Extrauterine Adenomyoma With Atypical (Symplastic) Smooth Muscle Cells

Two particular issues raised by the cases presented in this report are the nature and preferred terminology of the lesions described, and the significance of the cytologic atypia within the smooth muscle component. With regard to the first point, we classified the lesions as extrauterine adenomyomas as they were circumscribed tumorlike masses consisting of endometrioid (or Müllerian type) glands, endometrioid stroma, and smooth muscle tissue, similar in most respects to their more common uterine counterparts (). It should be noted that some authors do not favor the term adenomyoma for the corresponding uterine lesions as the term implies a neoplastic process (). We cannot comment on whether the lesions presented herein are truly neoplastic but consider adenomyoma to be a reasonable and concise descriptive title. Several alternate diagnoses might be considered in our cases and perhaps the foremost is endometriosis. Traditionally, endometriosis is considered to comprise endometrioid glands and stroma but it is well recognized that many lesions also have a smooth muscle component (). The latter may be derived from normal smooth muscle tissue, for example, when endometriosis involves the muscularis of the fallopian tube or bowel wall, or it may represent a metaplastic process occurring within the endometriotic stroma. It is difficult to exclude the possibility that the predominant mesenchymal component of our cases represented hyperplasia or hypertrophy of native smooth muscle. However, the cells were arranged in disorganized short fascicles and expansile nodules, more reminiscent of a uterine leiomyoma or adenomyoma, and there was no obvious continuity with normal stromal tissue. Smooth muscle metaplasia within endometriosis is also a possibility but usually this is a focal and minor microscopic feature in contrast to the dominant smooth muscle component of the lesions that we describe. The adenomyomas described herein also share some features of the “uteruslike mass lesions” that have been recorded in various extrauterine sites including the broad ligament, ovary, and small bowel (). Some of these cases have been associated with renal or urinary tract anomalies and it has been suggested that they arise as a result of congenital abnormalities such as Müllerian duct fusion defects. However, not all uteruslike mass lesions are associated with developmental abnormalities and some authors have considered them to represent examples of endometriosis with extreme smooth muscle metaplasia (endomyometriosis) (). In any case, uteruslike mass lesions typically exhibit an organoid arrangement consisting of a single central cavity lined by endometrial type mucosa with surrounding myometrial-like tissue. In contrast, the lesions described in this report showed multifocal glandular and stromal elements distributed in random fashion within disorganized smooth muscle. It also seems that the extrauterine adenomyoma in our first patient developed several years after hysterectomy and as no lesion was evident at the time of her initial surgery a congenital anomaly seems unlikely. A further consideration is that the lesions we describe were essentially extrauterine leiomyomas with entrapped (rather than intrinsic) endometrioid glandular and stromal elements. Within the uterus, it has been proposed that similar lesions may represent primary smooth muscle neoplasms with entrapment of eutopic endometrium (submucosal leiomyomas) or serosal endometriosis (subserosal leiomyomas) (). Conversely, it has been suggested recently that uterine leiomyomas may be infiltrated by adenomyosis (so-called adenomyotic leiomyomas), and this may better explain the presence of endometrial elements within the center of such tumors (). It would seem possible that endometriosis could show analogous invasion of extrauterine smooth muscle tumors and interestingly endometriosis has rarely been noted within ovarian and retroperitoneal leiomyomas (). However, whether such a process could be distinguished from an extrauterine adenomyoma histologically is not clear and the classification of such lesions therefore may be somewhat arbitrary. The second unusual aspect of our cases was the presence of focal marked atypia within the smooth muscle component, similar to that more commonly encountered in atypical (bizarre or symplastic) leiomyomas of the uterus. Analogous cytologic changes have also been described within leiomyoma variants such as intravenous leiomyomatosis () and in the smooth muscle component of uterine adenomyomas (). That similar changes might occur occasionally in extrauterine sites is not surprising and indeed cellular atypia has been reported in leiomyomas of the ovary, round ligament, vagina, and vulva (). Bizarre cytologic changes have also been recorded within the stroma of cutaneous endometriotic lesions but these may represent degeneration within native skeletal muscle rather than smooth muscle cells (). The benign nature of the cytologic atypia in our cases is supported by the absence of mitotic activity and tumor type necrosis and by the uneventful clinical courses, albeit with relatively short-term follow-up. However, it was noteworthy that many of the atypical smooth muscle cells expressed p53 protein immunohistochemically as this finding is more common in uterine leiomyosarcomas than in leiomyomas (). Nevertheless, p53 expression has been recorded in “variant” smooth muscle tumors of the uterus including bizarre leiomyoma where it has been considered most likely a result of cellular oxidative stress rather than mutation (). The absence of ki-67 labeling and p16 expression in our cases is also supportive of a degenerative rather than malignant process. Finally, it is worth noting that thorough sampling may be required to demonstrate the endometrioid elements of the lesions that we describe as these were not evident in all of the sections examined. Thus, depending on the site of the lesion, it may not be apparent whether the smooth muscle component represents a “gynecologic type” proliferation such as extrauterine adenomyoma, or an unrelated deep soft tissue neoplasm. The distinction is important as cytologic atypia in the latter normally would be considered a malignant feature (). Immunohistochemical analysis can be a useful adjunct to diagnosis in this situation since, as in our cases, the gynecologic type tumors often express WT1, estrogen receptor, and progesterone receptor immunohistochemically ().

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