The adenomatoid tumor is a benign neoplasm of mesothelial origin that preferentially involves the genital tract. In the gynecologic tract, the adenomatoid tumor is more common in the uterus and fallopian tube 1. The pathologic diagnosis of an adenomatoid tumor is usually straightforward, with tumors showing typical histologic findings, bland cytomorphology, and lack of mitotic activity 1,2. To our knowledge, decidual-like or “deciduoid” morphology has not been reported in the adenomatoid tumor. Moreover, some unusual histologic features including nuclear atypia, multinucleation, or mitoses may raise the question of malignancy 1–3. Failure to recognize the unusual morphology in the adenomatoid tumor may cause diagnostic confusion.
Herein we present a case of adenomatoid tumor of the fallopian tube with diffuse deciduoid morphology and atypical nuclear features in a patient with prolonged progestin therapy.
A 39-yr-old gravida 7 para 5 Caucasian female presented with a prolonged abnormal uterine bleeding. The patient was treated with progestin for 8 mo. The transvaginal ultrasound showed a 1.5 cm left paratubal cyst with an unremarkable uterus and both ovaries. No abnormal finding was noted on clinical examination. The patient underwent a total laparoscopic hysterectomy with bilateral salpingectomy.
The left fallopian tube showed an incidental 0.4 cm adenomatoid tumor involving the muscular wall (Fig. 1A) with a small paratubal cyst. The adenomatoid tumor appeared as a nodule with ill-defined border and consisted of diffuse large polygonal cells with round nuclei, and abundant eosinophilic cytoplasm that resembled decidual cells (Fig. 1B). These cells were arranged in small nests, tubules, cords, and trabecula that dissected through intervening smooth muscle wall. Focal peripheral lymphoid aggregates were present. Thread-like bridging strands were rarely observed (Fig. 1C). The tumor cells occasionally showed large nuclei with irregular nuclear borders and distinct nucleoli, multinucleation, and nuclear grooves (Fig. 1D). Rare individual mitosis was also identified (0–1 in 10 high power fields) (Fig. 1D, inset). No necrosis or destructive invasion into surrounding tissue was observed. The uterus showed adenomyosis, with unremarkable endometrium and cervix. Right fallopian tube was histologically unremarkable.
The adenomatoid tumor was diffusely positive for WT-1 (6F-H2, Dako), calretinin (DAK-calret 1, Dako) (nuclear and cytoplasmic staining) (Fig. 2A), D2-40 (D2-40, Dako) (cell membrane with luminal staining) (Fig. 2B), focal weak to moderate nuclear staining for estrogen receptor (EP1, Dako) and progesterone receptor (1294, Dako) (~10% of tumor) (Fig. 2C), and rare membranous positivity for HBME-1 (HBME-1, Agilent). Keratin 5/6 (D5/16 B4, Dako) was negative and PHH-3 stained rare nuclei (polyclonal, Cell Marque) (<1%). The tumor showed retained nuclear expression of BAP-1 (clone C4, Santa Cruz, Biotechnology) (Fig. 2D). Ki-67 (MIB-1, Dako) proliferative index was low (~1%).
The adenomatoid tumor was first described by Golden and Ash 4, representing an incidental, benign, well-circumscribed neoplasm of mesothelial origin. The tumor involves the genital tract and extragenital organs such as the adrenal gland, liver, pleura, and mediastinum 1–3. Approximately <1% to 5% of tumors are described in the female genital tract 3. Myometrium is the most common location, accounting for 81% of cases 1. The majority of cases arising in the female genital tract are usually small and not detected grossly 2,3. Most adenomatoid tumors in the fallopian tube are found incidentally, ranging from 0.1 to 0.4 cm in size 1.
In mesotheliomas, decidual-like or deciduoid morphology has been described as a distinct diagnostic entity 5. Some mesotheliomas with deciduoid features have been described during or after pregnancy, suggesting a potential role of progesterone 6. To our knowledge, deciduoid change has not been reported in adenomatoid tumors. Although some adenomatoid tumors with epithelioid cells and eosinophilic cytoplasm may have represented deciduoid morphology 1,3,7, exposure to progesterone was not described in these reports. Our case is the first report of deciduoid morphology in an adenomatoid tumor that is associated with prolonged progestin therapy.
The diagnosis of adenomatoid tumor in our case was based on the presence of characteristic morphologic features, including small tubular spaces with rare thread-like bridging strands and peripheral lymphoid aggregates 1–3. The positivity for mesothelial markers (WT-1, calretinin, and D2-40) with a low proliferative index supported this diagnosis. The negativity for CK5/6 can be occasionally found in the adenomatoid tumor as this marker has relatively low sensitivity compared to other mesothelial markers (positive in only 16% of cases, with focal or faint staining) 1. Because of deciduoid morphology and atypical nuclear features, BAP-1 immunohistochemistry was performed. Retained nuclear expression of BAP-1 excluded mesothelioma 8. BRCA1-associated protein or BAP-1 is a highly sensitive and specific marker for distinguishing adenomatoid tumor from mesothelioma 8.
In our case the etiology of deciduoid morphology and atypical nuclear changes is unclear. The prolonged progestin exposure may be responsible for deciduoid morphology; mesothelial cells have a particular susceptibility to steroid hormones and can undergo cytologic differentiation or metaplastic changes 2,6. Moreover, focal staining of hormonal receptors (estrogen receptor and progesterone) supports hormonal sensitivity in this case. Our findings correspond to the study of Terada 9 that described a hormone receptor-positive adenomatoid tumor and suggested the hormonal sensitive nature of this tumor. HBME-1 is another mesothelial marker that is invariably expressed in the adenomatoid tumor 2,3. Reduced positivity for HBME-1 in our case is similar to Hashimoto and colleagues that reported a uterine adenomatoid tumor with epithelioid eosinophilic cells. Authors suggested that eosinophilic change indicated a lack of differentiation in mesothelial cells, and they noted higher proliferative potential based on the increased Ki-67 labeling index 7. However, in our case, the “deciduoid” morphologic change occurred in the setting of active progestin therapy, and the tumor cells displayed a low proliferative index, therefore, we hypothesize that deciduoid morphology in our case is likely related to progestin exposure.
Other interesting finding in our case is the presence of atypical nuclear features, including variation in nuclear size and shape, multinucleation, and mitoses. These unusual nuclear changes may cause diagnostic dilemmas and confusion with mesothelioma. However, the areas of atypical nuclear features were focal. Mesothelioma often exhibits diffuse nuclear atypia, with increased mitoses, and apparent invasion into underlying tissue 3,10. The exact etiology of atypical nuclear changes in our case is unclear; these nuclear changes can be attributed to hormonal effects. Our case findings also raise a question of malignant transformation of adenomatoid tumor. In general, the adenomatoid tumor has benign behavior. There is only one report of paratesticular adenomatoid tumor with malignant transformation that recurred as epithelioid mesothelioma 11. Interestingly, the morphologic features of adenomatoid tumor were not reviewed in this study. Although the morphologic spectrum of nuclear atypia in adenomatoid tumor and their clinical significance has not yet been clarified, we believe this could be an area of interest for future study.
The most important differential diagnosis is adenomatoid mesothelioma, which can closely mimic adenomatoid tumor histologically and immunophenotypically 12. The presence of characteristic morphologic features and lack of invasion into underlying tissue, together with retained BAP-1 nuclear expression support the diagnosis of adenomatoid tumor. Other differential diagnoses of intramural fallopian tube tumor with deciduoid feature include non-neoplastic lesions (such as peritoneal deciduosis and extraovarian sex cord-stromal proliferation), benign tumor (sex cord tumor of fallopian tube), and malignancy, both primary and metastatic, such as clear cell carcinoma, hepatoid carcinoma, malignant melanoma, large cell variant of small cell carcinoma hypercalcemic type, and hepatoid yolk sac tumor. As described earlier, the diagnosis of our case was based on morphologic features and confirmatory immunohistochemical stains.
In conclusion, we report the first case of adenomatoid tumor with atypical features possibly related to hormone effects. Future studies are needed to clarify the pathogenesis and clinical significance of these changes. Awareness of the existence of deciduoid morphology with unusual features in adenomatoid tumor and judicious use of immunohistochemistry will help in making a correct diagnosis.
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