Adenomatoid tumours of the gastrointestinal tract - a case-series and review of the literature.

AIMS: Adenomatoid tumours are mesothelial-derived benign neoplasms with a predilection for the genital tract. Extragenital sites are rare and can cause significant diagnostic challenges. Herein, we describe the clinicopathological features of a cohort of adenomatoid tumours involving the gastrointestinal tract and liver in order to more clearly characterise their histological findings and aid in diagnosis. METHODS AND RESULTS: The pathology databases at four institutions were searched for adenomatoid tumours involving the gastrointestinal tract or liver, yielding eight cases. Available clinicoradiological and follow-up data were collected from the medical records. Six tumours were incidentally discovered during imaging studies or at the time of surgical exploration for unrelated conditions; presenting symptoms were unknown in two patients. Histologically, the tumours were well-circumscribed, although focal ill-defined borders were present in four cases. No infiltration of adjacent structures was identified. Architectural heterogeneity was noted in five (63%) tumours; an adenoid pattern often predominated. The neoplastic cells were flattened to cuboidal with eosinophilic cytoplasm. Cytoplasmic vacuoles mimicking signet ring-like cells were present in five (63%) cases. Three (38%) cases showed involvement of the mesothelium with reactive mesothelial hyperplasia. Cytological atypia or increased mitotic activity was not identified. The surrounding stroma ranged from oedematous/myxoid to densely hyalinised. Immunohistochemistry confirmed mesothelial origin in all cases evaluated. No patients developed recurrence of disease. CONCLUSIONS: The current study evaluates the clinicopathological findings in a collective series of gastrointestinal and hepatic adenomatoid tumours, correlating with those described in individually reported cases. We highlight common histological features and emphasise variable findings that could mimic a malignant neoplasm.

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.

Adenomatoid tumors have been described almost a century ago, and their nature has been the subject of debate for decades. They are tumors of mesothelial origin usually involving the uterus, the Fallopian tubes, and the paratesticular region. Adenomatoid tumors of the adrenal gland, the liver, the extragenital peritoneum, the pleura, and the mediastinum have been rarely reported. They are usually small incidental findings, but large, multicystic and papillary tumors, as well as multiple tumors have been described. Their pathogenesis is related to immunosuppression and to TRAF7 mutations. Despite being benign tumors, there are several macroscopic or clinical aspects that could raise diagnostic difficulties. The aim of this review was to describe the microscopic and macroscopic aspects of adenomatoid tumor with a special focus on its differential diagnosis and pathogenesis and the possible link of adenomatoid tumor with other mesothelial lesions, such as the well-differentiated papillary mesothelioma and the benign multicystic mesothelioma, also known as multilocular peritoneal cysts.

Non-random adenomatoid tumours of the female genital system: A comparative clinicopathologic analysis of 14 cases.

The aim of this study was to evaluate adenomatoid tumours (AT) clinicopathologically in the female genital tract and compare the histomorphological features of ATs according to their uterine or tuba-ovarian location. Cases of AT were excised and collected from female genital tracts between the years of 2010-2017. Cases were evaluated depending on their clinical findings, localisation and pathological properties. There were 14 cases of AT. Ten cases were uterine, and 4 cases were adnexal tumours. The diagnostic ratio of uterine ATs was 64.3%, and of tuba-ovarian ATs was 21.4% (P > 0.05). The size of the largest tumour was 6 cm. Two of the uterine and one of the ovarian cases had a macrocyst; 2 uterine and one ovarian case had a microcyst; and 6 uterine had a combined microcystic/trabecular pattern. Uterine cases showed a higher number of smooth muscle component, signet-ring cells and infiltrative nature compared with other cases (P < 0.05). All uterine cases were infiltrative. Most of ATs of the female genital system were small in size and incidentally diagnosed in our cases but rarely detected as an adnexal mass forming lesion which mimics a malignancy. A comparative clinicopathologic analysis of these cases should be considered with the histomorphological and immunohistochemical features for an accurate differential diagnosis.

BAP1 Loss is a Useful Adjunct to Distinguish Malignant Mesothelioma Including the Adenomatoid-like Variant From Benign Adenomatoid Tumors.

Malignant mesothelioma (MM) can show areas closely mimicking reactive mesothelial proliferations or recapitulating benign adenomatoid tumors (ATs) making distinction on occasion impossible on morphologic ground alone, particularly in limited biopsy material. Recently, loss of BAP1 by immunohistochemistry (IHC) has been suggested as a potential marker for identifying MM, but data is still limited. We studied 264 MM cases (257 using tissue microarrays; 7 on conventional slides) and 42 genital ATs for BAP1 immunohistochemical expression. Loss of BAP1 protein expression was observed in 119/211 of MM cases (56.4%). Taken by histologic type, 64.3% of biphasic, 55.4% of epithelioid, and 41.7% of sarcomatoid MM were BAP1-deficient. In contrast, all 42 ATs showed retained BAP1 immunoreactivity. Notably, all 4 MM cases with variable adenomatoid-like features were BAP1-deficient. Surface components of MM of the pleura showed concordant loss as the invasive tumor suggesting a potential role for BAP1 loss for recognizing so-called early mesothelioma. In conclusion, BAP1 loss demonstrated by IHC is seen in more than half of MM cases but none of ATs. Thus, BAP1 IHC represents a potential adjunct for distinguishing MM from benign mesothelial proliferations including in particular "MM with bland adenomatoid-like pattern versus benign ATs" on biopsy material and early mesothelioma with limited invasion.

A Case Report of an Adenomatoid Tumor of the Uterus Mimicking an Endometrioid Adenocarcinoma on Endometrial Curetting: a Diagnostic Pitfall.

Adenomatoid tumors (AT) arising in the female genital tract are usually incidental findings occurring most often in the fallopian tube and uterine serosa and rarely in the myometrium. In the myometrium, they appear grossly as deep seated, small, firm, ill circumscribed nodules mimicking leiomyoma. Histologically they show a glandular and invasive pattern making well-differentiated/low-grade endometrioid adenocarcinoma a major differential diagnosis. However, this differential is rarely encountered in practice because myometrial AT is usually seen on the hysterectomy specimen, because of their anatomic position in the deep myometrium, and only rarely in endometrial curettings. Our case is the first to report an AT, which presented as a polyp with associated fibroid on hysterescopic examination. Microscopically, the endometrial curetting and myomectomy showed irregular glands and cystic structures with occasional cytokeratin positive single signet-ring like cells invading into the myometrium, features consistent with low-grade endometrioid adenocarcinoma. On hysterectomy specimen, there was an ill-defined 5 cm mass in the myometrium with protrusion into the endometrium. The morphology was similar to that seen in the endometrial curetting. A larger panel of immunostains was done and the neoplastic cells were positive for AE1/3, CK7, CAM5.2, calretinin, and D2-40 and negative for CD34. A diagnosis of AT was rendered and no further treatment was required. Although AT is rarely seen in endometrial curetting, they should be in the differential diagnosis of glandular lesions to avoid pitfalls and unnecessary management especially in young patients desiring fertility.

Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation.

Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs). These mutations all clustered into one of five recurrent hotspots within the WD40 repeat domains at the C-terminus of the protein. Functional studies in vitro revealed that expression of mutant but not wild-type TRAF7 led to increased phosphorylation of nuclear factor-kappa B (NF-kB) and increased expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation. Immunohistochemistry demonstrated robust L1CAM expression in adenomatoid tumors that was absent in normal mesothelial cells, malignant peritoneal mesotheliomas and multilocular peritoneal inclusion cysts. Together, these studies demonstrate that adenomatoid tumors of the male and female genital tract are genetically defined by TRAF7 mutation that drives aberrant NF-kB pathway activation.

Expression of GATA-3 in Testicular and Gynecologic Mesothelial Neoplastic and Non-neoplastic Tissues.

GATA-3 expression in testicular/gynecologic mesothelial neoplasms and benign mesothelia have not been completely investigated. We graded GATA-3, calretinin, and WT1 staining in 20 adenomatoid tumors [9/20 (para)testicular and 11/20 tubal/uterine] and 38 normal mesothelia (20/38 tunica vaginalis and 18/38 fallopian tubes) as either 0 (≤5%), +1 (>5% and <25%), +2 (≥25% and ≤50%), and +3 (>50%). Adenomatoid tumor GATA-3 staining: 2 urologic cases were positive (2/9, +3 and +1), no gynecologic cases were positive (0/11), and all were positive for WT1/calretinin (20/20,+2 to +3). The normal tunica vaginalis mesothelia: 3 of 20 were GATA-3 positive (+2) while 20 of 20 were WT1/calretinin (+2 to +3) positive. The gynecologic cases with walthard nests: are positive for GATA-3 (18/18,+3), WT1 (11/18, +2 to +3), and calretinin (1/18,+2). The nonmetaplastic gynecologic mesothelia were GATA-3 negative (18/18) and WT1/calretinin postive (18/18,+2 to +3). All 18 epididymi were GATA-3 positive (+3) and negative for WT1/calretinin. All 11 efferent ductules examined were negative for GATA-3, WT1/calretinin (0/11). Although GATA-3 rarely stains adenomatoid tumors, gynecologic walthard nests are consistently positive with GATA-3 staining but lose mesothelial markers reflecting a metaplastic change. Excluding the walthard nests, GATA-3 is rarely positive in normal urologic and gynecologic mesothelia. GATA-3 is uniformally positive in epididymi and negative in efferent ductules, which may be due to their embryological evolvement. Awareness of the GATA-3 staining patterns in the genitourinary and gynecologic mesothelial tissues and their respective neoplasms is important to prevent misdiagnosis and possible unnecessary interventions.

An immunohistochemical study of adenomatoid tumors of the uterus and fallopian tube.

Immunohistochemical studies of adenomatoid tumor (AT) are rare in the English literature. The author reports herein immunoprofile of AT of the female genital organs. The materials are 4 cases of AT of the uterus and 1 case of AT of the fallopian tube. The ages of the patients were 37, 41, 43, 45, and 56 years. The sizes of ATs were 0.8 cm, 1 cm, 1.5 cm, 2 cm, and 4 cm. The 4 ATs of the uterus were composed of tubules and smooth muscles, whereas 1 AT of the fallopian tube was composed only of tubules. Immunohistochemically, the ATs were consistently positive for pancytokeratin AE1/3+++, pancytokeratin CAM5.2 ++, cytokeratin (CK) 7 +++, CK8 +, CK18++, CK19++, calretinin +++, and D2-40 ++. Estrogen receptor (ER) and progesterone receptor (PgR) was positive in 4 of 5 cases. CK34ßE12 was positive in 1 of 5 case. The Ki-67 labeling ranged from 0.2% to 3%. The smooth muscles in uterine ATs were positive for α-smooth muscle actin, ER, and PgR. The ATs were consistently negative for CK5/6, CK14, CK20, EMA, HMB45, vimentin, desmin, CD31, CD34, factor VIII-relatedantigen, S100 protein, p53, CD68, CDK4, MDM2, and Ber-EP4. These data indicate that ATs consistently express pancytokeratin AE1/3, pancytokeratin CAM5.2, CK7, CK8, CK18, CK19, calretinin, and D2-40, that some ATs express CK34ßE12, ER, and PgR, that ATs show little proliferative activity, and that ATs were consistently negative for CK5/6, CK14, CK20, EMA, HMB45, vimentin, desmin, CD31, CD34, factor VIII-related antigen, S100 protein, p53, CD68, CDK4, MDM2, and Ber-EP4.

Adenomatous tumors of the middle ear and temporal bone: clinical, morphological and tumor biological characteristics of challenging neoplastic lesions.

Adenomatous tumors of the middle ear and temporal bone are rare tumors. In this retrospective study, we examined nine patients who underwent surgery for an adenomatous tumor of the middle ear, mastoid cavity or eustachian tube. In seven patients, a middle ear adenoma (MEA) and in two patients an aggressive papillary tumor (APT) was diagnosed. We report the clinical, radiologic, morphologic, immunohistochemical and DNA image cytometrical characteristics that can help to correctly classify these tumors. Therapy consisted of surgical excision of the tumors in eight cases. In one elderly patient, only a large biopsy was taken, because this patient suffered from cardial and kidney disorders and was not suitable for an extended surgical approach. This patient received stereotactic radiotherapy. Seven patients underwent planned second look operation. Recurrences occurred in three patients (one with APT, two with MEA), whereas in two of these cases rather a residual tumor due to initial incomplete tumor resection occurred. By image analysis, DNA cytometry MEA were considered benign, whereas the appearance of aneuploid tumor cells in APT confirmed these tumors as low grade malignant lesions. The proliferation rates were equally low in both entities. APT and MEA are tumor entities which can only be correctly classified by a synopsis of histopathology, immunohistochemistry and DNA image cytometry. The recommended therapy is the complete tumor excision. In cases of APT, von Hippel-Lindau syndrome has to be excluded.

Adenomatoid tumors of the female and male genital tract. A comparative clinicopathologic and immunohistochemical analysis of 47 cases emphasizing their site-specific morphologic diversity.

Adenomatoid tumors (ATs) are uncommon benign mesothelial tumors with a predilection for the genital tract. We reviewed 47 ATs diagnosed at our institutions during 10-year period. Thirty tumors (64%) originated in the female (21 uterine, 8 tubal, and 1 ovarian) and 17 (36%) in the male (9 epididymal and 8 testicular) genital tract. The median age for females and males was 47.5 and 51 years, respectively. While 83% of tumors in females were incidental findings in resections for unrelated diseases, 94% of male lesions presented as clinical masses leading to surgery. The median size was 2, 1, and 0.5 cm for uterine, epididymo-testicular, and tubo-ovarian lesions, respectively. Architecturally, the microcystic/angiomatoid pattern was the most frequent (32/47; 68%), followed by combined microcystic/trabecular (26/47; 55%) and retiform/adenoid (15/47; 32%) pattern. The trabecular/solid (6%) and macrocystic (4%) patterns were uncommon. However, 57% of cases revealed ≥2 growth patterns. Taken by anatomic site, 20 of 21 uterine cases were at least focally microcystic but none was retiform. In contrast, the retiform pattern dominated in male genital tract tumors (12/17; 71%). Immunohistochemistry showed expression of calretinin (36/36) and D2-40 (30/30) and lack of CD34 (0/30) and PAX8 (0/32). GLUT-1 was expressed in 11/11 male genital tract tumors but in none of the microcystic uterine lesions. Estrogen and progesterone receptor expression was weak and focal (two and three uterine cases, respectively). None stained for the androgen receptor. Our study illustrates the great site-specific morphological diversity of ATs emphasizing their wide site-dependent differential diagnosis.

Malignant mesothelioma with prominent adenomatoid features: a clinicopathologic and immunohistochemical study of 10 cases.

The clinicopathologic and immunohistochemical features of 10 cases of pleural malignant mesothelioma with predominantly adenomatoid growth pattern are described to determine the clinical, histologic, and behavioral features of these tumors and to highlight the importance of separating this unusual pattern from the benign adenomatoid tumor. Seventy-seven cases of pleural biopsy and extrapleural pneumonectomy specimens for malignant mesothelioma were examined to identify the specific type of histologic growth pattern exhibited by the tumors. The 10 cases herein described were identified as an unusual histopathologic subset of these tumors. Nine patients were men and one was a woman with an age range of 56 to 82 years (mean, 68.5 years). The main presenting symptoms included cough, dyspnea, and chest pain. The typical features of pleural malignant mesothelioma were noted both radiologically and macroscopically. The tumors were characterized by diffuse pleural thickening with confluent nodular patches of tumor obliterating the pleural space. Histologically, a distinct morphology was observed composed of small tubular spaces lined by epithelioid cells, reminiscent of adenomatoid tumors of the genital tract. Immunohistochemical studies confirmed the mesothelial nature of the tumors. Clinical follow-up in 7 of 7 patients demonstrated a mean survival of 10 months from time of diagnosis. Adenomatoid mesothelioma is an unusual variant of epithelioid malignant mesothelioma that histologically may mimic a range of other tumors, including benign adenomatoid tumors and metastases of adenocarcinoma to the pleura. The clinical presentation, infiltrative growth, distinct histologic features, cytologic atypia and immunohistochemical profile all serve to differentiate adenomatoid malignant mesothelioma from other infiltrative processes involving the pleura.

Adenomatoid tumour of the adrenal gland: a case report and literature review.

Adenomatoid tumour (AT) is a rare, benign neoplasm of mesothelial origin, which usually occurs in the genital tract of both sexes. Occasionally these tumours are found in extra genital locations such as heart, pancreas, skin, pleura, omentum, lymph nodes, retroperitoneum, intestinal mesentery and adrenal gland. Histologically ATs show a mixture of solid and cystic patterns usually with focal presence of signet-ring like cells and scattered lymphoid infiltration. The most important thing about these tumours is not to mis-diagnose them as primary malignant or metastatic neoplasms. We present a case of an adrenal AT in a 29-year-old asymptomatic male. The tumour was an incidental finding during abdominal CT-scan for an unrelated condition. We also present a review of the literature concerning adrenal gland AT and give possible differential diagnosis.

Epithelial versus endothelial CEACAM1 expression and angiogenesis in epididymal adenomatoid tumor.

BACKGROUND/AIM: To study the expression of the pro-angiogenic factor carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) in epididymal adeno-matoid tumor tissue, a very rare benign neoplasia, in relation to its vascularization. MATERIALS AND METHODS: Immunohistochemistry for CEACAM1 and for both endothelial markers CD31 and CD34 was performed in normal human epididymal and epididymal adenomatoid tumor tissue. The vessel density was calculated in four tumor regions with different degrees of vascularization in comparison to the vascularization of the normal epididymal tissue. RESULTS: CEACAM1 was found in normal epididymal epithelium, while the epithelium of tumor glands was mostly negative. Only few blood vessels and lymphatics in adenomatoid tumor tissue expressed CEACAM1. The assessment of vascularization revealed either equal or a significantly lower vessel density in some adenomatoid tumor regions in comparison to normal epididymal tissue. DISCUSSION: These data demonstrate that despite its epithelial down-regulation, CEACAM1 is not present in the majority of adenomatoid tumor blood vessels, which might be related to the lower angiogenic activity and benign behaviour of this tumor.

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate.

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate is a rare lesion. Here we report the seventh case of such lesions. Histological examination of the transurethral resection of the prostate of a 83-year-old Japanese man showed a small lesion consisted of sclerosing adenosis and basal cell hyperplasia, in addition to the diffuse glandular and fibromuscular hyperplasia. Immunohistochemically, many basal cells in sclerosing adenosis and basal cell hyperplasia areas showed a positive reaction for p63, cytokeratin 5, and D2-40. Additionally, many basal cells in the sclerosing adenosis area and some basal cells in the basal cell hyperplasia area were positive for S-100 protein and alpha-smooth muscle actin, which are myoepithelial cell markers. Finally, we suggest that hybrid sclerosing adenosis and basal cell hyperplasia may be actually a special form of hyperplastic lesion of all components of prostatic tissue, reflecting the unbalanced distribution of glandular, stromal (sclerosing adenosis), and basal cell hyperplasia with the differentiation toward myoepithelial cells predominantly occurring in a sclerosing adenosis area. Additionally, this case showed that D2-40 is a useful marker of basal cells.

Expression of extracellular matrix proteins in ameloblastomas and adenomatoid odontogenic tumors.

This study evaluated the expression of fibronectin, tenascin and type I collagen in ameloblastomas and adenomatoid odontogenic tumors (AOTs) aiming to contribute with the comprehension of the differences in the biological behavior of these tumors. Immunohistochemical technique was performed in 20 cases of ameloblastoma (16 solid and 4 desmoplastic) and in 10 cases of AOT. All tumors presented moderate fibronectin expression in the stroma. Solid ameloblastomas showed intense expression of fibronectin at the epithelial-mesenchymal interface, whereas desmoplastic ameloblastomas revealed no immunoexpression of fibronectin at this site. Ameloblastomas presented stronger immunoreactivity to tenascin than AOTs, especially at the epithelial-mesenchymal interface. AOTs and desmoplastic ameloblastomas showed intense labeling for type I collagen. The patterns of expression of the proteins studied agree with the locally more invasive behavior of ameloblastomas in comparison to AOTs. Our results might suggest a less invasive behavior of desmoplastic ameloblastoma in comparison to solid ameloblastoma.

Adenomatoid tumor of the pleura.

A case of adenomatoid tumor of the pleura is reported, and its differential diagnosis from benign and malignant pleural lesions is discussed. A small pleural nodule was incidentally found during a thoracic operation in a 54-year-old woman with esophageal cancer. The patient had no history of exposure to asbestos, and was well with no sign of recurrence 14 months after the operation. A 7 mm, circumscribed tumor had characteristic features of adenomatoid tumor. The tumor was composed of an aggregation of irregularly shaped tubulocystic spaces with fibrous stoma. The spaces were lined by flattened and occasional cuboidal epithelioid cells with cytoplasmic vacuolization, and several spaces contained pale blue mucinous fluid. On immunohistochemistry the tumor cells were positive for AE1/AE3, CAM5.2, vimentin, cytokeratin 5/6, D2-40, calretinin, thrombomodulin, and WT-1, but negative for CEA, Leu M1 (CD15), thyroid transcription factor-1, epithelial membrane antigen, desmin, glucose transporter-1 (GLUT-1), CD31, and CD34. The MIB-1 (Ki-67) labeling index was 1-2%, indicating low proliferative activity. Adenomatoid tumor of the pleura is rare, and the pathogenesis has not been elucidated. Recognition of these benign mesothelial lesions in the pleura is important to avoid misdiagnosis. The immunohistochemistry in the present case supports its mesothelial origin.

Adenomatoid tumors of the female and male genital tracts: a clinicopathological and immunohistochemical study of 44 cases.

Adenomatoid tumors of the female and male genital tracts are well characterized as mesothelial in origin, but a detailed histological and immunohistochemical analysis comparing both traditional and newer mesothelial markers across gender and site has not been formally conducted. A variety of morphologic features previously described as characteristic of adenomatoid tumors were evaluated in 44 adenomatoid tumors from the male and female genital tracts. Immunohistochemical analysis with pankeratin (AE1/CAM5.2), WT-1, calretinin, CK5/6, D2-40, and caldesmon was also performed. The extent and intensity of staining were scored semiquantitatively on one representative section per case and mean value for each parameter was calculated. All (n=44) the adenomatoid tumors from both the female and male genital tracts demonstrated a distinctive thread-like bridging strand pattern. Lymphoid aggregates were seen in all 12 adenomatoid tumors of male patients, but in only 4 of 32 (13%) tumors in female patients (P<0.0001). The remaining morphologic features were variably present with no clear sex predilection. Pankeratin, calretinin, and D2-40 reactivity were identified in all female (n=32) and male (n=12) genital tract adenomatoid tumors. Adenomatoid tumors expressed WT-1 in 11/12 (92%) male patients and in 31/32 (97%) female patients. In male patients, reactivity for CK5/6 and caldesmon was found in 1/12 (8%) and 0/12 (0%) adenomatoid tumors (respectively), whereas reactivity in female patients was found in 5/32 (16%) and 1/32 (3%); respectively. Female tumors differ from their male counterparts by the frequent absence of lymphoid aggregates and the presence of a circumscribed margin when occurring in the fallopian tube. Of the putative mesothelial markers evaluated, calretinin, D2-40, and WT-1 show a similar immunoprofile and have a higher sensitivity than CK5/6 and caldesmon in genital tract adenomatoid tumors. However, the presence of additional, often strong expression of WT-1 in normal tissues of the female genital tract limits the utility of WT-1 in this setting.

Adenomatoid odontogenic tumor (AOT) originating in a unicystic ameloblastoma: a case report.

The follicular variant of the adenomatoid odontogenic tumor (AOT) is thought to originate from the reduced enamel epithelium of the dental follicle. The origin of the extra-follicular variant however, remains less clear. This paper presents a case of an extra-follicular AOT, which we believe originated from the epithelial lining of a unicystic ameloblastoma, and reviews the literature. The available evidence seems to indicate that some extra-follicular AOTs might arise as secondary phenomena within pre-existing odontogenic cysts or cystic tumors.