World Journal of Surgical Oncology Open Access Low Grade Epithelial Stromal Tumour of the Seminal Vesicle

Background: The mixed epithelial stromal tumour is morphologically characterised by a mixture of solid and cystic areas consisting of a biphasic proliferation of glands admixed with solid areas of spindle cells with variable cellularity and growth patterns. In previous reports the seminal vesicle cystoadenoma was either considered a synonym of or misdiagnosed as mixed epithelial stromal tumour. The recent World Health Organisation Classification of Tumours considered the two lesions as two distinct neoplasms. This work is aimed to present the low-grade epithelial stromal tumour case and the review of the literature to the extent of establishing the true frequency of the neoplasm.


Background
The mixed epithelial and stromal tumour (MEST) is morphologically characterised by a mixture of solid and cystic areas with a biphasic proliferation of glands admixed with solid areas of spindle cells, with variable cellularity and growth patterns. We report a low grade MEST of the seminal vesicle and we emphasize the diagnostic criteria and the different diagnosis as cystoadenoma.

Case presentation
A 50-year-old man was admitted in November 2005 to our hospital with disuria, fever and gradual decrease in urinary stream for several months. On ultrasound (US) a hynomogeneous, hypoechoic pelvic mass of the posterior side of the bladder was demonstrated. Abdominal computed tomography (CT) revealed a 9 × 4.5 cm pelvic mass in the side of the seminal vesicles displacing the prostate and urinary bladder. On precontrast CT, the mass showed fluid heterogeneous content, well-defined margins, and irregular thin enhanced internal septa after intravenous contrast material administration. On axial spin-echo T1weighted and axial and sagittal T2-weighted ( Fig. 1a-c) magnetic resonance imaging (MRI), a large well defined multilocular pelvic mass was revealed in the side of the seminal vesicles, contiguous to the posterior wall of the urinary bladder, above the prostate and anterior to the rectum. On T1 and T2-weighted images, the mass showed internal septa that delimited heterogeneous iso-hyperintense areas with proteinaceus content. On axial T1weighted fat-suppression gradient-echo images, before and after intravenous administration of gadopentetatedimeglumine (gadolinium-DTPA), no enhancement of the mass occurred. The exploratory laparotomy revealed a retrovesical mass, which was well defined and not firmly adherent anteriorly to the bladder. It was supposed that the origin of the mass might be the right seminal vesicle. The tumour was totally dissected from the attachments to the bladder anteriorly ad rectum posteriorly, which required the removal of the left seminal vesicle and a portion of both vasa deferens. 14 months after surgery, the patient is currently alive with no evidence of disease. The tumour measured 9 × 6 × 6 cm and consisted of an oval rubbery mass. The cut surfaces showed multilocular cysts of variable sizes and shapes filled with gelatinous material (Fig. 2). The histological examination revealed two distinctive but intermixed components, one glandular and the other stromal (Fig. 3). The glandular proliferation was characterized by cystically dilated glandular spaces, containing pale eosinophilic intraluminal secretions and lined by one to two layers of cuboidal or low columnar cells. There was either no significant cytologic atypia or appreciable mitotic activity. The epithelial cells were uniformly reactive against all keratin proteins (AE1/AE3, CAM5.2, and high-molecular-weight keratin). Monoclonal and polyclonal carcinoembryonic antigen (CEA), Axial spin-echo T1-weighted (a) and axial (b) and sagittal T2-weighted (c) MRI showed a large, well-defined, multilocular pelvic mass in the side of the seminal vesicles, contiguous to the posterior wall of the urinary bladder and the prostate Figure 1 Axial spin-echo T1-weighted (a) and axial (b) and sagittal T2-weighted (c) MRI showed a large, well-defined, multilocular pelvic mass in the side of the seminal vesicles, contiguous to the posterior wall of the urinary bladder and the prostate. On T1 and T2-weighted images the mass showed internal septations that delimited heterogeneous iso-hyperintense areas with proteinaceus content.
The cut surface showed multilocular cists of varying size and shapes Figure 2 The cut surface showed multilocular cists of varying size and shapes. The segments of both the right and the left vas deferens were evident. Inset: the external surface was yellow, smooth and glistening.
prostate acid phosphatase (PAP) and prostate -specific antigen (PSA) stains gave negative results. The stromal component was composed by extensive loosely cellular areas with mixoid content. The stromal cells were spindleshaped and showed pleomorphism. The stroma was at least focally densely cellular and tended to condense around distorted glands. No mitoses were found (Fig. 4). The spindle-shaped cells showed strong reactivity for vimentin, CD34, and patchy weaker reactivity (30%) for α-smooth muscle actin ( Fig. 5a-c) and desmin, but were negative for cytokeratin and PSA. We preferred a diagnosis of low grade MEST because of the presence of cellular pleomorphism of the stromal component. 26 months after surgery, the patient is still alive, with no evidence of disease.

Discussion
In our case the low-grade MEST diagnosis was made in accordance with the World Health Organization (WHO) classification criteria [1]. The lesion arose from the seminal vesicle and did not: a) present normal tissue, b) invade the prostate, and it was not immunoreactive for monoclonal and polyclonal CEA, PAP and PSA. The glandular proliferation was benign. Mitosis and atypia of the epithelium were not found. The stromal cellularity was mostly pronounced in the tissue adjacent to intratumoural glands. Focal cellular pleomorphism was present, but mitoses were not found. The examined lesion was categorized into low-grade MEST because of the presence of atypia in the spindle-shaped cells. The former literature reviews reported MEST under different names: cystomyoma [2], cystadenoma [3][4][5][6][7][8][9][10][11][12], mesonephric hamartoma Microscopically the tumour showed cistically dilatated glands containing pale eosinophilic intraluminal secretions and lined by one to two layers of cuboidal or low columnar cells (H&E ×40) Figure 3 Microscopically the tumour showed cistically dilatated glands containing pale eosinophilic intraluminal secretions and lined by one to two layers of cuboidal or low columnar cells (H&E ×40).
The stromal cells were spindle-shaped and showed pleomor-phism Figure 4 The stromal cells were spindle-shaped and showed pleomorphism. The stroma was at least focally densely cellular and tended to condense around distorted glands (H&E ×200).
These tumours have been considered to represent morphological variants of the same neoplasm, which may reveal local recurrence but not malignant transformation [7,10]. In the WHO classification [1], the seminal vesicle cystoadenoma (SVC) was excluded from the category of MESTs and considered as a distinct neoplasm; it should be histologically distinguished from MEST by its non-neoplastic stroma. Consequently the previous reports of MESTs have been critically revised (table 1). In the reviews of 10 and 14 MESTs, Baschinsky et al., [9] and Son et al., [19] reported respectively 6 and 8 cases of SVC. According to WHO criteria, the cases of SVC reported by Lagalla et al., [8], Bullock et al [6], Damjanov and Apic [22], Lundhus et al., [23], should be excluded from MESTs. This is because the description of stromal component is absent [6] or because microscopically they showed a non-neoplastic stromal component, that is typical of benign glandular tumours. The SVC described by Soule and Dockerty [3], Baschinky et al., [9], Mazzucchelli et al., [7], Gil et al., [11], the mesonephric hamartoma of Kinas et al., [13], the benign fibroepithelial of Zanetti et al., [20], should be considered MEST, because all these tumours showed simultaneous ductal and stromal proliferations. In the histological grading of stromal component, the WHO classification categorised MESTs in low or high grade, depending on mitotic activity and necrosis [1]. But the number of mitosis is not specified. In the high-grade MEST the stroma should be at least focally densely cellular and condensed around distorted glands. In the differential diagnosis between low and high-grade MEST the histological features reported by WHO classification are not exhaustive to achieve a conclusive diagnosis. The WHO rejected the concept of phylloides tumour despite the evidence that it is a separate entity from cystadenoma. In the MEST review of Son et al., [19] and Hoshi et al., [20] the classification of Baschinsky et al., [9] in low, intermediate, high-grade MEST was reported. Surprisingly this distinction is not described in the original paper of Baschinsky et al., [11]. In the description of cystosarcoma phyllodes, Fain et al., [17] examined the tumours reported by Mazur et al., [15] and Soule and Dockerty [3]: obviously the spectrum of phyllodes tumour reported by Fain et al., may be not accepted as conclusive because only three cases were considered. In our case US was only useful to detect the lesion, but both its site and relations with adjacent organs were not established. CT confirmed the presence, size, location, internal consistency, extension of the primary tumour, and the absence of distant metastases. MRI was useful in establishing the tumour origin from the seminal vesicles and its relations with the adjacent organs (Fig. 1). MRI with fat-suppression and administration of paramagnetic contrast agent is recommended to demonstrate the absence of tumour vascularisation and to indicate the benign non-vascular nature of the mass.

Conclusion
SVC and MEST are two distinct pathological entities with different histological features and clinical outcome. Predicting the potential biological behaviour of MEST remains difficult because accurate prognostic parameters are not available. In our case MRI was able to avoid an exploratory laparotomy and to establish an accurate conservative surgical treatment of the tumour.

Consent
Written informed consent was obtained from the patient for publication of this case report.