Japanese Journal of Clinical Oncology 30:30-32 (2000)
© 2000 Foundation for Promotion of Cancer Research
Atypical Medullary Carcinoma of the Breast with Cartilaginous Metaplasia in a Patient with a BRCA1 Germline Mutation
1Department of Surgical Oncology, National Cancer Center Hospital, Tokyo, 2Pathology Division and 3Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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We examined a 34-year-old premenopausal woman who had noticed a left-breast lump a month previously. She had no past history of malignancies but had a family history of breast and ovarian cancers. Her mother had suffered from ovarian cancer when aged 47 years and had died of the disease at age 52. The younger two of the patient’s four aunts had developed breast cancer when they were 37 and 48 years old. A physical examination showed an ill-defined mass, 1.5 cm in diameter, located in the upper outer quadrant of the patient’s left breast. Mammography revealed diffuse microcalcification in both breasts but ultrasonography revealed an irregular tumorous lesion only in the left breast. Aspiration breast cytology revealed adenocarcinoma of the left breast. Modified radical mastectomy of the left breast and excision of a biopsy specimen from the right breast were carried out simultaneously. Histopathologically the left-breast tumor was an atypical medullary carcinoma with cartilaginous metaplasia, of histological grade 3, and the right-breast specimen showed fibrocystic changes with atypical ductal hyperplasia. Estrogen receptors were positive, but progesterone receptor was not detected on the tumor cells, which were immunopositive for nuclear p53 although c-erbB-2 overexpression was not observed. A nonsense germline mutation of the BRCA1 gene (exon5) was detected. The patient has been well since the operation (10 months). These findings may provide useful information about the carcinogenesis and biological behavior of BRCA1-associated breast cancers.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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BRCA1-linked familial breast cancer is reported to include cases of multiple breast and ovarian cancers (1). However, the genotype–phenotype relationships in hereditary breast cancer are still controversial (2–5). Previously we reported a case of bilateral non-palpable, predominantly intraductal breast carcinoma; the patient was a 34-year-old woman with BRCA2 germline mutation (6). In this paper we report a rare case of atypical medullary carcinoma with cartilaginous metaplasia seen in a patient with a BRCA1 germline mutation and a family history of breast and ovarian cancers. This is a rare case of the histopathological features and biological characteristics in a breast cancer with BRCA1 mutation.
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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We examined a 32-year-old premenopausal woman who had developed a left-breast lump a month previously. She had no past history of malignancy but had a family history of breast and ovarian cancers (Fig. 1). Her family pedigree revealed that her mother had suffered from ovarian cancer when 47 years old and had died of the disease at 52. One of the patient’s younger aunts was diagnosed with breast cancer when she was 48 years old but is currently disease free, 6 years after surgical treatment.
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A physical examination showed an ill-defined mass, 1.5 cm in diameter, located in the upper outer quadrant of the patient’s left breast. Diagnostic imaging showed diffuse microcalcification in both breasts on mammograms (Fig. 2) but ultrasonography and helical CT scans showed an irregular tumorous lesion only in the left breast (Fig. 3). Adenocarcinoma of the left breast was identified by aspiration breast cytology.
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Modified radical mastectomy of the left breast and excision of a biopsy specimen from the right breast were carried out simultaneously.
The histopathological examination revealed that the left-breast tumor was an atypical medullary carcinoma with cartilaginous metaplasia, of histological grade 3, without lymph node metastasis (0/15) (Figs 4 and 5). We defined atypical medullary carcinoma as a well-circumscribed case with some but not all of the features of medullary carcinoma. Medullary carcinoma is characterized by histological features of irregular but solid pattern, smooth borders, connective tissue stroma with lymphocytic infiltrate, nuclei with atypical or bizarre features and eosinophilic, granular cytoplasm, sometimes with syncytial pattern (7). Neither lymphatic nor vascular invasion by tumor cells was observed in the resected specimen. The right-breast tissue showed fibrocystic changes with atypical ductal hyperplasia. The estrogen receptor status of the left-breast tumor was positive, whereas the progesterone receptor status was negative. p53 nuclear immunoreactivity (Nichirei, Tokyo, Japan), but not c-erbB-2 overexpression (Nichirei), was observed in the tumor tissue. The patient received postoperative adjuvant chemotherapy, which consisted of six cycles of CMF. We decided to monitor the patient closely to check for right-breast and ovarian lesions. She is currently disease free 10 months after the operation.
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BRCA1 and BRCA2 Germline Mutation Analysis
After obtaining the written informed consent of the patient, we examined the patient’s DNA, which we extracted from lymphocytes, for BRCA1 and BRCA2 germline mutations. The patient was given basic information about the genes and the possible risks of psychological distress and social discrimination. The entire coding regions and the intronic regions flanking exons 2–24 were analyzed for BRCA1 and exons 2–27 were analyzed for BRCA2 by polymerase chain reaction-single strand conformation polymorphism analysis. A nonsense germline mutation of the BRCA1 gene (exon5) was detected. No BRCA2 mutation was detected in the regions tested. No other family members were examined.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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It has been suggested that a BRCA1 mutation increases the risk of breast and ovarian cancers (1). Previously we reported two cases of a nonsense mutation of BRCA1 (exon5 codon63) in patients with family histories of breast carcinoma; histologically the BRCA1-linked tumors looked like a common type of invasive ductal carcinoma of histological grade3 (8). In the present case, the same nonsense germline mutation of BRCA1 was detected. It is possible that this type of mutation is a founder mutation in Japanese breast cancer families (9). The genotype–phenotype relationships in hereditary breast cancer are still controversial and whether nonsense BRCA gene mutations are directly linked to a specific histological type is not clear.
Patients with BRCA1- or BRCA2-associated familial breast cancer have a histological grade3 tumor with nuclear atypia, structural atypia and mitotic activity (10).
BRCA1-related familial breast cancers are more likely to be aneuploid and to have higher tumor cell proliferation rates than other familial breast cancers (3). However, a Japanese collaborative study showed no clear evidence of a genotype–phenotype relationship in hereditary breast cancers (11,12). On the other hand, Bieche et al. (2) reported that loss of heterozygosity at BRCA2 correlates with low estrogen and progesterone receptor levels.
In the present case, the histological diagnosis was atypical medullary carcinoma with cartilaginous metaplasia. Marcus et al. (3) reported that medullary or atypical medullary carcinoma is a typical feature of BRCA1-associated breast cancers and Eisinger et al. (13) suggested that morphological features including medullary carcinoma may lead to the identification of a subgroup of breast carcinoma cases with a high prevalence of BRCA1 mutation. Lynch et al. (14) reported that BRCA1- or BRCA2-associated carcinomas are more likely to lack hormone receptors and to test positive for p53 protein. These tumor suppressor genes may be involved in cell cycle regulations, but the function of BRCA1 and BRCA2 and their relation with the p53 gene are still under investigation (15).
Extensive studies will be required to determine the relationship between BRCA1 mutation and the phenotype of breast carcinomas. The present case may provide useful information about the carcinogenesis and biological behavior of breast carcinomas that develop in patients with BRCA1 germline mutations.
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FOOTNOTES |
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+ For reprints and all correspondence: Takashi Fukutomi, Department of Surgical Oncology, National Cancer Center Hospital, 1–1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
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REFERENCES |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Received October 19, 1999; accepted October 21, 1999.
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