α-Methylacyl-CoA racemase: a useful immunohistochemical marker of breast carcinoma with apocrine differentiation.

Carcinoma with apocrine differentiation is an androgen receptor (AR)-positive subset of triple-negative breast carcinomas. In addition to carcinoma with apocrine differentiation, other AR-positive triple-negative breast carcinomas occur, albeit less frequently. We found that α-methylacyl-CoA racemase (AMACR), also known as P504S, is overexpressed in carcinoma with apocrine differentiation and non-neoplastic apocrine metaplasia. We aimed to evaluate AMACR as a possible marker of carcinoma with apocrine differentiation. We immunohistochemically examined the expression of AMACR in carcinoma with apocrine differentiation and nonapocrine carcinomas and compared it with that of gross cystic disease fluid protein-15 (GCDFP-15). In total, 212 breast carcinomas were evaluated: 39 carcinomas with apocrine differentiation, 28 ductal carcinomas in situ with apocrine morphology (ADCIS), and 145 nonapocrine breast carcinomas. AMACR was expressed in 38 of 39 (97.4%) carcinomas with apocrine differentiation and in 27 of 28 (96.4%) ADCIS, consistent with the expression of GCDFP-15. However, in nonapocrine carcinomas, AMACR expression was observed in 32 of 145 (22.0%) lesions, whereas GCDFP-15 expression was observed in 91 of 145 (62.7%) lesions. For carcinoma with apocrine differentiation, AMACR was as sensitive as GCDFP-15 (both 97.1%) but more specific (77.9% versus 37.2%). In selected cases, AMACR messenger RNA (mRNA) levels were quantitatively determined relative to that of TATA-binding protein mRNA, and they comprised 5.23, 1.33, and 0.60 for carcinomas with apocrine differentiation, nonapocrine carcinomas, and normal breast tissue, respectively. CONCLUSION: Our findings demonstrate that AMACR expression may be used for differentiating carcinoma with apocrine differentiation from nonapocrine carcinomas and indicate that AMACR is a more sensitive carcinoma with apocrine differentiation marker than GCDFP-15.

Multicenter Prospective Study of Color Doppler Ultrasound for Breast Masses: Utility of Our Color Doppler Method.

The use of color Doppler ultrasound (CD) for distinguishing between benign and malignant breast lesions remains controversial. This study (JABTS BC-04 study) was aimed at confirming the usefulness of our CD diagnostic criteria. We evaluated ultrasound images of 1408 solid breast masses from 16 institutions in Japan (malignant: 839, benign: 569). Multivariate analysis indicated that vascularity (amount of blood flow), vascular flow pattern ("surrounding marginal flow" or "penetrating flow") and the incident angle of penetrating flow were significant findings for distinguishing between benign and malignant lesions. However, the sensitivity and specificity of B-mode alone did not improve significantly with CD addition (97.6% → 97.9%, 38.3% → 41.5%, respectively). We explored the causes of these negative results and found that age should have been considered when evaluating vascularity. Simulation experiments suggested that specificity is significantly improved when age is taken into consideration (38.3% → 46.0%, p < 0.001) and we thereby improved our diagnostic criteria.

A multicenter, observational study of metastatic breast cancer patients who were treated with eribulin mesylate or taxane-based regimens.

AIM: This multicenter, observational study aimed to investigate the survival benefit of eribulin as well as that of taxane-based regimens in Japanese patients with metastatic breast cancer (MBC) in a real-world setting. METHODS: This study enrolled women with MBC who received eribulin or taxane-based regimens with or without bevacizumab in routine clinical practice from July 2011 to March 2014. Patients were followed until September 2015. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), post-progression survival (PPS) and adverse events. Efficacy findings were adjusted according to demographics. RESULTS: In total, 216 patients receiving eribulin monotherapy (n = 101), taxane monotherapy (n = 73) or taxane plus bevacizumab (n = 42) were followed for a median time of 15.4 months. Median OS, PFS and PPS were 22.3, 8.1 and 14 months in the eribulin monotherapy group; 13.2, 3.6 and 7.6 months in the taxane monotherapy group; and 12.9, 5.7 and 6.3 months, in the taxane plus bevacizumab group, respectively. The incidence of neutropenia was 67.3, 41.1 and 16.7%, and the incidence of grade 4 neutropenia was 1.0, 8.2 and 7.1% in the eribulin monotherapy, taxane monotherapy and taxane plus bevacizumab groups, respectively. One patient (1.0%) discontinued eribulin and 18 patients (15.7%) discontinued taxane-based regimens because of adverse events. CONCLUSION: In Japanese MBC patients in a real-world setting, eribulin showed a survival benefit and tolerability similar to that in previous reports.

Ultrasound Image Classification of Ductal Carcinoma In Situ (DCIS) of the Breast: Analysis of 705 DCIS Lesions.

The Japan Association of Breast and Thyroid Sonology (JABTS) proposed, in 2003, a conceptual classification system for non-mass abnormalities to be applied in addition to the conventional concept of masses, to facilitate detecting ductal carcinoma in situ (DCIS) lesions. The aim of this study was to confirm the utility of this system and to clarify the distribution of these findings in DCIS lesions. Data on 705 surgically treated DCIS lesions from 16 institutions in Japan were retrospectively reviewed. All 705 DCIS lesions could be classified according to the JABTS classification system. The most frequent findings were hypo-echoic areas in the mammary gland (48.6%), followed by solid masses (28.0%) and duct abnormalities (10.2%) or mixed masses (8.1%). Distortion (1.3%), clustered microcysts (1.4%) and echogenic foci without a hypo-echoic area (2.5%) were uncommon. These results suggest that the concept of non-mass abnormalities is useful in detecting DCIS lesions.

Educational program and testing using images for the standardization of breast cancer screening by ultrasonography.

BACKGROUND: To improve the quality of breast cancer screening by ultrasonography, both effective training and evaluation of the performance of the examiners of breast ultrasound are essential. METHODS: The Educational Committee of the Japan Association of Breast and Thyroid Sonology, an NPO, has established 2-day training programs on breast ultrasonography with tests at the end of the programs. The tests are performed using images to evaluate the ability of observers to detect and evaluate lesions on ultrasound. Ability to detect lesions was examined by using videos, and ability to evaluate lesions was examined by using still images. The results of tests taken by 422 physicians and 415 technologists were analyzed. RESULTS: In a comparison between physicians and technologists, the video specificity, the still image sensitivity, and the percentage of category agreement did not show any significant differences. The video sensitivity, the still image specificity, and the percentage of disease name agreement were significantly higher in technologists. Observers who had experienced <100 cases showed significantly poorer results in all subjects except for the video specificity in physicians and the still image specificity in technologists. CONCLUSIONS: Ultrasound technologists perform as well as physicians in recognizing and interpreting cancers on breast ultrasound, which supports their role in performing the initial screening examination.

A patient with diabetes and breast cancer in whom virilization was caused by a testosterone-producing mature cystic teratoma containing a Brenner tumor.

A 74-year-old woman with impaired glucose tolerance exhibited virilization. An examination of various hormone levels showed normal pituitary hormone and adrenal hormone levels. However, the patient's blood testosterone level was remarkably high and was suspected of having caused the virilization. An abdominal computed tomography revealed a multilocular cystoma in the left ovary with the features of a mature cystic teratoma. In addition, a chest computed tomography revealed the presence of a mass in the left breast that was subsequently diagnosed as breast cancer based on the results of a biopsy. After the simultaneous surgical resection of the ovarian and breast tumors, her blood testosterone level decreased. The mature cystic teratoma containing a Brenner tumor was considered to be responsible for the high testosterone level because of the presence of androgenic enzymes. This case is extremely rare, but the case was accurately diagnosed through a comprehensive analysis.

Concepts, rationale, and current outcomes of less invasive surgical strategies for early gastric cancer: data from a quarter-century of experience in a single institution.

Previously proposed criteria of less invasive surgery for early gastric cancer (EGC) were based mainly on the pathological analyses of the resected specimens; however, preoperative and intraoperative information are also obviously essential for decision making on stage-dependent patient management. Furthermore, most indications and treatment options have not been systematically integrated or evaluated by treatment outcomes. We investigate in this report the rationality of less invasive surgery employed for EGC. Distribution analyses of positive nodes were investigated among 684 patients with primary solitary EGC (379 mucosal and 305 submucosal) who underwent curative resection between 1976 and 2000. Clinicopathological factors highlighted and analyzed included clinical (preoperative and intraoperative) and pathological (postoperative) cancer depth and nodal involvement, gross form, histological type, and maximum cancer diameter, as well as postoperative morbidity and mortality. The scope of lymphadenectomy can be reduced to a modified D1 for clinically mucosal, node-negative, nonpalpable gastric cancer, or for clinically submucosal, node-negative gastric cancer < or = 1.5 cm for intestinal type, or < or = 1.0 cm for diffuse type. Otherwise, a modified D2 lymphadenectomy is sufficient. Local resection can be recommended for clinically mucosal, node-negative gastric cancer without apparent ulceration < or = 4 cm if adjacent lymph nodes are proved cancer negative by a frozen section examination. If the gastric cancer has spread beyond the above criteria, a pylorus-preserving gastrectomy (PPG) can be recommended for tumors located in the middle or lower third of the stomach, provided the distal margin of the cancer is at least 4.5 cm from the pyloric ring. The PPG can be accompanied by a modified D1 or a modified D2 lymphadenectomy according to the respective dissection criteria. Results of these less invasive strategies showed reduced morbidity and mortality, as well as no recurrence or cancer-related deaths. These results suggest that each of our criteria for less invasive surgery for EGC is realistic, well stratified, and satisfactory.

Accuracy of linear-array EUS for preoperative staging of gastric cardia cancer.

BACKGROUND: The feasibility of a less invasive operation for early stage cancer of the gastric cardia with a low frequency of lymph node involvement has been previously demonstrated by us. Precise discrimination among mucosal, submucosal, and advanced cancers, as well as accurate evaluation of the proximal tumor margin are prerequisites for such stage-specific treatment. EUS is considered the most reliable staging modality. However, there is no EUS study specifically of cardia cancer. METHODS: Forty-five patients with gastric cardia cancer who underwent gastrectomy with at least first-tier lymphadenectomy were retrospectively analyzed. The results of preoperative linear-array echoendoscopy (7.5 MHz) with respect to cancer depth, lymph node involvement, and esophageal invasion were compared with postoperative histopathologic findings. RESULTS: Overall diagnostic accuracy for depth of invasion was 71%. Sensitivity for T1, T2, and T3 lesions was 100%, 31% and 75%, respectively. Overstaging of T2 cancers was the main diagnostic error. Mucosal (pT1-m) and submucosal (pT1-sm) cancers were correctly discriminated in 81% of patients. Diagnostic accuracy for lymph node involvement was 80%. EUS had positive and negative predictive values of 90% and 80%, respectively, for esophageal invasion. CONCLUSIONS: For gastric cardia cancer, the linear-array echoendoscope yielded satisfactory results with respect to depth of invasion, lymph node involvement, and esophageal invasion evaluation. The information obtained is useful to the performance of stage-specific treatment.

Diabetic mastopathy in an advanced elderly woman with insulin-dependent type 2 diabetes mellitus.

Diabetic mastopathy is an unusual stromal fibrotic lesion, but typically occurs in long-standing insulin dependent and younger diabetic patients. We report a case of diabetic mastopathy in an older diabetic patient. The patient was a 76-year-old woman with a history of type 2 diabetes mellitus for 13 years and 3 years of insulin treatment. She developed a 3 cm, hard, mobile nodule in the left breast. Mammography revealed a dense mass. Ultrasonography showed an irregular-shaped hypoechoic lesion with an unclear boundary and acoustic shadowing. Since fine needle aspiration biopsy delivered insufficient material and core needle biopsy did not yield any specific findings for diagnosis, clinically diabetic mastopathy was the prime suspect but breast cancer could be completely ruled out. Surgical excision was thus performed and diabetic mastopathy was confirmed pathologically. We report on this rare case of diabetic mastopathy in a 76 year-old type 2 diabetic patient.

Indications of a minimized scope of lymphadenectomy for submucosal gastric cancer.

BACKGROUND: A recent trend for less invasive surgery has increased consideration for a minimized scope of lymphadenectomy for submucosal cancer; however, feasibility criteria have not been precisely established. METHODS: Patterns and sites of nodal involvement were retrospectively investigated in 294 patients with solitary submucosal gastric cancer in association with other clinicopathologic characteristics, including pre- and intraoperative evaluations of cancer depth (cT) and nodal involvement (cN). RESULTS: Among the early (cT1) and node-negative (cN0) cancer, intestinal (< or =1.5 cm) and diffuse types (< or =1.0 cm) of submucosal cancer showed low incidences of nodal involvement (3%) confined to the first tier. When the cancer exceeded these cutoff diameters, positive nodes of the second tier were confined to three priority stations (left gastric, common hepatic, and celiac arteries) at an incidence of 2.3%. Perigastric and preferential dissection of these three node stations (modified D2 dissection) showed survival benefits identical to those of a conventional D2 dissection. CONCLUSIONS: When submucosal cancer is evaluated as cT1cN0, a virtually sufficient minimized scope of lymphadenectomy is a D1 dissection for that within the cutoff diameter and a modified D2 dissection for that exceeding the cutoff diameter. These two types of dissection can even cover the infrequently observed node-positive stations and can realize no residual disease at surgery.