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Malignant Phyllodes Tumor of the Breast with Predominant Chondrosarcomatous Differentiation
PATHOLOGY
Teaching Case
RESEARCH AND PRACTICE © Urban & Fischer Verlag http://www.urbanfischer.de/journals/prp
Malignant Phyllodes Tumor of the Breast with Predominant Chondrosarcomatous Differentiation Francisco Vera-Sempere and Ana García-Martínez Service of Pathology, University Hospital La Fe, Valencia, Spain
Summary Malignant phyllodes tumor of the breast is a rare biphasic neoplasm, the stromal component of which may show homologous and heterologous sarcomatous elements. We present a case of a histologically malignant phyllodes tumor with sarcomatous overgrowth, affecting a 37-year-old woman in whom a chondrosarcomatous component constituted over 80% of the tumor volume. A malignant phyllodes tumor displaying a predominant chondrosarcomatous component is indeed rare, and the differential diagnosis could well affect the therapeutic approach, mainly with regard to metaplastic carcinoma and primary chondrosarcoma of the mammary gland. Thus, it is important to sample the tumor thoroughly to detect the presence of any area of typical phyllodes tumor, which could be very small. Immunohistochemical stains also should be performed so as to exclude a malignant epithelial component. After the final morphological diagnosis, our patient underwent a complete mastectomy without axillary disection. One year later, no local recurrence or metastasis was apparent.
is stromal overgrowth [10] relative to the epithelium; the stromal component may show homologous and/or heterologous sarcomatous elements, including a wide variety of possible differentiations (particularly liposarcoma, rhabdomyosarcoma, chondrosarcoma, and osteosarcoma). We present a case of a histologically malignant phyllodes tumor with sarcomatous stromal overgrowth showing heterologous differentiation, including scant foci of osteosarcoma and a predominantly (over 80% of the tumor volume) chondrosarcomatous component. The differential diagnosis and the therapeutic approach for this tumor are discussed, with the results of the pathological examination serving as a basis.
Case Report
Introduction
A 37 year-old woman presented with a painful mass in the left breast that increased in size over a period of several weeks. The patient gave no history of nipple discharge or hormone treatment, and there was no family history of breast cancer. Physical examination revealed a palpable mass over the upper outer quadrant of the left breast, measuring 2 × 2 cm in size, mobile, not fixed to deeper structures, and not involving the overlying skin. There were no palpable left axillary lymph nodes. Bilateral mammograms revealed a nodular calcified mass measuring 2 cm in diameter. The right breast was unremarkable, as were the right and left axillae. Mammographic diagnosis (Fig. 1) suggested a possible calcified
Phyllodes tumor of the breast is a rare biphasic neoplasm, with epithelial and stromal components, accounting for less than 1% of all breast neoplasms [6]. Malignant phyllodes tumors account for approximately 30 to 50% of all phyllodes tumors [9, 15], representing only 0.18% of all breast malignancies. The most reliable histologic criterion for malignant behavior in such tumors
Address for correspondence: Francisco Vera-Sempere, Servicio de Anatomía Patológica, Hospital Universitario La Fe, Avda. Campanar 21, Valencia 46009, Spain. Phone: +34+6-3862799, Fax: +34 +6-1973089. E-mail: [email protected]
Key words: Breast – Malignant phyllodes tumor – Chondrosarcoma – Metaplastic carcinoma
Pathol. Res. Pract. 199: 841–845 (2003)
0344-0338/03/199/12-841 $15.00/0
842 · F. Vera-Sempere and A. García-Martínez
fibroadenoma; yet, the possibility of mammary carcinoma could not be excluded. Fine-needle aspiration revealed dissociated and atypical cells, both spindle-shaped and round, with polymorphic and hyperchromatic nuclei, occasionally in a muco-myxoid background, associated with very scant giant cells of osteoclast-like appearance. The cytological diagnosis was positive for malignancy, with suspicion of a possible malignant non-epithelial lesion. A complete excision was advised. The patient underwent complete surgical excision; frozen-section examination postponed the pathological diagnosis, which suggested chondrosarcoma. Following the final morphological diagnosis, re-excision was planned, followed by simple mastectomy. Axillary lymph node dissection was not considered. After a one-year follow-up, the patient had no sign of local recurrence. Routine X-ray of the chest plus a radionuclide study of the skeleton failed to detect any evidence of apparent metastatic disease.
Pathologic Findings The surgical specimen measured 4 × 4 × 3 cm (Fig 2). Sectioning revealed a partial cystic tumor of 3 × 3 × 2.5 cm with foci of hemorrhage, nodular areas of pearly-white appearance with a poorly circumscribed, irregular periphery. Multiple sections were taken from the tumoral mass, and twelve tissue blocks were prepared for histologic examination. Moreover, the entire margin was sampled for histology after painting with Indian ink.
Fig. 1. Mediolateral oblique mammogram of the left breast showing a dense mass of well-defined borders, suggesting calcified fibroadenoma. Fig. 2. Gross appearance of cut surface of the tumor showing a whitish and hemorrhagic mass with focal clefts (arrows) and a poor and irregular periphery. Careful examination of the entire gross specimen and plentiful sampling for histology is of paramount importance for recognizing focal areas of phyllodes tumor. Fig. 3. Low power view showing lobules of cartilaginous neoplasm with variable grades of differentiation emerging from stromal wall of typical phyllodes tumor. H&E ×25.
Chondrosarcomatous Phyllodes Tumor · 843
Fig. 4. Immunohistochemical stain for cytokeratin CAM 5.2 (a) and p63 (b). CAM 5.2 (cytoplasmic stain) was unreactive in sarcomatous stroma (asterisks) of the tumor, unlike positive lining of split-like duct element of phyllodes tumor (stars). Likewise, p63 stained myoepithelial nuclei of mammary ducts (arrows) as distinct from unreactive nuclei of sarcomatous stroma (asterisks) (CAM, 5.2 × 100; p63, 100×).
Fig. 5. Electron micrograph showing an atypical chondral cell with a bizarre and folded nucleus and scant cytoplasm containing some lipid inclusion. Cytoplasmic surface shows short villiform projections surrounded by an abundant granular matrix with vacuolated areas and calcification foci (EM ×10,000).
Microscopically, most of the tumor tissues consisted of chondrosarcoma of varying grades of differentiation, occupying over 80% of the neoplasm. Only a small amount of the typical leaf-like pattern of phyllodes tumor, mainly noted in cystic areas of gross specimens, was found in direct continuity, merging to chondrosarcomatous areas (Fig. 3). Cellularity of the stromal component, in phyllodes tumor, was slightly high, with mildly atypical nuclei. The epithelial lining of split-like ducts appeared to be histologically benign. Cartilaginous areas showed foci of degeneration and calcification, as well as small and isolated foci of round to oval cells embedded in a dense eosinophilic stroma, consistent with osteoid; occasional osteoclast-like multinucleated giant cells also were seen, although the entire predominant histologic pattern of the neoplasm was that of chondrosarcoma. The tumor periphery showed pushing rather than infiltrating growth, although margins of the specimen were infiltrated by atypical stromal cells in abnormal basophylic matrix. Therefore, a breast re-excision was performed. Immunohistochemical study performed by standard methods (peroxidase-antiperoxidase – PAP – for polyclonal antibodies and labeled streptavidin-biotin – LASB – for monoclonals) revealed that chondrosarcomatous elements were positive for S-100 (polyclonal, Dako, 1/400) and vimentin (monoclonal V9, Dako, 1/50), but negative for cytokeratins AE1/3 (monoclonal, Signet, 1/40), CAM 5.2 (monoclonal, Medac, 1/40), CK7 (monoclonal OV-TL 12/30, Dako, 1/100), and also for estrogen and progesterone receptors (Dako ER/PR System, K1900). High molecular weight cytokeratin 34BE12 (monoclonal, Biogenex, 1/100) and p63 (monoclonal 4A4, Neomarkers, 1/200), both myoepithelial markers, also were unreactive (Fig. 4) in sarcomatous
844 · F. Vera-Sempere and A. García-Martínez
stromal areas and in the chondrosarcomatous heterologous component of the tumor. Electron microscopic examination of a tumor sample showed frequent atypical chondral cells with folded and irregular nuclei (Fig. 5). The cells, at the cytoplasmic level, contained some lipid inclusions and occasionally elaborate profiles of endoplasmic reticulum. Cellular surface of chondrocytic cells frequently appeared with villiform projections and ruffled appearance, often surrounded by abundant and finely granular matrix with occasional calcified bodies. Finally, desmosomal attachments were not identified at all.
Discussion In human breast tissue, the incidence of bone lesions is rare [16] if compared with those of other mammals, particularly with canine mammary tumors, in which there is a strikingly high incidence of cartilaginous and osseous metaplasia [18]. In reference to cartilaginous differentiation, several benign breast tumors, such as chondrolipoma [5], choristoma [13], or pleomorphic adenoma [2], may contain benign chondroid islets, although the presence of malignant cartilage (chondrosarcoma) is indeed rare. As a primary breast tumor, chondrosarcoma may occur in three different forms: as a pure neoplasm (pure chondrosarcoma), as the stromal component of a histologically malignant phyllodes tumor, or as chondrosarcomatous differentiation in a metaplastic carcinoma. In this report we document a case of histologically malignant phyllodes tumor displaying a predominantly chondrosarcomatous component, making up over 80% of the tumor volume. The behavior of a histologically malignant phyllodes tumor is notoriously difficult to predict, because not all the cases behave in a clinically malignant fashion [14]. Stromal overgrowth [10] has been reported to be an important prognostic factor by some, but not by all authors. Of particular interest is the report of a significant correlation between the presence of heterologous stromal elements and malignant behavior [4], although the prognostic significance of various types of sarcoma, arising in phyllodes tumor, is not fully known. Pietruszka and Barnes [15] proposed that when rhabdomyosarcoma accounts for the major component of a phyllodes tumor, it has essentially the same prognosis as pure and primary rhabdomyosarcoma. Similar conclusions have been reported by Silver and Tavassoli [17] in the case of osteosarcomatous phyllodes tumors. Prognosis of chondrosarcomatous breast tumors is not fully known, because many of the reported cases [1, 7, 8, 11, 12, 19] are difficult to analyze owing to lack of detailed clinical or morphologic information. Only in one case of pure chondrosarcoma grade III/IV of the
breast documented the follow-up a malignant behavior with pulmonary metastasis, developing within four months after diagnosis [1]. The clinical courses of pure chondrosarcoma of the breast and phyllodes tumor with predominant chondrosarcomatous differentiation are possibly similar, as in the case of rhabdomyosarcomatous[15] and osteosarcomatous tumors [17]. Conversely, it may be difficult to differentiate a pure chondrosarcoma of the breast from one arising within a phyllodes tumor, particularly if not well sampled for the presence of an area of a typical phyllodes tumor, which could be very small, as in the present case and in others reported [7, 11]. In fact it is quite possible that some examples of so-called “pure” chondrosarcoma of the breast [1, 8, 12, 19] really represent the chondrosarcomatous overgrowth of a biphasic neoplasm; in this sense, the report of Beltaos and Bernajee [1] on two pure mammary chondrosarcomas failed to address the issue of completeness of tumor sampling, thus raising the question of positively ruling out the possibility of malignant phyllodes tumor. However, in patients with either of these two neoplasms (pure chondrosarcoma or malignant phyllodes tumor with chondrosarcomatous differentiation), therapy and clinical course are similar. Hence, it is of great importance to distinguish a primary mammary chondrosarcoma – whether or not associated with a biphasic neoplasm – from a metaplastic carcinoma of the breast with chondrosarcomatous heterologous elements; this requires treatment as a primary breast carcinoma in a comparable stage [3, 17]; in that case, axillary lymph node dissection must be considered. Such distinction may be achieved mainly by immunohistochemical stains that include a panel for epithelial markers that, as in our case, was nonreactive at the sarcomatous level. Furthermore, in our observation, high molecular-weight cytokeratin 34βE12 and also p63 were negative in the sarcomatous component, ruling out the hypothetic myoephitelial origin of heterologous elements, proposed by several authors [3] in metaplastic carcinoma of the breast and also supported by a recent study [20] with a panel of novel (p63, maspin and P-cadherin) and classic myoepithelial cell markers. Acknowledgements. The authors are grateful to Dr. F. RuizPerales, Division of Radiology, for the mammographic study.
References 1. Beltaos E, Nanerjee TK (1979) Chondrosarcoma of the breast. Report of two cases. Am J Clin Pathol 71:345–349 2. Ballance WA, Ro JY, El-Naggar AK, Grignon DJ, Ayala AG, Romsdalh MG (1990) Pleomorphic adenoma (benign mixed tumor) of the breast. An immunohistochemical, flow cytometric, and ultrastructural study and review of the literature. Am J Clin Pathol 93: 795–801
Chondrosarcomatous Phyllodes Tumor · 845 3. Chhieng C. Cranor M, Lesser ME, Rosen PP (1998) Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. Am J Surg Pathol 22: 188–194 4. Cohn-Cedermark G, Rutqvist LE, Rosendahl I, Silfversward C (1991) Prognostic factors in cystosarcoma phyllodes. A clinicopathologic study of 77 cases. Cancer 68: 2017–2022 5. Dharkar DD, Kraft JR (1981) Benign chondrolipomatous tumor of the breast. Postgrad Med J 7: 129–131 6. Elston CW, Ellis IO (1998) The breast. In: Systemic Pathology, 3rd ed. vol 13, p 168. Churchill Livingstone, Edinburgh 7. Garcia FU, Soans S, Galindo LM (1999) Malignant phyllodes tumor with chondrosarcomatous differentiation: report of a case with cytological presentation. Diagn Cytopathol 20: 241–245 8. Guymar S, Ferlicot S, Genestie C, Gelbert JJ, Blondon J, LeCharpentier Y, Zafrani B (2001) Chondrosarcome du sein: à propos d’un cas. Ann Pathol 21: 168 –171 9. Hart WR, Bauer RC, Oberman HA (1978) Cystosarcoma phyllodes. A clinicopathologic study of twenty-six hypercellular periductal stromal tumours of the breast. Am J Clin Pathol 70: 211–216 10. Hawkins RE, Schofield JB, Fisher C, Wiltshaw E, McKinna JA (1992) The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes. Cancer 69: 141–147 11. Iihara K, Machinami R, Kubota S, Itoyama S, Sato A (1997) Malignant cystosarcoma phyllodes tumor of the breast mainly composed of chondrosarcoma: A case report. Gen Diagn Pathol 142: 241–245
12. Kennedy T, Biggard JD (1967) Sarcoma of the breast. Br J Cancer 21: 635 –644 13. Metcalf JS, Ellis B (1985) Choristoma of the breast. Hum Pathol 16: 739 –740 14. Moffat CJC, Pinder SE, Dixon AR, Elston CW, Blamey RW (1995) Phyllodes tumours of the breast. A clinicopathological review of thirty-two cases. Histopathology 27: 205 –218 15. Pietruszka M, Barnes L (1978) Cystosarcoma phyllodes. A clinicopathologic analysis of 42 cases. Cancer 41: 1974 –1983 16. Rosen PP, Oberman HA (1993) Tumors of the mammary gland (Atlas of Tumor Pathology, 3rd ser, fasc 7), p 316. Armed Forces Institute of Pathology, Washington 17. Silver SS, Tavassoli FA (1999) Osteosarcomatous differentiation in phyllodes tumors. Am J Surg Pathol 23: 815 – 821 18. Smith BH, Taylor HB (1969) The occurrence of bone and cartilage in mammary tumors. Am J Clin Pathol 51: 610 – 618 19. Thilagavathi G, Subramanian S, Samuel AV, Rani U, Somasundaram C (1992) Primary chondrosarcoma of the breast. J Indian Med Assoc 90: 16 –17 20. Reis-Filho JS, Milanezi F, Paredes J, Silva P, Pereira EM, Maeda SA, de Carvalho LV, Schmitt FC (2003) Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast. Appl Immunohistochem Mol Morphol 11: 1– 8 Received: May 20, 2003 Accepted in revised version: November 3, 2003
Teaching Case
RESEARCH AND PRACTICE © Urban & Fischer Verlag http://www.urbanfischer.de/journals/prp
Malignant Phyllodes Tumor of the Breast with Predominant Chondrosarcomatous Differentiation Francisco Vera-Sempere and Ana García-Martínez Service of Pathology, University Hospital La Fe, Valencia, Spain
Summary Malignant phyllodes tumor of the breast is a rare biphasic neoplasm, the stromal component of which may show homologous and heterologous sarcomatous elements. We present a case of a histologically malignant phyllodes tumor with sarcomatous overgrowth, affecting a 37-year-old woman in whom a chondrosarcomatous component constituted over 80% of the tumor volume. A malignant phyllodes tumor displaying a predominant chondrosarcomatous component is indeed rare, and the differential diagnosis could well affect the therapeutic approach, mainly with regard to metaplastic carcinoma and primary chondrosarcoma of the mammary gland. Thus, it is important to sample the tumor thoroughly to detect the presence of any area of typical phyllodes tumor, which could be very small. Immunohistochemical stains also should be performed so as to exclude a malignant epithelial component. After the final morphological diagnosis, our patient underwent a complete mastectomy without axillary disection. One year later, no local recurrence or metastasis was apparent.
is stromal overgrowth [10] relative to the epithelium; the stromal component may show homologous and/or heterologous sarcomatous elements, including a wide variety of possible differentiations (particularly liposarcoma, rhabdomyosarcoma, chondrosarcoma, and osteosarcoma). We present a case of a histologically malignant phyllodes tumor with sarcomatous stromal overgrowth showing heterologous differentiation, including scant foci of osteosarcoma and a predominantly (over 80% of the tumor volume) chondrosarcomatous component. The differential diagnosis and the therapeutic approach for this tumor are discussed, with the results of the pathological examination serving as a basis.
Case Report
Introduction
A 37 year-old woman presented with a painful mass in the left breast that increased in size over a period of several weeks. The patient gave no history of nipple discharge or hormone treatment, and there was no family history of breast cancer. Physical examination revealed a palpable mass over the upper outer quadrant of the left breast, measuring 2 × 2 cm in size, mobile, not fixed to deeper structures, and not involving the overlying skin. There were no palpable left axillary lymph nodes. Bilateral mammograms revealed a nodular calcified mass measuring 2 cm in diameter. The right breast was unremarkable, as were the right and left axillae. Mammographic diagnosis (Fig. 1) suggested a possible calcified
Phyllodes tumor of the breast is a rare biphasic neoplasm, with epithelial and stromal components, accounting for less than 1% of all breast neoplasms [6]. Malignant phyllodes tumors account for approximately 30 to 50% of all phyllodes tumors [9, 15], representing only 0.18% of all breast malignancies. The most reliable histologic criterion for malignant behavior in such tumors
Address for correspondence: Francisco Vera-Sempere, Servicio de Anatomía Patológica, Hospital Universitario La Fe, Avda. Campanar 21, Valencia 46009, Spain. Phone: +34+6-3862799, Fax: +34 +6-1973089. E-mail: [email protected]
Key words: Breast – Malignant phyllodes tumor – Chondrosarcoma – Metaplastic carcinoma
Pathol. Res. Pract. 199: 841–845 (2003)
0344-0338/03/199/12-841 $15.00/0
842 · F. Vera-Sempere and A. García-Martínez
fibroadenoma; yet, the possibility of mammary carcinoma could not be excluded. Fine-needle aspiration revealed dissociated and atypical cells, both spindle-shaped and round, with polymorphic and hyperchromatic nuclei, occasionally in a muco-myxoid background, associated with very scant giant cells of osteoclast-like appearance. The cytological diagnosis was positive for malignancy, with suspicion of a possible malignant non-epithelial lesion. A complete excision was advised. The patient underwent complete surgical excision; frozen-section examination postponed the pathological diagnosis, which suggested chondrosarcoma. Following the final morphological diagnosis, re-excision was planned, followed by simple mastectomy. Axillary lymph node dissection was not considered. After a one-year follow-up, the patient had no sign of local recurrence. Routine X-ray of the chest plus a radionuclide study of the skeleton failed to detect any evidence of apparent metastatic disease.
Pathologic Findings The surgical specimen measured 4 × 4 × 3 cm (Fig 2). Sectioning revealed a partial cystic tumor of 3 × 3 × 2.5 cm with foci of hemorrhage, nodular areas of pearly-white appearance with a poorly circumscribed, irregular periphery. Multiple sections were taken from the tumoral mass, and twelve tissue blocks were prepared for histologic examination. Moreover, the entire margin was sampled for histology after painting with Indian ink.
Fig. 1. Mediolateral oblique mammogram of the left breast showing a dense mass of well-defined borders, suggesting calcified fibroadenoma. Fig. 2. Gross appearance of cut surface of the tumor showing a whitish and hemorrhagic mass with focal clefts (arrows) and a poor and irregular periphery. Careful examination of the entire gross specimen and plentiful sampling for histology is of paramount importance for recognizing focal areas of phyllodes tumor. Fig. 3. Low power view showing lobules of cartilaginous neoplasm with variable grades of differentiation emerging from stromal wall of typical phyllodes tumor. H&E ×25.
Chondrosarcomatous Phyllodes Tumor · 843
Fig. 4. Immunohistochemical stain for cytokeratin CAM 5.2 (a) and p63 (b). CAM 5.2 (cytoplasmic stain) was unreactive in sarcomatous stroma (asterisks) of the tumor, unlike positive lining of split-like duct element of phyllodes tumor (stars). Likewise, p63 stained myoepithelial nuclei of mammary ducts (arrows) as distinct from unreactive nuclei of sarcomatous stroma (asterisks) (CAM, 5.2 × 100; p63, 100×).
Fig. 5. Electron micrograph showing an atypical chondral cell with a bizarre and folded nucleus and scant cytoplasm containing some lipid inclusion. Cytoplasmic surface shows short villiform projections surrounded by an abundant granular matrix with vacuolated areas and calcification foci (EM ×10,000).
Microscopically, most of the tumor tissues consisted of chondrosarcoma of varying grades of differentiation, occupying over 80% of the neoplasm. Only a small amount of the typical leaf-like pattern of phyllodes tumor, mainly noted in cystic areas of gross specimens, was found in direct continuity, merging to chondrosarcomatous areas (Fig. 3). Cellularity of the stromal component, in phyllodes tumor, was slightly high, with mildly atypical nuclei. The epithelial lining of split-like ducts appeared to be histologically benign. Cartilaginous areas showed foci of degeneration and calcification, as well as small and isolated foci of round to oval cells embedded in a dense eosinophilic stroma, consistent with osteoid; occasional osteoclast-like multinucleated giant cells also were seen, although the entire predominant histologic pattern of the neoplasm was that of chondrosarcoma. The tumor periphery showed pushing rather than infiltrating growth, although margins of the specimen were infiltrated by atypical stromal cells in abnormal basophylic matrix. Therefore, a breast re-excision was performed. Immunohistochemical study performed by standard methods (peroxidase-antiperoxidase – PAP – for polyclonal antibodies and labeled streptavidin-biotin – LASB – for monoclonals) revealed that chondrosarcomatous elements were positive for S-100 (polyclonal, Dako, 1/400) and vimentin (monoclonal V9, Dako, 1/50), but negative for cytokeratins AE1/3 (monoclonal, Signet, 1/40), CAM 5.2 (monoclonal, Medac, 1/40), CK7 (monoclonal OV-TL 12/30, Dako, 1/100), and also for estrogen and progesterone receptors (Dako ER/PR System, K1900). High molecular weight cytokeratin 34BE12 (monoclonal, Biogenex, 1/100) and p63 (monoclonal 4A4, Neomarkers, 1/200), both myoepithelial markers, also were unreactive (Fig. 4) in sarcomatous
844 · F. Vera-Sempere and A. García-Martínez
stromal areas and in the chondrosarcomatous heterologous component of the tumor. Electron microscopic examination of a tumor sample showed frequent atypical chondral cells with folded and irregular nuclei (Fig. 5). The cells, at the cytoplasmic level, contained some lipid inclusions and occasionally elaborate profiles of endoplasmic reticulum. Cellular surface of chondrocytic cells frequently appeared with villiform projections and ruffled appearance, often surrounded by abundant and finely granular matrix with occasional calcified bodies. Finally, desmosomal attachments were not identified at all.
Discussion In human breast tissue, the incidence of bone lesions is rare [16] if compared with those of other mammals, particularly with canine mammary tumors, in which there is a strikingly high incidence of cartilaginous and osseous metaplasia [18]. In reference to cartilaginous differentiation, several benign breast tumors, such as chondrolipoma [5], choristoma [13], or pleomorphic adenoma [2], may contain benign chondroid islets, although the presence of malignant cartilage (chondrosarcoma) is indeed rare. As a primary breast tumor, chondrosarcoma may occur in three different forms: as a pure neoplasm (pure chondrosarcoma), as the stromal component of a histologically malignant phyllodes tumor, or as chondrosarcomatous differentiation in a metaplastic carcinoma. In this report we document a case of histologically malignant phyllodes tumor displaying a predominantly chondrosarcomatous component, making up over 80% of the tumor volume. The behavior of a histologically malignant phyllodes tumor is notoriously difficult to predict, because not all the cases behave in a clinically malignant fashion [14]. Stromal overgrowth [10] has been reported to be an important prognostic factor by some, but not by all authors. Of particular interest is the report of a significant correlation between the presence of heterologous stromal elements and malignant behavior [4], although the prognostic significance of various types of sarcoma, arising in phyllodes tumor, is not fully known. Pietruszka and Barnes [15] proposed that when rhabdomyosarcoma accounts for the major component of a phyllodes tumor, it has essentially the same prognosis as pure and primary rhabdomyosarcoma. Similar conclusions have been reported by Silver and Tavassoli [17] in the case of osteosarcomatous phyllodes tumors. Prognosis of chondrosarcomatous breast tumors is not fully known, because many of the reported cases [1, 7, 8, 11, 12, 19] are difficult to analyze owing to lack of detailed clinical or morphologic information. Only in one case of pure chondrosarcoma grade III/IV of the
breast documented the follow-up a malignant behavior with pulmonary metastasis, developing within four months after diagnosis [1]. The clinical courses of pure chondrosarcoma of the breast and phyllodes tumor with predominant chondrosarcomatous differentiation are possibly similar, as in the case of rhabdomyosarcomatous[15] and osteosarcomatous tumors [17]. Conversely, it may be difficult to differentiate a pure chondrosarcoma of the breast from one arising within a phyllodes tumor, particularly if not well sampled for the presence of an area of a typical phyllodes tumor, which could be very small, as in the present case and in others reported [7, 11]. In fact it is quite possible that some examples of so-called “pure” chondrosarcoma of the breast [1, 8, 12, 19] really represent the chondrosarcomatous overgrowth of a biphasic neoplasm; in this sense, the report of Beltaos and Bernajee [1] on two pure mammary chondrosarcomas failed to address the issue of completeness of tumor sampling, thus raising the question of positively ruling out the possibility of malignant phyllodes tumor. However, in patients with either of these two neoplasms (pure chondrosarcoma or malignant phyllodes tumor with chondrosarcomatous differentiation), therapy and clinical course are similar. Hence, it is of great importance to distinguish a primary mammary chondrosarcoma – whether or not associated with a biphasic neoplasm – from a metaplastic carcinoma of the breast with chondrosarcomatous heterologous elements; this requires treatment as a primary breast carcinoma in a comparable stage [3, 17]; in that case, axillary lymph node dissection must be considered. Such distinction may be achieved mainly by immunohistochemical stains that include a panel for epithelial markers that, as in our case, was nonreactive at the sarcomatous level. Furthermore, in our observation, high molecular-weight cytokeratin 34βE12 and also p63 were negative in the sarcomatous component, ruling out the hypothetic myoephitelial origin of heterologous elements, proposed by several authors [3] in metaplastic carcinoma of the breast and also supported by a recent study [20] with a panel of novel (p63, maspin and P-cadherin) and classic myoepithelial cell markers. Acknowledgements. The authors are grateful to Dr. F. RuizPerales, Division of Radiology, for the mammographic study.
References 1. Beltaos E, Nanerjee TK (1979) Chondrosarcoma of the breast. Report of two cases. Am J Clin Pathol 71:345–349 2. Ballance WA, Ro JY, El-Naggar AK, Grignon DJ, Ayala AG, Romsdalh MG (1990) Pleomorphic adenoma (benign mixed tumor) of the breast. An immunohistochemical, flow cytometric, and ultrastructural study and review of the literature. Am J Clin Pathol 93: 795–801
Chondrosarcomatous Phyllodes Tumor · 845 3. Chhieng C. Cranor M, Lesser ME, Rosen PP (1998) Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. Am J Surg Pathol 22: 188–194 4. Cohn-Cedermark G, Rutqvist LE, Rosendahl I, Silfversward C (1991) Prognostic factors in cystosarcoma phyllodes. A clinicopathologic study of 77 cases. Cancer 68: 2017–2022 5. Dharkar DD, Kraft JR (1981) Benign chondrolipomatous tumor of the breast. Postgrad Med J 7: 129–131 6. Elston CW, Ellis IO (1998) The breast. In: Systemic Pathology, 3rd ed. vol 13, p 168. Churchill Livingstone, Edinburgh 7. Garcia FU, Soans S, Galindo LM (1999) Malignant phyllodes tumor with chondrosarcomatous differentiation: report of a case with cytological presentation. Diagn Cytopathol 20: 241–245 8. Guymar S, Ferlicot S, Genestie C, Gelbert JJ, Blondon J, LeCharpentier Y, Zafrani B (2001) Chondrosarcome du sein: à propos d’un cas. Ann Pathol 21: 168 –171 9. Hart WR, Bauer RC, Oberman HA (1978) Cystosarcoma phyllodes. A clinicopathologic study of twenty-six hypercellular periductal stromal tumours of the breast. Am J Clin Pathol 70: 211–216 10. Hawkins RE, Schofield JB, Fisher C, Wiltshaw E, McKinna JA (1992) The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes. Cancer 69: 141–147 11. Iihara K, Machinami R, Kubota S, Itoyama S, Sato A (1997) Malignant cystosarcoma phyllodes tumor of the breast mainly composed of chondrosarcoma: A case report. Gen Diagn Pathol 142: 241–245
12. Kennedy T, Biggard JD (1967) Sarcoma of the breast. Br J Cancer 21: 635 –644 13. Metcalf JS, Ellis B (1985) Choristoma of the breast. Hum Pathol 16: 739 –740 14. Moffat CJC, Pinder SE, Dixon AR, Elston CW, Blamey RW (1995) Phyllodes tumours of the breast. A clinicopathological review of thirty-two cases. Histopathology 27: 205 –218 15. Pietruszka M, Barnes L (1978) Cystosarcoma phyllodes. A clinicopathologic analysis of 42 cases. Cancer 41: 1974 –1983 16. Rosen PP, Oberman HA (1993) Tumors of the mammary gland (Atlas of Tumor Pathology, 3rd ser, fasc 7), p 316. Armed Forces Institute of Pathology, Washington 17. Silver SS, Tavassoli FA (1999) Osteosarcomatous differentiation in phyllodes tumors. Am J Surg Pathol 23: 815 – 821 18. Smith BH, Taylor HB (1969) The occurrence of bone and cartilage in mammary tumors. Am J Clin Pathol 51: 610 – 618 19. Thilagavathi G, Subramanian S, Samuel AV, Rani U, Somasundaram C (1992) Primary chondrosarcoma of the breast. J Indian Med Assoc 90: 16 –17 20. Reis-Filho JS, Milanezi F, Paredes J, Silva P, Pereira EM, Maeda SA, de Carvalho LV, Schmitt FC (2003) Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast. Appl Immunohistochem Mol Morphol 11: 1– 8 Received: May 20, 2003 Accepted in revised version: November 3, 2003