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8. Rhodes J, Bemado DE, Philips SF, et al: Increased reflux of bile into the stomach in patients with gastric ulcer. Gastro-' enterology 57:241-252, 1969 9. Schrumpf E, Stadass J, Myren J, et al: Mucosal changes in the gastric stirup 20-25 years after partial gastrectomy. Lancet 2:467-469, 1977
10. Stalsberg H, Taksdal S: Stomach cancer following gastric surgery for benign condition. Lancet 2:1175-1177, 1971 11. Stemmermann GN, Haenszel W, Locke F: Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii. J Natl Cancer Inst 58:13-20, 1977 12. Tomasulo J: Gastric polyps. Histologic types and their relationship to gastric carcinoma. Cancer 27:1346-1355, 1971
Chondrosarcoma of the Breast Report of Two Cases
Beltaos, Efstathios, and Banerjee, Tarit K: Chondrosarcoma of the breast. Report of two cases. Am J Clin Pathol. 71: 3 4 5 349, 1979. The clinical and pathologic findings in two cases of pure chondrosarcoma of the breast are presented. As with other sarcomas, both tumors were large (5.5 and 25 cm in greatest diameter), did not invade the skin or axillary lymph nodes, and occurred in women more than 40 years old. Infiltrating margins, cellular atypism, and high mitotic rates adversely affected the prognosis. (Key words: Chondrosarcoma; Breast; Sarcoma.)
SARCOMAS of the breast are relatively rare, accounting for less than 1% of all primary malignant tumors of the female breast.1,612 Of these, some have a definite or probable origin in a fibroadenoma5,6,91213 and have been variously called adenosarcoma (adenofibrosarcoma) or malignant cystosarcoma phylloides. Others are carcinosarcomas, and still others pure sarcomas lacking an epithelial component. Of the pure sarcomas, the majority are fibrosarcomas with or without focal heterologous elements such as bone, cartilage, muscle, and fat.1,5,8,915,17 Rhabdomyosarcomas,4,12,16 osteosarcomas, 41112 liposarcomas,10 angiosarcomas,1418 and dermatofibrosarcoma protuberans-like,15,16 and desmoid-like15 lesions have also been reported. We could find only one reference to a pure chondrosarcoma.12 Below we present the pathologic and clinical manifestations and courses of two cases of pure chondrosarcoma of the breast. Received April 25,1978; received revised manuscript and accepted for publication May 26, 1978. Address reprint requests to Dr. Beltaos: Department of Pathology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, Wisconsin 54449.
Departments of Pathology and Medical Oncology, Marshfield Clinic, Marshfield, Wisconsin
Reports of Two Cases Patient 1: A 73-year-old white woman was seen in January 1973 with an enlarging painless mass of the left breast, which had been present for the preceding eight years. Because of its size, she decided to have the mass removed. She had no other symptom. She had had a subtotal hysterectomy for "fibroids" in 1947, conization of the uterine cervix for chronic inflammation in 1949, and a cholecystectomy for cholelithiasis in 1964. On examination, her general status and vital signs were normal. The left breast was very large due to the presence of a largelobed, very firm mass, which was movable over the chest wall and did not involve the overlying skin. There were no palpable left axillary lymph nodes. The right breast was normal. There was no organomegaly. Complete blood count, SMA results, urinalysis, and roentgenograms of the chest disclosed no abnormality. Mammograms showed a large, dense mass occupying two thirds of the left breast, which was thought to be a cystosarcoma phylloides (Fig. 1). A bone survey showed no metastasis. The patient underwent a left simple mastectomy on January 31, 1973. The surgeon was able to remove the entire mass and close the skin margins. She did not need skin grafting. The tumor was reported on frozen-section examination to be a low-grade chondrosarcoma. The surgeon inspected the left axilla, and because there was no obvious enlargement of any lymph node, he did not remove the axillary contents. Pathologic Findings on Gross Examination. The specimen included the left breast with segments of pectoral muscles attached. The breast was almost completely replaced by a huge, lobulated, hard, pearly-white tumor, measuring 15 x 20 x 25 cm and weighing 2,450 g. The cut surfaces of the tumor had a gelatinous, multinodular appearance and showed areas of cystic degeneration as large as 3 cm in greatest dimension and numerous foci of calcifica-
0002-9173/79/0300/0345 $00.75 © American Society of Clinical Pathologists
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A.J.C.P. • March 1979
FIG. 2 (right). Cut surfaces of tumor. Note lobulated, white, glistening, cartilaginous appearance.
tion (Fig. 2). The margins of the tumor were pushing the overlying skin and underlying voluntary muscle. Only a few areas of breast tissue could be identified, and they showed dilated ducts, some filled with green, thick secretions. Microscopic Examination. Multiple sections were taken. The tumor was a grade I chondrosarcoma throughout without other sarcomatous elements (Figs. 3 and 4). The matrix was hyaline in most areas, resembling the matrix of normal hyaline cartilage. The tumor cells were in lacunae. The cellularity varied in different places, but it was never very prominent. Two or more cells were often observed lying within the same lacuna. The nuclei of the chondrocytes were enlarged and showed slight hyperchromatism and pleomorphism. Binucleate cells were also present. Mitoses were not found. The tumor was made up of lobules separated by thin or thick fibrous
septa, containing lymphocytes, often forming nodules, and phagocytes, many with foamy cytoplasm. The tumor showed areas of degeneration and calcification. It was in intimate relationship with the stroma of the breast in many places. The margins of the tumor were pushing rather than infiltrating and did not invade the overlying skin or the underlying muscle. The breast, where not involved by the tumor, showed changes of fibrocystic disease in places. Clinical Course. The patient had no postoperative complications. She was later followed as an outpatient in the clinic. In February 1973, a liver scan showed a 5-cm lesion in the right lobe of the liver that was suggestive of a neoplasm, although a cyst could not be ruled out. The liver scan was repeated in April 1973; the lesion did not show any significant change. Bone scan was reported as normal in February 1973. The patient refused to have a liver biopsy
FIG. 3 (upper, left). Well-differentiated chondrosarcoma with adjacent normal mammary tissue. Note pushing margins. Hematoxylin and eosin. x 100. FIG. 4 (upper, right). The cartilaginous nature and the differentiation of the tumor can be seen. The matrix is hyaline, and the cells are in lacunae. There are only slight nuclear pleomorphism and hyperchromatism. Hematoxylin and eosin. x 100. FIG. 5 (lower, left). Lobules of a high-grade cartilaginous tumor with infiltrating margins, right. Note the mammary tissue in the left half of the photograph. Hematoxylin and eosin. x25. FIG. 6 (lower, right). At higher magnification, the cartilaginous matrix, high cellularity, and prominent nuclear hyperchromatism and pleomorphism can be seen. Hematoxylin and eosin. x 100.
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FIG. 1 (left). Mammogram of the left breast, showing huge, dense mass.
Vol. 71 • No. 3
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CASE REPORTS
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Discussion
The so-called pure sarcomas of the breast apparently originate in the intralobular, interlobular, and peri-
ductal fibrous stroma of the breast.3,915 They differ from malignant cystosarcoma phylloides or adenosarcoma and from carcinosarcoma in that an epithelial benign or malignant component is absent. These tumors are similar to soft-tissue tumors elsewhere in the body.915 Most of them are fibrosarcomas (29 of 32 cases ofNorris,15 13 of 18 cases of Kennedy,12 14 of 24 cases of Botham,4 15 of 15 cases of Ludgate,13 7 of 13 cases of Oberman,16 5 of 5 cases of Fawcett,6 6 of 6 cases of Gogas,8 and 5 of 10 cases of Barnes2). In general, sarcomas of the breast are large tumors that occur primarily in women more than 40 years of age.4,7,9'13,15 They rarely invade the overlying skin and axillary lymph nodes,1,3_7'12,13'15,16 but are capable of metastasizing and often do so, primarily via the bloodstream, most frequently to the lungs and bones.4,12'1315 Metastatic capability has been difficult or impossible to predict, but there are certain characteristics, such as large size,1,13,15'16 cellular atypism and high mitotic activity,2,4,5,12'13'15 and infiltrating margins,2'15 that indicate tumors capable of metastasis. Sarcomas containing a cartilage or bone, or both, do not necessarily have bad prognoses. Like other sarcomas, both of our patients' tumors were large (5.5 and 25 cm in greatest diameter), did not invade the skin or lymph nodes, and occurred in relatively old women. In the first case the tumor was present for eight years, and in the second case, for four months. Both tumors were made up of malignant cartilage and did not contain any other sarcomatous element or carcinomatous element. Probably both originated from the fibrous tissue stroma of the breast, through metaplasia or heteroplasia.9-15-17 In the first case, the tumor was a grade I chondrosarcoma without pulmonary or osseous metastasis, but with possible hepatic metastasis. The death of the patient probably was not related to the neoplasm. In the second case, in which the tumor was a high-grade chondrosarcoma, there were pulmonary metastases, and the patient's death was related to the tumor. The lymph nodes were clinically negative in the first case and pathologically negative in the second, in agreement with previous experience. Infiltrating margins, prominent cellular atypicalities, and high mitotic rates adversely affected prognosis, but not size, since the smaller tumor was the more aggressive. The operation performed in the first case was appropriate. Simple mastectomy with removal of the underlying pectoral muscles is what most investigators recommend for sarcoma of the breast. 1 ' 3-612,1516 With sarcomas, death usually occurs within three years,13 and in Norris's series,15 all eight patients who died of tumor did so within five years. After five years, recurrence is uncommon, as is indicated by only two deaths in a combined series of 92 cases. 5,61213
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done. The last time she was seen in the clinic was in July 1973, when examination showed no abnormality. The results of SMA studies remained normal. The patient refused to have further follow-up studies. It was learned that she died at home in November 1973. An autopsy was not performed. Patient 2: A 51-year-old white woman sought medical treatment in March 1976 because of a mass in the left breast of about four months' duration. She had first noticed the mass two weeks after injuring the breast with a lawn-mower handle. She denied any systemic symptom. Physical examination disclosed no abnormality other than a 7-cm hard, nontender mass of the left breast, immediately underneath the skin and freely movable over the chest wall. The complete blood count and urine were normal. Lactate dehydrogenase (LDH) was elevated to 333 IU/1. A roentgenogram of the chest showed an infiltrative type of density superimposed over and adjacent to the left heart border. Mammograms were not done. On April 20, 1976, with the clinical diagnosis of cystosarcoma phylloides of the left breast, she underwent a left radical mastectomy. She had primary closure of the skin. Pathologic Findings on Gross Examination. The tumor was removed first, and then the breast and axillary tissues were removed. The tumor was a lobulated, white, firm, focally cystic 5 x 5 x 5.5 cm mass, surrounded by a thin layer of fat. Its cut surfaces had a multinodular, glistening, gelatinous appearance. There was a large, central, 3.5-cm cyst containing mucoid material. The left breast showed no other tumor, and the axillary lymph nodes were not tumorous. Microscopic Examination. The tumor was a grade III/IV pure chondrosarcoma, consisting of lobules (Figs. 5 and 6). Toward the centers of the lobules the tumor was definitely cartilaginous, with a basophilic matrix and cells lying in lacunae individually, and two or three together. The cellularity increased at the periphery of the lobules, where occasionally the tumor cells were spindle-shaped and in bundles and gave the appearance of a spindle-cell sarcoma. The neoplastic cells had large, irregular, hyperchromatic nuclei with frequent mitoses, particularly in the periphery of the lobules. Multinucleated tumor cells were also present. The margins of the tumor were infiltrating. The rest of the breast showed no abnormality. Of eight axillary lymph nodes, none contained metastatic tumor. Clinical Course. There was no postoperative complication. The patient was followed in the Clinic as an outpatient. In May 1976, she had a cough. Roentgenograms of the chest showed an infiltrate in the lower portion of the left lung, which was more extensive than a month previously. In addition, there were many nodular lesions, most clearly visible in the right lung, interpreted as metastatic malignancy. In June 1976 bronchoscopy showed narrowing of the left lower-lobe bronchus, and of its branch to the superior segment. A biopsy from this area was interpreted as probable metastatic chondrosarcoma. Cytologic examination of the sputum showed tumor cells. The patient was then treated with a regimen of doxorubicin hydrochloride (Adriamycin®) 60 mg/m2, given intravenously once every three weeks on an outpatient basis. She had temporary symptomatic improvement, but there was objective progression of the tumor, with cutaneous metastases, increased sizes and numbers of pulmonary nodules, and an increase in serum LDH. In December 1976 the doxorubicin hydrochloride was discontinued, and high doses of cyclophosphamide (Cytoxan®), actinomycin (Actinomycin D®), and vincristine sulfate (Oncovin®) were started. The patient became acutely ill. She was hospitalized with increasing dyspnea and evidence of congestive heart failure and died in congestive heart failure in December 1976. Permission for an autopsy was not granted.
A.J.C.P. • March 1979
CASE REPORTS
Vol. 71 • No. 3
References 1. Adair FE, Herrmann JB: Sarcoma of the breast. Surgery 19: 55-73, 1946 2. Barnes L, Pietruszka M: Sarcoma of the breast. Cancer 40:15771585, 1977 3. Berg JW, DeCrosse JJ, Fracchia AA, et al: Stromal sarcomas of the breast. Cancer 15:418-424, 1962 4. Botham RJ, McDonald JR, Clagett OT: Sarcoma of the mammary gland. Surg Gynecol Obstet 107:55-61, 1958 5. Curran RC, Dodge OG: Sarcoma of breast, with particular reference to its origin from fibroadenoma. J Clin Pathol 15:1-16, 1962 6. Fawcett FJ: Sarcoma of breast. Br J Cancer 21:285-294, 1966 7. Fox SL: Sarcoma of the breast with a report of sixty cases. Ann Surg 100:401-421, 1934 8. Gogas JG, Kotisianos G, Gogas KG: Sarcoma of the breast. Am Surg 42:812-816, 1976
349
9. Hill RP, Stout AP: Sarcoma of the breast. Arch Surg 44:723-759, 1942 10. Hummer CD Jr, Burkart TJ: Liposarcoma of the breast. Am J Surg 113:558-561, 1967 11. Jernstrom P, Lindberg AL, Meland ON: Osteogenic sarcoma of the mammary gland. Am J Clin Pathol 40:521-526, 1963 12. Kennedy T, Biggart JD: Sarcoma of the breast. Br J Cancer 21:635-644, 1967 13. Ludgate CM, Anderson TJ, Langlands AO: Sarcoma of the female breast—Report of a series of 30 cases. Clin Oncol 3: 97-105, 1977 14. McClanahan BJ, Hogg, L Jr: Angiosarcoma of the breast. Cancer 7:586-594, 1954 15. Norris HJ, Taylor HB: Sarcomas and related mesenchymal tumors of the breast. Cancer 22:22-28, 1968 16. ObermanH: Sarcomas of the breast. Cancer 18:1233-1243, 1965 17. Smith BH, Taylor HB: The occurrence of bone and cartilage in mammary tumors. Am J Clin Pathol 51:610-618. 1969 18. Steingaszner LC, Enzinger FM. Taylor HB: Hemangiosarcoma of the breast. Cancer 18:352-361, 1965
LEWIS G. LEFER, M.D., AND R. PETER ROSIER, M.D.
Lefer, Lewis G., and Rosier, R. Peter: Ochronosis in the breast. Am J Clin Pathol 71: 349-352, 1979. A patient who had masses in the breasts clinically suggestive of neoplasia had fibrous mastopathy and striking deposition of ochronotic pigment within the soft tissue of the breast. The gross appearance and light microscopic features are illustrated. The histochemical features of ochronotic pigment and the difficulty in differentiating it from melanin are discussed. (Key words: Breast; Ochronosis.) OCHRONOSIS is part of a clinical syndrome characterized by the presence of homogentisic acid in the urine (alcaptonuria) and deposition of pigment within the soft tissues. The disease may be explained by the presence of a rare, simple autosomal recessive allele resulting in homogentisic acid oxidase deficiency. This report describes the light microscopic and histochemical characteristics of ochronotic pigment that had been deposited in the breast and was associated with many nodules, suggesting neoplasia. Report of a Case A white woman first came to medical attention in 1951, at the age of 46 years, for evaluation of several tender nodules of the right breast. Biopsy revealed typical fibrocystic mastopathy. In 1967 she had costochondritis, and roentgenograms of the chest revealed calcification of the aortic valve, the arch of the aorta, and the articuReceived February 27, 1978; received revised manuscript and accepted for publication May 10, 1978. Address reprint requests to Dr. Lefer: Pathology and Laboratory Medicine, P.O. Box 1625, Fort Myers, Florida 33902.
Pathology and Laboratory Medicine, Fort Myers, Florida
lar disks of the entire thoracic spine. The diagnoses of ochronosis and alcaptonuria with associated degenerative joint disease were made when homogentisic acid was found in the urine. Three of the patient's sisters were found to have ochronosis. The patient did well until 1972, when she noticed a mass in her left breast. Physical examination revealed marked darkening over the ears, nose, and nails. Examination of the left breast revealed a firm, immobile, subareolar mass, approximately 1 x 3 x 4 cm, without skin retraction, nipple discharge, or lymph nodes palpable within the axilla. A left mastectomy was performed. The postoperative course was uneventful, and the patient has remained well until the present. Pathologic Findings The surgical specimen consisted of the left breast. Two centimeters lateral to the nipple and beneath the areola was a very firm, lobulated, immobile mass, 4.0 x 2.5 x 2.0 cm, with a diffuse brown to black discoloration (Fig. 1). A very similar but smaller mass was located 4.0 cm medial to the nipple. Multiple microscopic sections from these lesions showed dense, virtually acellular fibrosis with atrophic epithelium, consistent with a diagnosis of fibrous mastopathy. Much of the connective tissue was diffusely yellow-brown on routine hematoxylin-and-eosin-stained sections. In areas, however, pigment was finely particulate (Figs. 2 and 3). Pigment was deposited freely within the connective tissue stroma, as well as within connective tissue cells.
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8. Rhodes J, Bemado DE, Philips SF, et al: Increased reflux of bile into the stomach in patients with gastric ulcer. Gastro-' enterology 57:241-252, 1969 9. Schrumpf E, Stadass J, Myren J, et al: Mucosal changes in the gastric stirup 20-25 years after partial gastrectomy. Lancet 2:467-469, 1977
10. Stalsberg H, Taksdal S: Stomach cancer following gastric surgery for benign condition. Lancet 2:1175-1177, 1971 11. Stemmermann GN, Haenszel W, Locke F: Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii. J Natl Cancer Inst 58:13-20, 1977 12. Tomasulo J: Gastric polyps. Histologic types and their relationship to gastric carcinoma. Cancer 27:1346-1355, 1971
Chondrosarcoma of the Breast Report of Two Cases
Beltaos, Efstathios, and Banerjee, Tarit K: Chondrosarcoma of the breast. Report of two cases. Am J Clin Pathol. 71: 3 4 5 349, 1979. The clinical and pathologic findings in two cases of pure chondrosarcoma of the breast are presented. As with other sarcomas, both tumors were large (5.5 and 25 cm in greatest diameter), did not invade the skin or axillary lymph nodes, and occurred in women more than 40 years old. Infiltrating margins, cellular atypism, and high mitotic rates adversely affected the prognosis. (Key words: Chondrosarcoma; Breast; Sarcoma.)
SARCOMAS of the breast are relatively rare, accounting for less than 1% of all primary malignant tumors of the female breast.1,612 Of these, some have a definite or probable origin in a fibroadenoma5,6,91213 and have been variously called adenosarcoma (adenofibrosarcoma) or malignant cystosarcoma phylloides. Others are carcinosarcomas, and still others pure sarcomas lacking an epithelial component. Of the pure sarcomas, the majority are fibrosarcomas with or without focal heterologous elements such as bone, cartilage, muscle, and fat.1,5,8,915,17 Rhabdomyosarcomas,4,12,16 osteosarcomas, 41112 liposarcomas,10 angiosarcomas,1418 and dermatofibrosarcoma protuberans-like,15,16 and desmoid-like15 lesions have also been reported. We could find only one reference to a pure chondrosarcoma.12 Below we present the pathologic and clinical manifestations and courses of two cases of pure chondrosarcoma of the breast. Received April 25,1978; received revised manuscript and accepted for publication May 26, 1978. Address reprint requests to Dr. Beltaos: Department of Pathology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, Wisconsin 54449.
Departments of Pathology and Medical Oncology, Marshfield Clinic, Marshfield, Wisconsin
Reports of Two Cases Patient 1: A 73-year-old white woman was seen in January 1973 with an enlarging painless mass of the left breast, which had been present for the preceding eight years. Because of its size, she decided to have the mass removed. She had no other symptom. She had had a subtotal hysterectomy for "fibroids" in 1947, conization of the uterine cervix for chronic inflammation in 1949, and a cholecystectomy for cholelithiasis in 1964. On examination, her general status and vital signs were normal. The left breast was very large due to the presence of a largelobed, very firm mass, which was movable over the chest wall and did not involve the overlying skin. There were no palpable left axillary lymph nodes. The right breast was normal. There was no organomegaly. Complete blood count, SMA results, urinalysis, and roentgenograms of the chest disclosed no abnormality. Mammograms showed a large, dense mass occupying two thirds of the left breast, which was thought to be a cystosarcoma phylloides (Fig. 1). A bone survey showed no metastasis. The patient underwent a left simple mastectomy on January 31, 1973. The surgeon was able to remove the entire mass and close the skin margins. She did not need skin grafting. The tumor was reported on frozen-section examination to be a low-grade chondrosarcoma. The surgeon inspected the left axilla, and because there was no obvious enlargement of any lymph node, he did not remove the axillary contents. Pathologic Findings on Gross Examination. The specimen included the left breast with segments of pectoral muscles attached. The breast was almost completely replaced by a huge, lobulated, hard, pearly-white tumor, measuring 15 x 20 x 25 cm and weighing 2,450 g. The cut surfaces of the tumor had a gelatinous, multinodular appearance and showed areas of cystic degeneration as large as 3 cm in greatest dimension and numerous foci of calcifica-
0002-9173/79/0300/0345 $00.75 © American Society of Clinical Pathologists
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A.J.C.P. • March 1979
FIG. 2 (right). Cut surfaces of tumor. Note lobulated, white, glistening, cartilaginous appearance.
tion (Fig. 2). The margins of the tumor were pushing the overlying skin and underlying voluntary muscle. Only a few areas of breast tissue could be identified, and they showed dilated ducts, some filled with green, thick secretions. Microscopic Examination. Multiple sections were taken. The tumor was a grade I chondrosarcoma throughout without other sarcomatous elements (Figs. 3 and 4). The matrix was hyaline in most areas, resembling the matrix of normal hyaline cartilage. The tumor cells were in lacunae. The cellularity varied in different places, but it was never very prominent. Two or more cells were often observed lying within the same lacuna. The nuclei of the chondrocytes were enlarged and showed slight hyperchromatism and pleomorphism. Binucleate cells were also present. Mitoses were not found. The tumor was made up of lobules separated by thin or thick fibrous
septa, containing lymphocytes, often forming nodules, and phagocytes, many with foamy cytoplasm. The tumor showed areas of degeneration and calcification. It was in intimate relationship with the stroma of the breast in many places. The margins of the tumor were pushing rather than infiltrating and did not invade the overlying skin or the underlying muscle. The breast, where not involved by the tumor, showed changes of fibrocystic disease in places. Clinical Course. The patient had no postoperative complications. She was later followed as an outpatient in the clinic. In February 1973, a liver scan showed a 5-cm lesion in the right lobe of the liver that was suggestive of a neoplasm, although a cyst could not be ruled out. The liver scan was repeated in April 1973; the lesion did not show any significant change. Bone scan was reported as normal in February 1973. The patient refused to have a liver biopsy
FIG. 3 (upper, left). Well-differentiated chondrosarcoma with adjacent normal mammary tissue. Note pushing margins. Hematoxylin and eosin. x 100. FIG. 4 (upper, right). The cartilaginous nature and the differentiation of the tumor can be seen. The matrix is hyaline, and the cells are in lacunae. There are only slight nuclear pleomorphism and hyperchromatism. Hematoxylin and eosin. x 100. FIG. 5 (lower, left). Lobules of a high-grade cartilaginous tumor with infiltrating margins, right. Note the mammary tissue in the left half of the photograph. Hematoxylin and eosin. x25. FIG. 6 (lower, right). At higher magnification, the cartilaginous matrix, high cellularity, and prominent nuclear hyperchromatism and pleomorphism can be seen. Hematoxylin and eosin. x 100.
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FIG. 1 (left). Mammogram of the left breast, showing huge, dense mass.
Vol. 71 • No. 3
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CASE REPORTS
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.4
348
BELTAOS AND BANERJEE
Discussion
The so-called pure sarcomas of the breast apparently originate in the intralobular, interlobular, and peri-
ductal fibrous stroma of the breast.3,915 They differ from malignant cystosarcoma phylloides or adenosarcoma and from carcinosarcoma in that an epithelial benign or malignant component is absent. These tumors are similar to soft-tissue tumors elsewhere in the body.915 Most of them are fibrosarcomas (29 of 32 cases ofNorris,15 13 of 18 cases of Kennedy,12 14 of 24 cases of Botham,4 15 of 15 cases of Ludgate,13 7 of 13 cases of Oberman,16 5 of 5 cases of Fawcett,6 6 of 6 cases of Gogas,8 and 5 of 10 cases of Barnes2). In general, sarcomas of the breast are large tumors that occur primarily in women more than 40 years of age.4,7,9'13,15 They rarely invade the overlying skin and axillary lymph nodes,1,3_7'12,13'15,16 but are capable of metastasizing and often do so, primarily via the bloodstream, most frequently to the lungs and bones.4,12'1315 Metastatic capability has been difficult or impossible to predict, but there are certain characteristics, such as large size,1,13,15'16 cellular atypism and high mitotic activity,2,4,5,12'13'15 and infiltrating margins,2'15 that indicate tumors capable of metastasis. Sarcomas containing a cartilage or bone, or both, do not necessarily have bad prognoses. Like other sarcomas, both of our patients' tumors were large (5.5 and 25 cm in greatest diameter), did not invade the skin or lymph nodes, and occurred in relatively old women. In the first case the tumor was present for eight years, and in the second case, for four months. Both tumors were made up of malignant cartilage and did not contain any other sarcomatous element or carcinomatous element. Probably both originated from the fibrous tissue stroma of the breast, through metaplasia or heteroplasia.9-15-17 In the first case, the tumor was a grade I chondrosarcoma without pulmonary or osseous metastasis, but with possible hepatic metastasis. The death of the patient probably was not related to the neoplasm. In the second case, in which the tumor was a high-grade chondrosarcoma, there were pulmonary metastases, and the patient's death was related to the tumor. The lymph nodes were clinically negative in the first case and pathologically negative in the second, in agreement with previous experience. Infiltrating margins, prominent cellular atypicalities, and high mitotic rates adversely affected prognosis, but not size, since the smaller tumor was the more aggressive. The operation performed in the first case was appropriate. Simple mastectomy with removal of the underlying pectoral muscles is what most investigators recommend for sarcoma of the breast. 1 ' 3-612,1516 With sarcomas, death usually occurs within three years,13 and in Norris's series,15 all eight patients who died of tumor did so within five years. After five years, recurrence is uncommon, as is indicated by only two deaths in a combined series of 92 cases. 5,61213
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done. The last time she was seen in the clinic was in July 1973, when examination showed no abnormality. The results of SMA studies remained normal. The patient refused to have further follow-up studies. It was learned that she died at home in November 1973. An autopsy was not performed. Patient 2: A 51-year-old white woman sought medical treatment in March 1976 because of a mass in the left breast of about four months' duration. She had first noticed the mass two weeks after injuring the breast with a lawn-mower handle. She denied any systemic symptom. Physical examination disclosed no abnormality other than a 7-cm hard, nontender mass of the left breast, immediately underneath the skin and freely movable over the chest wall. The complete blood count and urine were normal. Lactate dehydrogenase (LDH) was elevated to 333 IU/1. A roentgenogram of the chest showed an infiltrative type of density superimposed over and adjacent to the left heart border. Mammograms were not done. On April 20, 1976, with the clinical diagnosis of cystosarcoma phylloides of the left breast, she underwent a left radical mastectomy. She had primary closure of the skin. Pathologic Findings on Gross Examination. The tumor was removed first, and then the breast and axillary tissues were removed. The tumor was a lobulated, white, firm, focally cystic 5 x 5 x 5.5 cm mass, surrounded by a thin layer of fat. Its cut surfaces had a multinodular, glistening, gelatinous appearance. There was a large, central, 3.5-cm cyst containing mucoid material. The left breast showed no other tumor, and the axillary lymph nodes were not tumorous. Microscopic Examination. The tumor was a grade III/IV pure chondrosarcoma, consisting of lobules (Figs. 5 and 6). Toward the centers of the lobules the tumor was definitely cartilaginous, with a basophilic matrix and cells lying in lacunae individually, and two or three together. The cellularity increased at the periphery of the lobules, where occasionally the tumor cells were spindle-shaped and in bundles and gave the appearance of a spindle-cell sarcoma. The neoplastic cells had large, irregular, hyperchromatic nuclei with frequent mitoses, particularly in the periphery of the lobules. Multinucleated tumor cells were also present. The margins of the tumor were infiltrating. The rest of the breast showed no abnormality. Of eight axillary lymph nodes, none contained metastatic tumor. Clinical Course. There was no postoperative complication. The patient was followed in the Clinic as an outpatient. In May 1976, she had a cough. Roentgenograms of the chest showed an infiltrate in the lower portion of the left lung, which was more extensive than a month previously. In addition, there were many nodular lesions, most clearly visible in the right lung, interpreted as metastatic malignancy. In June 1976 bronchoscopy showed narrowing of the left lower-lobe bronchus, and of its branch to the superior segment. A biopsy from this area was interpreted as probable metastatic chondrosarcoma. Cytologic examination of the sputum showed tumor cells. The patient was then treated with a regimen of doxorubicin hydrochloride (Adriamycin®) 60 mg/m2, given intravenously once every three weeks on an outpatient basis. She had temporary symptomatic improvement, but there was objective progression of the tumor, with cutaneous metastases, increased sizes and numbers of pulmonary nodules, and an increase in serum LDH. In December 1976 the doxorubicin hydrochloride was discontinued, and high doses of cyclophosphamide (Cytoxan®), actinomycin (Actinomycin D®), and vincristine sulfate (Oncovin®) were started. The patient became acutely ill. She was hospitalized with increasing dyspnea and evidence of congestive heart failure and died in congestive heart failure in December 1976. Permission for an autopsy was not granted.
A.J.C.P. • March 1979
CASE REPORTS
Vol. 71 • No. 3
References 1. Adair FE, Herrmann JB: Sarcoma of the breast. Surgery 19: 55-73, 1946 2. Barnes L, Pietruszka M: Sarcoma of the breast. Cancer 40:15771585, 1977 3. Berg JW, DeCrosse JJ, Fracchia AA, et al: Stromal sarcomas of the breast. Cancer 15:418-424, 1962 4. Botham RJ, McDonald JR, Clagett OT: Sarcoma of the mammary gland. Surg Gynecol Obstet 107:55-61, 1958 5. Curran RC, Dodge OG: Sarcoma of breast, with particular reference to its origin from fibroadenoma. J Clin Pathol 15:1-16, 1962 6. Fawcett FJ: Sarcoma of breast. Br J Cancer 21:285-294, 1966 7. Fox SL: Sarcoma of the breast with a report of sixty cases. Ann Surg 100:401-421, 1934 8. Gogas JG, Kotisianos G, Gogas KG: Sarcoma of the breast. Am Surg 42:812-816, 1976
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9. Hill RP, Stout AP: Sarcoma of the breast. Arch Surg 44:723-759, 1942 10. Hummer CD Jr, Burkart TJ: Liposarcoma of the breast. Am J Surg 113:558-561, 1967 11. Jernstrom P, Lindberg AL, Meland ON: Osteogenic sarcoma of the mammary gland. Am J Clin Pathol 40:521-526, 1963 12. Kennedy T, Biggart JD: Sarcoma of the breast. Br J Cancer 21:635-644, 1967 13. Ludgate CM, Anderson TJ, Langlands AO: Sarcoma of the female breast—Report of a series of 30 cases. Clin Oncol 3: 97-105, 1977 14. McClanahan BJ, Hogg, L Jr: Angiosarcoma of the breast. Cancer 7:586-594, 1954 15. Norris HJ, Taylor HB: Sarcomas and related mesenchymal tumors of the breast. Cancer 22:22-28, 1968 16. ObermanH: Sarcomas of the breast. Cancer 18:1233-1243, 1965 17. Smith BH, Taylor HB: The occurrence of bone and cartilage in mammary tumors. Am J Clin Pathol 51:610-618. 1969 18. Steingaszner LC, Enzinger FM. Taylor HB: Hemangiosarcoma of the breast. Cancer 18:352-361, 1965
LEWIS G. LEFER, M.D., AND R. PETER ROSIER, M.D.
Lefer, Lewis G., and Rosier, R. Peter: Ochronosis in the breast. Am J Clin Pathol 71: 349-352, 1979. A patient who had masses in the breasts clinically suggestive of neoplasia had fibrous mastopathy and striking deposition of ochronotic pigment within the soft tissue of the breast. The gross appearance and light microscopic features are illustrated. The histochemical features of ochronotic pigment and the difficulty in differentiating it from melanin are discussed. (Key words: Breast; Ochronosis.) OCHRONOSIS is part of a clinical syndrome characterized by the presence of homogentisic acid in the urine (alcaptonuria) and deposition of pigment within the soft tissues. The disease may be explained by the presence of a rare, simple autosomal recessive allele resulting in homogentisic acid oxidase deficiency. This report describes the light microscopic and histochemical characteristics of ochronotic pigment that had been deposited in the breast and was associated with many nodules, suggesting neoplasia. Report of a Case A white woman first came to medical attention in 1951, at the age of 46 years, for evaluation of several tender nodules of the right breast. Biopsy revealed typical fibrocystic mastopathy. In 1967 she had costochondritis, and roentgenograms of the chest revealed calcification of the aortic valve, the arch of the aorta, and the articuReceived February 27, 1978; received revised manuscript and accepted for publication May 10, 1978. Address reprint requests to Dr. Lefer: Pathology and Laboratory Medicine, P.O. Box 1625, Fort Myers, Florida 33902.
Pathology and Laboratory Medicine, Fort Myers, Florida
lar disks of the entire thoracic spine. The diagnoses of ochronosis and alcaptonuria with associated degenerative joint disease were made when homogentisic acid was found in the urine. Three of the patient's sisters were found to have ochronosis. The patient did well until 1972, when she noticed a mass in her left breast. Physical examination revealed marked darkening over the ears, nose, and nails. Examination of the left breast revealed a firm, immobile, subareolar mass, approximately 1 x 3 x 4 cm, without skin retraction, nipple discharge, or lymph nodes palpable within the axilla. A left mastectomy was performed. The postoperative course was uneventful, and the patient has remained well until the present. Pathologic Findings The surgical specimen consisted of the left breast. Two centimeters lateral to the nipple and beneath the areola was a very firm, lobulated, immobile mass, 4.0 x 2.5 x 2.0 cm, with a diffuse brown to black discoloration (Fig. 1). A very similar but smaller mass was located 4.0 cm medial to the nipple. Multiple microscopic sections from these lesions showed dense, virtually acellular fibrosis with atrophic epithelium, consistent with a diagnosis of fibrous mastopathy. Much of the connective tissue was diffusely yellow-brown on routine hematoxylin-and-eosin-stained sections. In areas, however, pigment was finely particulate (Figs. 2 and 3). Pigment was deposited freely within the connective tissue stroma, as well as within connective tissue cells.
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Ochronosis in the Breast
