Rosen's Breast Pathology, 4e

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Chapter 33

subsequently reported. 99–103 Carcinoma occurs in less than 0.5% of FA, 101,104 and in 1% to 2% of PT. 101,102

More information about secretory carcinoma can be found in Chapter 22. Among the 132 BRCA-positive women with breast ­carcinoma who participated in a high-risk protocol at The University of Texas M.D. Anderson Cancer ­Center, 106 ­second-­­generation women could be paired with a family member in the previous (first) generation who was diagnosed with a BRCA-­related carcinoma in either breast or ovarian carcinoma. 93 The median age of carcinoma ­diagnosis in the first-­generation patients was 48 years (range, 30 to 72 years) and in the second-generation patients, it was 42 years (range, 28 to 55 years). This trend was found in subgroups with either a BRCA1 or BRCA2 mutation. The statistically sig­ nificant difference in age at diagnosis suggests that BRCA - mutation–related carcinomas in at least one subsequent generation occur at an earlier age after the first case is identi­ fied. The prognosis of breast carcinoma patients in BRCA 1 and BRCA 2 carriers has been controversial. In a large inter­ national population-based cohort study BRCA1 and BRCA2 mutation carriers were found to have no significant differ­ ence in outcome when compared with patients with sporadic breast carcinoma after adjusting for age, stage and grade of tumor, lymph node and hormone receptor status, and year of diagnosis. 94 Li–Fraumeni syndrome is a rare autosomal dominant disorder that is linked to germline mutations of the p53 tumor suppressor gene. The syndrome increases sus­ ceptibility to certain forms of cancer, including those of the breast, bone, and soft tissues. A cohort of eight breast ­carcinoma patients with a median age at diagnosis of 30 from ­Li–­Fraumeni families with the associated germline p53 mutations was studied in France. 95 Six of eight ­received ­radiation (including three after mastectomy). After a ­median follow-up of 6 years, an extraordinarily high ­incidence of subsequent events occurred in the six radiated patients ­consisting of three ipsilateral breast recurrences; three ­contralateral breast carcinomas; two radiation-­associated sarcomas; one thyroid carcinoma in field. The data suggest that bilateral mastectomy is appropriate and that radiation therapy is contraindicated in this setting because the patients appear to have a genetic predisposition to develop radiation-­ associated malignant neoplasms. CARCINOMA ARISING IN FIBROEPITHELIAL NEOPLASMS Fibroepithelial neoplasms consist of proliferating epithelial and stromal mammary tissues. Fibroadenomas (FA) arise from the stroma and epithelium of lobular-terminal duct units, whereas phyllodes tumors (PT) are composed pre­ dominantly of periductal stroma and duct epithelium. In 1931, Cheatle and Cutler 96 described carcinoma aris­ ing in a FA, and similar lesions were reported in 1940 by Harrington and Miller. 97 The first series, consisting of 26 patients, was published in 1967. 98 Numerous cases have been

Clinical Presentation The age of patients with carcinoma arising in a FA ranges from 15 to 70 years, with a mean age of 42 to 44 years. 101,104 Women with in situ carcinoma have a mean age of 42 to 45 years, and the mean age for patients with invasive carci­ noma in a FA is 47 to 52 years. 99 Because patients who have carcinoma in a FA tend to be somewhat older than those with FA that lack carcinoma, the possibility of encountering carcinoma should be anticipated when a FA is excised from a patient 35 years or older. The age distribution of women with carcinoma in or associated with a PT is not appreciably different from women with PT generally, reflecting the older age distribution of PT. There are no specific clinical or radiologic clues to indi­ cate the presence of in situ carcinoma within a FA or a PT. Invasive carcinoma in or associated with a FA may distort or blur the margin of the tumor in a mammogram. 105,106 Rarely, the pattern of calcifications in a FA can suggest intraductal carcinoma. 105,107 Carcinoma is more likely to be detected in a fine-needle aspirate from a FA if the carcinomatous compo­ nent is extensive. The diagnosis depends upon recognizing neoplastic cells in the customary background of benign epi­ thelium and stromal cells obtained from a typical FA. 108,109 If the lesion consists of in situ carcinoma limited to a small part of the tumor, there may not be sufficient material in a FNA or a needle core biopsy specimen to be diagnos­ tic. 110 Because there are no good clinical indicators of the presence of carcinoma in a fibroepithelial tumor, the diag­ nosis is generally not suspected until a needle core biopsy has been obtained or the excised tumor has been examined pathologically. Gross Pathology When in situ carcinoma is present in a FA or PT, it will of­ ten not be apparent on gross inspection. 99 FA that harbor carcinoma may not be especially large and many do not exceed 2 cm. Unusual firmness may develop at the site of intraductal carcinoma, particularly in those which are of high-grade with necrosis and calcifications. Invasive carci­ noma confined to a FA is generally inconspicuous grossly, but invasion into the adjacent breast tissue can distort the tumor enough to be evident. Microscopic Pathology The distinction between atypical hyperplasia and in situ carcinoma in a FA or PT is based on the same criteria that are used to assess epithelial proliferation in the mammary parenchyma. The characteristics of epithelial abnormalities within a FA or PT do not necessarily reflect the proliferative status of the surrounding breast tissue.