Case Series: Rare cystic variant of adenomatoid tumor of the uterus

Our patient is a 37-year-old G6P3033 female presenting for further evaluation and management of an enlarged pelvic mass with cystic features. The patient has a history of anemia requiring transfusions and menorrhagia secondary to growing fibroids. She reports a one year history of watery, pink vaginal discharge and 4–5 months of urinary incontinence. The patient reports intentional weight loss of 30 lbs over the past year secondary to healthy lifestyle changes in diet and exercise. She denies fevers, chills, changes in bowel habits or appetite, palpitation, or lightheadedness. During abdominal examination, a mass was palpable without tenderness in the bilateral upper quadrants approximately 6 cm above the umbilicus. Pelvic examination revealed an enlarged, approximately 24 week sized, fibroid uterus with adnexa unable to be palpated separate from the mass. Recent endometrial biopsy by the gynecologist did not contain endometrial tissue, and tumor markers CEA, Ca 19-9, and Ca-125 are all normal. A previous pelvic ultrasound showed a 13 cm multiseptated cystic mass within the fundus of a 16.9 cm uterus and poor visualization of endometrial stripe. Both ovaries were approximately 3 cm and had normal vascular flow. Further imaging with pelvic MRI, with and without contrast, showed a 13.9 cm cystic mass of the uterus with irregular septations and abnormal enhancement. The mass extended above the umbilicus. Both ovaries were normal in size with the left ovary displaced to the midline and inseparable from the cystic lesion of the uterus. There was small pelvic free fluid and no lymphadenopathy was noted ( Fig. 1 , Fig. 2 ). Fig. 1 Sagittal T2 MRI image showing 13.9 × 8.5 × 18.3 cm cystic mass of the enlarged uterus with irregular, septic septations and abnormal enhancement extending into abdominal cavity. Fig. 2 Axial T1 post-contrast MRI image showing the pelvic mass is associated with the right and left pelvic sidewalls with extension of cystic mass into anterior abdominal wall. Sagittal T2 MRI image showing 13.9 × 8.5 × 18.3 cm cystic mass of the enlarged uterus with irregular, septic septations and abnormal enhancement extending into abdominal cavity. Axial T1 post-contrast MRI image showing the pelvic mass is associated with the right and left pelvic sidewalls with extension of cystic mass into anterior abdominal wall. After evaluation of the patient, gynecologic oncology recommended surgical intervention for diagnostic and therapeutic purposes. During surgery, there was significant scar tissue present due to the patient's prior history of multiple caesarean births. The left ovary was adhered to the uterus at the midline, with poor visualization of the associated infundibulopelvic ligament and vasculature. The uterus, cervix and adherent left ovary were dissected and removed and sent for frozen section ( Fig. 3 ). The frozen section pathology revealed a tentative diagnosis of serous cystadenoma of the uterus and benign endometrium. The appendix was also removed intraoperatively as it was noted to be dilated. The right ovary was preserved in-situ given the patient's age and premenopausal status. The full procedure performed was a total abdominal hysterectomy, bilateral salpingectomy, left oophorectomy, appendectomy, and lysis of adhesions. Fig. 3 Excised uterus, left adnexa, and cervix sent for frozen section. Excised uterus, left adnexa, and cervix sent for frozen section. Final pathology of the mass revealed cystic adenomatoid tumor of the uterus with multiloculated myometrial cysts measuring up to 6.3 cm and containing serous fluid ( Fig. 4 ). The specimen included a uterus and attached left fallopian tube and ovary weighing 1916 g. There was no evidence of carcinoma. The cysts were lined by a single layer of benign cuboidal epithelium which was immunohistochemically positive for pancytokeratin, WT-1, D2-40, and calretinin ( Fig. 5 , Fig. 6 ). The cells tested negative for CD31, supporting the diagnosis. Fig. 4 Gross pathology of cyst with the largest measuring 6.3 cm in diameter. The inner linings of the cysts are smooth and did not show evidence of papillary excrescence.Evacuation of one cystic portion of the CATU consisting of clear serous fluid. Fig. 5 Immunostains show the cyst lining cells are mesothelial cells which are positive for pancytokeratin (brown membranous staining). Fig. 6 Immunostains show the cyst lining cells are mesothelial cells which are positive for WT-1 (brown nuclear staining). Gross pathology of cyst with the largest measuring 6.3 cm in diameter. The inner linings of the cysts are smooth and did not show evidence of papillary excrescence.Evacuation of one cystic portion of the CATU consisting of clear serous fluid. Immunostains show the cyst lining cells are mesothelial cells which are positive for pancytokeratin (brown membranous staining). Immunostains show the cyst lining cells are mesothelial cells which are positive for WT-1 (brown nuclear staining).

Prasanna Tati: Writing – review & editing, Writing – original draft, Methodology, Investigation, Data curation. Muhammad Omar Afridi: Formal analysis, Data curation, Conceptualization. Angelica Patel: Resources, Project administration. Monika Mansmann: Write this paper, Data collection, Editing during the initial stages of our writing. Victoria Petty: Conceptualization, Methodology. Joyce Varughese: Editing, Methodology, Conceptualization.

Cystic adenomatoid tumors of the uterus are rare. As a result, they are often not considered as a part of the differential diagnosis when evaluating a pelvic mass. They are often confused for leiomyoma or adnexal masses. We report a case and provide a review of the literature to encourage consideration of CATU in the differential diagnosis and well as to encourage consideration of excision of the mass or performance of a hysterectomy if fertility is no longer desired. Reassurance can be taken that there have been no reported cases of recurrence despite the poor delineation of the barrier between normal myometrium and tumor.

The term adenomatoid tumor was first introduced in 1945 by Golden and Ash to describe benign lesions with adenomatous features ( Golden & Ash, 1945 ). ATUs are thought to originate from mesenchymal tissue and are histopathologically formed from tubules with a single layer of flattened mesothelial cells with interspersed hypertrophied smooth muscle ( Manucha et al., 2015 ). The histological origin of ATUs was once controversial and involved endothelial, Wolffian and Mullerian, and mesothelial theories, with the latter as the established origin ( Stephenson and Mills, 1986 ) due to positive expression of HBME-1 and calretinin ( Chen et al., 2017 ). The pathogenesis of ATUs involves either origin from uterine peritoneum, muscle ( Tiltman, 1980 ), or both ( Mazur and Kraus, 1980 ). In 2015, Meng et al . studied the MRI features of ATUs and found that ATUs were hypointense on T2 weighted images, 90 % exhibited a solid pattern and 75 % had a lower degree of gadolinium enhancement than the surrounding myometrium. While MRI findings may indicate a diagnosis of ATU, pathology is still the gold standard in diagnosis ( Meng et al., 2015 ). Although no malignant transformation of ATUs has yet been reported, management is with simple excision of the tumor or hysterectomy for diagnostic as well as therapeutic purposes ( Manucha et al., 2015 ). No cases of recurrence or metastasis have been reported in the literature, including a study that followed 29 patients for 22 years ( Young & Tay lor, 1967 ). Hormone therapy is not considered an appropriate treatment as hormone markers are usually negative in ATUs. The incidence of ATU is likely higher than the reported 0.2–1.2 % due to their small size, gross appearance, and benign symptomatic nature ( Wakita et al., 2020 ). ATUs are solitary in nature with a size range of 2–10 cm and a mean diameter of 2.1 cm ( Nogales et al., 2002 ). Even if they are seen on gross examination, they may be mistaken for leiomyoma or adenomyosis and are therefore often not evaluated via microscopic examination ( Quigley and Hart, 1981 ). ATUs are reported most often in women 26–55 years of age with a mean age of 41 years ( Huang et al., 1995 ). Clinical manifestations are nonspecific, ranging from menorrhagia to abdominal masses ( Schwartz & Longacre, 2004 ). Classifications of ATUs include adenoid, angiomatoid, solid, and cystic (CATU). One type may dominate in a specimen, but it is most common to have a mixture of two. The least common type is cystic ( Wakita et al., 2020 ). Instances of CATUs have only been published as single case reports, which have all been compiled to accompany this report ( Table 1 ). Table 1 Summary of case reports with age, parity, diagnosis, location, size, presenting complaint, immunohistochemistry, and treatment. Author Age Parity Diagnosis Location Size of mass Presenting Complaint Immunohistochemical Markers Treatment Kim et al., 2002 40 cystic adenomatoid tumor left anterior subserosal myometrium 5.2 × 3.2 × 4.3 cm menorrhagia, anemia (+) cytokeratin Ex lap, hysterectomy Palacios et al., 1991 38 G2P2 cystic adenomatoid tumor right posterior subserosal cornual region 8 cm lower abdominal pain (+) cytokeratin, vimentin (−) EMA Ex lap, excision of mass Manucha et al., 2015 40 cystic adenomatoid tumor left anterior and posterior myometrium 4.1 × 3.1 × 5 cm left lower quadrant pain (+) calretinin, broad spectrum keratin (AE1/AE3) (−) CD31, ER hysterectomy, R salpingo-oophorectomy Leaha et al., 2009 42 cystic adenomatoid tumor 5 cm utrine leiomyomas, metrorrhagia (+) keratin, anticytokeratin 7, antivimentin, anti-HMBE-1, anticalretinin (−) anti-CD31, anti-CD34 Kim and Gu, 2004 67 giant cystic adenomatoid tumor right cornus 7 × 7 cm lower abdominal pain (+) cytokeratin 7, vimentin, calretinin, cytokeratin, HBME-1 (−) EMA, cytokeratin 20, CEA, CD31, actin, factor 8, HMB-45 Ex lap Iwasaki et al. 1985 32 G0 cystic adenomatoid tumor right posterior cornu 4 × 4.5 cm Infertility with 6 years of trying Ex lap Wakita et al., 2020 49 G0 cystic adenomatoid tumor right posterior myometrium 10 cm menorrhagia (+) calretinin, CAM 5.2, D2-40 (−) desmin, αSMA, CD34 Ex lap Quigley and Hart, 1981 1 of 12 49 cystic adenomatoid tumor right cornus 2.5 cm adenomyosis Bisset et al. 1988 45 giant cystic adenomatoid tumor 10 cm (including solid component) frequent menstrual bleeding Rosa et al., 1992 Case 1 40 giant cystic adenomatoid tumor lateral subserosal 12 cm metrorrhagia (+) cytokeratin (−) endothelium (factor VIII, Ulex europaeus ) Ex lap, TAH, BSO Case 2 50 giant cystic adenomatoid tumor 13 × 13 × 12 cm abdominal pain (+) cytokeratin (−) endothelium (factor VIII, Ulex europaeus ) Ex lap, TAH, BSO Livingston et al., 1992 39 G0 adenomatoid tumor with cystic component serosal surface of fundus 4 × 3 × 1.5 cm profuse vaginal bleeding requiring transfusion (+) high-molecular-weight keratin (−) factor VIII, Ulex europaeus Ex lap, TAH Tiras et al., 2000 24 G0 adenomatoid tumor with cystic features multiple (8) 5 × 4 × 4 cm lower abdominal pain and irregular uterine bleeding (+) pancytokeratin (−) mucicarmen, factor VIII Myomectomy Present Case 37 G6P3033 cystic adenomatoid tumor 6.3 cm anemia secondary to menorrhagia from fibroids (+) pancytokeratin, WT-1, D2-40, calretinin (−) CD31 TAH, bilateral salpingectomy, left oophorectomy Summary of case reports with age, parity, diagnosis, location, size, presenting complaint, immunohistochemistry, and treatment. CATUs are reportedly most common in subserosal surfaces and are most often located in the cornual regions of the uterus. They are different from other ATUs, as they tend to be larger in size, ranging from 7 to 11 cm ( Nogales et al., 2002 ). Our literature review found cases with the largest diameters ranging from 2.5 to 13 cm and with a median of 5.75 cm. Rosa et al . reported two giant adenomatoid tumors of the uterus (GATU) with cystic features measuring 12 cm and 13 cm, supporting the idea that GATUs show a predominance of cystic features over adenomatoid features ( Rosa et al., 1992 ). CATUs are distinguished by their large sizes and their demand for clinical attention. Because most ATUs are usually small in size, they are often not a consideration in the differential diagnosis for pelvic masses. In cases where the pathology confirms CATU, the masses have often been confused for leiomyoma or adnexal masses due to their large size and ultrasonographic appearance ( Nogales et al., 2002 ). All reported CATUs ( Table 1 ) stained immunohistochemically positive for some form of keratin, supporting the taxonomic classification of CATUs as mesothelial in origin. All incidences of CD31, CD34, EMA, estrogen, and progesterone staining were negative, rejecting possibilities that CATUs are of endothelial origin or hormonally influenced. Consistent with other ATUs, the cases of CATU we reviewed revealed that most occur in women between the ages of 24 and 67 with a median age of 40. There is no clear difference in parity due to lack of reporting this detail. Most patients, due to age, no longer desired fertility and underwent subsequent hysterectomy with excision of mass. All reported CATUs were treated with excision, most commonly to relieve menorrhagia or lower abdominal pain. It is important to note that the border between normal myometrium and ATUs is poorly defined. Therefore, postoperative residual lesions are higher for ATUs than for other lesions such as leiomyoma. If fertility is not desired, total hysterectomy is recommended for treatment. As of the time of this review, no malignant transformation or recurrence has been reported. ( Matsuhashi et al., 2017 ).

Adenomatoid tumors of the uterus (ATU) are rare, benign lesions of mesothelial origin that most commonly occur in the genital tract at a rate of 0.12–1.2 % of all women ( Tiltman, 1980 , Chen et al., 2017 ). ATUs are often incidental findings on hysterectomy samples with the most common preoperative diagnosis being that of uterine fibroids ( Matsuhashi et al., 2017 ). Up to 60 % of ATUs coexist with uterine leiomyomas ( Nogales et al., 2002 ). Adenomatoid tumors can be subdivided into multiple categories including adenoid, angiomatoid, solid and cystic, with the cystic type being the least common ( Kim et al., 2002 ). They are most commonly found in the fallopian tubes and uterus with prevalence in the subserosa ( Quigley and Hart, 1981 ), but rarely in the ovary and paraovarian connective tissue ( Tiras et al., 2000 ). Cystic adenomatoid tumor of the uterus (CATU) is an exceptionally rare and the largest type of ATU, often confused for leiomyoma or adnexal masses. They are excised through the process of a hysterectomy. No recurrence or metastases has been reported after removal in the literature. Here we present a report of a cystic adenomatoid tumor of the uterus and subsequent review of case reports with a similar diagnosis.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.