Adenomyoma
Adenomyoma is a tumor including components derived from glands and muscle. It is a type of complex and mixed tumor, and several variants have been described in the medical literature. Uterine adenomyoma, the localized form of uterine adenomyosis, is a tumor composed of endometrial gland tissue and smooth muscle in the myometrium. Adenomyomas containing endometrial glands are also found outside of the uterus, most commonly on the uterine adnexa but can also develop at distant sites outside of the pelvis. Gallbladder adenomyoma, the localized form of adenomyomatosis, is a polypoid tumor in the gallbladder composed of hyperplastic mucosal epithelium and muscularis propria.
Classification
Uterine Adenomyoma
Uterine adenomyoma is the focal form of uterine adenomyosis. Adenomyosis most commonly presents with numerous small collections of endometrial glands and stroma spread diffusely throughout the myometrium, intermixed with the myometrial smooth muscle. In contrast, a uterine adenomyoma is an isolated nodular mass of endometrial tissue with surrounding smooth muscle, either embedded within the myometrium or extending from the endometrium into the uterine cavity in the form of a polyp.Extrauterine Adenomyoma
Though less common, adenomyomas with endometrial tissue can also be found outside the uterus. The majority of cases of extrauterine adenomyomas described in the literature have been located in the pelvis, growing on the ovaries, uterine ligaments, and space surrounding the rectum. Several cases have been located outside of the pelvis, such as in the liver, appendix, upper abdomen, and mesentery of the small bowel. There have also been patients with adenomyomas found at multiple locations in the body.Gallbladder Adenomyoma
Gallbladder adenomyomatosis is a benign disease of the gallbladder characterized by hyperplasia of the mucosal epithelium and smooth muscle cells inside the muscularis propria. The excessive proliferation of epithelial cells causes the mucosa to invaginate into the muscular layer lining the gallbladder wall, resulting in characteristic diverticula known as Rokitansky-Aschoff sinuses. These sinuses may be filled with biliary sludge, cholesterol crystals, or gallstones.There are three morphologic variants described in the literature – diffuse, segmental, and localized. Diffuse, also known as generalized, adenomyomatosis has a widespread distribution of hyperplastic changes and thickening across the gallbladder wall. The localized form of adenomyomatosis is also known as a gallbladder adenomyoma. The localized form is a single mass, typically in the fundus, that protrudes into the lumen of the gallbladder in the form of a polyp. The segmental form is characterized by its annular distribution of adenomyomatosis in the body of the gallbladder, often giving it an hourglass-like appearance.
Signs and symptoms
Uterine Adenomyoma
The clinical features of uterine adenomyosis vary widely and may include dysmenorrhea, pelvic pain, menorrhagia, and/or infertility, with about one in three affected women remaining asymptomatic. Women with uterine adenomyomas more commonly have co-existing endometriosis and a higher likelihood of infertility compared to women presenting with diffuse adenomyosis. However, a causal link between adenomyomas and the development of infertility has not been established, and further investigation is needed.Extrauterine Adenomyoma
The most frequent complaint in cases of extrauterine adenomyomas is pain in the pelvis or abdomen, with a small proportion of women also presenting with abnormal bleeding and/or infertility. In half the cases described in the literature, the patient had a history of gynecologic surgery before diagnosis, and several patients also had a medical history of endometriosis.Gallbladder Adenomyoma
Most patients with adenomyomatosis are asymptomatic. Among symptomatic patients, the most common symptom is abdominal pain in the right upper quadrant or epigastrium. Patients may also present with nausea, dyspepsia, or fatty food intolerance, likely due to altered flow of bile. Some data suggest that the features of clinical presentation may frequently differ based on the variant of adenomyomatosis, as the diffuse and segmental forms appear to have more significant inflammation and a higher incidence of gallstones compared to the localized form. Other symptoms are often related to frequently co-occurring gallbladder diseases such as gallstones, cholecystitis, and choledocholithiasis. These may present with fever, pain, jaundice, or other symptoms.Causes
Uterine Adenomyoma
The underlying cause is not fully understood. A prominent theory is the invagination theory, in which tissue injuries and inflammatory changes due to chronic uterine contractions allow endometrial tissue to pass into the neighboring myometrium. Based on differences in the proteins expressed in adenomyomas located in the inner part of the myometrium versus the outer part of the myometrium, it is possible that adenomyomas can also result from the invasion of ectopic endometrial cells originating from nearby regions of endometriosis.Extrauterine Adenomyoma
No exact risk factors have been described for adenomyomas that develop outside the uterus. A history of prolonged hormone therapy is reported in two cases of patients diagnosed with an extrauterine adenomyoma, including estrogen and a gonadotropin releasing hormone agonist. Though adenomyosis has demonstrated sensitivity to estrogen, further investigation is needed to explore the relationship between hormone therapy and extrauterine adenomyomas.Several theories have been hypothesized to explain the pathogenesis. One theory describes extrauterine adenomyomas resulting from an error in Müllerian duct fusion during embryonic development, resulting in an abnormal uterus containing a horn-like structure. This horn may then be prone to breaking away and depositing elsewhere, later developing into an adenomyoma. As errors in Müllerian duct fusion also impact the development of the kidneys, urinary tract, and genitals, this theory would explain the multiple cases of extrauterine adenomyomas with co-existing congenital abnormalities of these anatomic structures.
Another theory suggests that extrauterine adenomyomas may result from smooth muscle metaplasia in areas of pre-existing endometriosis. In this theory, areas of endometrial tissue that have developed outside the uterus undergo cellular changes that provide the muscular component of the adenomyoma.
Gallbladder Adenomyoma
The specific cause of gallbladder adenomyomatosis remains unclear. Some of the risk factors for gallstone formation have also been reported in patients with adenomyomatosis such as hemolytic disease, congenital biliary abnormalities, obesity, and inflammatory bowel disease, but whether these are also risk factors for adenomyomatosis requires further investigation.The disease is currently thought to be a degenerative process and unlikely to be the result of congenital malformation. The cell proliferation seen in adenomyomatosis is theorized to result from increased pressure inside the gallbladder due to abnormal muscle contractions or excessive absorption of bile by the gallbladder wall.
Diagnosis
Uterine Adenomyoma
The most common diagnostic imaging modalities for uterine adenomyosis include transvaginal ultrasonography and magnetic resonance imaging. Though surgical excision and microscopic examination of the tumor allow for a definitive diagnosis, these imaging studies offer a non-invasive approach and have a sufficient resolution for a diagnosis.Diagnosis with transvaginal ultrasonography can potentially be challenging due to the similar appearance of uterine leiomyomas. Careful evaluation of the margins of the mass, the vascular flow patterns through the tumor, and the degree to which the tumor distorts the uterus may aid in differentiating these masses with ultrasound. MRI is highly effective at distinguishing between uterine adenomyomas and leiomyomas.
Extrauterine Adenomyoma
The most common imaging techniques include ultrasound, computed tomography, and MRI. Intravenous pyelography has also been used in some cases to assess for possible congenital anomalies of the kidneys. The appearance of these rare tumors on diagnostic imaging has not been extensively described, and in each case documented in the literature, the diagnosis was ultimately made after surgical removal using histologic analysis.On microscopic examination, patterns of smooth muscle and endometrial tissue must be assessed with care to differentiate adenomyomas from masses of similar appearances, such as endometriosis containing smooth muscle and leiomyomas containing endometriosis.
Gallbladder Adenomyoma
Adenomyomatosis is frequently associated with gallstones and is often diagnosed incidentally, either from a cholecystectomy specimen or autopsy. No serologic test exists to specify adenomyomatosis and laboratory studies are often normal. Co-existing diseases like cholecystitis may result in abnormal test results, such as elevated levels of white blood cells, liver enzymes, or bilirubin.Ultrasound is the preferred initial diagnostic choice for suspected gallbladder disease. Several distinct features of adenomyomatosis are discernable using ultrasound, making it a reliable modality for diagnosis. The most characteristic features seen on ultrasound are the Rokitansky-Aschoff sinuses, which present either as echogenic foci when filled with biliary sludge/gallstones or anechogenic foci when filled with normal bile. Other key features that may be seen include wall thickening and ring-down artifacts known as "comet tails". Ultrasound can also distinguish between diffuse, segmental, and localized variants of adenomyomatosis based on morphology.
In some cases, gallbladder wall thickening may be seen on ultrasound but is poorly defined and lacking specificity, particularly if the characteristic Rokitansky-Aschoff sinuses are not visualized. This can make it difficult to distinguish adenomyomatosis from other conditions that result in gallbladder wall thickening such as gallbladder cancer. In these cases, MRI can prove helpful in providing the resolution needed for diagnosis. Especially effective is the T2-weighted MRI at visualizing the pathognomonic Rokitansky-Aschoff sinuses, which appear as round-shaped hyperintense cystic spaces that align in a curvilinear fashion along the gallbladder wall in a pattern described as the ”pearl necklace sign”.