Moderators: Dr. John R. Srigley and Dr. Rodolfo Montironi
Case 3 -
Phyllodes Tumor of the Prostate Gland
Edward C. Jones MD, FRCPC
Vancouver Hospital and University of British Columbia
Vancouver, BC, Canada
A 48-year-old man presented with obstructive renal failure secondary to an enlarged prostate gland.
After treatment by transurethral curettage, the patient was lost to follow-up for two years when he
presented with recurrent renal failure. A CT scan demonstrated a markedly enlarged, inhomogeneous,
lobulated prostate with cystic and solid areas. The seminal vesicles were not identified. There was no
pelvic lymphadenopathy. At the time of the repeat transurethral curettage, 23 grams of tissue were
Case 3 - Slide 1
The submitted slide, a section from the most recent operation, demonstrates a diffuse proliferation of
cystic glands and elongated glands with slit-like spaces. The glands are distorted and compressed by a
cellular proliferation of plump oval to spindled stromal cells. Broad stromal polypoid processes push
into the gland spaces. There is variable stromal cellularity with cellular tracts and occasional small
nodules of spindle cells between the glandular elements, alternating with areas of sclerosis and patchy
edema. An alcian blue stain at pH 2.5 identifies foci of stromal acid mucin, predominantly in the
sub-epithelial zone. The stromal spindle cells lack mitotic activity and nuclear anaplasia, although an
occasional enlarged hyperchromatic smudged nucleus is present. Heterologous stromal elements are
absent. The epithelium is hyperplastic with foci of papillary tufting and cribriform pattern. An
occasional focus of squamous metaplasia is present. The cysts are lined by columnar to low-cuboidal
epithelium. A basal cell layer is apparent in most of the glands. A PAS stain demonstrates abundant
glycogen within the stromal cell cytoplasm and, to a lesser extent, within the epithelium. The prostatic
tissue from the previous transurethral curettage had similar histological findings.
Immunohistochemical study reveals diffuse, strong immunoreactivity for muscle-specific actin and
desmin, with no reactivity for S-100 or cytokeratin, within the spindle cells. This correlates with the
reported ultrastructural evidence of stromal smooth muscle differentiation . The stromal cells are
variably positive for vimentin. The cytokeratin immunostain highlights a near continuous layer of basal
cells beneath the epithelial secretory cells. The latter are strongly positive for prostate-specific
antigen (PSA), and prostatic acid phosphatase (PAP). An occasional chromogranin-positive and a rare
serotonin-positive epithelial cell are present. Flow cytometric DNA content analysis reveals a diploid
Low grade phyllodes tumor of the prostate
Phyllodes tumor of the protate gland is a rare lesion that has been referred to by a variety of terms,
including prostatic cystic epithelial-stromal tumor , phyllodes type of atypical prostatic hyperplasia
and cystosarcoma phyllodes of the prostate . It typically presents
with a urinary obstruction, hematuria, or dysuria. There may be severe obstruction, often occurring at
an age when symptomatic prostatic hyperplasia would be unexpected. The youngest reported case is
that of a 22-year old man who had a 20 cm retrocystic mass . Most reported tumors
range from 4 cm to 25 cm
but there is one report of a 58 cm tumor weighing
11.2 kg .
The tumor can arise centrally from the verumontanum region
or it can involve one
side of the gland more peripherally
At the time of transurethral curettage the urologist may
note an unusual spongy of cystic texture of the tissue .
The diagnosis is usually made on curetted tissue, as it may be overlooked on needle biopsy, in which
it is difficult to appreciate the distinctive architecture of the tumor. Even in curetted tissue, a low
grade tumor may blend with otherwise unremarkable hyperplastic nodules, leading to under diagnosis. The
major clue to the diagnosis is the presence of a diffuse proliferative process with an unusually cellular
stroma lying between, and invaginating into, cysts and compressed elongated glands. Analogous to
phyllodes tumor of the breast, phyllodes tumor of the prostate may exhibit a spectrum of low to high
grade histological features
A high-grade tumor is recognized by an elevated
stromal-epithelial ratio with increased stromal cellularity and overgrowth, marked cytologic atypia,
increased mitotic activity, and necrosis
A sarcomatous component may consist of a solid nodule
that grossly contrasts with the cystic areas of a co-existent low-grade tumor , or it may be admixed
with the glandular component . A sarcomatous component may arise within a low-grade tumor over time
often after multiple recurrences over many years . There is a report of a phyllodes tumor
of the prostate containing an incidental focus of well-differentiated prostatic adenocarcinoma .
The differential diagnosis of phyllodes tumor of the prostate includes prostatic stromal hyperplasia
with bizarre nuclei
leiomyoma with or without cytologic atypia
prostatic cystadenoma , benign prostatic hyperplasia with cystic glands and other benign cysts such
as mullerian duct cysts and congenital or acquired seminal vesicle cysts . Of note, phyllodes tumor
may arise in the seminal vesicle as a supraprostatic mass with an epithelial component that is PSA and
Prostatic stromal hyperplasia with bizarre nuclei is a hypocellular lesion with
enlarged hyperchromatic degenerative appearing nuclei dispersed between ordinary hyperplastic glands or
within nodules of stromal hyperplasia , without mitotic activity.
arbitrarily distinguished from a hyperplastic stromal nodule simply by its large size, will typically
have interlacing fascicles of bland smooth muscle cells forming a discrete, circumscribed nodule without
a glandular component, as seen in leiomyomas found at other sites, such as the uterus. Atypical
leiomyoma or leiomyoma with bizarre nuclei may occur in the prostate. These lesions may be referred to
as atypical smooth-muscle tumor of uncertain behavior as the criteria to distinguish between benign and
malignant smooth muscle tumors of the prostate are not as well defined as they are in the uterus
Giant multilocular cystadenoma of the prostate is a tumor with cysts lined by prostate-type epithelium
surrounded by dense fibrous stroma. A cystic adenoma of the prostate characterized by a complex inward
growth of papillary epithelial fronds with little stroma has also been described . Phyllodes tumor
of the prostate may show exuberant glandular hyperplasia, a feature that may lead to misinterpretation if
the stromal component is overlooked . Benign prostatic hyperplasia commonly contains small cystic
glands within easily recognized hyperplastic nodules. One should not over interpret the small
fibradenoma-like foci that may be uncommonly found in otherwise unremarkable cases of prostatic nodular
Mullerian duct cysts (typically midline lesions) and seminal vesicle cysts (typically
lateral lesions) are usually unilocular cysts that lack the prostatic epithelial lining and the stromal
cellularity of a prostatic phyllodes tumor . If the biphasic nature of a phyllodes tumor is not
recognized, a number of spindle cell lesions known to rarely involve the prostate, such as post-operative
spindle cell nodule, inflammatory myofibroblastic proliferations, nerve sheath tumors, fibromyxoma , and
solitary fibrous tumor, may be considered. Primary sarcomas of the prostate such as leiomyosarcoma
may be a consideration but, in contrast to phyllodes tumor, are a monophasic tumor . The latter may
occur as a dominant pattern in a sarcomatous transformation of a phyllodes tumor . Carcinosarcoma or
sarcomatoid carcinoma are possible considerations when an overtly malignant spindle cell component is
present, but, unlike phyllodes tumor, they have a malignant epithelial component or evidence of
epithelial differentiation in the neoplastic spindle cells
Stromal tumors of uncertain malignant potential (STUMP)
[20-22] is a recently introduced term intended
to provide a unifying classification for stromal tumors of the prostate , including phyllodes tumor, that
are not overt sarcomas. There remains some controversy regarding definition, and it is not clear that
this term refers to a group of lesions that share a common pathogenesis or biology. The term most often
refers to a pattern of atypical, degenerative appearing, stromal cells distributed diffusely, with
variable cellularity, amongst benign glands
with an appearance of diffuse prostatic stromal
hyperplasia with bizarre nuclei, but with the potential to recur
Three additional patterns are
described. They are, in order of decreasing reported frequency; i) hypercellular stroma in a
gland-stromal nodule, without cytologic atypia or mitoses, resembling benign prostatic hyperplasia (BPH),
ii) extensive overgrowth of bland, mitotically inactive stromal cells with myxoid stroma, resembling the
stromal nodules of BPH, but lacking discrete nodularity, iii) phyllodes-type growth. This diverse group
appears to have in common the risk of being associated with sarcoma, suggesting that any of these lesion
may undergo sarcomatous transformation, albeit rarely, necessitating thorough and cautious evaluation
whenever any of these patterns is encountered.
Phyllodes tumor is a distinct biphasic lesion that can be separately identified from the other stromal
lesions . Its clinicopathological features are more in keeping with a neoplasm than an "atypical
hyperplasia". There is genetic evidence for different clonal origins of the stromal and epithelial
Although a benign clinical course has been emphasized in some reports
accumulated experience in the literature indicates that many of these patients develop local recurrence
Rarely, tumors with overtly malignant stroma have given rise to distant lung, bone and
abdominal wall sarcomatous metastases
Lymph node metastases have not been observed.
Additional prognostic information may be provided by subdivision of these tumor into low and high-grade
groups. Of note, however, as in the submitted case, even low-grade tumors may recur . Phyllodes
tumor of the prostate must be considered as potentially aggressive, and an individualized approach to
complete excision of the tumor is needed.
- Young JF, Jensen PE, Wiley CA. Malignant phyllodes tumor of the prostate: a case report with immunohistochemical and ultrastructural studies. Arch Pathol Lab Med 1992;116:296-299
- Kevwitch MK, Walloch JL, Waters WB, Flanigan RC. Prostatic cystic epithelial-stromal tumors: a report of 2 new cases. J Urol 1993;149:860-864.
- Reese EH, Lombard CM, Krone K, Stamey TA. Phyllodes type of atypical prostatic hyperplasia: a report of 3 new cases. J Urol 1987;138:623-626.
- Cox R,Dawson IMP. A curious prostatic tumour: probably a true mixed tumour (cystadeno-leiomyofibroma) Br J Urol 1960;32:306-311
- Manivel C, Shenoy V, Wick MR, Dehner LP. Cystosarcoma phyllodes of the prostate. A pathologic and immunohistochemical study. Arch Pathol Lab Med 1986;110:534-538.
- Bostwick DG, Hossain D, Qian J, Neumann RM, Yang P, Young RH, Di Sant'agnese PA, Jones EC. Phyllodes tumor of the prostate: Long-term followup study of 23 cases. J Urol 2004;172:894-899.
- Kerley SW, Pierce P, Thomas J. Giant Cystosarcoma phyllodes of the prostate associated with adenocarcnoma. Arch Pathol Lab Med 1992;116:195-197.
- Attah EB, Nkposong EO. Phyllodes type of atypical prostatic hyperplasia. J Urol 1976;115:762-764.
- Lopez-Beltran A, Gaeta JF, Huben R, Croghan GA. Malignant phyllodes tumor of prostate. Urology 1990;35:164-167.
- Yum M, Miller JC, Agrawal BL. Leiomyosarcoma arising in atypical fibromuscular hyperplasia (phyllodes tumor) of the prostate with distant metastasis. Cancer 1991;68:910-915.
- Eble JN, Tejada E. Prostatic stromal hyperplasia with bizarre nuclei. Arch Pathol Lab Med 1991;115:87-89.
- Maluf HM, King ME, DeLuca FR, Navarro J, Talerman A, Young RH. Giant multilocular prostatic cystadenoma: a distinctive lesion of the retroperitoneum in men. Am J Surg Pathol 1991;15:131-135.
- Kendall AR, Stein BS, Shea FJ, Petersen RO, Senay B. Clinicopathological conference: cystic pelvic mass. J Urol 1986;135:550-553.
- Mazur MT, Myers JL, Maddox WA. Cystic epithelial-stromal tumor of the seminal vesicle. Am J Surg Pathol 1987;11:210-217.
- Kirkland KL, Bale PM. Cystic adenoma of the prostate J Urol 1967;97:324-327.
- Kafandaris PM, Polyzonis MB. Fibroadenoma-like foci in human prostatic nodular hyperplasia. Prostate 1983;4:33-36.
- Smith BH, Dehner LP. Sarcoma of the prostate gland. Am J Clin Pathol 1972;58:43-50.
- Wick RM, Young RH, Malvesta R, Beebe DS, Hansen JJ, Dehner LP. Prostatic carcinosarcomas: clinical, histologic, and immunohistochemical data on two cases, with a review of the literature. Am J Clin Pathol 1989;92:131-139.
- Shannon RL, Ro JY, Grignon DJ, Ordonez NG, Johnson DE, Mackay B, Tetu B, Ayala AG. Sarcomatoid carcinoma of the prostate: a clinicopathologic study of 12 patients. Cancer 1992;69:2676-2682.
- Tetu B, Ro JY, Ayala AG, Srigley JR, Begin LR, Bostwick DG. Atypical spindle cell lesions of the prostate. Semin Diagn Pathol 1988;5:284-293.
- Gaudin PB, Rosai J, Epstein JI. Sarcomas and related proliferative lesions of specialized prostatic stroma: a clinicopathologic study of 22 cases. Am J Surg Pathol 1998;22:148-162.
- Herawi M, Epstein JI. Specialized stromal tumors of the prostate: a clinicopathologic study of 50 cases Am J Surg Pathol 2006;30:694-704.
- Regan JB, Barrett DM, Wold LE. Giant leiomyoma of the prostate. Arch Pathol Lab Med 1987;111:381.
- Fain JS, Cosnow I, King BF, Zincke H, Bostwick DG. Cystosarcoma phyllodes of the seminal vesicle. Cancer 1993;71:2055-61.
- Yamamoto S, Ito T, Miki M, Serizawa H, Maekawa S, Furusato M. Malignant phyllodes tumor of the prostate. Int J Urol 2000;7:378
- Chen TA, Chou JM, Sun GH, Lee HS. Malignant phyllodes tumor of the prostate. Int J Urol 2005;12:1007-9.
- Kim HS, Lee JH, Nam JH, Lee MC, Park CD, Juhng SW, Ro JY, Choi C. Malignant phyllodes tumor of the prostate. Pathol Int. 1999;49:1105-8.
- Morikawa T, Nagata M, Tomita K, Kitamura T, Goto A, Chong JM, Fukayama M. Phyllodes tumor of the prostate with exuberant glandular hyperplasia. Pathol Int 2006;56:158-61.
- McCarthy RP, Zhang S, Bostwick DG, Qian J, Eble JN, Wang M, Lin H, Cheng L. Molecular genetic evidence for different clonal origins of epithelial and stromal components of phyllodes tumor of the prostate. Am J Pathol 2004;165:1395-400.