Pathologic Quiz Case: A 52-Year-Old Woman With a Uterine Mass

Abstract

A 52-year-old, sexually active, gravida 7, para 6 woman, with a history of hypertension, diabetes, and hypercholesterolemia, presented with menorrhagia. The patient noticed increased and irregular bleeding during menstruation with passage of clots. Her last menstrual period was 3 months before presentation. There was no pain during menses and no history of pelvic inflammatory disease. A transvaginal ultrasound, performed a few months prior, showed an anteverted uterus that measured 11.9 × 6.7 × 7.3 cm, with 2 discrete intramural fibroids in the left lateral anterior aspect that measured 2.2 and 2.8 cm in largest dimension (Figure 1) and a small hemorrhagic cyst in the left ovary. An endometrial biopsy specimen taken at this time showed proliferative endometrium, and her Papanicolaou smear results to date were negative. On pelvic examination at the current admission she had a mobile anteverted uterus of 10 weeks' size without adnexal masses. Results of the patient's laboratory tests were significant for mild anemia secondary to bleeding and a slightly elevated serum creatinine level. She underwent a vaginal hysterectomy and bilateral salpingo-oophorectomy.The hysterectomy specimen consisted of a 160-g, previously opened uterus that measured 10 × 7 × 4 cm with a myometrial thickness of 2.5 cm. Three distinct pale tan nodules with well-circumscribed borders and whorled cut surfaces were noted. Two of the nodules, which measured 0.8 and 1 cm, were present subserosally on the right side, and the third nodule, which measured 1.5 cm, was located intramurally. The cervix, fallopian tubes, and ovaries showed no significant pathologic features. The patient had an uneventful postoperative recovery.On microscopic examination of the lesion in question, low-power examination showed prominent fascicles of smooth muscle separated by narrow cords of vacuolated cells with a signet ring–like appearance that infiltrated the interstitium (Figure 2, hematoxylin-eosin, original magnification ×20). On higher-power microscopy, these cells showed a narrow rim of condensed, pale eosinophilic cytoplasm and a central vacuole (Figure 3, hematoxylin-eosin, original magnification ×40). The round to oval nucleus, seated within the cytoplasmic rim, displayed a slightly irregular, folded contour with pale vesicular chromatin and a distinct nucleolus. No mitoses or pleomorphism was seen. Cytokeratin (AE1/AE3) was strongly positive in these cells (Figure 4, hematoxylin-eosin, original magnification ×20).What is your diagnosis?Epstein1 used the term leiomyo-adenomatoid tumor to describe a variant of adenomatoid tumor with a prominent smooth muscle component. Sometimes the smooth muscle overgrowth is so extensive that it obscures the adenomatoid tumor. Adenomatoid tumors have a predilection for the male and female genital tracts, but rare examples of extragenital adenomatoid tumors have been described at various sites.2 Adenomatoid tumor is a benign tumor of the uterus seen subserosally near the cornua or within the outer part of the myometrium. Another common location in the female genital tract is around the fallopian tubes. These tumors usually occur as incidental findings in hysterectomy specimens and on occasion can be multiple. They are difficult to differentiate from leiomyomata on clinical examination, ultrasound, or magnetic resonance imaging.3 Grossly, uterine adenomatoid tumors range in size from 0.5 to 4 cm. They tend to be slightly less well circumscribed than leiomyomata and appear more yellow to tan-gray. On cut section, some of them reveal a whorled appearance, whereas others show irregular fibrous trabeculae or small vesicles.4 A cystic variant is also well recognized.5 They are often accompanied by leiomyomata or adenomyosis. Microscopically, the tumor can have an adenoid, angiomatoid, solid, or cystic architecture, and combinations of more than one type may occur. The adenoid type is the most common and, as described in our case, shows small, often slitlike interconnecting spaces within the myometrium on low power. On higher power, an infiltrative pattern of tubules lined by cuboidal or attenuated epithelium is identified. There is little nuclear atypia or mitotic activity and no stromal desmoplastic response. Some adenomatoid tumors can have prominent chronic inflammation and are considered to be a peculiar variant of nodular mesothelial hyperplasia.6 Other tumors, such as that seen in the present case, can have a striking smooth muscle component.Uterine adenomatoid tumors, in particular the intramural types, are often accompanied by bundles of smooth muscle, which usually represent entrapped myometrium permeated by the adenomatoid tumor. In some instances, the abundance of smooth muscle simulates a leiomyoma and obscures the adenomatoid tumor. Some believe this to be reactive hyperplasia of indigenous myometrial smooth muscle; this contention was supported by the absence of smooth muscle in adenomatoid tumors that occur at other sites, such as the ovary, mesentery, adrenal glands, and omentum. Others postulate that this represents a neoplastic component, and the possibility of a collision tumor composed of leiomyoma and adenomatoid tumor cannot be completely disallowed.4 Our search revealed one other reported case of leiomyo-adenomatoid tumor of the epididymis, which is not an anatomic site associated with prominent smooth muscle.7The histogenesis of adenomatoid tumor was debated, but it was ultimately proven by ultrastructural and immunohistochemical studies to be a tumor of mesothelial origin. The cells are strongly positive for cytokeratin, vimentin, HBME-1 (anti-human mesothelioma antibody), and calretinin but negative for epithelial membrane antigen and carcinoembryonic antigen.35 Ultrastructural examination shows numerous apical microvilli, abundant cytoplasmic filaments, and desmosomes, which explains their strong keratin reactivity.8 The characteristic subserosal location is in keeping with their mesothelial origin, although continuity with overlying serosa is rarely observed. A possible explanation for this phenomenon is that adenomatoid tumors arise from inclusions of mesothelium incorporated into subserosal connective tissue or myometrium. In some cases, these mesothelial inclusion cysts can undergo metaplasia into tubal-type epithelium, producing the lesion known as endosalpingiosis. Patients who develop adenomatoid tumors may have a labile peritoneum with a propensity to form a variety of proliferative lesions of mesothelial cells. Another theory proposes that some adenomatoid tumors could arise directly from uterine mesenchymal cells, which have retained a potential to differentiate into mesothelial cells.4 The other intramural nodules in the present case were benign leiomyomata that were associated with adenomyosis and disordered proliferative endometrium, constituting the most likely cause of her symptoms.This study was supported by the Department of Pathology at St Luke's-Roosevelt Hospital Center.