.
Endometrial adenofibroma was first described in 1959 as a benign form of mixed mesodermal tumor . This rare type of noninvasive neoplasm is composed of benign epithelial and mesenchymal components, which can usually be sharply delineated from the underlying myometrium and adjacent endometrium. A similar type of tumor, Mullerian adenosarcoma, was first described in 1974 . Mullerian adenosarcoma is a mixed mesodermal tumor in which the epithelium is benign, but the stromal component is histologically sarcomatous . It is important to distinguish adenofibroma from adenosarcoma, as their expected clinical behavior differs. The most useful criterion for distinguishing adenofibroma from adenosarcoma is the frequency of mitotic figures in the stroma, with adenofibromas having three or fewer mitotic figures per 10 high-power fields (HPFs) and adenosarcomas having four or more mitotic figures per 10 HPFs . Moreover, in contrast to adenosarcomas, adenofibromas do not have a marked degree of atypical mesenchymal cells, a histologically malignant heterologous element, or myometrial invasion . However, one study described two adenofibromas that infiltrated deep into the myometrium, with one invading the lumen of myometrial veins . The latter case resembles intravenous leiomyomatosis, a histologically benign leiomyoma derived from a uterine leiomyoma or intrauterine venous wall that grows and extends intravenously. The origin and malignant potential of these tumors remain unclear.
To date, approximately 30 cases of adenofibroma have been reported in the literature (considering only English publications) (Table 1) [1-18]. Adenofibromas occur primarily in postmenopausal women, of an average age of 57 years, but may also occur in women of reproductive age . The chief complaints are usually abnormal vaginal bleeding and/or abdominal pain. About 90% of adenofibromas arise in the endometrium, with the other 10% reported to originate from the uterine endocervix. These tumors range in size from 2 to 14 cm, with an average diameter of 7.1 cm. Adenofibroma has been associated with tamoxifen therapy for breast cancer [10, 12,18]. Tamoxifen is a selective estrogen receptor modulator widely used to treat patients with estrogen-dependent breast cancer. Tamoxifen is thought to act as a partial estrogen agonist on the endometrium, thereby increasing the incidence of proliferative endometrial lesions, including adenofibromas, polyp, endometrial hyperplasia, and endometrioid adenocarcinomas.
Although attempts have been made to diagnose adenofibroma using ultrasonography, CT, MRI, hysteroscopy, and/or biopsy, these methods were successful in only three patients [3,16,17]. To date, only three patients each have been evaluated using MRI [11,12,14] and hysteroscopy [5,15,16]. To our knowledge, this is the first patient who was diagnosed using both MRI and hysteroscopy. MRI findings in this patient were consistent with those previously described [11, 12,14]. However, to our knowledge, highly detailed findings of flexible hysterofiberscopy have not been reported previously in patients with adenofibroma. Our findings of cobblestone-like surface and easy deformation by perfusion fluid reflect the histological features of adenofibroma with multilocular cysts containing secreted fluid.
Although endometrial adenofibromas are benign lesions, total hysterectomy is recommended, because these neoplasms may recur if incompletely curetted or locally excised [4, 5]. Hysterectomy assures complete excision, as well as permitting the thorough sampling needed to exclude the possibility of adenosarcoma. Indeed, most patients with adenofibroma underwent hysterectomy, with none showing tumor recurrence [1-14,16-18].
Young women with adenofibroma may be given the option of lesion removal under hysteroscopic visualization, allowing retention of the uterus and reproductive potential. Surgical excision of adenofibromas in two patients, including one who underwent operative hysteroscopy with wide local excision, was successful, with no evidence of recurrence . Recurrence associated with conservative treatment may be due to incomplete excision. Operative hysteroscopy with wide local excision may be considered an alternative to hysterectomy for women, who wish to preserve their reproductive function, provided that the completeness of excision is verified and long-term follow-up is possible.
The tumor in our patient was well demarcated, with no evidence of invasion into the myometrium on MRI. Necrotic tissue, likely the adenofibroma, was present in the uterine cavity after hysterectomy. Transcervical exeresis may have caused twisting of the tumor, resulting in necrosis. The tumor could be completely removed after hysterofiberscopy. The uterus did not contain any residual adenofibroma tissue, but the endometrium contained an endometrial polyp. Because the pathological morphology of these tumors differed completely, their causal relationship could not be determined.
Flexible hysterofiberscopy and MRI are also useful for the diagnosis of adenofibroma, which formed a polypoid mass in the uterine cavity.
Conflicts of Interest
All authors declare that there are no conflicts of interest regarding the publication of this paper.
 W. B. Ober, "Uterine sarcomas: histogenesis and taxonomy," Annals of the New York Academy of Sciences, vol. 75, no. 2, pp. 568-585, 1959.
 C. J. Zaloudek and H. J. Norris, "Adenofibroma and adenosarcoma of the uterus: a clinicopathologic study of 35 cases," Cancer, vol. 48, no. 2, pp. 354-366, 1981.
 M. Altaras, I. Cohen, M. Cordoba, and N. Ben Aderet, "Papillary adenofibroma of the endometrium: Case report and review of the literature," Gynecologic Oncology, vol. 19, no. 2, pp. 216-221, 1984.
 P. B. Clement and R. E. Scully, "Mullerian adenofibroma of the uterus with invasion of myometrium and pelvic veins," International Journal of Gynecological Pathology, vol. 9, no. 4, pp. 363-371, 1990.
 V. L. Seltzer, A. Levine, G. Spiegel, D. Rosenfeld, and E. L. Coffey, "Adenofibroma of the uterus: Multiple recurrences following wide local excision," Gynecologic Oncology, vol. 37, no. 3, pp. 427-431, 1990.
 P. K. Agarwal, N. Husain, and Chandrawati, "Adenofibroma of uterus and endocervix," Histopathology, vol. 18, no. 1, pp. 79-80, 1991.
 K. N. Miller and S. P. McClure, "Papillary adenofibroma of the uterus: Report of a case involved by adenocarcinoma and review of the literature," American Journal of Clinical Pathology, vol. 97, no. 6, pp. 806-809, 1992.
 O. Gemer, C. Mor, and S. Segal, "Uterine adenofibroma presenting as a cystic adnexal mass," Archives of Gynecology and Obstetrics, vol. 256, no. 2, pp. 99-101, 1995.
 Y. Horie, S. Ikawa, K. Kadowaki, Y. Minagawa, J. Kigawa, and N. Terakawa, "Lipoadenofibroma of the uterine corpus. Report of a new variant of adenofibroma (benign mullerian mixed tumor)," Archives of Pathology & Laboratory Medicine, vol. 119, no. 3, pp. 274-276, 1995.
 K.-T. Huang, C.-A. Chen, W.-F. Cheng et al., "Sonographic characteristics of adenofibroma of the endometrium following tamoxifen therapy for breast cancer: Two case reports," Ultrasound in Obstetrics & Gynecology, vol. 7, no. 5, pp. 363-366, 1996.
 H. K. Lee, S. H. Kim, J. Y. Cho, and K. M. Yeon, "Uterine adenofibroma and adenosarcoma: CT and MR findings," Journal of Computer Assisted Tomography, vol. 22, no. 2, pp. 314-316, 1998.
 H. Oshima, H. Miyagawa, Y. Sato et al., "Adenofibroma of the endometrium after tamoxifen therapy for breast cancer: MR findings," Abdominal Imaging, vol. 27, no. 5, pp. 592-594, 2002.
 A. Haberal, A. P. Cil, M. Gunes, and D. Cavusoglu, "Papillary adenofibroma of the cervix: A case report," Ultrasound in Obstetrics & Gynecology, vol. 26, no. 2, pp. 186-187, 2005.
 Y. Konishi, H. Sato, T. Fujimoto, H. Tanaka, O. Takahashi, and T. Tanaka, "Adenofibroma of the endometrium protruding into the vaginal cavity: Findings on transvaginal ultrasonography, MRI and CT," Journal of Obstetrics and Gynaecology Research, vol. 32, no. 6, pp. 623-627, 2006.
 I. Bettaieb, A. Mekni, K. Bellil et al., "Endometrial adenofibroma: A rare entity," Archives of Gynecology and Obstetrics, vol. 275, no. 3, pp. 191-193, 2007.
 K. Skorupskaite, A. Al-Nafussi, and G. McKillop, "Diagnostic challenges in a rare case of mullerian adenofibroma of the uterus: Instructive case and literature review," Diagnostic Histopathology, vol. 17, no. 12, pp. 557-561, 2011.
 H. M. Navada, B. P. Bhat, G. Ramani, R. R. Gatty, and C. S. Jayaprakash, "Unusual presentation of rare case of papillary adenofibroma of cervix in a young woman," Case Reports in Oncological Medicine, vol. 2012, pp. 1-3, 2012.
 H. Shi, X. Chen, B. Lv, and X. Zhang, "Concurrent tamoxifen-related Mullerian adenofibromas in uterus and ovary," International Journal of Clinical and Experimental Pathology, vol. 8, no. 11, pp. 15381-15385, 2015.
 P. B. Clement and R. E. Scully, "Mullerian adenosarcoma of the uterus. A clinicopathologic analysis of ten cases of a distinctive type of mullerian mixed tumor," Cancer, vol. 34, no. 4, pp. 1138-1149, 1974.
Hideki Watanabe, Naoya Harada (iD), Ichiro Nobuhara, Noriko Haruta, Yumi Higashiura, and Shioka Watanabe
Department of Obstetrics and Gynecology, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara City, Nara Prefecture 630-8305, Japan
Correspondence should be addressed to Naoya Harada; email@example.com
Received 12 December 2017; Accepted 9 January 2018; Published 31 January 2018
Academic Editor: Giampiero Capobianco
Caption: Figure 1: Figures on transvaginal color Doppler ultrasonography, showing a mass in the uterine cavity, measuring 3 x 2 cm and consisting of multiple cysts differing in size (triangle) and without pulsatile blood flow.
Caption: Figure 2: Magnetic resonance imaging of this patient, (a) Sagittal T2-weighted images (T2WI), showing an intrauterine tumor (triangle), which exhibited punctate heterogeneous hyperintensity or islands of isointense-to-hypointense signals. (b) View of the tumor (triangle) on axial T2WI. (c) Axial T1-weighted images (T1WI), showing that the tumor was detected as a hypointense signal with focal areas of high signal intensity (arrow), suspected of being hemorrhagic foci. (d) Axial contrast-enhanced T1WI showing a little tumor enhancement (triangle).
Caption: Figure 3: Hysterofiberscopy findings in this patient, showing (a) a red-yellow-white polyp with a partially reticulated surface (triangle) in the uterine cavity; (b) the lesion was easily deformed by perfusion fluid (arrow).
Caption: Figure 4: Microscopic findings, showing that (a) the tumor resulted from the benign biphasic proliferation of epithelial and mesenchymal components. The epithelial elements were endometrial glands of benign appearance (HE stain, objective magnification x20). The inset shows that the mesenchymal component consisted of endometrial stroma containing fibroblasts of benign nuclear features and very low mitotic activity (HE stain, objective magnification x40): (b) the mesenchymal part was strongly positive on Masson's trichrome staining, confirming the presence of collagen fibers (Masson's trichrome stain, objective magnification x10).
Caption: Figure 5: Macroscopic findings, showing a gray-semitransparent-edematous necrotic tumor, measuring approximately 4 x 2.5 cm, in the uterine cavity. The attached area could not be identified.
Table 1: List of previously described patients with uterine adenofibroma. Authors [reference Published Age number] year (y) Gravida Para Ober  1959 NM NM NM 46 NM NM 79 NM NM 71 NM NM Zaloudek 60 NM NM and 1981 Norris  62 NM NM 73 NM NM 84 NM NM 48 NM NM 70 NM NM 66 NM NM Altaras 1984 78 1 1 et al.  70 2 2 Clement and 1990 Scully  51 4 2 Seltzer 1990 28 0 0 et al.  Agarwal 1991 38 NM multi et al.  Miller and 1992 68 2 2 McClure  Gemer 1995 48 NM NM et al.  Horie 1995 67 NM 0 et al.  Huang 1996 70 4 4 et al.  56 6 3 Lee 1998 31 NM 0 et al.  Oshima 2002 69 1 1 et al.  Haberai 2005 55 NM NM et al.  Konishi 2006 42 NM 0 et al.  Bettaieb 2007 31 0 0 et al.  55 8 6 63 4 4 Skorupskaite 2011 60 1 1 et al.  Navada 2012 21 NM NM et al.  Shi et 2015 45 NM NM al.  Present 75 0 0 case Authors Maximum [reference diameter number] Chief complaint Locations (cm) Ober  Abnormal vaginal Endometrium NM bleeding Abnormal vaginal Endometrium NM bleeding Abnormal vaginal Endometrium NM bleeding Abnormal vaginal Endometrium NM bleeding Zaloudek Abnormal vaginal Endometrium NM and bleeding Norris  Abnormal vaginal Endometrium NM bleeding Abnormal vaginal Endometrium NM bleeding Abnormal vaginal Endometrium NM bleeding Abdominal pain Endometrium NM Abnormal vaginal Endometrium NM bleeding Abnormal vaginal Endometrium NM bleeding Altaras Abnormal vaginal Endometrium 8 et al.  bleeding Abnormal vaginal Endometrium 4.5 Clement and bleeding Scully  Abdominal pain, Endometrium NM vomiting Seltzer Abnormal vaginal Endometrium NM et al.  bleeding, abdominal pain Agarwal Hypermenorrhea, Endometrium, 12 et al.  low back pain endocervix Miller and Abnormal vaginal Endometrium 12 McClure  bleeding, abdominal pain Gemer None Uterine serosa 6 et al.  Horie Abdominal pain Endometrium 6 et al.  Huang Abnormal vaginal Endometrium 7 et al.  bleeding Abnormal vaginal Endometrium 5.5 bleeding Lee Abdominal vaginal Endometrium NM et al.  bleeding, hypermenorrhea Oshima Abnormal vaginal Endometrium 5 et al.  bleeding Haberai Abnormal vaginal Endocervix 7 et al.  bleeding, anemia Konishi Abnormal vaginal Endometrium 8 et al.  bleeding, anemia Bettaieb Abnormal vaginal Endometrium 13 bleeding et al.  Abnormal vaginal Endometrium 2 bleeding Uterine prolapse Endometrium 5 Skorupskaite Abnormal vaginal Endometrium 4 et al.  bleeding, abdominal pain Navada Abnormal vaginal Endocervix 14 et al.  bleeding, abdominal pain Shi et None Endometrium, 6.5 & 6.5 al.  right ovary Present None Endometrium 3 case Authors [reference Initial Initial number] examinations diagnosis Treatment Ober  NM NM TAH NM NM TAH, BS O NM NM TAH, BS O NM NM TAH, BS O Zaloudek NM NM TAH, BSO and Norris  NM Carcinosarcoma TAH, BSO, radiation NM NM TAH, BSO NM NM TAH, BSO NM NM TAH, BSO NM NM TAH, BSO NM NM TAH, BSO Altaras Biopsy Adenofibroma TAH, BSO et al.  Ultrasonography Endometrial TAH, BSO Clement and adenocarcinoma Scully  NM NM TAH, BSO Seltzer Laparoscope, Endometrial TAH, LSO et al.  hysteroscope, polyp (after biopsy recurrence) Agarwal NM Uterine myoma TAH et al.  Miller and Ultrasonography Uterine myoma TAH, BSO, McClure  CT radiation Gemer Ultrasonography NM TAH, RSO et al.  Horie Ultrasonography, CT NM TAH, BSO et al.  Huang Ultrasonography Myomatous TAH, BSO et al.  biopsy polyp Ultrasonography NM TAH biopsy Lee CT, MRI, Adenofibroma TAH et al.  biopsy or adenosarcoma Oshima Ultrasonography Endometrial TAH et al.  CT, MRI, biopsy polyp Haberai Ultrasonography NM TAH, BSO et al.  biopsy Konishi Ultrasonography, Mullerian TAH, BSO et al.  CT, MRI, biopsy mixed tumor Bettaieb Ultrasonography NM Excision et al.  Ultrasonography, NM Excision with hysteroscope hysteroscope NM Uterine TAH prolapse Skorupskaite Ultrasonography Adenofibroma TLH, RSO et al.  hysteroscope, biopsy Navada Ultrasonography, Adenofibroma TAH, BSO et al.  CT, biopsy Shi et Ultrasonography, Endometrial TAH, BSO al.  biopsy hyperplasia Present Ultrasonography, Adenofibroma TAH, BSO case MRI, hystero- fiberscopy, biopsy Authors Mitotic Follow-up [reference figures/ period number] 10 HPF (years) Characteristics Ober  NM NM 2 10 2 9 1 8 Zaloudek 3 5 and Norris  2 4 2 4 1 1.5 3 1 1 Died of other disease 2 Died of other disease Altaras 0 NM et al.  <1 3.5 Myometrial Clement and invasion Scully  Myometrial <1 3.25 invasion, intravenous invasion Seltzer <1 3 Recurrence et al.  2 years after excision Agarwal <1 2 Arising from et al.  the uterine body and the endocervix Miller and 0 0.75 Involvement McClure  of adenocarcinoma Gemer 0 NM Invasion et al.  through the uterine serosa to the right adnexa Horie NM 2 et al.  Huang NM NM NM Treated with et al.  tamoxifen NM Treated with tamoxifen Lee NM NM et al.  Oshima NM NM Treated with et al.  tamoxifen Haberai NM NM et al.  Konishi 0 NM et al.  Bettaieb <1 4 et al.  <1 2 <1 Not available Skorupskaite <1 5 et al.  Navada 0 NM et al.  Shi et <1 1 Treated al.  with tamoxifen Present <1 1 Coexisting case endometrial polyp NM, not mentioned; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; LSO, left salpingo-oophorectomy; RSO, right salpingo-oophorectomy; TLH, total laparoscopic hysterectomy; CT, computed tomography; MRI, magnetic resonance imaging; and HPF, high power field.
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Case Report|
|Author:||Watanabe, Hideki; Harada, Naoya; Nobuhara, Ichiro; Haruta, Noriko; Higashiura, Yumi; Watanabe, Shiok|
|Publication:||Case Reports in Obstetrics and Gynecology|
|Date:||Jan 1, 2018|
|Previous Article:||Uterine Necrosis after Uterine Artery Embolization for Symptomatic Fibroids.|
|Next Article:||Recurrent Nausea and Vomiting in a Pregnant Woman with Chronic Marijuana Use.|