Breast carcinoma with osteoclastic giant cells (OGCs) is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1) had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2) with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K) and a histiocyte marker (CD68), but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.

Background: Axillary lymph node dissection is an important procedure in the surgical treatment of breast cancer. Axillary lymph node dissection is still performed in over half of breast cancer patients having histologically negative nodes, regardless of the morbidity in terms of axillary pain, numbness and lymphedema. The first regional lymph nodes draining a primary tumor are the sentinel lymph nodes. Sentinel node biopsy is a promising surgical technique for predicting histological findings in the remaining axillary lymph nodes, especially in patients with clinically node-negative breast cancer, and a worldwide feasibility study is currently in progress. Methods: Intraoperative lymphatic mapping and sentinel node biopsy were performed in the axilla by subcutaneous injection of blue dye (indigocarmine) in 88 cases of stage 0-IIIB breast cancer. Sentinel lymph nodes were identified by detecting blue-staining lymph nodes or dye-filled lymphatic tracts after total or partial mastectomy. Finally, axillary lymph node dissection was performed up to Levels I and II or more. Results: Sentinel lymph nodes were successfully identified in 65 of the 88 cases (74%). In the final histological examination, the sentinel lymph nodes in 40 cases were negative, including four cases with non-sentinel-node-positive breast cancer (specificity, 100%; sensitivity, 86%). In nine (31%) of the 29 cases with histologically node-positive breast cancer, the sentinel lymph nodes were the only lymph nodes affected. Axillary lymph node status was accurately predicted in 61 (94%) of the 65 cases. Conclusions: Although it was the initial experience at the National Cancer Center Hospital East, sentinel node biopsy proved feasible and successful. This method may be a reasonable alternative to the standard axillary lymph node dissection in patients with early breast cancer.

Neoadjuvant endocrine therapy (NAE) has been employed to improve surgical outcomes for hormone receptor-positive breast cancers in postmenopausal women. Endocrine responsiveness is estimated by expressions of hormone receptors, but its heterogeneity has been recognized. Autophagy is an evolutionally conserved process associated with cell survival and cell death and has been implicated in cancer treatment. In order to examine the possible association between autophagy and response to endocrine therapy, we evaluated the status of autophagy-associated markers, beclin 1 and LC3, and apoptosis-associated markers, TUNEL and M30, in pre- and post-treatment specimens from 71 patients in a multicenter prospective study of neoadjuvant exemestane (JFMC34-0601). Immunoreactivity of the autophagy-associated markers, beclin 1 and LC3, in carcinoma cells increased in 14 % and 52 % of the patients, respectively, following the exemestane treatment. These increases were statistically significant (beclin 1, p = 0.016, N = 49; LC3, p < 0.0001, N = 33). The status of M30 immunoreactivity decreased (p = 0.008, N = 47) and TUNEL remained unchanged (N = 53). In addition, tumors with pre-treatment stromal beclin 1 immunoreactivity revealed poor clinical and pathological responses compared with those without stromal beclin 1 immunoreactivity (25 % vs 67 % for clinical response, p = 0.011, N = 51; 0 % vs 41 % for pathological response, p = 0.0081, N = 49). Tumors with positive pre-treatment stromal beclin 1 had a higher baseline Ki-67 labeling index (both hot spot and overall average) than those without (p = 0.042 and 0.0075, respectively, N = 53). Results of logistic regression analyses revealed that stromal beclin 1 was a predictor for clinical and pathological responses while ER, PR, Ki-67, and stromal LC3 expressions were not. Results of our present study demonstrated that beclin 1 and LC3 immunoreactivity increased in carcinoma cells following exemestane treatment and that the status of pre-treatment stromal beclin 1 is associated with higher carcinoma cell proliferation and poor clinical and pathological responses to NAE. UMIN C000000345 (2006/03/06)

We report a case of intracystic papillary carcinoma of the breast in a 62-year-old Japanese man, who came to our hospital complaining of a right subareolar mass. Imaging diagnosis was a cyst with an intracystic component. Since repeated aspiration biopsy cytology was interpreted as a borderline lesion, no additional treatment had been given. Because he wanted the removal of the mass 14 months after his first visit, an excisional biopsy was performed under local anesthesia. Pathological examination revealed the intracystic component to be non-invasive papillary carcinoma. Although the incidence of male breast cancer is ∼1% of all breast cancer, intracystic papillary carcinoma in the male is very rare. From a review of the literature on this disease in Japanese men, an intracystic component can often be demonstrated by ultrasound. However, it is difficult to confirm malignant cells by aspiration biopsy cytology of cyst fluid. Since some cases have a local relapse, excisional biopsy and long-term follow-up are indicated.