Can Adenomyosis Cause Cancer? Insights on Uterine Health

Adenomyosis is a condition where endometrial-like tissue grows into the muscular wall of the uterus, leading to heavy periods, pain, and an enlarged uterus. While it is considered benign, concerns sometimes arise about whether it could increase cancer risk.

Understanding how adenomyosis affects uterine health requires examining its cellular behavior, hormonal influences, and genetic factors.

Adenomyosis And Tissue Growth Patterns

Adenomyosis results from the infiltration of endometrial-like glands and stroma into the myometrium, the muscular layer of the uterus. Unlike normal endometrial tissue, which sheds during menstruation, these misplaced cells remain embedded, responding to hormonal fluctuations without an exit pathway. This leads to localized thickening, increased vascularization, and chronic inflammation, contributing to the condition’s symptoms. Unlike fibroids, which form discrete masses, adenomyosis causes diffuse, irregular expansion within the myometrium.

Histological examinations show adenomyotic lesions with increased cellular density and altered extracellular matrix composition, often leading to fibrosis. Immunohistochemical markers such as vimentin and desmin indicate hypertrophy and hyperplasia of surrounding smooth muscle cells, contributing to uterine enlargement. Aberrant expression of matrix metalloproteinases (MMPs) suggests dysregulated tissue remodeling. However, adenomyosis does not exhibit uncontrolled proliferation or invasive behavior beyond the uterine wall, confirming its benign nature.

MRI and transvaginal ultrasound provide insights into adenomyosis. A thickened junctional zone, appearing hyperintense on T2-weighted imaging due to increased water content and tissue edema, is a hallmark of the condition. Doppler ultrasound studies show increased blood flow in affected areas, reflecting heightened vascular activity. These imaging techniques aid diagnosis and clarify how adenomyotic tissue interacts with the surrounding uterine structure.

Molecular Signals In Abnormal Cell Proliferation

Adenomyotic tissue growth is driven by molecular signals regulating cell proliferation, differentiation, and survival. One key pathway is estrogen-mediated activation of the PI3K/AKT/mTOR signaling cascade. Research shows adenomyotic tissue has increased phosphorylated AKT and mTOR, promoting cell growth and inhibiting apoptosis. This prolongs the survival of ectopic endometrial-like cells despite cyclical hormonal changes.

Another relevant pathway is Wnt/β-catenin signaling, which regulates tissue homeostasis and cellular differentiation. Adenomyotic lesions often show increased nuclear accumulation of β-catenin, indicating Wnt pathway activation. This promotes epithelial-to-mesenchymal transition (EMT), allowing cells to infiltrate the myometrium without uncontrolled metastatic behavior.

Growth factors and cytokines also influence adenomyotic proliferation. Elevated transforming growth factor-beta (TGF-β) contributes to fibrosis and stromal remodeling, activating fibroblasts and increasing extracellular matrix deposition. Vascular endothelial growth factor (VEGF) is upregulated, promoting angiogenesis and increased blood supply to affected areas, sustaining the growth of ectopic endometrial-like cells.

Cellular Differences Between Adenomyosis And Malignancies

Adenomyosis differs from malignant uterine tumors in cellular behavior. Adenomyotic cells invade the myometrium but retain normal nuclear morphology, organized glandular structures, and intact basement membranes, preventing uncontrolled growth. In contrast, malignancies like endometrial carcinoma or leiomyosarcoma display nuclear atypia, high mitotic indices, and disrupted cell adhesion, leading to unchecked expansion and metastasis.

Cell cycle regulation further separates adenomyotic tissue from cancer. While adenomyotic cells show increased expression of cyclin D1 and CDK4, they do not bypass normal regulatory checkpoints. Unlike cancer cells, which often have mutations in tumor suppressor genes like TP53 or PTEN, adenomyotic cells maintain functional apoptotic pathways. Immunohistochemical studies show that while adenomyotic tissue may have elevated proliferative markers like Ki-67, levels remain significantly lower than in malignant uterine neoplasms.

The extracellular environment also distinguishes adenomyosis from cancer. Stromal remodeling in adenomyosis results from localized inflammation and fibrosis, leading to increased extracellular matrix deposition and myometrial thickening. Unlike malignant tumors, which secrete enzymes to degrade surrounding tissue and facilitate metastasis, adenomyotic lesions show controlled extracellular matrix remodeling without widespread tissue destruction.

Hormonal Influences On Uterine Tissue

Estrogen and progesterone play a critical role in adenomyosis. Endometrial-like cells embedded in the myometrium exhibit an exaggerated response to these hormones, leading to persistent proliferation and abnormal tissue remodeling. Studies show overexpression of estrogen receptor-alpha (ER-α) in adenomyotic lesions, increasing sensitivity to circulating estrogen. Progesterone, which counteracts estrogen’s effects, has a reduced impact due to downregulated progesterone receptors (PRs), preventing normal differentiation and shedding of endometrial-like tissue.

Local estrogen production within adenomyotic tissue further fuels its growth. Aromatase, an enzyme responsible for estrogen biosynthesis, is highly expressed in ectopic endometrial-like cells but largely absent in normal myometrial tissue. This creates an autocrine loop where locally produced estrogen continuously stimulates proliferation. Aromatase inhibitors have shown promise in reducing lesion size and alleviating symptoms. Altered progesterone signaling also disrupts key regulatory genes involved in uterine function, further impairing normal tissue homeostasis.

Genetic Factors In Abnormal Tissue Changes

Genetic research on adenomyosis has identified molecular alterations contributing to its development. Unlike malignant uterine tumors, which often involve mutations in tumor suppressor genes or oncogenes, adenomyotic tissue primarily exhibits changes linked to abnormal differentiation and localized proliferation. Whole-genome and transcriptomic analyses reveal differential gene expression patterns affecting extracellular matrix remodeling, inflammation, and hormone signaling. Key implicated genes include ESR1 and ESR2, which encode estrogen receptors, and Wnt pathway regulators CTNNB1 and APC.

Epigenetic modifications also play a role. DNA methylation and histone modifications affect progesterone responsiveness, leading to PR downregulation and progesterone resistance. This allows adenomyotic tissue to grow unchecked despite hormonal fluctuations. MicroRNA (miRNA) profiling has identified dysregulated miRNAs, such as miR-200b and miR-29c, influencing cell adhesion, apoptosis, and tissue remodeling. While adenomyosis does not share the mutational burden of uterine malignancies, its unique molecular alterations drive pathological expansion within the myometrium.

Differentiating Adenomyosis From Other Uterine Growths

Accurate diagnosis is essential to differentiate adenomyosis from other uterine conditions like fibroids and endometriosis, which share symptoms such as pelvic pain and heavy menstrual bleeding. Unlike fibroids, which are well-demarcated fibrous tumors composed of smooth muscle cells, adenomyosis involves diffuse infiltration of endometrial-like tissue into the myometrium. Clinically, fibroids present as firm, nodular masses, while adenomyosis leads to a uniformly enlarged, softer uterus. MRI helps distinguish these conditions, as fibroids appear as well-circumscribed masses with low T2 signal intensity, whereas adenomyosis shows a thickened junctional zone with high T2 signal intensity.

Endometriosis, another condition involving ectopic endometrial tissue, differs in location and behavior. While both involve hormonally responsive cells outside the endometrium, endometriosis primarily affects the peritoneal surfaces, ovaries, and pelvic organs, forming adhesions and cystic lesions. Adenomyosis remains confined to the myometrium, causing diffuse uterine thickening rather than discrete cystic structures. Histological analysis also differentiates them, as endometriosis often exhibits hemosiderin-laden macrophages and chronic inflammatory infiltrates, while adenomyotic tissue shows smooth muscle hyperplasia and glandular proliferation. A combination of clinical evaluation, imaging, and histopathology is necessary for accurate diagnosis.