—  SPECIALTY CONFERENCE  —

Surgical Pathology

Case 4 - Adenomyoma of Uterine Corpus

Robert Young
Massachusetts General Hospital
Boston, Massachusetts


Click on each slide thumbnail image for an enlarged view
Clinical History:
A 36 year old woman with vague abdominal pain underwent laparotomy. This disclosed a polypoid mass attached to the serosa of the uterine fundus. The mass was dissected from the uterus. Pathologic examination disclosed a 16x14x7 cm, 780gm, bosselated mass that was solid and cystic on cut section. The cysts contained serous fluid. No papillary excrescences were noted within the cyst.


Case 4 - Figure 1 - Low power view showing biphasic neoplasm with cleft-like spaces and cysts lined by a single layer of epithelial cells and an intervening mesenchymal compartment that varies from hypocellular to hypercellular.
Case 4 - Figure 2 - Medium power view showing small ball-like hypercellular areas within mesenchymal compartment.
Case 4 - Figure 3 - High power view showing mullerian type epithelium with bland cytologic features and myogenic nature of mesenchymal component.

Diagnosis - Adenomyoma of Uterine Corpus

Comment:
There are in surgical pathology occasional entities which are actually quite common but for whatever combination of reasons do not get much attention and sometimes are even a source of diagnostic confusion for experienced pathologists despite what, in many cases, is a rather mundane appearance. This comment, in my opinion, pertains as much to the adenomyoma of the uterus of the usual type as it does anything else I can think of. I have seen many cases in which this diagnosis has been overlooked, sometimes by eminent pathologists, I can only assume because of the relative paucity of consideration of this lesion in recent times. As Washington is not far from Baltimore, and the latter city was where the pioneering gynecologist pathologist, Dr. Thomas S. Cullen spent most of his active career, it is appropriate that an adenomyoma be the subject of one of tonight's cases and allows me to highlight one of that great pathologist's four monumental works, namely his book of almost a century ago entitled "Adenomyoma of the Uterus".1 The entity of adenomyoma was not the subject of much attention until 1981 when Dr. Michael Mazur made a major contribution by drawing attention to the atypicality that may be seen in some cases.2  More recently, prompted by cases of adenomyoma of usual type, meaning by that those which were not atypical but still caused diagnostic difficulty, we (Dr. Blake Gilks et al) wrote another contribution on the topic.3  I will discuss some of the issues that can come up in evaluating typical adenomyomas, atypical adenomyomas, and finally adenomyomas of endocervical type.

Typical adenomyoma of endometrioid type:
Women with these tumors are almost always in the reproductive or postmenopausal age groups and usually present with abnormal vaginal bleeding; some tumors are an incidental finding on clinical or pathologic examination. In our series, 90% of the tumors were in the corpus, and were usually submucosal, but occasionally mural or subserosal; the rest were in the cervix.3  The subserosal and submucosal tumors are typically polypoid. Maximal dimensions of up to 17 cm have been recorded. The sectioned surfaces are usually firm with occasional cysts.

On microscopic examination, the tumors are composed of glands and cysts lined predominantly by bland endometrioid epithelium separated by benign-appearing endometrial stroma (which typically form periglandular cuffs) and smooth muscle, with the latter predominating. Minor foci of other epithelia, including tubal-type, mucinous endocervical-type, and squamous, may also occur. Any of the many changes that may be seen in pure smooth muscle tumors can be encountered in the smooth muscle component of an adenomyoma, including hydropic change which is sometimes striking as well as foci with an epithelioid morphology or a pseudoepithelioid morphology when edema or hyalinization causes tumor cells to grow in cords or nests. Unusual findings in the smooth muscle component include marked cellularity (as focally seen in the seminar case in the form of small "blue balls") and cells with bizarre nuclei. Sex cord-like foci were present within the endometrial stromal component in one of our tumors, and rare tumors have contained foci of adipose tissue ("adenomyolipoma"). There is usually no mitotic activity in the epithelial or mesenchymal elements, but in occasional cases an appreciable mitotic rate is seen. When an adenomyoma has appreciable cytologic epithelial atypia and is polypoid it obviously falls in the category of the atypical polypoid adenoma, which is considered separately below.

The major differential is with a mullerian adenosarcoma but that neoplasm definitionally has a malignant (usually low-grade) stromal component of endometrial stromal type that predominates, and smooth muscle is usually absent or inconspicuous. It is important to remember that the adenomyoma characteristically has a cuff of endometrial type stroma around the glandular component and this should not be confused with the cuffing typical of an adenosarcoma. The endometrial stroma in an adenomyoma appears morphologically benign and the glandular component of an adenomyoma lacks the typical polypoid intraluminal stromal fronds that are so frequent in the adenosarcoma. This is particularly important to look for in the occasional case of adenosarcoma which has abundant smooth muscle. The potential problems caused by adenomyomas can be many when one reflects on the fact that they have mullerian-type epithelium which can undergo varying degrees of precancerous change including even the development of frank adenocarcinoma, endometrial stroma which may show its interesting diversity of features including smooth muscle and fibrous morphology, the sex cord-like differentiation referred to briefly earlier and even potentially malignant change although that has not been encountered yet to the best of my knowledge. Finally, as already mentioned the smooth muscle may undergo any of the changes seen in leiomyomas of which there are, of course many, several of them as already also noted being present in one or more of the cases in the Gilks study.3  Two or potentially more of the changes noted can conceivably be present in an individual tumor potentially leading to remarkably diverse morphologies. Dissecting out the background architecture upon which the variant features are placed is crucial in arriving at the correct diagnosis.

Atypical Polypoid Adenomyoma (APA)
are encountered in the reproductive age group (average age 39 years), but occasionally the patients are postmenopausal.2,4-6  Rare cases are associated with long-term estrogen therapy.5  The patients typically present with abnormal vaginal bleeding. Pelvic examination is usually negative, although occasionally there is a polypoid mass at the external os. APAs most commonly arise in the lower uterine segment, and less commonly the endocervix or corpus. The tumors are usually solitary, well-circumscribed, pedunculated or sessile, and typically less than 2 cm in maximum dimension. The sectioned surfaces are yellow-tan to gray to white, solid, and firm to rubbery.

Endometrioid glands with varying degrees of architectural and cytological atypia and mitotic activity are admixed with a cellular myofibromatous stroma. Squamous morules, present in 90% of tumors, can obliterate gland lumens and exhibit central necrosis. Transtubal spread of keratin derived from the morules can result in peritoneal keratin granulomas. Rare features include a cribriform glandular pattern, severe cytological epithelial atypia, or both. Almost half the APAs in one study 6) had foci that architecturally resembled well-differentiated adenocarcinomas "APAs of low malignant potential" [APAs-LMP] Additionally, rare APAs are contiguous to, and appear to be the origin of, a well-differentiated myoinvasive endometrioid adenocarcinoma (see below).

The cellular stromal component consists of smooth muscle cells and/or myofibroblasts. The stromal cells appear benign, but exhibit mild to moderate atypia in a minority of cases. Occasional mitotic figures are often present. APAs are usually non-invasive, with a well-circumscribed border in hysterectomy specimens, although some tumors involve the superficial myometrium. In the study cited above,6  none of the usual APAs invaded the myometrium, whereas 2 of 12 APAs-LMP were superficially myoinvasive. The uninvolved endometrium typically reflects hyperestrinism (normal proliferative, endometrial hyperplasia), but rarely is normal secretory.

The APA is most often confused with endometrial adenocarcinoma, although the latter, in contrast to the APA, is composed of glands with architecturally and cytologically malignant features. The two tumors, however, may have a similar myofibromatous stroma.7  An APA may also be confused with an MMMT or adenosarcoma if its cellular stroma is mistaken for sarcoma. Differential features from APA include a usual absence of prominent smooth muscle component (MMMT and adenosarcoma), periglandular stromal condensation and intraglandular stromal papillae (adenosarcoma), a glandular component that is often predominantly cystic and less atypical than that of the APA (adenosarcoma), and overtly malignant epithelial and stromal components (MMMT). Typical polypoid adenomyomas are distinguished from APAs by their usual absence of architectural and cytological glandular atypia and a paucicellular smooth muscle component.

Longacre et al 6 found intrauterine persistence or recurrence in as many as 45% of women treated by D&C or polypectomy; the AMPs-LMP had a higher local persistence/recurrence rate that the APAs of usual type (60% vs. 33%). Evidence that some APAs progress to carcinoma is suggested by reports of well-differentiated myoinvasive endometrioid adenocarcinomas contiguous with an APA.8,9  In one study currently available only in abstract form,9  6 of 15 APAs were associated with an endometrioid adenocarcinoma in the same uterus, 3 of which were myoinvasive; two of the latter appeared to arise from the APA.

Adenomyoma of Endocervical Type are usually an incidental finding in women of reproductive or postmenopausal age.10  A polypoid mucosal mass, typically less than 8 cm in maximal dimension, is present in most cases, but occasionally the cervix is enlarged by a mural mass without mucosal involvement. Gross examination reveals a grey-white to tan, well-circumscribed tumor, with mucin-filled cysts in half the cases. Microscopically, the tumor is well-circumscribed and composed of benign endocervical-type glands, often in a lobular arrangement, admixed with benign smooth muscle resembling that in typical leiomyomas. Tubal-type or endometrioid glands are present in some cases. Follow-up reveals a benign course. The tumors occasionally persist or recur following incomplete excision. No cases of extracervical spread have been reported. The differential diagnosis is usually with adenoma malignum (minimal deviation adenocarcinoma of mucinous type), a diagnosis that can be excluded by the presence of a non-invasive border, a lobular arrangement of the glands, a background of myomatous smooth muscle, an absence of invasive glands with a desmoplastic reaction, and a lack of even focal atypia.

References

  1. Cullen TS. Adenomyoma of the Uterus. Philadelphia: W.B. Saunders, 1908.
  2. Mazur MT. Atypical polypoid adenomyomas of the endometrium. Am J Surg Pathol 1981;5:473-482.
  3. Gilks CB, Clement PB, Hart WR, Young RH. Uterine adenomyomas excluding atypical polypoid adenomyomas and adenomyomas of endocervical type: A clinicopathologic study of 30 cases of an underemphasized lesion that may cause diagnostic problems with brief consideration of adenomyomas of other female genital tract sites. Int J Gynecol Pathol 2000;19:195-205.
  4. Young RH, Treger T, Scully RE. Atypical polypoid adenomyoma of the uterus. A report of 27 cases. Am J Clin Pathol 1986;86:139-145.
  5. Clement PB, Young RH. Atypical polypoid adenomyoma of the uterus associated with Turner's syndrome. A report of three cases, including a review of "estrogen-associated" endometrial neoplasms and neoplasms associated with Turner's syndrome. Int J Gynecol Path 1987;6:104-113.
  6. Longacre TA, Chung MH, Rouse RV, Hendrickson MR. Atypical polypoid adenomyofibromas (atypical polypoid adenomyomas) of the uterus. A clinicopathologic study of 55 cases. Am J Surg Pathol 1996;20:1-20.
  7. Soslow RA, Chung MH, Rouse RV, Hendrickson MR, Longacre TA. Atypical polypoid adenomyofibroma (APA) versus well-differentiated endometrial carcinoma with prominent stromal matrix: An immunohistochemical study. Int J Gynecol Pathol 1996;15:209-216.
  8. Sugiyama T, Ohta S, Nishida T, Okura N, Tanabe K, Yakushiji M. Two cases of endometrial adenocarcinoma arising from atypical polypoid adenomyoma. Gynecol Oncol 1998;71:141-4.
  9. Zhang SL, Steinhof MM, Sung CJ. Atypical polypoid adenomyoma: Re-exploration of its natural history. A clinicopathologic study of 15 cases. Abstract. Mod Pathol 2000;13:135A.
  10. Gilks CB, Young RH, Clement PB, Hart WR, Scully RE. Adenomyomas of the uterine cervix of endocervical type: A report of 10 cases of a benign cervical tumor that may be confused with adenoma malignum. Mod Pathol 1996;9:220-224.