Purpose: To investigate the relationship between the tumor size of breast cancer by palpation and the sensitivity of mammography (MMG) and ultrasonography (US), and which modality can detect nonpalpable breast cancer in women aged 30 to 39 years.
Methods: We retrospectively evaluated the tumor size by palpation, breast density, and the sensitivity of MMG and US in 165 patients aged 30 to 39 years. Palpation, US, and MMG were performed with prior knowledge of the results of other modalities. The tumor size on palpation were classified into Tnp; nonpalpable, T1p; 2 cm or less, T2p; more than 2 cm, but not more than 5 cm, and T3p; more than 5 cm.
Results: Of 165 patients, 147 patients (89%) showed mammographically dense breasts. Of 165 cancers, 14 (8%) were Tnp, 40 (24%) were T1p, 82 (50%) were T2p, and 29 (18%) were T3p. The sensitivity of MMG was 57% (8 of 14) for Tnp, 78% (31 of 40) for T1p, 90% (74 of 82) for T2p, and 97% (28 of 29) for T3p. The sensitivity of US was 43% (6 of 14) for Tnp and 100% for palpable cancers. Of 14 nonpalpable cancers, 4 (29%), 4 (29%), and 2 (14%) could be detected by only MMG, bloody nipple discharge, and US.
Conclusions: The sensitivity of MMG depends on the tumor size on palpation in this age range. MMG fails to detect relatively large palpable cancers. On the other hand, US can detect all palpable cancers. However, the sensitivity of US declines for nonpalpable cancers. For the detection of nonpalpable cancers, MMG, US, and nipple discharge are complementary modalities.

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Background: Positron emission tomography (PET) is a non-invasive imaging modality used in the diagnosis and staging of breast cancer. However, several factors can affect fluoro-deoxyglucose (FDG) uptake by a tumor. To clarify the parameters that most affect FDG accumulation in tumors, the relationship between standardized uptake values (SUVs) and clinicopathological factors and immunohistopathological analysis was investigated in breast cancer.
Material and Methods: PET studies were performed preoperatively on 37 patients with breast carcinoma. SUVs were counted at one hour (early phase) and at two hours (delayed phase) after FDG injection. The relationships between SUVs and 13 clinical, pathological and immunohistchemical factors were studied.
Results: A significant association was found between FDG accumulation and early and delayed phase mitotic counts (p=0.0018 and 0.0010, respectively), Ki67 positive cell percentage (p=0.0098 and 0.0062, respectively), and nuclear grade (p=0.0232 and 0.0195, respectively). On the other hand, nodal status weakly correlated with the delayed phase (p=0.0907). However, other clinicopathological parameters and immunohistopathological status, which included tumor size, age, histology, estrogen receptor, progesterone receptor and Her2/neu overexpression, did not correlate significantly with FDG uptake.
Conclusion: Mitotic count and Ki67 reflect cellular aggressiveness. These parameters were strongly correlated with tracer uptake. Thus our data suggested that the biological behavior of breast cancer is reflected in the variation of FDG uptake by the tumor. However, whether FDG uptake is a true prognostic and predictive factor remains to be confirmed in larger studies over an extended period of time.

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Background: It is hypothesized that breast cancer may consist of heterogeneous diseases with different hormonal environments classified by hormone receptor status. Epidemiologic studies evaluating risk factors for breast cancer by hormone receptor status have supported the hypothesis. However, there are inconsistencies in the risk factor profiles by estrogen receptor (ER) and progesterone receptor (PR) across the studies. To clarify the heterogeneity of the disease, it is necessary to understand not only risk factor profiles but also the biologic characteristics such as the relationships among endogenous sex hormone levels and hormone receptors.
Methods: We measured serum levels of estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) in 142 postmenopausal women aged 50 and over with primary breast cancer who had undergone surgical treatment, and investigated the heterogeneity in the relations of endogenous sex hormone levels to hormone receptor status, using the case-series study method. Subjects were categorized into 3 classes based on tertiles of each hormone level in receptor-negative subjects, and odds ratios (ORs) for receptor-positive status compared with receptor-negative status were computed, taking the lowest category as a reference category.
Results: There were clear trends toward higher serum levels of E1, E2, and DHEAS in women with PR+ cancer. The case-series approach revealed that PR+ status might be strongly associated with serum sex hormone levels. In particular, the OR of PR+ was large for a high DHEAS level (OR for the highest category=4.28). No significant association between serum hormone levels and ER status was observed.
Conclusion: The association of serum sex hormone levels with hormone receptor status may differ by PR status, but not by ER status. This finding suggests that PR status may be related to the heterogeneity in hormonal environments associated with breast cancer risk.

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Background: Scirrhous carcinoma has been known to have more aggressive biological behavior than other histologic subtypes of invasive ductal carcinoma of the breast. The significance of expression of p27kip1, which is thought to be a tumor suppressor gene, in breast carcinoma remains controversial. The aim of the current study was to clarify clinicopathologic significance of scirrhous carcinoma of the breast with special reference to p27 expression.
Methods: Clinicopathologic features including immunohistochemical expression of p27 were compared between scirrhous carcinoma (n=42) and non-scirrhous invasive ductal carcinoma (papillotubular and solid-tubular carcinoma, n=63) of the breast.
Results: The proportion of pathologic lymph node metastasis among scirrhous carcinomas was significantly higher than that among carcinomas of other histologic types (papillotubular or solid-tubular carcinomas, p=0.029). The proportion of strong expression of p27 among scirrhous carcinomas was significantly lower than that among tumors of other histologic types (p<0.0001).
Conclusions: Biological behavior of scirrhous carcinoma was found to be aggressive. The aggressiveness and poor cellular differentiation of scirrhous carcinoma of the breast might be related to low p27 expression.

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Background: Patients with mammograms showing architectural distortion often have an invasive carcinoma with noticeable fibrosis, such as scirrhous carcinoma or invasive lobular carcinoma. However, architectural distortion is also seen in some cases of ductal carcinoma in situ (DCIS).
Methods: Of the 316 patients operated on in our hospital from October 2003 to June 2004, 54 were histopathologically diagnosed as having DCIS (excluding cases with microinvasion). Of these 54 patients, 5 exhibited architectural distortion on the preoperative mammogram. The aim of this study was to correlate the radiologic and pathologic features of DCIS showing architectural distortion on the mammogram.
Results: The mammograms of the 5 patients revealed clusters of calcifications in the architectural distortion. Sclerosis was seen in the interstitium around the DCIS in 3 cases, and DCIS components were found in Cooper's ligament in 4 cases. In 2 cases, sclerosing adenosis was seen in the background of the DCIS.
Conclusion: It is generally accepted that architectural distortion in DCIS is due to sclerosing adenosis, but sclerosis in the interstitium around the DCIS and presence of DCIS components in Cooper's ligament proved to be the cause of architectural distortion in the cases described here. Since architectural distortion is also seen in DCIS cases, we think that besides the diagnosis of malignancy, the presence or absence of infiltration should be histopathologically established before surgery.

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Background: Since microcalcifications classified as category 3 on mammography include not only malignant lesions but also benign lesions, it is difficult to decide whether stereotactic vacuum-assisted breast biopsy (Mammotome®, MMT) should be performed or the patient should merely be follows. The purpose of this study is to adequately diagnose microcalcifications classified as category 3 and to formulate a correct clinical policy. In addition, we examined the characteristics of the calcifications.
Methods: This study included 51 patients who underwent MMT from July 2003 to October 2004. All the cases were evaluated as category 3, and no abnormal findings were detected on ultrasonography. We classified the pattern of calcifications based on three aspects: 1. density and size, 2. pleomorphic appearance 3. number of calcifications per square centimeter.
Results: Of the 51 patients, 14 were histologically diagnosed with ductal carcinoma in situ (DCIS). Heterogeneity in the density and size were observed in 9 of 14 patients (64.3%). The calcifications had a pleomorphic appearance in 6 of 14 patients (42.9%). A large number of calcifications (20/cm²) were observed in 8 of 14 patients (57.1%). Better examination characteristics were obtained with heterogeneity in density and size (AUC=0.72 95%C.I: 0.56-0.89) compared with pleomorphic appearance and the number of calcifications per square centimeter. The potential for malignancy was an average of 6 times higher for calcifications with heterogeneity in density and size compared to that for calcifications which were homogeneous in these aspects.
Conclusion: Attention should be paid to prevent unnecessary mammotome procedures. Heterogeneity in the density and size of calcifications is a reliable criterion for clinical decision-making.

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Background: The Mammotome is a diagnostic tool used under stereotactic or with ultrasound guidance. A clear indication for Mammotome use under stereotactic guidance is when a non-palpable microcalcification is a target. However, the indications for the use of the Mammotome under ultrasound guidance vary among institutions, and it is difficult to find a place for the Mammotome among conventional biopsy techniques. The Mammotome biopsy has been available in our hospital since July 1999. We assessed the effectiveness and indications of ultrasound-guided Mammotome biopsy.
Methods: We performed Mammotome biopsies in 433 cases requiring histological diagnosis from July 1999 to September 2006, using an 11-gauge articulated arm-type Mammotome under ultrasound guidance. There were 377 mass lesions including 83 non-palpable cases and 56 hypoechoic lesions.
Results: The indications for Mammotome biopsy were 162 cases with inconsistent fine needle aspiration (FNA) and imaging findings, 114 cases indeterminate by FNA, 68 cases of an identified pathological type before neoadjuvant chemotherapy and confirmation of hormone receptor status, 36 inadequate cases by FNA, 20 cases of confirmation of fibroadenoma and other benign tumors, 8 removal cases of fibroadenoma, 8 microcalcification cases, and 17 others. The target lesion was obtained in 99.5% of the cases.
Conclusions: Ultrasound-guided Mammotome biopsy is an accurate and useful diagnostic method that enables sufficient amounts of tissue to be obtained with minimal invasion and few complications. The Mammotome is the first choice for obtaining a definitive pathological diagnosis in breast lesions.

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A 32-year-old woman underwent modified radical mastectomy for right breast cancer (invasive ductal carcinoma, f, INF β, v0, ly1, pT2, pN1, M0, Stage II B ER (±), PR (-), Her2 (3+)) in June 2003, and received postoperative systemic adjunctive chemotherapy using epirubicin combined with cyclophosphamide, followed by paclitaxel. In August 2004, after a disease-free interval of 14 months, liver metastasis appeared, and therefore from September 2004, combination chemotherapy with oral capecitabine (2,400 mg/day) and injected trastuzumab (120 mg/week) was started. After 3 cycles, all the metastases responded and this marked response has been maintained for 16 months. This therapy is currently being continued (19 cycles), and no serious side effects have been encountered.
Capesitabine and trastuzumab combination therapy is effective for recurrent breast cancer showing overexpression of HER2 and resistance to taxane, and can be considered as a first-line therapy for this purpose. It is anticipated that many cases treated with this regimen will be reported and discussed in the near future.

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We report here a rare form of invasive ductal carcinoma composed of a mass protruding from the tip of the nipple in a 43-year-old woman with hyperprolactinemia. She had been amenorrheic for 15 years following an incomplete pituitary adenomectomy for prolactinoma. She presented with a mass on the left nipple that had been growing for 6 months. Morphologically, the mass resembled adenoma of the nipple. Another mass was located in the subareolar region. She underwent mastectomy after invasive ductal carcinoma was diagnosed. Histopathologically, the tumor of the nipple was invasive ductal carcinoma, which had extended intraductally from another invasive ductal carcinoma in the subareolar region, and had infiltrated the epidermis of the nipple (Paget's disease). MR mammography successfully detected the relationship between the tumors. Postoperatively, the plasma prolactin level was abnormally high, while the plasma estradiol level was quite low, although macro-pituitary adenoma was not detected by MRI. The patient was treated with bromocriptine mesilate, in addition to adjuvant chemotherapy for breast cancer, and the plasma prolactin level has since normalized.

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Clear cell hidradenoma of the breast is rare. A 55-year-old woman demonstrated a left breast tumor during follow-up examination of the right breast. Focal asymmetric density was shown on mammogram, and ultrasonography showed an intracystic tumor. Since the diagnosis was not clear on aspiration cytology, excisional biopsy was performed. The lesion was an intracystic tumor macroscopically. Histological examination demonstrated characteristic histological features of clear cell hidradenoma, such as proliferation of uniform epithelial cells, clear or slightly eosinophilic cytoplasm, and cuboidal cell-lined ductal structures. Immunohistochemically, these proliferating epithelial cells were negative for myoepithelial markers, such as alpha-smooth muscle actin, CD10 and anti-muscle actin, but positive for p63. These features were consistent with clear cell hidradenoma.

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A 39-year-old Japanese woman noticed a right breast tumor in July 2004. Mammography (MMG) demonstrated an oval tumor without calcification. Dynamic Magnetic Resonance Imaging (D-MRI) demonstrated a high-intensity mass on T2-weighted images, showing mild enhancement during the arterial phase and persistent enhancement during the arterial late phase. Core needle biopsy revealed papillary carcinoma suggestive of Intracystic Papillary Carcinoma (IPC). Auchincloss operation was performed following a partial mastectomy, as the surgical margin after partial mastectomy was positive for carcinoma. Histopathologic mapping of her right breast revealed wide and extensive intraductal spread of DCIS around the IPC. IPC was originally reported to be a localized non-invasive mammary carcinoma. But approximately, half of IPC cases are associated with invasive carcinoma or DCIS beyond the tumor. Careful selection of operative procedure is needed after localized non-invasive IPC or IPC associated with DCIS around the main tumor or invasive carcinoma is diagnosed.

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Diffuse large B cell lymphoma (DLBL) of the breast is a rare subtype of breast tumor, the diagnosis of which is based on the cytological and histopathological features of this unique neoplasm. A 28-year-old woman noticed a mass in her right breast. It could not be definitely diagnosed clinically by diagnostic imaging (mammography, ultrasonography), so malignant tumor not otherwise specified was diagnosed. Fine-needle aspiration cytology (FNAC) suggested that it was malignant lymphoma; however it was difficult to distinguish from reactive lymphocytes. Excisional biopsy of the breast mass suggested malignant lymphoma. Based on the diagnosis of malignant lymphoma by FNAC and excisional biopsy, lumpectomy was performed and DLBL was diagnosed histologically according to the World Health Organization classification. DLBL is difficult to distinguish from other types of malignant lymphoma by routine immunohistochemical evaluation. Some previous studies have showed that the octamer-binding transcription factor 2 (Oct2) and coactivator B-cell Oct-binding protein 1 (BOB.1) and the pan-B-cell markers CD20 and CD79a may aid in the diagnosis of malignant lymphoma. In our case, the staining of large atypical lymphocytes for CD20, CD79a, BOB.1 and Oct2 was strongly positive and supports the notion that BOB.1 and Oct2 are also useful immunohistochemical markers for DLBL of the breast.

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Background: Invasive micropapillary carcinoma (IMP) of the breast is uncommon and has only recently been characterized. Knowing the cytological appearance of IMP is important to enable early diagnosis by fine needle aspiration cytology (FNAC). We describe a case of IMP diagnosed by preoperative FNAC.
Case: A 48-year-old menopausal woman presented in 2003 with a mass in her left breast. Mammogram and ultrasound findings indicated that the tumor was malignant. Cytological examination showed papillary clusters of hyperchromatic cells with irregular and crowded nuclei, but lacking papillary cores. No myoepithelial cells were seen. Based on the cytological findings, invasive micropapillary carcinoma was diagnosed. Microscopic findings showed cancer cells with moderate atypia in abundant micropapillary cancer nests without a fibrovascular core. These cancer nests were morula-like, surrounded by empty, clear spaces lined with delicate strands of fibrocollagenous stroma. The polarity of each cancer nest was reversed, with the secretion border facing fibrocollagenous stroma. These pathological features occupied the invasive part of the primary tumor.
Conclusion: The cytologic features of IMP are distinctive and correlate with histology. FNAC of IMP is important role to confirm the diagnosis.

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Carcinoma derived from the lining epithelial cells in malignant phyllodes tumor is a rare neoplasm of the breast and belongs to the category of carcinosarcoma. We report a case of ductal carcinoma with squamous differentiation arising in malignant phyllodes tumor. A 54-year-old woman was admitted with a rapidly enlarging left breast mass. A breast tumor with a diameter of 6 cm was located mainly in the left outer area of the breast. Mammography revealed a high-density mass with an irregular margin and ultrasound showed a cystic tumor. A pathological diagnosis of ductal carcinoma with squamous differentiation was made by fine needle aspiration and a core needle biopsy. She underwent neoadjuvant chemotherapy followed by a modified radical mastectomy with a skin flap. Histopathological examination revealed that the invasive ductal carcinoma with squamous differentiation originated from the lining epithelial cells in malignant phyllodes tumor and that there was no transition area between the carcinomatous and the sarcomatous component. She experienced lung and facial bone metastases, microscopic features of which were consistent with the sarcomatous component of the original breast carcinosarcoma. This is an extremely rare case of carcinosarcoma and the histopathological findings and review of the literature are discussed.

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Lobular carcinoma of the breast is known to metastasize to unusual sites such as the gastrointestinal tract, peritoneum, and gynecologic organs.
We report a patient with intraperitoneal metastases from lobular carcinoma who was originally treated for an unknown primary cancer.
Ten years later, a tumor was found in her left breast and the diagnosis was changed to peritoneal metastases from invasive lobular carcinoma. Immunohistochemistry revealed that the metastases were high molecular weight cytokeratin (CK34betaE12) and estrogen receptor-positive, but were E-cadherin-negative. These results assisted in diagnosis. Surgeons should be aware of the characteristics of metastasis lobular carcinoma.

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We report a case of nodular fasciitis of the breast, which is a rare histological type of breast tumor. A 41-year-old woman had noticed a mass in her right breast. The mass was elastic-hard, 15 mm×15 mm in size, and located mainly in the upper outer quadrant of the right breast. Mammography demonstrated an oval dense mass with spiculation. Ultrasonography revealed a hypoechoic lesion, 8 mm×10 mm in size. Fine needle aspiration cytology and core needle biopsy showed no evidence of malignancy. Excisional biopsy was performed. The tumor was characterized by a proliferation of fibroblastic cells. Histologically, the excised tumor was consistent with nodular fasciitis of the breast. Nodular fasciitis should be considered in the differential diagnosis of a mass suspicious for breast cancer.

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