—  SPECIALTY CONFERENCE  —

Genitourinary Pathology

Case 2 - Cystadenoma of the Prostate

Brett Delahunt
Wellington School of Medicine and Health Sciences
Wellington, New Zealand


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Clinical History
A 48-year-old male was referred to a specialist surgical centre with a provisional diagnosis of pseudomyxoma peritonei. In the last 5-6 years, he had noted a steady increase in abdominal girth and this had become particularly pronounced over the preceding 6 months. During this time he had also noted a loss of abdominal muscle bulk. He reported no difficulty with micturation or bowel function.

Examination on admission confirmed marked abdominal distension. Computerized tomography showed a large multicystic mass almost entirely confined to the infracolic compartment, however, somewhat atypical for pseudomyxoma peritonei was the lack of extensive involvement in the subdiaphragmatic space and spleen. The patient went forward to laparotomy and a large cystic mass involving the rectosigmoid and prostate was found. The tumor was removed in two stages with resection of an extensive mass measuring 37 x 31 x 13 cm. Residual tumor was noted to be adherent to the rectum and bladder, and there was an attachment to the left posterior-lateral surface of the prostate. In the second stage procedure, the bladder and prostate were removed en bloc with all residual tumor.


Case 2 - Figure 1 - Cystadenoma of prostate, gross specimen.
Case 2 - Figure 2 - Cystadenoma of prostate, cystically dilated glands within fibromuscular stroma.
Case 2 - Figure 3 - Cystadenoma of prostate, mucinous metaplasia of epithelium.


Case 2 - Figure 4 - Cystadenoma of prostate, squamous metaplasia of epithelium.
Case 2 - Figure 5 - Cystadenoma of prostate, epithelium shows focal PSA immunoexpression.
Case 2 - Figure 6 - Cystadenoma of prostate, focal areas showing typical prostate architecture.

Pathological Findings
Sections taken from the tumor showed numerous multilocular cysts lined by simple cuboidal to columnar epithelium with a prominent underlying basal cell layer. Focally the epithelium formed papillary tufts while elsewhere there was early squamous metaplasia. In the areas of squamous metaplasia the basal cell layer was not discernible. Many of the cysts contained basophilic mucin, often intermixed with fibrin, while in others desquamated epithelial cells were seen. The supporting stroma consisted of fibrous connective tissue with prominent collagen bundles and strands of smooth muscle. Numerous telangiectatic vessels and occasional neural bundles were also present. The stroma showed mild to moderate edema and there was a diffuse inflammatory cell infiltrate consisting of lymphocytes and plasma cells.

In occasional areas within the tumor mass the epithelium and stroma resembled normal prostate tissue and here the acini contained corpora amylacea.

The tumor was adherent to the serosa of the large bowel and bladder, and blended with the tissue of the prostate removed during the second stage operative procedure.

Immunohistochemical studies showed prostate specific antigen (PSA) and prostate specific acid phosphatase (PAP) to be strongly positive in the glandular epithelium, in areas that resembled normal prostate tissue. Cystically dilated glands showed sparse focal positivity for both PSA and PAP. All epithelial cells were negative for Cytokeratin 7 and 20. There was almost 100% positivity for estrogen receptor (ER) alpha in the stroma with positive labeling confined to stromal nuclei. Focal areas of ER alpha positivity were seen in acinar epithelium exhibiting squamous metaplasia. Progesterone receptor antigen expression had a similar distribution although both glandular and squamous epithelial elements showed focal positivity.

Diagnosis
Cystadenoma of the Prostate

Discussion
Cystadenoma of the prostate is a rarely recognized neoplasm and, to date, 12 cases have been reported in the literature (Table). In the majority of cases either acute or chronic urinary retention was the presenting symptom, while less frequent symptoms included abdominal mass, hematuria and abdominal/testicular pain. Patient age ranged from 23 to 80 years (mean 54 years) with 75% of cases occurring in patients greater than 50 years of age.

Cystadenomas ranged in size from approximately 2 cm to 45 cm in maximum diameter. In the majority of cases the tumors were situated within the rectovesical space and, while infiltration of adjacent structures was not seen, tumors were frequently adherent to the serosal surface of the rectum, [5, 7, 8, 9] bladder, [5, 7, 9] and ureter. [5, 8]

In the majority of reported cases a connection between the tumor mass and the prostate gland was determined at operation, and for large tumors - as in the present case - this usually consisted of an attenuated pedicle. In some cases no pedicle was detected and it was suggested that the prostatic connection was lost as tumors grew in size and expanded along existing tissue planes. In such cases it was speculated that the tumor developed a local extra-prostatic vascular supply in a manner somewhat similar to a parasitic uterine leiomyoma.

An alternative suggestion for the origin of extraprostatic tumors is that they arise in ectopic prostatic tissue separate from the prostate gland. Prostatic tissue has been reported from a variety of ectopic sites being most commonly found in the urethra and bladder wall. [12] Other sites of ectopic prostatic tissue include the subvesical, retrovesical and pararectal spaces, the anal wall, pericolic fat, epididymis, penis and testis. [12, 13, 14, 15] The distribution of ectopic prostatic tissue indicates that the deposits result either from migration failure of preprostatic tissue [12] or from a persistent ability of the tissues of the posterior cloacal compartment - which form the rectum - to undergo differentiation into prostatic epithelium and stroma. [14] Occasional examples of ectopic prostate exhibit extensive cyst formation with apparent stroma overgrowth. [14, 15] As these are features that associated with cystadenoma, this suggests that these lesions may represent examples of these tumors in an early stage of evolution.

Published Cases of Cystadenoma of the Prostate
Author Age Presenting symptoms Maximum
diameter 		Attachment
to prostate
Melen 1932 [1] 65 yr Obstructive symptoms 1 year +- 2cm Yes
Cummine 1950 [2] 59 yr Acute urinary retention 20cm No
Blum 1960 [3] 56 yr Obstructive symptoms >40 gms Yes
Pyrah 1964 [4] 63 yr Obstructive symptoms 7.5cm Yes
Kendall 1986 [5] 23 yr Testicular pain 18 mths
Flank pain 18 mths
Nausea and vomiting 18 mths		 14cm No
Watanabe 1990 [6] 80 yr Urinary retention 11cm Yes
Maluf 1991 [7] 28 yr Acute urinary retention 19cm No
Maluf 1991 [7] 37 yr Obstructive symptoms
Difficulty urinating		 45cm No
Levy 1993 [8] 56 yr Obstructive symptoms 4 mths
Abdominal distension 3 days		 13cm Yes
Lim 1993 [9] 64 yr Obstructive symptoms 3 mths
Abdominal pain 1 mth		 17cm Yes
Kirsch 1996 [10] 65 yr Obstructive symptoms 4 weeks
Hematuria 3 weeks		 15cm Yes
Allen 2003 [11] 52 yr Obstructive symptoms
Hematuria 		14cm No


The clinical differential diagnosis of cystadenoma of the prostate is somewhat dictated by the site of the tumor and includes a wide variety of cystic structures of the prostate and periprostatic organs including simple/multilocular prostatic cysts, seminal vesicle cyst, Müllerian duct cyst, utricular cyst, ejaculatory duct cyst and inflammatory cyst (abscess) of the prostate. Neoplastic lesions that should be considered include prostatic sarcoma/phyllodes tumor, retroperitoneal teratoma/sarcoma and cystic mesothelioma.

The histological features of cystadenoma permit differentiation of the lesion from cysts of the periprostatic organs and most tumors, however, the architecture of phyllodes tumor can mimic cystadenoma. In previous studies phyllodes tumor has been mistaken for cystadenoma, [16] while a case of so-called cystadeno-leiomyofibroma, which was included by the authors in the general category of prostate cystadenoma, shows typical features of phyllodes tumor. [17] In general, phyllodes tumor may be differentiated from cystadenoma by the presence of stromal hypercellularity which may or may not show nuclear atypia. In equivocal cases, ER expression by stroma cells may be helpful as this is not seen in phyllodes tumor. [18]

The pathogenesis of these tumors is uncertain and in one case it has been noted that they resemble benign prostate tissue. [11] In the present case, the bulk of the tumor shows extensive cyst formation and bears little resemblance to normal prostate, although focally more typical prostate glands, often with corpora amylacea, were seen. In much of the tumor, despite the often extensive cyst formation, there is a relative paucity of epithelial elements and the stroma appears to be the predominant growth fraction. Evidence of apparent stromal overgrowth may also be deduced from those areas of the tumor that architecturally resemble fibroadenoma of the breast. The expression of ER alpha within the stroma of the tumor is of interest and may provide some clues as to the pathogenesis of the lesion. Normal prostatic tissue shows positive immunostaining for ER alpha in 15% of cells of the stromal compartment, while only 0.4% of epithelial cells are positive. [19] More recent studies have indicated that stroma ER alpha expression is zone dependent, being absent in transitional zone but present in "occasional" cells within the stroma of the peripheral zone. [20] In cystadenoma virtually all stroma cells show positive ER alpha immunoexpression, while expression in epithelial cells is seen only infrequently. It is possible that cystadenomas arise as a result of tissue hypersensitivity to estrogens and, as such, the pathogenesis of these lesions would appear to be similar to that proposed for giant fibroadenoma/virginal hypertrophy of the breast. [21]

There is some debate in the literature as to appropriate treatment for cystadenoma of the prostate, with both conservative [10] and radical surgery [7] being advocated. In all but one of the cases treated surgically, either by enucleation or en bloc resection, there has been no evidence of recurrence. The solitary example of recurrent cystadenoma occurred in a 38-year-old male treated initially by a two-stage procedure with resection of the abdominal component followed 4 months later by resection of the pelvic component. [7] Sixteen months after the initial procedure, tumor recurred in the pelvis and this was treated by pelvic exenteration and irradiation. Following this, the patient remained tumor-free. The histologic features of the tumor were similar to other cases of cystadenoma, and in particular there was no evidence of stromal hypercellularity indicative of phyllodes tumor.

Radical surgery was chosen as the appropriate option in the present case due to the large size of the lesion and the extensive involvement of the rectum and bladder. At operation no clear dissection plane was apparent and it was considered that if a conservative approach was followed there would be a high risk of incomplete resection and possible recurrence.

References

  1. Melen DR. Multilocular cyst of the prostate. J Urol 1932; 27:343-349.
  2. Cummine HG, Johnson AS. Report of a case of retrovesical polycystic tumor of probable prostatic origin. Aust NZ J Surg 1950; 19:91-92.
  3. Blum E, Batzenschlager A, Le Gal Y. Adenome prostatique cystico-papillaire a évolution polykystique. J d'Urol (Paris) 1960; 66:411-415.
  4. Pyrah LN. Retrovesical tumors. A report of three cases. Brit J Urol 1964; 26: 75-83.
  5. Kendall AR, Stein BS, Shea FJ, Petersen RO, Senay B. Cystic pelvic mass. J Urol 1986; 135:550-553.
  6. Watanabe J. A case of giant prostatic cystadenoma. Acta Urol Jpn 1990; 36: 1077-1079.
  7. Maluf HM, King ME, DeLuca FR et al. Giant multilocular prostatic cystadenoma. A distinctive lesion of the retroperitoneum in men. A report of two cases. Am J Surg Pathol 1991; 15:131-135.
  8. Levy DA, Gogate PA, Hampel N. Giant multilocular prostatic cystadenoma. A rare clinical entity and review of the literature. J Urol 1993; 150:1920-1922.
  9. Lim DJ, Hayden RT, Murad T etal. Multilocular prostatic cystadenoma presenting as a large complex pelvic cystic mass. J Urol 1993; 149:856-859.
  10. Kirsch AJ, Newhouse J, Hibshoosh H et al. Giant multilocular cystadenoma of the prostate. Urology 1996; 48:303-305.
  11. Allen EA, Brinker DA, Coppola D, Diaz JI, Epstein JI. Multilocular prostatic cystadenoma with high-grade prostatic intraepithelial neoplasia. Urology 2003; 61:644.
  12. Kanomata N, Eble JN, Ohbayashi C et al. Ectopic prostate in the retrovesical space. J Urol Pathol 1997; 7:121-126.
  13. Yasukawa S, Aoshi H, Takamatsu M. Ectopic prostatic adenoma in retrovesical space. J Urol 1987; 137:998-999.
  14. Gledhill A. Ectopic prostatic tissue. J Urol 1985; 133:110-111.
  15. Goodale RH. Cystadenoma of the bladder from aberrant prostatic gland. Arch Pathol 1928; 6:210-214.
  16. Kirkland KL, Bale PM. A cystic adenoma of the prostate. J Urol 1967;97:324-327.
  17. Cox R, Dawson IMP. A curious prostatic tumor. Probably a true mixed tumor (cystadeno-leiomyofibroma). Brit J Urol 1960; 32:306-311.
  18. Bostwick DG. Case 5 (Stromal sarcoma arising in phyllodes tumor of prostate) USCAP Genitourinary Specialty Conference Publication 2002, pp 25-34.
  19. Royuela M, de Miguel MP, Bethencourt FR et al. Estrogen receptors a and b in the normal, hyperplastic and carcinomatous human prostate. J Endocrinol 2001; 168:447-454.
  20. Tsurusaki T, Aoki D, Kanetake H et al. Zone-dependent expression of estrogen receptors a and b in human benign prostatic hyperplasia. J Clin Endocrinol Metab 2003; 88:1333-1340.
  21. Baker SB, Burkey BA, Thornton P, La Rossa D. Juvenile gigantomastia: Presentation of four cases and review of the literature. Ann Plast Surg 2001; 46: 517-526.