G¥
MALIGNANT PHYLLODES TUMOR OF PROSTATE
A. LOPEZ-BELTRAN, M.D. J. E GAETA, M.D. R. HUBEN, M.D. G. A. CROGHAN, PH.D. From the Departments of Pathology and Urology, Roswell Park Memorial Institute, Buffalo, New York
ABSTRACT--A case o] malignant phyllodes tumor o] the prostate, with cl~ rence and pulmonary metastasis is described in a thirty-eight-year-old man. H' was characterized by a fibrosarcoma-like pattern with adjacent changes , phyllodes type o] prbstatic atypical hyperplasia. The pathology, histogenesis, and the role o] immunohistochemistry in the diagnosis and demonstration reviewed.
Malignant: cystosarcoma phyllodes involving the prostate gland is a highly unusual lesion and the literature contains only occasional examples. 1-~ Histologically the tumor typically exhibits a foliated ductal component along with a sarcomatous pattern, most commonly occurring in the female mammary gland, s-13 The clinical course is characterized by slow growth, local invasion, and rare metastasis. It is commonly accepted that those exhibiting a metastatic spread usually document the presence of a markedly atypical stromal component including pronounced cellularity, nuclear pleomorphism, and mitotic activity. Previous reports illustrating examples of cystosarcoma phyllodes involving the prostate gland ~-7 have called attention to a possible relationship to prostate stromal hyperplasia and some investigators have designated as "phyllodes" a rare group of prostatic hypertrophy exhibiting atypical features in the stroma. 7 We describe a new case of cystosareoma phyllodes of the prostate demonstrating recurrence and pulmonary metastases and some of its immunohistochemical features that may enhance our know]edge of this interesting neoplasm. 164
Case Re A thirty-eight-year-old hospital in June, 1981, co ria and weak urinary stre arising in the urethra bq tanum and the bladder 1 transurethral resection diagnosis of benign nod m ade. In August, 1983, he ha and another 2.5-em noc sected; an intravenous P3 time had normal findings amination again showed ] November, 1984, he pres. pital with a weak urinar ria. IVP again had norrr physical examination, amination. Cystoseopy re poid nodule in the prosta again resected with the : polypoid urethritis. One month later, urge1 oped followed by acute rectal examination the I;
UROLOGY
/
FEBRUARY 1990
/
VOLUME XXXV, N
Computerized tomography scan o] ab)elvis revealing large, irregular tumor ate.
.
md tender. IVP showed normal kidneys n enlarged prostate pushing the base of ~dder upward. He was treated with anti;for presumed prostatic abscess, and, all he rcsponded~obriefly, hematuria and clot ion developed.~ Two weeks later, a catheLiid not be passed into the bladder. A subic eystostomy was done, and a large hetumor was found at the base of the ~ Biopsies of the tumor demonstrated ,r: ;ately pleomorphic spindle cells arranged seieular pattern with areas of definite palg. It was interpreted as leiomyosareoma Lrogeme sarcoma, and the patient was reto RPMI. On rectal examination there huge, rubbery prostatic mass. Computeromography scan (CT) of abdomen and revealed a large, irregular tumor mass in :ostate with no evidence of lymph node iement (Fig. 1). Pulmonary tomograms ~ne scan findings were negative. patient underwent radical cystoprosta:y and ileal loop diversion. Three weeks radial:ion of the pelvis was started, with a 5,000 tad to the pelvis with an addiI;100 rad boost to the prostatic area. In nber, 1986, a solitary lung metastasis de,~d that was treated by surgical excision nally in February, 1987, presented a new 'ence with extension to soft tissue of abdomd peripancreatic fat with desperate ill-
~
)logic findings
e surgical specimen consisted of a removed ter, prostate, seminal vesicles, and pelvic h nodes The urinary bladder was thickand the mueosa was edematous. The ate was markedly enlarged, measuring 4.5 5 x 4.0 em. There was ulceration of the ~.0LOCy~,::
/
FEBRUARY 1990
/
FIGURE 2. High magnification o] malignant phyllodes tumor of prostate showing elongated duct surrounded by proli]erating cellular stroma (hematoxylin-eosin, original magni]ication x 240).
FIGURE 3. Low magnification of prostate section showing compression of elongated epithelial ducts resembling fibroadenoma and phyUodes tumor of breast and pure sarcomatous area (hematoxylineosin, original magnification x 25). prostatic urethra and bladder neck. On transetting the prostate, a pinkish gray tumor with an ill-defined border and necrotic, hemorrhagic, and cystic areas was seen. It extended from apex to bladder neck but did not appear to involve the seminal vesicles. Representative sections were embedded in paraffin and cut to 5micron sections. Microscopically, the prostate showed a neoplastic lesion composed of a wide range of cells very similar to cystosareoma phyllodes of the breast, and many areas, including well-circumscribed loci of proliferating cellular and compact stroma, with low mitotic index, less than 1 per high-power field (HPF) (Fig. 2). There was compression of elongate epithelial duets, resembling changes characteristic of fibroadenoma and phyllodes tumor of mammary gland (Fig. 3). Finally, there were sarcomatous, highly cellular areas composed of spindle-shaped cells
VOLUME XXXV, NUMBER 2
165
FmuaE 4. High magnification of sarcomatous area of malignant phyllodes tumor oJ prostate (hematoxylin-eosin, original magnification x 480). with pleomorphic oval or elongated nuclei relatively scant cytoplasm, and high mitotic activity (per HPF) (Fig. 4), Occasional palisading of spindle cells,, with scattered epithelial component was also seen and occasional focal necrosis was observed. The epithelial cells lining ducts were cuboidal to columnar, often forming two layers, and in some areas appeared to be flattened suggesting squamous metaplasia. The same sarcomatous pattern was found in the lung metastases and in the lesions infiltrating abdominal and peripancreatic fat. The biopsy slides from the original urethral lesions were subsequently obtained for review. The 1981 samples showed a stroma composed of loose network of spindle cells, but there were a few more cellular areas under the surface epithelium or surrounding small ducts and glands (Fig. 5). The cells were relatively uniform with little atypia and a mitotic rate of 1 per HPF. The findings on 1983 and 1984 biopsies showed similar histologic findings as those in 1981. In retrospect, the urethral nodules showed the early stages in the development of the disease. The diagnosis of recurrent cystosarcoma phyllodes (CSP) of the prostate with metastasis to the lung was made.
so). Immunohistochemistry Routinely processed 5 deparaffined in xylene ; alcohols. The method us the ABC 8 (Veetastain AI antibodies against S-100 antibodies including Vk cle-D-actin, prostate-spe, tokeratin AE 1/3, and E, I). Only Vimentin was " matous areas of prostate Comment The prostate lesion., tern of a phyllodes turn teristic organization ot duetal components aga highly cellular stromal ity and significant mit~ counterpart was first type of prostatic aty t consisted of a prolife with low or no mitotic lular atypia, compressJ in a manner similar tc the breast. T M The prol
TABLE I. DifJerent immunohistochemical markers analyzed in malignant ph Source Marker Animal Biogenex S-100 Rabbit Hybritech PSA Mouse Hybtiteeh AE1/3 Mouse Abbott Estrogen Mouse Boehringer/Mannheim Vimentin Mouse Enzo D-Aetin Mouse Dako Desmin Mouse
166
1/3 lii0@ Pr ..........s.
UROLOGY / FEBRUARY1990 / VOLUMEXXXV,NU~t~N~
h cellular, atypia and high mitotic index that ~enf the characteristics of a sarcoma are the st important findings in the malignant phyltur~ or of the prostate (MPT) 1-3 7 'he MPT of the prostate is a rare event with ~ses described so far, 1-3 and only one with ,~rologous elements, 2 closely resembling cysrcoma phyllodes of the breast, 1-3,n,13 not ~:by its morphology, but probably the outCealso, as suggested by the biologic behavior e prostatic MPT. Such cases present, like in ;feast, higher recurrence potential and late stases, as we found in our case. The histo~sof the MPT of the prostate, as well as SP of breast, remains unknown, but the race of c h a n g e s c o n s i s t e n t w i t h filenoma adjaceni: to the MPT 1-3 and the as!i0n in our ease of fibroadenoma of areas tcter:!stic ?pf benign phyllodes adjacent to rostatic M T suggest a kind of histogenetic ion between them. present, probably the most important em in MPT of the prostate is the histologic •entiation between benign, which present :cellent prognosis with low or no recurborderline, and malignant tumors. In iammary gland location, the presence of ~al stroma, high cellularity, and mitotic rhas been found to correlate clinically with s of metastasizing potential. Also imporn the present case is the retrospective re~f:the lesion indicative of the early devel,n[ of a phyllodes tumor in the presence of [duetal proliferation and increased cellularreminl[seent of fibroadenoma. At this time, ~ever, none of the characteristic features i correlate with a metastasizing potential e demonstrated. Clinically, the differential ,rnosis of this entity should include prostatic seminal vesicle cysts, and the CT scan ;ht be useful in such instanees o6,7 athologieally, different sarcomas should be uded in the ~tffferential diagnosis, expecially ?inosarcoma, malignant sehwannoma, or myosareoma. The absence of malignant belial component would discard the for.2,3 The lack of expression of tumor markers
~I~IOLOGy /
of neurogenic (S-100) or muscle derivation (Desmin, D-actin) determined by immunohistoehemistry, as well as the expression of Vimentin have proved very useful in such differential diagnosis. 3 Furthermore, the lack o f estrogen reeeptors found in our ease of prostate MPT is a phenomenon currently observed in CSP of the breast 14,1s and suggests further relationships between both tumors. 666 Elm Street Buffalo, New York 14263 (DR. GAETA) References 1. Gueft B, and Walsh MA: Malignant prostatic cystosarcoma phyllodes, NY State J Med 75:2226 (1975), 2. Yokota T, et ah Malignant cy-stosarcoma phyllodes of prostate, Acta Pathol Jpn 34:663 (1984). 3. Manivel C, Shenoy V, Wick MR, and Dehner LP: Cystosarcoma phyllodes of the prostate and pathologic and immunohistochemical study, Arch Pathol Lab Med 110:534 (1986). 4. Attah EB, and Nkposong EO: Phyllodes type of atypical prostatic hyperplasia, J Urol 115:762 (1976). 5. Attah EB, and Powell MEA: Atypical stromal hyperplasia of the prostate gland, Am J Clin Pathol 67. 324 (1977). 6. Kendall AR, et ah Cystic pelvic mass, Clinicopathological Conference, J Urol 135:550 (1986). 7. Reese JH, Lombard CM, Kroue K, and Starney TA: Phyllodes type of atypical prostatic hyperplasia: a report of 3 new cases, J Urol 138:623 (1987). 8. Hsu SM, Raine L, and Fanger H: Use of Avidine-Biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures, J Histoehem Cytochem 29:577 (1981). 9. Norris HJ, and Taylor HB; Relationship of hfstologlc features to behavior of cystosarcoma phyllodes, analysis of 94 cases, Cancer 20:2090 (1967). 10. Pietruszka M, and Barnes L: Cystosarcoma phyllodes, a clinicopathologic analysis of 42 eases, Cancer 41:1974 (1978). 1I. Inoshita S: Phyllodes tumor (eystosareoma phyllodes) of the breast, a elinieopathologicstudy of 45 eases, Aeta Pathol Jpn 38:21 (1988). 12. Fernandez BB, Hernandez FJ, and Spindler W. Metastatic eystosarcoma phyllodes, a light and electron microscopic study, Cancer 37:1737 (1976), 13. Murad TM, Hines JR, Beal J, and Bauer K: Histopathological and clinical correlations of eystoscarcoma phyl!odes, Arch Pathol Lab Med 112:752 (1988). 14. Rao BR, Meyer JS, and Fry G: Most cystosarcoma phyIlodes and fibroadenomas have progesterone receptor but lack estrogen receptor: stromal localization of progesterone receptor, Cancer 47:7016 0981). 15. Shintaku P, and Said JW: Detection of estrogen receptors with monoelonal antibodies in routinely prOcessed formalln-fixed paraffin sections of breast carcinoma. Use of DNase pretreatment to enhance sensitivity of the reaction, Am J Clin PathoI 87:161 (1987),
FEBRUARY 1990 / VOLUME XXXV, NUMBER 2
167
MALIGNANT PHYLLODES TUMOR OF PROSTATE
A. LOPEZ-BELTRAN, M.D. J. E GAETA, M.D. R. HUBEN, M.D. G. A. CROGHAN, PH.D. From the Departments of Pathology and Urology, Roswell Park Memorial Institute, Buffalo, New York
ABSTRACT--A case o] malignant phyllodes tumor o] the prostate, with cl~ rence and pulmonary metastasis is described in a thirty-eight-year-old man. H' was characterized by a fibrosarcoma-like pattern with adjacent changes , phyllodes type o] prbstatic atypical hyperplasia. The pathology, histogenesis, and the role o] immunohistochemistry in the diagnosis and demonstration reviewed.
Malignant: cystosarcoma phyllodes involving the prostate gland is a highly unusual lesion and the literature contains only occasional examples. 1-~ Histologically the tumor typically exhibits a foliated ductal component along with a sarcomatous pattern, most commonly occurring in the female mammary gland, s-13 The clinical course is characterized by slow growth, local invasion, and rare metastasis. It is commonly accepted that those exhibiting a metastatic spread usually document the presence of a markedly atypical stromal component including pronounced cellularity, nuclear pleomorphism, and mitotic activity. Previous reports illustrating examples of cystosarcoma phyllodes involving the prostate gland ~-7 have called attention to a possible relationship to prostate stromal hyperplasia and some investigators have designated as "phyllodes" a rare group of prostatic hypertrophy exhibiting atypical features in the stroma. 7 We describe a new case of cystosareoma phyllodes of the prostate demonstrating recurrence and pulmonary metastases and some of its immunohistochemical features that may enhance our know]edge of this interesting neoplasm. 164
Case Re A thirty-eight-year-old hospital in June, 1981, co ria and weak urinary stre arising in the urethra bq tanum and the bladder 1 transurethral resection diagnosis of benign nod m ade. In August, 1983, he ha and another 2.5-em noc sected; an intravenous P3 time had normal findings amination again showed ] November, 1984, he pres. pital with a weak urinar ria. IVP again had norrr physical examination, amination. Cystoseopy re poid nodule in the prosta again resected with the : polypoid urethritis. One month later, urge1 oped followed by acute rectal examination the I;
UROLOGY
/
FEBRUARY 1990
/
VOLUME XXXV, N
Computerized tomography scan o] ab)elvis revealing large, irregular tumor ate.
.
md tender. IVP showed normal kidneys n enlarged prostate pushing the base of ~dder upward. He was treated with anti;for presumed prostatic abscess, and, all he rcsponded~obriefly, hematuria and clot ion developed.~ Two weeks later, a catheLiid not be passed into the bladder. A subic eystostomy was done, and a large hetumor was found at the base of the ~ Biopsies of the tumor demonstrated ,r: ;ately pleomorphic spindle cells arranged seieular pattern with areas of definite palg. It was interpreted as leiomyosareoma Lrogeme sarcoma, and the patient was reto RPMI. On rectal examination there huge, rubbery prostatic mass. Computeromography scan (CT) of abdomen and revealed a large, irregular tumor mass in :ostate with no evidence of lymph node iement (Fig. 1). Pulmonary tomograms ~ne scan findings were negative. patient underwent radical cystoprosta:y and ileal loop diversion. Three weeks radial:ion of the pelvis was started, with a 5,000 tad to the pelvis with an addiI;100 rad boost to the prostatic area. In nber, 1986, a solitary lung metastasis de,~d that was treated by surgical excision nally in February, 1987, presented a new 'ence with extension to soft tissue of abdomd peripancreatic fat with desperate ill-
~
)logic findings
e surgical specimen consisted of a removed ter, prostate, seminal vesicles, and pelvic h nodes The urinary bladder was thickand the mueosa was edematous. The ate was markedly enlarged, measuring 4.5 5 x 4.0 em. There was ulceration of the ~.0LOCy~,::
/
FEBRUARY 1990
/
FIGURE 2. High magnification o] malignant phyllodes tumor of prostate showing elongated duct surrounded by proli]erating cellular stroma (hematoxylin-eosin, original magni]ication x 240).
FIGURE 3. Low magnification of prostate section showing compression of elongated epithelial ducts resembling fibroadenoma and phyUodes tumor of breast and pure sarcomatous area (hematoxylineosin, original magnification x 25). prostatic urethra and bladder neck. On transetting the prostate, a pinkish gray tumor with an ill-defined border and necrotic, hemorrhagic, and cystic areas was seen. It extended from apex to bladder neck but did not appear to involve the seminal vesicles. Representative sections were embedded in paraffin and cut to 5micron sections. Microscopically, the prostate showed a neoplastic lesion composed of a wide range of cells very similar to cystosareoma phyllodes of the breast, and many areas, including well-circumscribed loci of proliferating cellular and compact stroma, with low mitotic index, less than 1 per high-power field (HPF) (Fig. 2). There was compression of elongate epithelial duets, resembling changes characteristic of fibroadenoma and phyllodes tumor of mammary gland (Fig. 3). Finally, there were sarcomatous, highly cellular areas composed of spindle-shaped cells
VOLUME XXXV, NUMBER 2
165
FmuaE 4. High magnification of sarcomatous area of malignant phyllodes tumor oJ prostate (hematoxylin-eosin, original magnification x 480). with pleomorphic oval or elongated nuclei relatively scant cytoplasm, and high mitotic activity (per HPF) (Fig. 4), Occasional palisading of spindle cells,, with scattered epithelial component was also seen and occasional focal necrosis was observed. The epithelial cells lining ducts were cuboidal to columnar, often forming two layers, and in some areas appeared to be flattened suggesting squamous metaplasia. The same sarcomatous pattern was found in the lung metastases and in the lesions infiltrating abdominal and peripancreatic fat. The biopsy slides from the original urethral lesions were subsequently obtained for review. The 1981 samples showed a stroma composed of loose network of spindle cells, but there were a few more cellular areas under the surface epithelium or surrounding small ducts and glands (Fig. 5). The cells were relatively uniform with little atypia and a mitotic rate of 1 per HPF. The findings on 1983 and 1984 biopsies showed similar histologic findings as those in 1981. In retrospect, the urethral nodules showed the early stages in the development of the disease. The diagnosis of recurrent cystosarcoma phyllodes (CSP) of the prostate with metastasis to the lung was made.
so). Immunohistochemistry Routinely processed 5 deparaffined in xylene ; alcohols. The method us the ABC 8 (Veetastain AI antibodies against S-100 antibodies including Vk cle-D-actin, prostate-spe, tokeratin AE 1/3, and E, I). Only Vimentin was " matous areas of prostate Comment The prostate lesion., tern of a phyllodes turn teristic organization ot duetal components aga highly cellular stromal ity and significant mit~ counterpart was first type of prostatic aty t consisted of a prolife with low or no mitotic lular atypia, compressJ in a manner similar tc the breast. T M The prol
TABLE I. DifJerent immunohistochemical markers analyzed in malignant ph Source Marker Animal Biogenex S-100 Rabbit Hybritech PSA Mouse Hybtiteeh AE1/3 Mouse Abbott Estrogen Mouse Boehringer/Mannheim Vimentin Mouse Enzo D-Aetin Mouse Dako Desmin Mouse
166
1/3 lii0@ Pr ..........s.
UROLOGY / FEBRUARY1990 / VOLUMEXXXV,NU~t~N~
h cellular, atypia and high mitotic index that ~enf the characteristics of a sarcoma are the st important findings in the malignant phyltur~ or of the prostate (MPT) 1-3 7 'he MPT of the prostate is a rare event with ~ses described so far, 1-3 and only one with ,~rologous elements, 2 closely resembling cysrcoma phyllodes of the breast, 1-3,n,13 not ~:by its morphology, but probably the outCealso, as suggested by the biologic behavior e prostatic MPT. Such cases present, like in ;feast, higher recurrence potential and late stases, as we found in our case. The histo~sof the MPT of the prostate, as well as SP of breast, remains unknown, but the race of c h a n g e s c o n s i s t e n t w i t h filenoma adjaceni: to the MPT 1-3 and the as!i0n in our ease of fibroadenoma of areas tcter:!stic ?pf benign phyllodes adjacent to rostatic M T suggest a kind of histogenetic ion between them. present, probably the most important em in MPT of the prostate is the histologic •entiation between benign, which present :cellent prognosis with low or no recurborderline, and malignant tumors. In iammary gland location, the presence of ~al stroma, high cellularity, and mitotic rhas been found to correlate clinically with s of metastasizing potential. Also imporn the present case is the retrospective re~f:the lesion indicative of the early devel,n[ of a phyllodes tumor in the presence of [duetal proliferation and increased cellularreminl[seent of fibroadenoma. At this time, ~ever, none of the characteristic features i correlate with a metastasizing potential e demonstrated. Clinically, the differential ,rnosis of this entity should include prostatic seminal vesicle cysts, and the CT scan ;ht be useful in such instanees o6,7 athologieally, different sarcomas should be uded in the ~tffferential diagnosis, expecially ?inosarcoma, malignant sehwannoma, or myosareoma. The absence of malignant belial component would discard the for.2,3 The lack of expression of tumor markers
~I~IOLOGy /
of neurogenic (S-100) or muscle derivation (Desmin, D-actin) determined by immunohistoehemistry, as well as the expression of Vimentin have proved very useful in such differential diagnosis. 3 Furthermore, the lack o f estrogen reeeptors found in our ease of prostate MPT is a phenomenon currently observed in CSP of the breast 14,1s and suggests further relationships between both tumors. 666 Elm Street Buffalo, New York 14263 (DR. GAETA) References 1. Gueft B, and Walsh MA: Malignant prostatic cystosarcoma phyllodes, NY State J Med 75:2226 (1975), 2. Yokota T, et ah Malignant cy-stosarcoma phyllodes of prostate, Acta Pathol Jpn 34:663 (1984). 3. Manivel C, Shenoy V, Wick MR, and Dehner LP: Cystosarcoma phyllodes of the prostate and pathologic and immunohistochemical study, Arch Pathol Lab Med 110:534 (1986). 4. Attah EB, and Nkposong EO: Phyllodes type of atypical prostatic hyperplasia, J Urol 115:762 (1976). 5. Attah EB, and Powell MEA: Atypical stromal hyperplasia of the prostate gland, Am J Clin Pathol 67. 324 (1977). 6. Kendall AR, et ah Cystic pelvic mass, Clinicopathological Conference, J Urol 135:550 (1986). 7. Reese JH, Lombard CM, Kroue K, and Starney TA: Phyllodes type of atypical prostatic hyperplasia: a report of 3 new cases, J Urol 138:623 (1987). 8. Hsu SM, Raine L, and Fanger H: Use of Avidine-Biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures, J Histoehem Cytochem 29:577 (1981). 9. Norris HJ, and Taylor HB; Relationship of hfstologlc features to behavior of cystosarcoma phyllodes, analysis of 94 cases, Cancer 20:2090 (1967). 10. Pietruszka M, and Barnes L: Cystosarcoma phyllodes, a clinicopathologic analysis of 42 eases, Cancer 41:1974 (1978). 1I. Inoshita S: Phyllodes tumor (eystosareoma phyllodes) of the breast, a elinieopathologicstudy of 45 eases, Aeta Pathol Jpn 38:21 (1988). 12. Fernandez BB, Hernandez FJ, and Spindler W. Metastatic eystosarcoma phyllodes, a light and electron microscopic study, Cancer 37:1737 (1976), 13. Murad TM, Hines JR, Beal J, and Bauer K: Histopathological and clinical correlations of eystoscarcoma phyl!odes, Arch Pathol Lab Med 112:752 (1988). 14. Rao BR, Meyer JS, and Fry G: Most cystosarcoma phyIlodes and fibroadenomas have progesterone receptor but lack estrogen receptor: stromal localization of progesterone receptor, Cancer 47:7016 0981). 15. Shintaku P, and Said JW: Detection of estrogen receptors with monoelonal antibodies in routinely prOcessed formalln-fixed paraffin sections of breast carcinoma. Use of DNase pretreatment to enhance sensitivity of the reaction, Am J Clin PathoI 87:161 (1987),
FEBRUARY 1990 / VOLUME XXXV, NUMBER 2
167
