A Rare Large Cystic Adenomatoid Tumor of the Uterus: Diagnostic Challenges and Focused Literature Review ()
1. Introduction
A adenomatoid tumor is an uncommon benign mesothelial neoplasm of the genital tract. In women, it typically arises from the subserosal myometrium or serosal surfaces (peritoneum/mesosalpinx) and is most often an incidental small nodule discovered during surgery for other indications [1]. Histologically, adenomatoid tumors show tubular/microcystic mesothelial proliferations with bland cytology and low mitotic activity and express calretinin, WT1, CK5/6, and D2-40, while PAX8 is negative—helpful to exclude Müllerian lesions [2]. Although the typical lesion is small, atypically large or cystic uterine presentations are rare and diagnostically challenging, with MRI features recently described in dedicated series [3]-[7] and case compilations focusing on the cystic variant [8]. On the molecular side, TRAF7 mutations have been identified across genital-tract adenomatoid tumors, supporting a clonal benign neoplasm rather than a hamartoma and informing difficult differentials [9]-[11]. Misdiagnosis remains common, particularly as a degenerating leiomyoma or adnexal tumor [12].
2. Case Presentation
A 53-year-old G2P2 (two prior cesarean deliveries), menopausal for 12 years, presented with diffuse pelvic pain and rapidly progressive abdominal distension over one month. General examination was unremarkable; the abdomen was moderately distended with a centrally located, slightly tender pelvic mass. The Pfannenstiel incision scar appeared well healed.
Pelvic ultrasound showed a well-defined unilocular anechoic cystic lesion measuring 16 × 10 cm without septa or mural nodules. Pelvic MRI demonstrated a mixed solid-cystic mass arising from the posterior uterine body, extending cranially toward the right hypochondrium (maximal dimensions 216 × 154 × 94 mm), displacing adjacent structures without invasion (Figure 1). Differential diagnoses included a large exophytic degenerating leiomyoma versus an adnexal mass of uncertain origin.
Figure 1. Pelvic MRI showing a large mixed solid-cystic mass contiguous with the posterior uterine wall (max. 216 × 154 × 94 mm), displacing adjacent viscera without invasion.
Surgery: exploratory laparotomy identified a 17-cm cystic mass attached to the right uterine wall, with a highly vascular external surface and hemorrhagic intracystic fluid, without adhesions or organ invasion (Figure 2).
Figure 2. Intraoperative view of a 17 cm cystic mass attached to the right uterine wall; vascularized outer surface. The black arrow indicates the inclusion cyst, and the red arrow indicates the uterus.
Given the patient’s postmenopausal status, tumor size, and uncertain preoperative diagnosis, total hysterectomy with bilateral adnexectomy was performed. Peritoneal fluid was sampled for cytology (Figure 3). Postoperative recovery was uneventful.
Figure 3. Gross specimen: uterus with attached cystic mass; cut surface revealing hemorrhagic cyst contents. The brown arrow shows the cyst, the indigo arrow shows the uterus, and the indigo triangle indicates the cervix.
The hysterectomy specimen showed a benign spindle-cell proliferation arranged in short intersecting bundles (smooth muscle), no atypia, and 1 mitosis/10 HPF, without necrosis or intratumoral hemorrhage. The endometrium was atrophic; cervix and adnexa were unremarkable (Figure 4).
Figure 4. Microscopic image of the cyst. Inclusion cyst (×10, coloration with hematoxylin and eosin).
At the periphery of the mass, there was a well-circumscribed cyst with a fibrous wall lined by attenuated mesothelial epithelium, largely denuded, and without communication with the smooth-muscle bundles (Figure 5).
Figure 5. Inclusion cyst: fibrous wall (outlined with black oval) lined by mesothelial cells (two black arrows). ×4, coloration with hematoxylin and eosin.
These features support a benign mesothelial lesion with prominent smooth-muscle stroma. Peritoneal fluid cytology showed a hemorrhagic background with small pseudoglandular clusters of mesothelial cells with minimal atypia and no malignant features (Figure 6 & Figure 7).
Figure 6. Microscopic appearance of the ascitic fluid. Pseudoglandular clusters of mesothelial cells in a hemorrhagic background. ×4, coloration with hematoxylin and eosin.
Figure 7. Clusters of mesothelial cells in the ascitic fluid stained with Papanicolaou. Magnification ×20.
Immunohistochemistry performed on a cytoblock was calretinin-positive and PAX8-negative, corroborating mesothelial lineage and excluding Müllerian epithelium (Figure 8 & Figure 9).
Figure 8. Immunohistochemical analysis showing immunoreactivity of mesothelial cells with anti-calretinin antibody. Magnification ×20.
Figure 9. Immunohistochemical analysis showing no immunoreactivity of mesothelial cells with anti-PAX8 antibody. Magnification ×20.
3. Discussion
Uterine adenomatoid tumor is usually small, subserosal, and asymptomatic [1]. Large and cystic forms, although uncommon, can blur the distinction from degenerating leiomyoma, ovarian cystadenoma, or even metastatic adenocarcinoma when imaging is non-specific [3]-[8]. Recent MRI series describe heterogeneous T2 signal with mixed low-signal myoma-like areas and higher-signal microcystic components, sometimes with a peripheral rim, features that can raise suspicion for adenomatoid tumor when uterine continuity is evident [6] [7]. Misdiagnosis at presentation remains frequent [12], and giant cystic uterine adenomatoid tumors have been reported, underlining the potential for size-related symptoms and malignant mimicry [13].
3.1. Pathogenesis and Immunophenotype
The characteristic mesothelial immunoprofile (calretinin, WT1, D2-40 positive; PAX8 negative) distinguishes adenomatoid tumor from Müllerian lesions [2]. The discovery of TRAF7 mutations across genital-tract adenomatoid tumors supports a clonal, benign neoplasm with NF-κB pathway involvement and can aid in difficult differentials (e.g., atypical growth patterns or nerve adjacency) [9]-[11]. Associations with iatrogenic immunosuppression have been reported and may influence detection or growth [14] [15].
Adenomatoid tumors demonstrate diverse clinical presentations and anatomical distributions. While most commonly encountered in the uterus and fallopian tubes [16], these tumors can present with synchronous involvement of multiple sites [17] or multicentric patterns affecting the uterus, ovary, and appendix [18]. Clinical associations with systemic conditions have been documented, including cases occurring in patients with chronic renal failure [19]. Rare extragenital locations have also been reported, with documented cases in the omentum where adenomatoid tumors may coexist with well-differentiated papillary mesothelioma [20], and exceptionally rare presentations arising from the diaphragm [21]. Understanding this anatomical spectrum is essential for accurate diagnosis and appropriate management.
3.2. Variant with SmoothMuscle Stroma
When a prominent leiomyomatous component coexists with mesothelial microcysts/tubules, the lesion is referred to as a leiomyoadenomatoid tumor [22]. The present case—spindle-cell bundles plus a peripheral mesothelial-lined cyst—fits this spectrum and helps explain preoperative confusion with leiomyoma.
3.3. Management and Prognosis
Complete surgical excision is curative. There is no malignant potential, and recurrence is exceptional [1]. In postmenopausal patients with large or symptomatic lesions—and when malignancy cannot be confidently excluded—hysterectomy is reasonable; in younger patients with smaller, well-characterized lesions, conservative excision may be considered.
4. Conclusion
Uterine adenomatoid tumor—occasionally with leiomyoadenomatoid features—can present as a large cystic mass, posing diagnostic challenges. Histopathology with targeted IHC is decisive for confirming mesothelial origin and avoiding overtreatment. Prognosis after complete excision is excellent. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Institutional ethics committee approval was obtained, and written informed consent was obtained from the patient for publication of the clinical data and related images.
Conflicts of Interest
The authors declare no conflicts of interest.