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Diagnosis and Discussion: Case 1154

Discussion

Adenomatoid tumors are rare benign neoplasms of mesothelial origin that most frequently arise in the paratesticular region, uterus, and fallopian tubes. They have also been reported, albeit rarely, in the ovary, adrenal gland, liver, extragenital peritoneum, pleura, and mediastinum. The prevalence of uterine adenomatoid tumors is reported to be less than 1% to 5% in hysterectomy specimens. 1 Fallopian tube involvement is even more infrequent; in one study examining 7,500 hysterectomy specimens, the frequency was approximately 0.04% 2. It has been proposed that these tumors may be underrecognized due to their gross resemblance to leiomyomas, leading to under-sampling during routine histologic examination and, thus underestimate their true incidence. 3

In contrast, adenomatoid tumors are more frequently identified in the male genital tract. They are often found within the paratesticular region arising within the epididymis, spermatic cord, tunica albuginea, tunica vaginalis, prostate, ejaculatory duct, and rete testis, and have been reported to account for approximately 30% of all paratesticular masses. 4 Adenomatoid tumors involving the male and female genital tracts typically present between the late second and sixth decades of life, with a median age in the mid-thirties. In females, this corresponds to the reproductive age group. Clinical presentation varies and may include menstrual irregularities, vaginal bleeding, dysmenorrhea, or may be entirely asymptomatic. 1,3,5

Uterine adenomatoid tumors typically range in size from 0.3 to 7 cm, although larger tumors measuring up to 13–15 cm have been reported. 5 They are often found in subserosal locations within the myometrium, often near the uterine cornu. 6 While these tumors are most often solitary, multifocal or diffuse forms have been reported. An association between immunosuppression and the presence of multiple or diffuse adenomatoid tumors has been suggested. 7

Macroscopically, these tumors appear as nodular or tuberculate masses with ill-defined margins. The cut surface varies from solid to spongy with fibrous septations and often demonstrates cystic or cavitary spaces filled with mucinous material. 3 Histologically, adenomatoid tumors are characterized by architectural and cytologic heterogeneity. Growth patterns include tubulocystic, solid, angiomatoid, and slit-like arrangements composed of eosinophilic, flat to cuboidal cells with mild to moderate nuclear atypia and minimal mitotic activity. In cystic tumors, short papillary structures may also be seen. Additional cytologic features include hobnail-like cells, signet ring-like cells, and lipoblast-like cells. Prominent smooth muscle bundles resembling those of leiomyomas are commonly seen admixed with the mesothelial proliferation. 1,3,5 The prominent smooth muscle bands are more characteristic of adenomatoid tumors arising within the uterus as compared to other anatomic sites. 8  Given the morphologic heterogeneity, a broad differential diagnosis can be considered including leiomyoma, metastatic adenocarcinoma including those with signet ring morphology, lymphangioma, vascular tumors, benign mesothelial lesions, and malignant mesothelioma, particularly the adenomatoid variant of epithelioid mesothelioma.

The immunohistochemical profile of adenomatoid tumors is helpful in narrowing the differential diagnosis in the majority of cases. Adenomatoid tumors express multiple mesothelial markers, including calretinin, WT1, and D2-40, as well as cytokeratin AE1/AE3 and CAM5.2. Importantly, BAP1 is retained, assisting in the exclusion of malignant mesothelioma. 1,3,5 Molecularly, adenomatoid tumors are characterized by mutations in the TRAF7 gene, which lead to aberrant activation of the NF-κB pathway. Interestingly, TRAF7 mutations have also been identified in a subset of localized malignant mesotheliomas (MM), which frequently involve the pleura and, less commonly, the peritoneum. Despite overlapping molecular drivers and immunophenotypic features, localized MM is morphologically distinct from adenomatoid tumors, typically displaying biphasic, sarcomatoid, or epithelioid patterns with increased cytologic atypia and mitotic activity. Furthermore, localized MM may harbor additional genetic alterations such as BAP1 loss and CDKN2A (p16) deletion, which can aid in distinguishing it from adenomatoid tumors3.

The distinction between adenomatoid tumors and other benign or low-grade mesothelial lesions, such as peritoneal inclusion cysts and well-differentiated papillary mesothelial tumors (WDPMT), can be more challenging. These entities share similar immunohistochemical profiles, and TRAF7 mutations have also been detected in WDPMT. Moreover, morphologic overlap has been reported, with adenomatoid-like areas observed within inclusion cysts and WDPMT, as well as cystic and papillary features within adenomatoid tumors3. The precise relationship between these entities, particularly WDPMT, a relatively recently described neoplasm, is unclear and will require further studies to fully elucidate.

References

  1. Li YY, Kan GJ, Wang Q, Guo S, Wu CX, Zhu J. Adenomatoid tumor of the uterus: analysis of misdiagnosed cases and a literature review. J Int Med Res. Oct 2024;52(10):3000605241282389. doi:10.1177/03000605241282389
  2. Mitta K, Michos G, Athanasiadou E, Papanikolaou E, Tsakiridis I, Mamopoulos A. Adenomatoid tumor of the fallopian tube: A case report and a review of the literature. Int J Surg Case Rep. Oct 2024;123:110268. doi:10.1016/j.ijscr.2024.110268
  3. Karpathiou G, Hiroshima K, Peoc'h M. 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. Adv Anat Pathol. Nov 2020;27(6):394–407. doi:10.1097/PAP.0000000000000278
  4. Amin W, Parwani AV. Adenomatoid tumor of testis. Clin Med Pathol. Sep 09 2009;2:17–22. doi:10.4137/cpath.s3091
  5. Chen HF, Liu XL, Liu AZ, Shi JS, Cui Y, Gao P. Uterine adenomatoid tumor: a clinicopathologic study of 102 cases. Int J Clin Exp Pathol. 2017;10(9):9627–9632.
  6. Ranjan R, Singh L, Nath D, et al. Uterine Adenomatoid Tumors: A Study of Five Cases Including Three Cases of the Rare Leiomyoadenomatoid Variant. J Obstet Gynaecol India. Jul 2015;65(4):255–8. doi:10.1007/s13224-014-0557-9
  7. Tamura D, Maeda D, Halimi SA, et al. Adenomatoid tumour of the uterus is frequently associated with iatrogenic immunosuppression. Histopathology. Dec 2018;73(6):1013–1022. doi:10.1111/his.13726
  8. Sangoi AR, McKenney JK, Schwartz EJ, Rouse RV, Longacre TA. Adenomatoid tumors of the female and male genital tracts: a clinicopathological and immunohistochemical study of 44 cases. Mod Pathol. Sep 2009;22(9):1228–35. doi:10.1038/modpathol.2009.90