We report a case of mucinous cystadenocarcinoma (MCA) of the breast in a 96-year-old woman. This is an extremely rare variant of primary breast carcinoma that bears a striking resemblance to MCAs of the ovary and pancreas. The macroscopic appearance and secretion pattern (cytologic findings) resembled cystic hypersecretory carcinoma. However, microscopically, the epithelial cells were quite different from those of cystic hypersecretory carcinoma. In the present study as well as in the literature, MCAs tend to occur more frequently in elderly women. Immunohistochemical findings suggest that they may develop independently of estrogenic stimulation. Although MCAs show high proliferative activity, the prognosis was favorable in the present case as well as in the reported cases. Because MCAs appear to have a distinct pathogenesis and biologic behavior, they should be distinguished from ordinary mucinous carcinomas, cystic hypersecretory carcinomas, and carcinomas of other histologic subtypes.

Mucinous cystadenocarcinoma (MCA) is an unusual variant of primary breast carcinoma that bears a striking resemblance to MCAs of the ovary and pancreas. To our knowledge, only 6 cases of MCA of the breast have been reported.1–3 We report the case of a 96-year-old woman with MCA, along with the cytologic findings, immunohistochemical studies, and literature reviews that were associated with this case.

A 96-year-old woman presented with a 5-year history of a nodule, measuring 2 cm in diameter, immediately beneath the areola of the left breast. Conglomerated nodes, up to 6 cm in diameter, were located in the left axilla. Fine-needle aspiration cytology was performed on the breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells. A lumpectomy with a lymphadenectomy was performed at the Department of Surgery, Tokyo Metropolitan Geriatric Medical Center. No other treatment was given. The patient had no history of a concurrent or subsequent ovarian or pancreatic carcinoma or an invasive malignancy at any site. The patient died of senescence 46 months later, at the age of 100, without any symptom of recurrence.

Alcohol-fixed, direct smears from the breast nodule were stained with Papanicolaou stain.

The tissue was fixed in 10% buffered formalin and embedded in paraffin for routine histology. In addition, immunostaining with estrogen receptor-α (ER-α; clone 1D5, Dako Corporation, Carpinteria, Calif), estrogen receptor-β (ER-β; rabbit polyclonal, MYEB,4 supplied by M.Y.), progesterone receptor (PR; clone 1A6, Dako), androgen receptor (clone AR27, Novocastra Laboratories Ltd, Newcastle, United Kingdom), MIB-1 (clone MIB-1, Dako), P53 (clone DO-7, Novocastra), and c-Erb-B2 (rabbit polyclonal, Dako) was performed using standard immunohistochemical techniques with appropriate controls.

Atypical columnar cells with abundant clear cytoplasm were present in sheets or nests or as single cells, floating in the abundant, intensely stained, orange–to–gray-green material (Figure 1). Mitoses were observed. Necrotic material admixed with neutrophils and erythrocytes was present in the background.

Figure 1.

Fine-needle aspiration: atypical columnar cells with abundant clear cytoplasm present singly or in sheets or nests. Abundant, intensely stained, orange–to–gray-green material is seen in the background (Papanicolaou, original magnification ×125; inset, ×150). Figure 2. Gross appearance: cut surface showing cystic spaces filled with mucinous material beneath the areola and a white solid area. Figure 3. Microscopic appearance: cyst walls showing epithelial tufts or papillary proliferations with delicate fibrovascular cores (hematoxylin-eosin, original magnification ×150). Figure 4. Squamoid appearance: cells with more atypia and abundant eosinophilic cytoplasm (hematoxylin-eosin, original magnification ×300)

Figure 1.

Fine-needle aspiration: atypical columnar cells with abundant clear cytoplasm present singly or in sheets or nests. Abundant, intensely stained, orange–to–gray-green material is seen in the background (Papanicolaou, original magnification ×125; inset, ×150). Figure 2. Gross appearance: cut surface showing cystic spaces filled with mucinous material beneath the areola and a white solid area. Figure 3. Microscopic appearance: cyst walls showing epithelial tufts or papillary proliferations with delicate fibrovascular cores (hematoxylin-eosin, original magnification ×150). Figure 4. Squamoid appearance: cells with more atypia and abundant eosinophilic cytoplasm (hematoxylin-eosin, original magnification ×300)

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Gross inspection revealed a well-demarcated multilocular cystic tumor containing mucinous material beneath the areola. White firm areas were also present within the lesion (Figure 2). Microscopically, variably sized cystic spaces lined by columnar mucinous cells were observed near the nipple, just adjacent to the nonneoplastic mammary duct, expanding beneath the areola. An in situ carcinoma was not present in sections of the breast tissue outside the tumor mass. Cyst walls showed epithelial tufts or papillary proliferations with delicate fibrovascular cores (Figure 3). The degree of cytologic atypia was highly variable; some areas showed a bland mucinous epithelium with basally placed nuclei and abundant intracytoplasmic mucin, while others displayed more severe nuclear atypia with mucin depletion. Up to 3 mitotic figures per high-power field were seen in the most mitotically active part of the tumor. The mucinous cell type was transformed to one with more atypia and abundant eosinophilic cytoplasm, resulting in a squamoid appearance (Figure 4).2 A squamoid appearance was more prominent in a focal area of the metastatic tumor in the left axillary lymph node, which was mainly composed of mucinous cystic elements. Immunohistochemically, the tumor cells were negative for ER-α, ER-β, PR, and androgen receptor. MIB-1 (Ki-67)–positive cells were frequent, and an MIB-1 index of 35% was present in some areas. Strong p53 immunoreactivity was occasionally observed in scattered cells and was present in up to 5% of the cells in some areas. The tumor was completely negative for c-Erb-B2.

Unlike MCAs in the ovary and pancreas, MCAs as primary breast carcinomas are extremely rare. A review of the literature revealed only 6 cases of this histologic type,1–3 and the clinical features of these and of the present case are summarized in the Table. Because of this rarity, the possibility of metastasis from other organs is a subject for debate in the literature.2,3 In those studies, immunostaining showed MCAs to be cytokeratin 7 positive and cytokeratin 20 negative. This staining pattern is common in breast tumors and uncommon in ovarian or gastrointestinal tumors, suggesting that such tumors originate in the breast. In the present case, the patient had no symptom of carcinoma in the abdomen or at any other site up to her death, which was 4 years after the operation for the breast carcinoma. If there had been any primary site other than the breast, signs and symptoms associated with such a site should have become apparent in the 4 years between the removal of the breast tumor and the patient's death, since no treatment other than surgery was given. The clinical course strongly suggests that the breast was the primary site in the present case. The tumor seemed to originate from the main mammary duct, given its close association with the nipple.

Summary of Clinical Features of Previously Reported Cases and the Present Case*

Summary of Clinical Features of Previously Reported Cases and the Present Case*
Summary of Clinical Features of Previously Reported Cases and the Present Case*

A review of the literature reveals that the age at diagnosis ranges from 49 to 96 years, with a mean of 68 (Table). Most of the cases were in postmenopausal women, and 3 cases were in women older than 70 years. Similar to what Koenig and Tavassoli2 previously reported, we found the tumor cells negative for ER-α and PR in this case, suggesting that MCAs of the breast develop independently of estrogenic stimulation. This may partly account for the average age at diagnosis being higher for MCAs than for usual invasive ductal carcinomas. In addition, the tumor cells were negative for ER-β and androgen receptor in our case.

Mitoses and MIB-1–positive cells were frequently observed in the present case. MIB-1 positivity, along with ER-α negativity and PR negativity,2,3 has also been reported for MCAs. Although these findings are usually considered poor prognostic factors, most of the MCA cases have been lymph node negative, and patients have been free of recurrence during the follow-up period (up to 9 years) in the literature.1–3 In the present case, metastasis was observed in the left axilla; however, the patient was free of recurrence for 4 years before her death. Despite the high proliferative activity and metastatic potential, the prognosis seems favorable since no patient has died of the disease thus far (Table). However, more cases and longer follow-ups are needed to establish the natural course of the disease.

Ordinary mucinous carcinomas are also described more frequently in elderly women (mean age, 65 years);5 however, ER-α and PR are frequently expressed in mucinous carcinomas.6 MCAs probably have a pathogenesis that is different from those of ordinary mucinous carcinomas.

The gross appearance of MCA resembles that of cystic hypersecretory carcinoma.1 The comprehensive cytologic features of MCA have not yet been reported. Abundant, intensely stained, orange–to–gray-green secretions can also be seen in cytologic preparations from cystic hypersecretory carcinomas.7,8 However, the tall columnar cells with abundant cytoplasm found in MCAs are not a feature of cystic hypersecretory carcinomas.7,8 ER-α and PR are frequently expressed in cystic hypersecretory carcinoma.9 Finally, the age at diagnosis is higher for MCAs (mean, 68 years) than for cystic hypersecretory carcinomas (mean, 56 years).10 

Because MCA is an extremely rare variant of breast carcinoma, some cases may have been misclassified as mucinous carcinoma, cystic hypersecretory carcinoma, or another histologic subtype. Since MCAs appear to have a distinct pathogenesis and biologic behavior, they should be distinguished from other histologic subtypes of breast carcinoma. The study of additional cases and longer follow-ups will be necessary for a better definition of the nature of the disease.

The authors thank the following pathologists who contributed to this paper: Futoshi Akiyama, MD (Department of Breast Pathology, Cancer Institute, Tokyo, Japan), and Motoji Sawabe, MD, and Tomio Arai, MD (Department of Pathology, Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan). This work was partly supported by the 18th Research Grant in Medical and Health Science from the Meiji Life Foundation of Health and Welfare.

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Author notes

Reprints: Naoko Honma, MD, Human Tissue Research Group, Tokyo Metropolitan Institute of Gerontology, Sakaecho 35-2, Itabashi-ku, Tokyo 173-0015, Japan ([email protected])