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Cystosarcoma phylloides in the adolescent female
Cystosarcoma Phylloides in the Adolescent Female By Brent V. Stromberg and Eustace S. Golladay • Two cases of cystosarcoma phylloides in the adolescent female are presented and the literature reviewed. This lesion is usually benign. Even when malignant. simple excision has been curative in 2 or 3 cases. Therapy recommended is local excision with a small margin of normal tissue. INDEX WOR DS: Cystosarcoma phylloides.
C
YSTOSARCOMA phylloides was given its first complete description by Muller in 1838. 1 He emphasized the benign nature of the lesion and its distinct difference from adenocarcinoma. Unfortunately, he chose the term sarcoma to emphasize its fleshy appearance. This has been perpetuated in the literature despite agreement that the lesion is not sarcomatous in nature. Numerous excellent series have been written concerning the lesion in the adult female.~- " The recent series by Kessinger et al.~ is particularly comprehensive. However, little has been written concerning this lesion in the adolescent female (15 yr of age or younger). This communication reports two adolescent patients with cystosarcoma phylloides and reviews the literature. MATERIALS AND METHODS Using the rigid criteria of cystosarcoma phylloides of the Armed Forces Institute of Pathology (AFlP)O and Kessinger et al." of stromal connective tissue along with epithelial components, cystosarcoma phylloides is now considered a distinct entity from giant fibroadenoma. Two patients seen at The Johns Hopkins Hospital fulfilling these criteria were 13 and 15yr of age .
CASE REPORTS Cas e I. A .R . wa s a 13-yr-old black female who presented with 3 large breast mas ses . Two in the right breast measured 7 x 10 ern and 8 x 10 em at surgery. The one in the left breast measu red 7 x 9 em. Examination a t the time of excision showed all 3 to be benig n cystosarcom a phylloides. All masses were encapsulated . Local recurrences were excised on two occasions at 2 and 18 yr after initial excis ion. Further breast de velopment was normal. Case 2. C .B. was a IS-yr-old black female who presented with a S x 2 cm mass in her right breast which had been present for 3 mo . Examination of the mass at surgery showed it to be encapsulated and unilateral. Pathologically it was benign . There was no recurrence 15 mo later and breast development was norm al.
Journal of Pediatric Surgery. Vol. 13. No.4 (August). 1978
RESULTS
A review of the English language literature reveals 12other cases said to be cystosarcoma phylloides in an adolescent female at or below 15 yr of age. Giant fibroadenomas were not specifically excluded in any of these reported cases. Thus, the number of cases of cystosarcoma phylloides in this age group, by current concepts, may be much smaller. Reviewed cases plus the two in this report total 14 (Table I). Of these, 3 were malignant with I of the 3 metastatic and lethal. In 12 of the 14 cases, simple excision of the mass was curative. In one case, there were local recurrences on two occasions that were successfully excised. The one metastatic case was fatal in spite of radiotherapy and chemotherapy. DiSCUSSiON
Cystosarcoma was formerly believed to arise from preexisting fibroadenornas .!"" It is now generally felt that the lesion arises de novo from breast parenchyma. ~. 1 2 A variety of factors have been considered to stimulate tumor growth. Some of these are trauma / · , 0 - ' 6Iactation, 1 ~. 15. 16 pregnancy, lti.17 and elevated estrogen." None of these are supported by conclusive evidence. Lesions in the adolescent age group may not behave like those in adults. It is postulated that the hormonal stimulus of puberty may be irnportant.'" It is thought by some to be the only known breast lesion capable of changing from a benign to a malignant lesion ." Factors causing this causing this transformation are unknown. Pathologic differentiation of benign and malignant lesions is often difficult. Classically, cystosarcoma presents as a large, firm, painless, mobile breast mass that on palpation is multilobular." The tumor is not attached to the skin. 13 Large tumors may produce skin changes by exerting local pressure. The cut surface reveals a gritty surface alternating with From the Department of Surgery. The Johns Hopkins Hospital. Baltimore , Md. Address reprint requests to Brent V. Stromberg, M.D.. 866 Keyst one Dr.• Cleveland Heights. Ohio 44121. © /9 78 by Grune & Stratton , Inc . 0022-3468/78 /1304-001 7$01.00/0
423
STROMBERG AND GOLLADAV
424
Table 1. Description of Cases First Author
Age (yrl
Race
MG H31
14
Lester" Lester"
15 13 12 15
W hite Wh ite White Black Wh ite
12 10 12
Wh ite Black Black
Amerson" Arnerson'" Amerson" Hoover's
13
Stromberg" Stromberg'
13 15
Black Black Black Wh ite Black Black
Lester' Rissaneu" Gibbs'· Arnerson'" Amerson"
13 14 14
Size (em )
8 6 12
Malignant 7
Metastatic?
No No
No
No No Ves
8 8 15 11
Ves No No No
10 4 14 14 10 10 5
No No No No No No No
No No Ves No
No No No Ves No
No
No
Result No recurr ence No recurrence No No No No No No No
recurr ence recurr ence recurren ce recurr ence recurr ence recurr ence recurr ence
No recurrence No recurr ence Died 20 mo after diagnosis Recurrence x 3 No recurr ence
•This report .
soft fleshy areas and occ asional cysts filled with clear or mucoid fluid. 2•M Benign lesions are more often cystic than are malignant lesions.!" Most lesions are encapsulated." Metastatic lesions have included all organ systems." In the adult female, the reported incidence varies from 0.3 %2\ to 0.9% 1 1 of all breast tumors . The malignancy rate varies from 23% 22to 27%.7 The pediatric malignancy rate seems to be proport ionate.' -" In adults, 2.8 %2:1to 12%7of cystosarcomas are metastatic. In adult females the wh ite to black ratio is 4: 1. 16 Blacks tend to predominate in the pediatric group. No case of cystosarcoma in adolescent males has been reported and only a few in adult males." The differential diagnosis of a breast mass in the adolescent female usually includes fibroadenoma, cystosarcoma, and virginal hypertrophy. Virginal hypertrophy can often be excluded because it is usually bilateral. Cystosarcoma phylloides is usually a large mas s averaging 9.6 ern in this series. Mammography has not been helpful because of the density of the tumor. Currently, the only accurat e diagnostic method is biopsy. Controversy exis ts regarding origin and relationship to fibroadenoma, although it is now generally felt that cystosarcoma and fibroadenoma are two pathologically distinct
ent ities . Unfortunately, some authors st ill consider the two lesions identical v'':" in spite of distinct pathologic criteria now used.":" In the adolescent female, excision of the lesion with its capsule is usually curative (12 of 14 cases). The tumor may have many minor appendages . Inadvertent amputation of these appendages may result in recurrence'. This may have account ed for the recurrence in one of the cases reported here. When pres ented with an adolescent female with a firm breast mass, excision with a rim of normal tissue should prevent amputation of small appendages, and guidance by frozen section is optimal. As benign and malign ant lesions may be difficult to differentiate on frozen section, excision with a margin of normal tissue should provide adequate management. The literature cites numerous examples of adjuvant therapy for metastatic disease. R adiotherapY, 2.16.27 - 2D hormones, " castration,4.2Hand chemotherapy 16.22.26.2Hhave all been tried. All results with metastatic disease have been disappointing. Average survival of patients with metastatic disease is reported to be 29.9 mo." The longest survival is 14.5 yr. 20 Few patients have received the benefit of modern chemotherapy and radiotherapy techniques.
REFERENCES I. MUlier J: Uber den Feinern Bau and dre Formen der Kvankhaften Gesch wietste, Lfg I. Berlin, J Reimer, 1838 2. Kessinger A, Foley JF, Lemon HM , et al: Me tastatic cystosarcoma phylloides. J Surg OncoI 4:131, 1972 3. Lester J , Stout AP: Cy stosarcoma phylloides. Cancer 7:335, 1954
4. McDiv itt RW , Urban JA, Farrow JH, et al : Cystosarcoma phylloides , Johns Hopkins Moo J 120:33, [967 5. Maier WP , Rosemond OP , Wittenberg, et al : Cystosa rcoma phylloides mamm ae . Oncology 22:145, 1958 6. S tephen son HE, Gross S, Gumport SC, et al : Cystosarcoma phylloides of the breast. Ann Surg 136:56, 1952
CYSTOSARCOMA PHYLLOIDES IN THE ADOL ESCENT FEMALE
7. Treves N, Sutherland DA: Cystosarcoma phylloides of the breast: A malignant and a benign tumor. Cancer 4:1286, 1951 8. Treves N : A study of cystosarcoma phylloides . Ann NY Acad Sci 114:922, 1964 9. McDi vitt RW, et al: Atlas Tumor Patholl17, 1968 10. Coope r WG , Ackerman LV : Cystosarcoma phylloides with a cons ideration of its more malignan t variant. Surg Gynecol Obst et 77:279, \943 11. Dye r NH , Bridger JE. Taylor RS, et 01 : Cystosarcoma phylloides . Br J Surg 53:450, 1966 12. Hafner CD, Mezger E, Wylie JH Jr : Cystosarcoma phylloides of the breast. Surg Gynecol Obstet 115:29, 1962 13. Carpathios J, Raferty A: Cystosarcoma phylloides. Postgrad Moo J 28:42, 1960 14. Fox SL: Sarcoma of the breast with a report of 60 cases. Ann Surg 30: 105, \964 15. Lee BJ, Pack CT: Giant intercanalicular fibreadenomyxoma of the breast. Ann Surg 93:250, 193\ 16. West TL, Weiland LH, C lagett OT: Cystosarcoma phylloides . Ann Surg 173:520, 1971 17. Bade r E, Isaacson C: Bilateral malignant cystosarcoma phylloides. Br J Surg 48:5\9, 1967 \8. Gibbs BF, Row RD, Thomas OF: Malignant cysto sa rcoma phylloides in a pre-pubertal female . Ann Surg 167:229,1968 19. Block GE, Ziatnik PA : Giant fibroadenomata of the breast in a prepubertal girl. Arch Surg 80:665, 1960 20 . Reich T, Solomon C : Bilateral cystosarcoma
425
phylloides, malignant variant with 14 year follow-up case report. Ann Surg 147:39, 1958 21. Ariel L : Skeletal metastasis in cystosarcoma phylloides. Arch Surg 82:275, 1961 22. Notley RG, Griffiths HTL: Bilateral malignan t cystosarcoma phylloides. Br J Surg 52:36, 1965 23. Haagensen CD: Diseases of the Breast . Philadelphia, S aunder s, 1956 24 . Sabiston DC : Textbook of Surgery (ed 10). Philadelphia, Saunders, 1972, p 580 25. Schwartz S: Principles of Surgery (ed 2). New York, McGraw-H ili, 1974, p 540 26. Hoover HC, Trestroveanu A, Ketcham AS: Metastatic cystosarcoma phylloides in an adolescent girl: an unusually malignant tumor. Ann Surg 181 :279, 1975 27. Aronson W: Malignant cystosarcoma phylloides with lipo Sarcoma. Wis Med J 65: 184, 1966 28. Geist 0: Cystosarcoma phylloides of the female breast. Am J Surg 30:105, 1964 29. Norris HJ. Taylor HB: Relationship of histiologic features to behavior of cystosarcoma phylloides. Cancer 20:2090, 1967 30. Massachusetts General Hospital Case Report. N Engl J Moo 247:570, \952 31. Rissaneu PM , Holsti P: A retrospective study of sarcoma of the breast and results of treatment. Oncology 22:258, 1968 32. Amerson JR: Benign cystosarcoma phylJoides in adoles cent females. Ann Surg 171 :849, 1970
C
YSTOSARCOMA phylloides was given its first complete description by Muller in 1838. 1 He emphasized the benign nature of the lesion and its distinct difference from adenocarcinoma. Unfortunately, he chose the term sarcoma to emphasize its fleshy appearance. This has been perpetuated in the literature despite agreement that the lesion is not sarcomatous in nature. Numerous excellent series have been written concerning the lesion in the adult female.~- " The recent series by Kessinger et al.~ is particularly comprehensive. However, little has been written concerning this lesion in the adolescent female (15 yr of age or younger). This communication reports two adolescent patients with cystosarcoma phylloides and reviews the literature. MATERIALS AND METHODS Using the rigid criteria of cystosarcoma phylloides of the Armed Forces Institute of Pathology (AFlP)O and Kessinger et al." of stromal connective tissue along with epithelial components, cystosarcoma phylloides is now considered a distinct entity from giant fibroadenoma. Two patients seen at The Johns Hopkins Hospital fulfilling these criteria were 13 and 15yr of age .
CASE REPORTS Cas e I. A .R . wa s a 13-yr-old black female who presented with 3 large breast mas ses . Two in the right breast measured 7 x 10 ern and 8 x 10 em at surgery. The one in the left breast measu red 7 x 9 em. Examination a t the time of excision showed all 3 to be benig n cystosarcom a phylloides. All masses were encapsulated . Local recurrences were excised on two occasions at 2 and 18 yr after initial excis ion. Further breast de velopment was normal. Case 2. C .B. was a IS-yr-old black female who presented with a S x 2 cm mass in her right breast which had been present for 3 mo . Examination of the mass at surgery showed it to be encapsulated and unilateral. Pathologically it was benign . There was no recurrence 15 mo later and breast development was norm al.
Journal of Pediatric Surgery. Vol. 13. No.4 (August). 1978
RESULTS
A review of the English language literature reveals 12other cases said to be cystosarcoma phylloides in an adolescent female at or below 15 yr of age. Giant fibroadenomas were not specifically excluded in any of these reported cases. Thus, the number of cases of cystosarcoma phylloides in this age group, by current concepts, may be much smaller. Reviewed cases plus the two in this report total 14 (Table I). Of these, 3 were malignant with I of the 3 metastatic and lethal. In 12 of the 14 cases, simple excision of the mass was curative. In one case, there were local recurrences on two occasions that were successfully excised. The one metastatic case was fatal in spite of radiotherapy and chemotherapy. DiSCUSSiON
Cystosarcoma was formerly believed to arise from preexisting fibroadenornas .!"" It is now generally felt that the lesion arises de novo from breast parenchyma. ~. 1 2 A variety of factors have been considered to stimulate tumor growth. Some of these are trauma / · , 0 - ' 6Iactation, 1 ~. 15. 16 pregnancy, lti.17 and elevated estrogen." None of these are supported by conclusive evidence. Lesions in the adolescent age group may not behave like those in adults. It is postulated that the hormonal stimulus of puberty may be irnportant.'" It is thought by some to be the only known breast lesion capable of changing from a benign to a malignant lesion ." Factors causing this causing this transformation are unknown. Pathologic differentiation of benign and malignant lesions is often difficult. Classically, cystosarcoma presents as a large, firm, painless, mobile breast mass that on palpation is multilobular." The tumor is not attached to the skin. 13 Large tumors may produce skin changes by exerting local pressure. The cut surface reveals a gritty surface alternating with From the Department of Surgery. The Johns Hopkins Hospital. Baltimore , Md. Address reprint requests to Brent V. Stromberg, M.D.. 866 Keyst one Dr.• Cleveland Heights. Ohio 44121. © /9 78 by Grune & Stratton , Inc . 0022-3468/78 /1304-001 7$01.00/0
423
STROMBERG AND GOLLADAV
424
Table 1. Description of Cases First Author
Age (yrl
Race
MG H31
14
Lester" Lester"
15 13 12 15
W hite Wh ite White Black Wh ite
12 10 12
Wh ite Black Black
Amerson" Arnerson'" Amerson" Hoover's
13
Stromberg" Stromberg'
13 15
Black Black Black Wh ite Black Black
Lester' Rissaneu" Gibbs'· Arnerson'" Amerson"
13 14 14
Size (em )
8 6 12
Malignant 7
Metastatic?
No No
No
No No Ves
8 8 15 11
Ves No No No
10 4 14 14 10 10 5
No No No No No No No
No No Ves No
No No No Ves No
No
No
Result No recurr ence No recurrence No No No No No No No
recurr ence recurr ence recurren ce recurr ence recurr ence recurr ence recurr ence
No recurrence No recurr ence Died 20 mo after diagnosis Recurrence x 3 No recurr ence
•This report .
soft fleshy areas and occ asional cysts filled with clear or mucoid fluid. 2•M Benign lesions are more often cystic than are malignant lesions.!" Most lesions are encapsulated." Metastatic lesions have included all organ systems." In the adult female, the reported incidence varies from 0.3 %2\ to 0.9% 1 1 of all breast tumors . The malignancy rate varies from 23% 22to 27%.7 The pediatric malignancy rate seems to be proport ionate.' -" In adults, 2.8 %2:1to 12%7of cystosarcomas are metastatic. In adult females the wh ite to black ratio is 4: 1. 16 Blacks tend to predominate in the pediatric group. No case of cystosarcoma in adolescent males has been reported and only a few in adult males." The differential diagnosis of a breast mass in the adolescent female usually includes fibroadenoma, cystosarcoma, and virginal hypertrophy. Virginal hypertrophy can often be excluded because it is usually bilateral. Cystosarcoma phylloides is usually a large mas s averaging 9.6 ern in this series. Mammography has not been helpful because of the density of the tumor. Currently, the only accurat e diagnostic method is biopsy. Controversy exis ts regarding origin and relationship to fibroadenoma, although it is now generally felt that cystosarcoma and fibroadenoma are two pathologically distinct
ent ities . Unfortunately, some authors st ill consider the two lesions identical v'':" in spite of distinct pathologic criteria now used.":" In the adolescent female, excision of the lesion with its capsule is usually curative (12 of 14 cases). The tumor may have many minor appendages . Inadvertent amputation of these appendages may result in recurrence'. This may have account ed for the recurrence in one of the cases reported here. When pres ented with an adolescent female with a firm breast mass, excision with a rim of normal tissue should prevent amputation of small appendages, and guidance by frozen section is optimal. As benign and malign ant lesions may be difficult to differentiate on frozen section, excision with a margin of normal tissue should provide adequate management. The literature cites numerous examples of adjuvant therapy for metastatic disease. R adiotherapY, 2.16.27 - 2D hormones, " castration,4.2Hand chemotherapy 16.22.26.2Hhave all been tried. All results with metastatic disease have been disappointing. Average survival of patients with metastatic disease is reported to be 29.9 mo." The longest survival is 14.5 yr. 20 Few patients have received the benefit of modern chemotherapy and radiotherapy techniques.
REFERENCES I. MUlier J: Uber den Feinern Bau and dre Formen der Kvankhaften Gesch wietste, Lfg I. Berlin, J Reimer, 1838 2. Kessinger A, Foley JF, Lemon HM , et al: Me tastatic cystosarcoma phylloides. J Surg OncoI 4:131, 1972 3. Lester J , Stout AP: Cy stosarcoma phylloides. Cancer 7:335, 1954
4. McDiv itt RW , Urban JA, Farrow JH, et al : Cystosarcoma phylloides , Johns Hopkins Moo J 120:33, [967 5. Maier WP , Rosemond OP , Wittenberg, et al : Cystosa rcoma phylloides mamm ae . Oncology 22:145, 1958 6. S tephen son HE, Gross S, Gumport SC, et al : Cystosarcoma phylloides of the breast. Ann Surg 136:56, 1952
CYSTOSARCOMA PHYLLOIDES IN THE ADOL ESCENT FEMALE
7. Treves N, Sutherland DA: Cystosarcoma phylloides of the breast: A malignant and a benign tumor. Cancer 4:1286, 1951 8. Treves N : A study of cystosarcoma phylloides . Ann NY Acad Sci 114:922, 1964 9. McDi vitt RW, et al: Atlas Tumor Patholl17, 1968 10. Coope r WG , Ackerman LV : Cystosarcoma phylloides with a cons ideration of its more malignan t variant. Surg Gynecol Obst et 77:279, \943 11. Dye r NH , Bridger JE. Taylor RS, et 01 : Cystosarcoma phylloides . Br J Surg 53:450, 1966 12. Hafner CD, Mezger E, Wylie JH Jr : Cystosarcoma phylloides of the breast. Surg Gynecol Obstet 115:29, 1962 13. Carpathios J, Raferty A: Cystosarcoma phylloides. Postgrad Moo J 28:42, 1960 14. Fox SL: Sarcoma of the breast with a report of 60 cases. Ann Surg 30: 105, \964 15. Lee BJ, Pack CT: Giant intercanalicular fibreadenomyxoma of the breast. Ann Surg 93:250, 193\ 16. West TL, Weiland LH, C lagett OT: Cystosarcoma phylloides . Ann Surg 173:520, 1971 17. Bade r E, Isaacson C: Bilateral malignant cystosarcoma phylloides. Br J Surg 48:5\9, 1967 \8. Gibbs BF, Row RD, Thomas OF: Malignant cysto sa rcoma phylloides in a pre-pubertal female . Ann Surg 167:229,1968 19. Block GE, Ziatnik PA : Giant fibroadenomata of the breast in a prepubertal girl. Arch Surg 80:665, 1960 20 . Reich T, Solomon C : Bilateral cystosarcoma
425
phylloides, malignant variant with 14 year follow-up case report. Ann Surg 147:39, 1958 21. Ariel L : Skeletal metastasis in cystosarcoma phylloides. Arch Surg 82:275, 1961 22. Notley RG, Griffiths HTL: Bilateral malignan t cystosarcoma phylloides. Br J Surg 52:36, 1965 23. Haagensen CD: Diseases of the Breast . Philadelphia, S aunder s, 1956 24 . Sabiston DC : Textbook of Surgery (ed 10). Philadelphia, Saunders, 1972, p 580 25. Schwartz S: Principles of Surgery (ed 2). New York, McGraw-H ili, 1974, p 540 26. Hoover HC, Trestroveanu A, Ketcham AS: Metastatic cystosarcoma phylloides in an adolescent girl: an unusually malignant tumor. Ann Surg 181 :279, 1975 27. Aronson W: Malignant cystosarcoma phylloides with lipo Sarcoma. Wis Med J 65: 184, 1966 28. Geist 0: Cystosarcoma phylloides of the female breast. Am J Surg 30:105, 1964 29. Norris HJ. Taylor HB: Relationship of histiologic features to behavior of cystosarcoma phylloides. Cancer 20:2090, 1967 30. Massachusetts General Hospital Case Report. N Engl J Moo 247:570, \952 31. Rissaneu PM , Holsti P: A retrospective study of sarcoma of the breast and results of treatment. Oncology 22:258, 1968 32. Amerson JR: Benign cystosarcoma phylJoides in adoles cent females. Ann Surg 171 :849, 1970