California Tumor Tissue Registry

Case of the Month

May, 2004

“An Adult Male With Urinary Retention”

A 60 year old manwho presentedwith urinary retentionunderwent atransurethral resection of the prostate (TURP). Histologic sections showed a “biphasic” tumorconsisting mostly of mesenchymal elements admixed with slit-like spaces lined by epithelial cells (Fig.1). Thestromal componentconsisted mostly of spindled cells associated with a myxoid background. A prominent capillary network was also present (Fig. 2). The tumor displayed mild-moderate cellular atypia, and although the mitotic rate was low, atypical forms were focally encountered (Fig. 3). The epithelial component of the tumor consisted of glands and cystic spaces lined by cytologically bland cuboidal to columnar cells having an underlying layer of myoepithelial cells (Fig. 4). The bladder wall was involved (Fig. 5).

Several weeks after the first procedure, he underwent a second, “completion”TURP, at which time a small portion of residual tumor wasfound.

The patient was closely monitored, and twoyears later wasfound to have metastases to the lungs and ribs. A biopsy of one of the rib lesions showed a metastatic neoplasm morphologically identical to the primary prostatic tumor (Figs. 6 7).

Diagnosis:“Epithelial-stromal Tumor of the Prostate (Malignant Phyllodes Tumor)”

Ada M Winkielman, MD, andDonald R Chase, MD

Department of Pathology and Human Anatomy,
LomaLindaUniversity and MedicalCenter,
Loma Linda, CA92354

Epithelial-stromal tumors of the prostate are known under variety of names including “cystosarcoma phyllodes”, “phyllodes tumor” and “prostatic stromal sarcoma”. They are extremely rare neoplasms, especially in their malignant form. Although the patients are usually “middle-aged”, the tumor has been reported in a 22 year old, as well as in patients in their nineties. The presenting complaints are usually those of obstructive dysuria. Hematuria may also be present.

The tumor is usually non-tender and, on physical examination, is usually firm and compressible giving the impression of benign prostatic hyperplasia. The palpated neoplasm, however, may be remarkably large, with tumors up to 58 cm diameter havingbeen described. Grossly, the resected neoplasm is tan to white, solid, cystic or multicystic. Some are characterized as being soft or “spongy”. Focal hemorrhage or necrosis is also described.

Microscopically the tumor is“biphasic”, characterized asa cellular stromal proliferation of spindled cells forming leaf-like projections or elongated cysts and glands lined by columnar or low cuboidal epithelium. Like their more common breast counterparts, these tumors may show variation in stromal cellularity, proportion of stromal to epithelial elements, nuclear atypia, mitotic activity and necrosis.

Although the differential diagnosis includes other mesenchymal neoplasms, most notably rhabdomyosarcoma and leiomyosarcoma, the tumor is quite characteristic morphologically. Immunohistochemical stains do not provide a reproducible profile, and their importance is mostly anecdotal, rather than statistical. The literature indicates that the epithelial component is usually positive for PSA and PAP, while stromal cells may decorate for muscle specific actin, desmin, and to lesser degree, cytokeratin. Consistent positivity for progesterone receptorshas been seen in both benign and malignant proliferations, but estrogen receptors are usually not expressed. Expression of CD34 varies, with some reports suggesting thatbenign tumors express a higher degree of positivity (as reportedly do mammary phyllodes tumors). Although there is limited information on expression of CD117 antigen, if the staining pattern of prostatic lesions follows their breast counterparts, there would be a higher propensity of positive staining in malignant tumors. Since malignant phyllodes tumors of the breast have shown higher numbers of PCNA-positive cells than have benign tumors, a similar trend might be expected in prostatic tumors. Similarly, an increased reactivity of p53 in malignant tumors may be expected(up to 85% in mammary phyllodes tumors).

Of some interest is one literature report of a patient who underwent five biopsies over three years, documenting thetransition from benign prostatic hyperplasia into malignant phyllodes tumor. During this transformation the biopsied material showed changing expression of Ki-67 and p53, both markers becoming positive when the sampling became histologically malignant (Ki-67 became 21-32% and p53 became 16-18%). In this patient, CD34 staining was negativein all the samplings.

The behavior of prostatic phyllodes tumor is difficult to predict. Attempts to prognosticate mostly utilize grading schemes which parallel those of phyllodes tumors of the breast, with histologic divisions of benign, borderline, and malignant. This separation subjectively takes into consideration cellular atypia, mitotic rate, and proliferative activity of the stromal elements. Histologically malignant forms are usually infiltrative, and are found to have increased stromal cellularity and atypia, as well as increased mitotic activity (>10/10HPF). In malignant mammary phyllodes tumors, a marked increase in microvessels has been reported, a finding that may also be useful in prostatic forms.

Most reported cases follow a benign clinical course although a marked propensity for local recurrence has been reported. When malignant, the tumor isaggressive, with a propensity for pulmonary and/or osseous metastases. Curiously, several cases have seemingly evolved from the milieu of benign prostatic hyperplasia.

Suggested reading:

Watanabe M, Yamada Y, Kato H, Imai H, Nakano H, Araki T, Shiraishi T. Malignant phyllodes tumor of the prostate: retrospective review of specimensobtained by sequential transurethral resection. Pathol Int. 2002 Dec;52(12):777-83.

Kim HS, Lee JH, Nam JH, Lee MC, Park CS, Juhng SW, Ro JY, Choi C. Malignant phyllodes tumor of the prostate. Pathol Int. 1999 Dec;49(12):1105-8.

Gaudin PB, Rosai J, Epstein JI. Sarcomas and related proliferative lesions of specialized prostatic stroma: aclinicopathologic study of 22 cases. Am J Surg Pathol. 1998 Feb;22(2):148-62.

Shabaik A. Nonepithelial tumors and tumor-like lesions of the prostate gland. Crit Rev Clin Lab Sci. 2003 Aug;40(4):429-72.

Yamamoto S, Ito T, Miki M, Serizawa H, Maekawa S, Furusato M. Malignant phyllodes tumor of the prostate. Int J Urol. 2000 Oct;7(10):378-81.

Sawyer EJ, Poulsom R, Hunt FT, Jeffery R, Elia G, Ellis IO, Ellis P,Tomlinson IP, Hanby AM. Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit. J Pathol. 2003 May;2000(1):59-64.

Tse GM, Ma TK, Chan KF, Law BK, Chen MH, Li KH, Chan EC, Mak MK. Increased microvessel density in malignant and borderline mammary phyllodestumours. Histopath 2001 Jun;38(6):567-70.

Chen CM, Chen CJ, Chang CL, Shyu JS, Hsieh HF, Harn HJ. CD34, CD117, and actin expression in phyllodes tumor of the breast. J Surg Res. 2000 Dec;94(2):84-91.

CTTR’s Case of the MonthMay, 20041