Background
Uterine leiomyomas are the most common type of uterine tumor [
1], with its variants accounting for approximately 10 % of cases [
1]. Cotyledonoid dissecting leiomyoma is an extremely rare variant of uterine leiomyoma with an unusual pattern that is characterized by intramural dissection within the uterine corpus and often a placenta–like macroscopic appearance of its extrauterine component [
2]. David et al. originally reported this variant as grape–like leiomyoma in 1975 [
3], which was later named as cotyledonoid dissecting leiomyoma in a series of four cases by Roth et al. [
2]. Thereafter, over 30 cases have been reported thus far; all followed a clinically benign course [
4‐
6]. Although several cases indicated coexisting focal endometriosis, endosalpingiosis, and adenomyomatous components [
7‐
9], none showed obvious and abundant nontumoral components within the tumor. Here we present a unique case of cotyledonoid dissecting leiomyoma involving numerous non-neoplastic endometrial glands with endometrial stromal cells, indicating adenomyosis. To the best of our knowledge, this is the first description of cotyledonoid dissecting leiomyoma with ademomyosis.
Discussion
In the present case, the clinical manifestation, gross appearance, and histological findings were in good agreement with typical cotyledonoid dissecting leiomyoma. Leiomyomas of the uterus are the most common uterine tumor and usually affect women in their fourth and fifth decades [
1]. Most uterine leiomyomas are conventional types, whereas variant forms comprise approximately 10 % of all leiomyoma cases [
1]. Cotyledonoid dissecting leiomyoma is an extremely rare variant of uterine leiomyoma with an unusual growth pattern characterized by an extrauterine mass that resembles a placenta and histologically shows an intramural dissecting pattern in the uterus [
2,
3]. Saeed et al. reviewed 20 cases of cotyledonoid dissecting leiomyoma [
4]. The ages of patients ranged from 23 to 65 years (mean, 40.3 years), which were less than those of patients with conventional leiomyomas. The most common clinical presentation of this variant is a pelvic mass and is followed by abnormal uterine bleeding. The size of these tumors ranged from 10 to 41 cm (mean, 17.7 cm). Thus far, over 30 cases have been reported in the literature [
4,
5]. Histologically, the neoplastic smooth muscle cells form disorganized fascicles in cotyledonoid dissecting leiomyomas, in contrast to the organized pattern observed in conventional leiomyomas [
6]. In this case, both the intrauterine and extrauterine part of the tumor was composed of the same nodular masses of disorganized smooth muscle cells and collagen fibers as those of previous reports (Fig.
2c and
d). All cases reported to date were clinically benign, and only one case of recurrence after partial tumorectomy was reported [
10]. Cases of epithelioid cotyledonoid dissecting leiomyoma variant [
5] and cotyledonoid dissecting leiomyoma with intravenous leiomyomatosis [
7] were also recently reported. However, neither an epithelioid pattern nor intravascular tumor components were found in our case.
Interestingly, several reports alluded to cotyledonoid dissecting leiomyomas with non-neoplastic cystic lesions (Table
1). Conventional uterine leiomyoma does not usually contain cystic lesions, whereas one case of intravenous leiomyomatosis of the uterus with an endometrial component was previously reported [
11]. In addition, Fukunaga et al. described a cotyledonoid dissecting leiomyoma with limited foci of endometriosis in 1998 [
8]; the foci were located in the shallow portion of the extrauterine components and the left ovary and were considered as endometriosis. Conversely, Driss et al. reported a cotyledonoid dissecting leiomyoma case associated with endosalpingiosis in 2009 [
9]. The lesion was within the exophytic component with small cysts of 1–2 mm in diameter. These glands and cysts were lined by ciliated tubal type epithelium and surrounded by scanty, loose fibrous tissue. Immunohistochemistry revealed that the columnar epithelium was positive for cytokeratin 7, but the stromal cells were not characterized in detail. In a series of six cases, Jordan et al. described one tumor demonstrating cystic spaces within the extrauterine component [
7]. They reported the presence of tubo-endometrial glands without accompanying stroma; thus, that finding was interpreted as an unusual adenoleiomyomatous element. The cotyledonoid dissecting leiomyoma in our patient presented with the greatest extent of non-neoplastic cystic lesions compared with the three previous cases. However, all these cases, including ours, suggest that cotyledonoid dissecting leiomyoma might have a unique clinical presentation involving parts of benign non-neoplastic cystic lesions.
Table 1
Summary of all reported cases of cotyledonoid dissecting leiomyoma with non-neoplastic cystic lesions
1
| 35 | Abdominal pain and mass | Lateral wall | 18 | Endometriosis | Endometriosis in left ovary | |
2
| 47 | Abdominal mass | Posterior wall, broad ligaments, pelvic cavity | 25 | Endosalpingiosis | NA | |
3
a
| NA | NA | NA | NA | Adenoleiomyomatous component | NA | |
4
| 40 | Menorrhagia and severe anemia | Posterolateral wall, pelvic cavity | 14 | Adenomyosis | Adenomyosis | Present case |
We suppose the endometrial component in this tumor may be a part of adenomyosis, not endometriosis. It is because localization of the endometrial component is not superficial and endometriosis is not found in any part of the pelvic cavity. However, adenomyosis is distributed both in the tumor and tumor-free myometrium (Fig.
3d). Furthermore, some of these endometrial elements within the tumor are enclosed by non-neoplastic myometrial smooth muscle that is slightly immunopositive for Bcl-2 (Fig.
4a and b). Bcl-2 protein is known to be an apoptosis-inhibiting gene product, and it is also known to prevent apoptotic cell death in a variety of cells. Matsuo et al. reported that Bcl-2 immunopositivity was prominent in uterine leiomyoma cells and was scarcely present in normal myometrial smooth muscle cells [
12]. They supposed that Bcl-2 protein associated with progesterone is responsible for the growth of leiomyomas by preventing apoptotic cell death [
13].
On the other hand, adenomyoma should be an important differential diagnosis in the extrauterine part of the tumor. Adenomyoma is one of the mixed epithelial and mesenchymal tumors of the uterine corpus and is described as a well-circumscribed tumor composed of endometrial glands and endometrial-type stroma surrounded by abundant smooth muscle component [
1]. We cannot definitely distinguish adenomyoma with involved adenomyosis in a cotyledonoid dissecting leiomyoma, because each histological component is very similar and also because of degenerative changes in the extrauterine part caused by menstrual bleeding followed by inflammation. Typical adenomyomas are intramural, firm, and smooth-surfaced tumors [
14]. They show gray-white surfaces and are well demarcated from the myometrium on cut sections, and their smooth muscle component shows hypertrophy but does not make nodular proliferation with collagen fibers [
15]. However, we can also find a few previous case reports of adenomyoma with prominent cystic change extended to the pelvic cavity [
16,
17]. Since histological analysis of these tumors is not provided in detail, we cannot distinguish them from cotyledonoid dissecting leiomyoma with adenomyosis. Accumulation of similar cases will help us understand the nature and the difference between adenomyoma and cotyledonoid dissecting leiomyoma with adenomyosis.
The mechanism of tumor development in this patient is interesting. In this case, leiomyoma was first found in the uterine wall by transvaginal ultrasonography and was later noted to extend into the pelvic cavity. It is possible that during tumor growth from the myometrium, endometrial glands and stromal cells might have been captured by the intramural component of tumor during its dissection through the surrounding adenomyosis, to be located together with the extrauterine component. In this case, glandular components and stromal cells were also recognized in the intramural component, supporting this possibility. The cystic expansion of endometrial glands outside the uterus might be correlated with loose connective tissue with congestion and hydropic change.
The cotyledonoid dissecting leiomyoma in our case included a large number of non-neoplastic cystic lesions compared with previously reported three cases. This case indicated that cotyledonoid dissecting leiomyoma could occur with concomitant adenomyosis, depending on the pattern of tumor growth. These four cases, including ours, suggested that cotyledonoid dissecting leiomyoma might have a unique presentation with benign non-neoplastic cystic lesions, such as endometriosis, endosalpingiosis, adenoleiomyomatous component, and adenomyosis.
Acknowledgements
We would like to thank Drs. Shinichi Tejima, Akio Sakatani, Megumu Fujiwara, Yasunari Oda, and Kanako Hatanaka for their valuable advice. We also thank Mr. Makoto Imagawa, Mr. Atushi Minoshima, Ms. Madoka Yamaguchi, Ms. Yukiko Oda, Mr. Jun Koizumi, Mr. Yuji Meguro, and Ms. Kuniko Asahi for providing sections for routine hematoxylin-eosin staining and immunohistochemistry at the Department of Pathology of KKR Sapporo Medical Center. We thank Enago for English language review.