Adenomatoid tumors are benign growths that arise from mesothelial cells, the thin layer of tissue that lines body cavities and covers internal organs. They are among the most common benign tumors of the genital tract in both men and women, yet they rarely cause symptoms and are often discovered incidentally during surgery or imaging performed for unrelated reasons. Despite their harmless nature, they can mimic more serious conditions on scans and under the microscope, which makes accurate diagnosis critical to avoiding unnecessary aggressive surgery.
What Adenomatoid Tumors Actually Are
The name “adenomatoid” literally means “gland-like,” which is somewhat misleading because these tumors do not come from glandular tissue. They originate from mesothelial cells. Early pathology studies confirmed this by finding that the tumors contain acid mucopolysaccharides (a substance produced by normal and abnormal mesothelial tissue) and that under electron microscopy, the tumor cells show features characteristic of mesothelium, including microvilli, desmosomes, and dilated spaces between cells.1Cancer. Adenomatoid tumors: A light microscopic, histochemical, and ultrastructural study This mesothelial origin explains why adenomatoid tumors tend to appear in and around organs that are close to mesothelial-lined body cavities, particularly the reproductive tract.
Under the microscope, the tumor is made up of irregularly shaped tube-like and cyst-like spaces surrounded by fibrous tissue. These spaces are lined by flattened or slightly rounded cells, some of which have a distinctive vacuolated (bubble-like) appearance. The spaces sometimes contain pale mucinous fluid. This architectural pattern can look deceptively like several other tumors, both benign and malignant, which is where diagnostic challenges begin.
The Genetic Driver Behind Adenomatoid Tumors
For decades, the molecular basis of adenomatoid tumors was unknown. That changed when researchers discovered that virtually all of these tumors carry mutations in a gene called TRAF7, which produces a protein involved in regulating inflammation and cell survival. The mutations cluster in a specific region of the protein and lead to abnormal activation of a cellular signaling pathway called NF-kB.2PubMed Central. Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation In plain terms, a single genetic error in one gene appears to be sufficient to cause the growth.
This finding has practical value. In one study of uterine adenomatoid tumors, about 84% carried TRAF7 mutations, while none of the malignant mesotheliomas tested did.3PubMed. TRAF7 mutations and immunohistochemical study of uterine adenomatoid tumor compared with malignant mesothelioma Because adenomatoid tumors and mesotheliomas both come from mesothelial cells and can look similar under the microscope, a TRAF7 mutation can help confirm a benign diagnosis. The fact that malignant mesotheliomas do not share this mutation also underscores that adenomatoid tumors are a genetically distinct entity, not a precursor to cancer.
Where They Show Up in Men
In males, the most common location by far is the epididymis, the coiled tube that sits behind the testis and stores sperm. Adenomatoid tumors are the single most common tumor of the epididymis.4Urology Case Reports. Adenomatoid tumor of epididymis-A case report They tend to favor the tail end of the epididymis more than the head. Most present as a small, firm, painless lump in the scrotum that a man or his doctor notices on exam. The classic description, dating back to the 1940s, is a small asymptomatic mass without tenderness.
Less commonly, adenomatoid tumors can arise from the testicular tunica (the covering of the testis itself), the spermatic cord, the ejaculatory ducts, or the prostate.5PubMed Central. Epididymal Adenomatoid Tumour: A Case Report Roughly 14% of paratesticular adenomatoid tumors originate from the testicular tunica rather than the epididymis.4Urology Case Reports. Adenomatoid tumor of epididymis-A case report When they occur directly in or on the testis, they become a more urgent diagnostic concern because testicular cancer is far more common and needs to be ruled out quickly.
Where They Show Up in Women
In females, the uterus is the primary site. Adenomatoid tumors tend to grow within the muscular wall of the uterus (the myometrium), usually near the outer surface or at the cornua, the upper corners where the fallopian tubes connect.6PubMed Central. Uterine adenomatoid tumor: a clinicopathologic study of 102 cases Fallopian tubes are the other common female location. Because these tumors sit within the uterine wall, they are frequently mistaken for fibroids (leiomyomas) on imaging. In fact, adenomatoid tumors coexist with leiomyomas in about 60% of cases, making the diagnostic picture even muddier.7PubMed. A novel approach in the management of a recurrent adenomatoid tumor of the uterus utilizing a Strassman technique
Most uterine adenomatoid tumors are small and cause no symptoms. They are usually found incidentally when a uterus is removed for other reasons, such as fibroids, or during cesarean sections. Occasionally, larger ones can cause heavy menstrual bleeding or pelvic pain, symptoms that overlap entirely with fibroids, so the true diagnosis often comes only after the tissue is examined by a pathologist.
Unusual and Rare Locations
Although the genital tract accounts for the vast majority of cases, adenomatoid tumors have been reported in several other sites. The adrenal gland is the best-documented extragenital location, and these tumors are typically found as incidental masses on abdominal imaging done for other reasons.8PubMed. MR imaging of a case of adenomatoid tumor of the adrenal gland Rare cases have also been reported in the liver, the lining of the abdominal cavity (peritoneum), the lining of the chest cavity (pleura), and the mediastinum (the space between the lungs).9Advances in Anatomic Pathology. Adenomatoid Tumor: A Review of Pathology With Focus on Unusual Presentations and Sites, Histogenesis, Differential Diagnosis, and Molecular and Clinical Aspects With a Historic Overview of Its Description
Cases involving the gastrointestinal tract have also been documented, though they are exceedingly uncommon. Despite these varied locations, the behavior of the tumor remains consistently benign. None of the reported gastrointestinal or liver cases showed local recurrence or disease progression.10PubMed Central. Adenomatoid Tumors of the Gastrointestinal Tract – A Case Series and Review of the Literature The common thread in these extragenital locations is proximity to mesothelial-lined surfaces, which fits with the tumor’s mesothelial origin.
How Adenomatoid Tumors Are Diagnosed
Diagnosis is a multi-step process that often starts with imaging and ends with tissue analysis. On ultrasound, paratesticular adenomatoid tumors usually appear as bright (hyperechoic) masses near the epididymis. When ultrasound findings are ambiguous, MRI can help clarify the picture.11PubMed Central. Imaging Findings of Paratesticular Adenomatoid Tumor In the uterus, as mentioned, they are almost always assumed to be fibroids until tissue is examined after surgery.
The definitive diagnosis comes from looking at the tumor cells under a microscope and testing them with a panel of staining markers. Adenomatoid tumor cells reliably stain positive for certain mesothelial markers, with calretinin and D2-40 showing up in essentially 100% of cases, and WT-1 in about 95%.12PubMed Central. Adenomatoid Tumor of the Adrenal Gland: Report of Two Cases and Review of the Literature The cells also stain positive for certain epithelial markers like cytokeratin AE1/AE3 and CAM5.2, while being negative for endothelial markers like CD31 and CD34.13PubMed. Adenomatoid tumor of the adrenal gland: case report with immunohistochemical study This combination of positive and negative stains helps pathologists nail down the diagnosis and distinguish the tumor from vascular growths, glandular tumors, and malignancies.
In female genital tract cases, the staining profile has been further refined. Uterine and fallopian tube adenomatoid tumors consistently express pancytokeratin AE1/3, CAM5.2, CK7, calretinin, and D2-40, while being negative for markers like CK20, EMA, CD31, CD34, and S100.14Applied Immunohistochemistry & Molecular Morphology. An Immunohistochemical Study of Adenomatoid Tumors of the Uterus and Fallopian Tube The tumors also show very low proliferative activity, another reassuring sign of benign behavior.
Telling It Apart From Malignant Mesothelioma
The highest-stakes diagnostic challenge is distinguishing an adenomatoid tumor from malignant mesothelioma, since both arise from mesothelial cells and share many microscopic features. Mesothelioma is an aggressive cancer, so getting this distinction right has obvious consequences for treatment planning and prognosis.
Beyond the TRAF7 mutation difference described earlier, a protein called BAP1 has emerged as a useful tool. BAP1 is a tumor suppressor, and its loss is a hallmark of many mesotheliomas. In one study, more than half of malignant mesothelioma cases showed BAP1 loss, while all 42 adenomatoid tumors tested retained normal BAP1 expression. Even mesotheliomas that had a bland, adenomatoid-like microscopic pattern (the trickiest cases to distinguish) were BAP1-deficient.15Applied Immunohistochemistry & Molecular Morphology. BAP1 Loss is a Useful Adjunct to Distinguish Malignant Mesothelioma Including the Adenomatoid-like Variant From Benign Adenomatoid Tumors So when a pathologist sees a mesothelial-looking tumor and is uncertain whether it is benign or malignant, checking for BAP1 retention can push the diagnosis toward adenomatoid tumor.
The Role of Needle Biopsy Before Surgery
For scrotal masses in men, fine-needle aspiration cytology (FNAC) can play an important role in preoperative planning. A needle is used to withdraw a small sample of cells from the mass, which are then examined under a microscope. When pathologists are familiar with what adenomatoid tumor cells look like on cytology, this technique can provide a reliable and rapid diagnosis before any incision is made.16PubMed Central. Aspiration cytology of adenomatoid tumor of epididymis: An important diagnostic tool The value of getting this right preoperatively is straightforward: if the cytology confidently shows an adenomatoid tumor, the surgeon can plan a limited, organ-sparing procedure rather than removing the entire testis.17PubMed Central. Adenomatoid tumor of testis: A rare cytological diagnosis
The catch is that adenomatoid tumors are uncommon enough that many pathologists may not have seen their cytological appearance before. Awareness of the features is key to avoiding a misdiagnosis that could lead to unnecessarily aggressive surgery.18PubMed Central. Adenomatatoid tumor: Cytological diagnosis of two cases
Treatment in Men
Because adenomatoid tumors are benign, the overarching goal of treatment in men is to remove the tumor while preserving the testis. The biggest clinical concern is not the tumor itself but the risk that it might be mistaken for testicular cancer, which could lead to an unnecessary orchiectomy (removal of the entire testis).
When a scrotal mass is found, standard practice calls for checking serum tumor markers (alpha-fetoprotein, beta-HCG, and LDH), which are typically used to evaluate testicular cancer. In adenomatoid tumors, these markers come back normal, which is one early reassuring clue.19PubMed Central. Adenomatoid tumor of testis Ultrasound usually follows, and the mass tends to have a characteristic appearance.
During surgery, frozen section analysis is a critical step. The surgeon sends a slice of the excised tissue to a pathologist while the patient is still on the operating table. The pathologist examines it under the microscope within minutes and provides a preliminary diagnosis. One study found that frozen section assessment successfully allowed surgeons to avoid orchiectomy in about 84% of benign cases.20PubMed. Frozen section assessment in testicular and paratesticular lesions suspicious for malignancy: its role in preventing unnecessary orchiectomy The recommended approach for a confirmed adenomatoid tumor is partial excision through an inguinal incision, guided by frozen section results, to preserve the organ.21PubMed Central. Organ-sparing partial orchietectomy for testicular adenomatoid tumor
Treatment in Women
In women, most uterine adenomatoid tumors are diagnosed after tissue has already been removed for another reason, so “treatment” often amounts to confirmation that the incidental finding is benign. When a uterine adenomatoid tumor is identified preoperatively (usually because it is mistaken for a fibroid on imaging), myomectomy, or removal of the mass from the uterine wall, is the standard approach.22PubMed Central. Leiomyoadenomatoid Tumors of the Uterus: A Case Report and Literature Review
Fertility preservation can be a particular concern for younger women. In one published case, a young woman who had not yet had children developed a large, recurring adenomatoid tumor causing heavy bleeding and pain. Her surgeons used a specialized technique involving temporary clamping of blood supply to the uterus to safely remove the tumor while keeping the uterus intact.7PubMed. A novel approach in the management of a recurrent adenomatoid tumor of the uterus utilizing a Strassman technique Cases like this are rare, as recurrence itself is uncommon, but they illustrate that even in unusual circumstances, the guiding principle remains organ preservation whenever possible.
When the Microscope Gets Tricky
Although most adenomatoid tumors look straightforward under the microscope, a small number have atypical features that can alarm pathologists. Some tumors contain cells with a so-called “deciduoid” appearance (plump cells resembling a type normally seen in pregnancy tissue), along with unusual nuclear features that raise suspicion for malignancy.23PubMed. Adenomatoid Tumor of Fallopian Tube With “Deciduoid” Morphology and Atypical Nuclear Features Others show marked atypia, meaning the cell nuclei look irregular in size and shape, a feature more commonly associated with cancer.
One case report documented a uterine adenomatoid tumor with striking nuclear abnormalities in a patient who had been on prolonged hormone therapy. Despite the worrisome appearance, the tumor showed no signs of aggressive behavior or malignant transformation.24PubMed. Adenomatoid Tumor of the Uterus With Marked Nuclear Atypia: A Case Report Including Next-Generation Sequencing Analysis and Review of the Literature The researchers speculated that hormonal exposure might have driven the unusual appearance, but the mechanism remains unclear. The takeaway for patients is that even when a pathology report mentions “atypia” or “atypical features” in an adenomatoid tumor, it does not necessarily mean cancer. It does, however, mean the pathologist needs to be especially careful to rule out other diagnoses.
Prognosis and What to Expect Long Term
The prognosis for adenomatoid tumors is excellent. They do not metastasize, they almost never recur after complete removal, and there is no evidence that they transform into malignant tumors. Across all reported locations, from the genital tract to the adrenal gland to the gastrointestinal tract, the pattern is the same: once removed, the tumor does not come back and does not progress.10PubMed Central. Adenomatoid Tumors of the Gastrointestinal Tract – A Case Series and Review of the Literature
No chemotherapy, radiation, or further treatment is needed after surgical excision. Follow-up is generally minimal, though doctors may recommend periodic imaging after treatment of scrotal lesions to monitor for any other changes. The real risk with adenomatoid tumors is not the tumor itself but what might happen if it is misdiagnosed: an unnecessary radical surgery for a presumed malignancy, or conversely, a missed diagnosis of something that actually is malignant. That is why accurate pathological evaluation, using the immunohistochemical markers and molecular tools described above, matters so much.
Adenomatoid Tumors Mistaken for Other Conditions
Misdiagnosis runs in both directions. The tumor that most frequently gets confused with an adenomatoid tumor depends on the site. In the uterus, fibroids are by far the most common misidentification. On imaging, the two can look nearly identical, and since fibroids are vastly more common, a radiologist seeing a uterine wall mass will default to calling it a fibroid until proven otherwise. This usually has no real consequences, because the treatment (myomectomy or monitoring) is similar for both.
In the scrotum, the stakes are higher. A painless testicular or paratesticular mass triggers concern about testicular cancer, and the reflexive surgical response is radical orchiectomy. This is where negative tumor markers, characteristic ultrasound findings, and frozen section analysis become the patient’s best allies. In the adrenal gland, an incidentally discovered adenomatoid tumor can mimic a nonfunctioning adrenal adenoma or even an adrenal metastasis from cancer elsewhere. Here too, tissue diagnosis is usually needed to settle the question.
For tumors found in truly unusual locations like the pleura or mediastinum, the differential diagnosis widens considerably to include mesothelioma, lymphangioma, and various carcinomas. Immunohistochemistry is indispensable in these cases. The combination of positive calretinin and D2-40 with negative endothelial markers (CD31, CD34) points strongly toward a mesothelial origin, and the bland, low-proliferation pattern then distinguishes a benign adenomatoid tumor from mesothelioma.12PubMed Central. Adenomatoid Tumor of the Adrenal Gland: Report of Two Cases and Review of the Literature
Why These Tumors Remain Underrecognized
Adenomatoid tumors are probably more common than reported figures suggest. Many are small, silent, and never cause any symptoms. In the uterus, they are routinely buried within tissue removed for fibroids and may not be identified unless the pathologist specifically looks for them. In the epididymis, they may be stable enough that a man never seeks medical attention. Autopsy studies have occasionally turned up adenomatoid tumors that were never suspected during the patient’s lifetime.
The lack of a dedicated screening recommendation, no biomarker panel, and no characteristic set of symptoms means that awareness among non-specialist clinicians is uneven. When a pathologist encounters one for the first time without prior familiarity, the unusual microscopic architecture can be genuinely confusing. This is one of those medical situations where the tumor is harmless but the diagnostic journey matters, because a wrong turn can lead to unnecessary surgery or prolonged anxiety about a cancer diagnosis that never existed. The steadily expanding toolkit, from TRAF7 mutation testing to BAP1 staining, is making that diagnostic journey faster and more reliable.