Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod.

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.

Cytological features of complex type fibroadenoma in comparison with non-complex type fibroadenoma.

BACKGROUND: To determine the cytomorphological features of complex type fibroadenoma (CFA), we reviewed fine needle aspiration (FNA) cytology with correlation to its histopathology findings, and compared them with non-complex type fibroadenoma (NCFA). METHODS: From excisional biopsy or resected specimens of fibroadenoma (FA) cases treated at our institution from 2004 to 2013, we chose 46 patients who underwent FNA before a diagnosis of FA was established. We histologically re-classified them into two groups: CFA and NCFA. FNA diagnosis was retrospectively re-evaluated from FNA reports. We further re-assessed detailed characteristics of each FNA smears to identify cytomorphological features of CFA. RESULTS: We found that 15 cases fulfilled the diagnostic criteria of CFA, in which 7 (46.7 %) had an FNA diagnosis of "suspicious for malignancy" or "indeterminate" while only 2 NCFA cases had that of "indeterminate" (p = 0.004). FNA smears from CFA cases showed discohesiveness, enlarged nuclei, prominent nucleoli, and fewer myoepithelial cells more often than NCFA. Although no significant difference was noted in patients' age and tumor size between CFA and NCFA, 5 CFA cases (33.3 %) were accompanied by the presence of carcinoma in the same breast or the contralateral breast while no NCFA cases had carcinoma in the breast. CONCLUSIONS: FNA of CFA can lead to erroneous or indeterminate interpretation, due to proliferative and/or hyperplastic changes of ductal epithelium with or without atypia. It is important to recognize the disease entity and characteristic cytomorphological findings of CFA to reach accurate FNA diagnosis of breast lesions.

Characteristics of the Japanese histological classification for breast cancer: correlations with imaging and cytology.

The Japanese histological classification of breast cancer is a unique classification that was published as the 2nd edition of the General Rules for Clinical and Pathological Recording of Breast Cancer in 1971. According to this classification, breast cancers are divided into three subgroups: noninvasive, invasive, and Paget's disease. Invasive carcinomas are further divided into two groups: invasive ductal carcinomas (IDCs) and special types. IDCs are the most common types, representing 70-80 % of all breast cancers, and most of them correspond to invasive carcinoma-not special type-according to the latest WHO classification (4th edition). In particular, IDCs are subdivided into three subgroups as follows: (1) papillotubular carcinoma, which is characterized by the projection of papillae into spaces, and includes cribriform and comedo patterns; (2) solid-tubular carcinoma, which is a solid cluster of cancer cells with expansive growths that form relatively sharp borders; and (3) scirrhous carcinoma, which grows in a scirrhous manner characterized by cancer nests or cells accompanied by marked fibrosis. The concept of subclassification originated in Japan. The Japanese histological classification has taken on important roles since its publication, in particular for comparisons between histology and imaging or cytology.

Diagnostic value of fine needle aspiration and core needle biopsy in special types of breast cancer.

BACKGROUND: Although fine needle aspiration (FNA) biopsy is an established tool to assess breast lesions, there has been a trend toward using core needle biopsy (CNB) instead. The aim of this study was to compare the diagnostic accuracy of FNA and CNB in special types of breast cancer. METHODS: A retrospective review of diagnostic results of pre-operatively performed FNA or CNB, or a combination of the two, was conducted. The cases include histologically proven invasive ductal carcinoma of no special type (NST n = 159), invasive lobular carcinoma (ILC n = 65), mucinous carcinoma (MUC n = 51), and apocrine carcinoma (APO n = 25). RESULTS: The absolute diagnostic sensitivity of FNA to detect malignancy in ILC and APO patients was inferior to that of NST patients (p < 0.001 for ILC and APO). Within each cancer type, the sensitivity of CNB was higher than that of FNA in the ILC and APO patients (p < 0.001 and p < 0.05, respectively). As for NST and MUC patients, FNA and CNB had equivalent sensitivity. The sensitivity of FNA alone significantly improved when combined with CNB in NST, ILC and APO patients (p < 0.05, p < 0.001, and p < 0.05, respectively). CONCLUSIONS: Our results suggest that FNA has less diagnostic accuracy than CNB for ILC and APO; thus, the use of CNB should be encouraged when these types of cancer are clinically suspected or when the initial FNA is inconclusive.

Evaluation of inadequate, indeterminate, false-negative and false-positive cases in cytological examination for breast cancer according to histological type.

BACKGROUND: We previously investigated the current status of breast cytology cancer screening at seven institutes in our area of southern Fukuoka Prefecture, and found some differences in diagnostic accuracy among the institutions. In the present study, we evaluated the cases involved and noted possible reasons for their original cytological classification as inadequate, indeterminate, false-negative and false-positive according to histological type. METHODS: We evaluated the histological findings in 5693 individuals who underwent cytological examination for breast cancer (including inadequate, indeterminate, false-negative and false-positive cases), to determine the most common histological types and/or features in these settings and the usefulness/limitations of cytological examination for the diagnosis of breast cancer. RESULTS: Among 1152 cytologically inadequate cases, histology revealed that 75/173 (43.6%) cases were benign, including mastopathy (fibrocystic disease) in 38.6%, fibroadenoma in 24.0% and papilloma in 5.3%. Ninety-five of 173 (54.9%) cases were histologically malignant, with scirrhous growing type, invasive ductal carcinoma (SIDC) being significantly more frequent (49.5%) than papillotubular growing type (Papi-tub) (P < 0.0001), solid-tubular growing type (P = 0.0001) and ductal carcinoma in situ (DCIS) (P = 0.0001). Among 458 indeterminate cases, 54/139 (38.8%) were histologically benign (mastopathy, 30.0%; fibroadenoma, 27.8%; papilloma, 26.0%) and 73/139 (52.5%) were malignant, with SIDC being the most frequent malignant tumor (37.0%). Among 52 false-negative cases, SIDC was significantly more frequent (42.3%) than DCIS (P = 0.0049) and Papi-tub (P = 0.001). There were three false-positive cases, with one each of fibroadenoma, epidermal cyst and papilloma. CONCLUSIONS: The inadequate, indeterminate, false-negative and false-positive cases showed similar histological types, notably SIDC for malignant tumors, and mastopathy, fibroadenoma and papilloma for benign cases. We need to pay particular attention to the collection and assessment of aspirates for these histological types of breast disease. In particular, several inadequate, indeterminate and false-negative cases with samples collected by aspiration were diagnosed as SIDC. These findings should encourage the use of needle biopsy rather than aspiration when this histological type is identified on imaging. Namely, good communication between clinicians and pathological staff, and triple assessment (i.e., clinical, pathological and radiological assessment), are important for accurate diagnosis of aspiration samples. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7349809170055423.

Immunohistochemical study of metaplastic carcinoma and central acellular carcinoma of the breast: central acellular carcinoma is related to metaplastic carcinoma.

Metaplastic breast cancers (MBCs) [spindle cell carcinoma (SpCC), squamous cell carcinoma (SCC), and matrix-producing carcinoma (MPC)] and invasive carcinomas with central acellular zones (CACs) were analyzed with respect to biological potential by immunohistochemical analyses. Specimens from 40 patients [20 with MBCs (7 with SCC, 6 with SpCC, 5 with MPC, and 2 with mixed type)] and 20 with CACs were analyzed using antibodies to cytokeratin (CK) 8, 5/6, 14, AE1/AE3, 34αE12, involucrin, c-kit, vimentin (VIM), alpha-smooth muscle actin, p63, epidermal growth factor receptor, epithelial cell adhesion molecule, and estrogen receptor (ER)/progesterone receptor (PR)/HER2. Expression of CK5/6, 34ßE12, VIM, nuclear p63, and cytoplasmic p63 was significantly higher with MBCs than CACs (38%/13%, 70%/43%, 85%/33%, 68%/40%, and 48%/18%, respectively). Other markers were expressed at various levels in these tumors, but the difference between them was not significant. Eighteen MBC and 8 CAC cases were triple (ER/PR/HER2) negative; 17 MBCs and 7 CACs were basal-like tumors. Several differences were seen in MBCs and CACs, but they were heterogeneous, differentiating multipotentially into mesenchymal, myoepithelial, basal-like phenotypes with "stem cell-like" features. Thus, CACs are related to MBCs by immunohistochemical analyses as well as according to morphological findings.

Comparison of the accuracy of breast cytological diagnosis at seven institutions in southern Fukuoka Prefecture, Japan.

OBJECTIVE: Cytological examination is inexpensive and relatively simple to carry out and deserves utilization in breast cancer screening. We investigated the status of cytological diagnosis at seven facilities in southern Fukuoka Prefecture, Japan. METHODS: We collected data on the criteria for cytological judgments and status of breast cytological diagnosis at seven different facilities in this region. RESULTS: Among 5693 individuals who underwent breast cytological examination, analyses were conducted on 1250 individuals (22.0%) in whom cytological diagnoses were confirmed by histological diagnoses. Among these patients, cytological diagnosis had an absolute sensitivity of 71.9%, a specificity of 76.0%, a false-negative value of 6.7% and a false-positive value of 0.08%. At three facilities with relatively large numbers of cases (>300), excluding a facility for specialized breast disease, similar trends of high complete sensitivity (94.3, 95.6 and 97.1%, respectively) and low absolute sensitivity (60.4, 74.8 and 57.2%, respectively) were found. No false-negative or false-positive cases were seen in individual facilities with relatively low numbers of cases (<150). CONCLUSIONS: The accuracy of cytological diagnosis at the facilities we surveyed was relatively high compared with the goals of assessment of diagnostic accuracy. However, the performance was dependent on the facility type, i.e. number of cases, staff involved and whether it was specialized or not, making the diagnosis specific for this region. We recommend that management of the accuracy of cytological diagnosis be undertaken jointly by multiple facilities to establish systems in Japan that lead to more useful diagnostic tools.

Roles of fine-needle aspiration and core needle biopsy in the diagnosis of breast cancer.

BACKGROUND: There is controversy regarding which of the two biopsy methods, fine-needle aspiration (FNA) or core needle biopsy (CNB), should be routinely employed for diagnosis of breast cancer. The aim of this study was to evaluate the efficacy of FNA compared to CNB and to explore the value of performing both FNA and CNB. METHODS: Two hundred eighty-one patients with breast cancer received FNA alone (group 1: n = 182), CNB alone (group 2: n = 56), or a combination of FNA and CNB (group 3: n = 43). In group 3, FNA was combined with CNB because of an inadequate smear of FNA on immediate cytological examination. Subsequently, the patients underwent definitive surgery or open surgical biopsy based on the clinical findings, and the tumors were pathologically confirmed to be noninvasive or invasive breast cancer. RESULTS: There was no significant difference in the absolute sensitivity between group 1 (93% for FNA alone) and group 2 (86% for CNB alone). In group 3, on the other hand, the absolute sensitivity was significantly improved to 72% when FNA and CNB were combined (P < 0.05), although it was only 42% for FNA alone and 63% for CNB alone. CONCLUSIONS: The absolute sensitivity of FNA was equivalent to that of CNB when excluding patients who were converted from FNA to CNB based on immediate cytological examination. In the latter patients, however, it was improved by combining FNA and CNB. Therefore, these two techniques should be considered complimentary to one another.

Evaluation of primary prostate cancer using 11C-methionine-PET/CT and 18F-FDG-PET/CT.

OBJECTIVE: The objective of this study was to evaluate the capability of (11)C-methionine (MET)-PET/CT and (18)F-2-deoxy-2-fluoro-D: -glucose (FDG)-PET/CT to diagnose primary prostate cancer using recently developed Gemini TF PET/CT (Philips Healthcare, Cleveland, OH). METHODS: Twenty men who had been referred for a diagnostic work-up for prostate cancer were enrolled in this study. MET- and FDG-PET/CT by high-resolution mode were carried out on the same day prior to prostate biopsy and each maximum standardized uptake value (SUVmax) was compared with the pathological findings. The regions of interest (about 100 mm(2) small round) were placed at standard 6 points of the peripheral zone and 4 points in the apex of the transitional zone in cases that had undergone biopsy of the internal gland. We summed two scores if a specimen had inhomogeneous Gleason scores (e.g. GS 7; 4 + 3) and doubled the score when the Gleason score was the same (e.g. GS 8; 4 × 2). We divided the tumors into three groups. If the summed Gleason score of the specimens was 5 or less, they were grouped as NG (no grade with the Gleason score). If the summed Gleason score was 6 or 7, the tumors were defined as LG (low Gleason score group), and if the summed Gleason score was 8, 9 or 10, the tumors were classified as HG (high Gleason score group). The mean SUVmax was calculated and one-way analysis of variance or Kruskal-Wallis test and the Tukey post hoc test were performed for statistical comparisons. The capabilities of MET and FDG for diagnosing prostate cancer were evaluated through analysis of the area under the curve of the receiver operating characteristic (ROC) curve. The cut-off levels of SUVmax for the highest accuracy were determined by the results of the ROC analysis, and the sensitivity, specificity and accuracy were calculated. RESULTS: The PET images, obtained with Gemini TF PET/CT, allowed visual identification of anatomical locations within the prostate gland. Among the mean SUVmax of MET, FDG early phase and FDG delayed phase, the differences between NG and HG were all statistically significant (P < 0.01). With MET the difference between NG and LG was also significant (P < 0.05). And for the elevation rate from FDG early to delayed phase, the difference between NG and HG was significant (P < 0.05). The cut-off SUVmax, sensitivity, specificity, accuracy for distinguishing between NG and LG + HG by MET, FDG early and delayed phase were 3.15/78.7/75.6/78.3, 2.81/61.7/80.0/70.7 and 3.00/62.8/78.9/70.7, respectively. And the same factors between NG + LG and HG were 3.76/70.1/89.7/82.6, 2.88/70.1/82.9/78.3 and 3.47/62.7/86.3/77.7, respectively. CONCLUSIONS: In terms of the capability to diagnose prostate cancer of high Gleason score (≥8), there was no significant difference between MET and FDG. MET appears to be useful for detecting prostate cancer of both low and high Gleason score.

FDG-PET/CT in the diagnosis of recurrent breast cancer.

BACKGROUND: An advantage of PET/CT has been demonstrated for diagnosis of several tumor entities. In patients with breast cancer, early diagnosis and accurate restaging of recurrence after surgery is important for selection of the most appropriate therapeutic strategy. Purpose To evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG), for follow-up of patients with suspected recurrent breast cancer. MATERIAL AND METHODS: Forty-seven patients with suspected recurrent breast cancer underwent PET/CT. The PET and PET/CT images were interpreted without knowledge of the results of other diagnostic modalities, and compared with each other with reference to the final diagnosis. RESULTS: Twenty-five (53%) patients suffered tumor recurrence. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 96%, 91%, 92%, 95%, and 94%, respectively. In comparison with PET, PET/CT had a higher sensitivity and accuracy (96% vs. 80% and 94% vs. 81%, respectively). The difference in diagnostic accuracy between PET/CT and PET was significant (P < 0.05). CONCLUSION: The present findings indicate that PET/CT is an accurate, sensitive and reliable modality for screening and detection of breast cancer recurrence. PET/CT appears to be an effective surveillance tool, as it is able to cover the whole body in a single procedure and shows good performance.

"High-grade" central acellular carcinoma and matrix-producing carcinoma of the breast: correlation between ultrasonographic findings and pathological features.

High-grade carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrixproducing carcinoma (MPC) are aggressive tumors that both have a central myxomatous acellular zone. Their characteristic morphology may be useful in diagnostic imaging. Ultrasonographic findings based on the Breast Imaging Recording and Data System (BI-RADS) and detailed histological features were evaluated in 11 cases of CAC and 2 cases of MPC to characterize their features. Safranin-O staining was undertaken for the evaluation of central acellular zones in these tumors. Overall, ultrasonography demonstrated heterogeneous hyperechoic lesions in the center of the hypoechoic mass. Posterior echo enhancement was observed in all but 1 case. One case was classified as malignant and the others as "borderline." Histologically, cancer tissue was located in the periphery of the tumor with a ring-like structure and fewer cellular central areas comprising hyaline cartilage myxoid material such as those stained by safranin-O. The present study showed that the pathological findings of CACs and MPCs accurately reflect the ultrasonographic findings. Tumors that showed hyperechoic areas in the center of the hypoechoic mass, with posterior echo enhancement indicating acellular zones composed by myxochondroid material, and that were also relatively round on ultrasonography may be benign, but evaluation is required to exclude CAC and MPC.

Renal thrombotic microangiopathy associated with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Thrombotic microangiopathy (TMA) is a major complication after hematopoietic stem cell transplantation (HSCT). In this study, we examined the clinical and pathologic features of 2 patients and 5 autopsy cases with HSCT-associated renal TMA to clarify the association between graft-versus-host disease (GVHD) and renal TMA. The median interval between HSCT and renal biopsy or autopsy was 7 months (range 3-42 months). Clinically, acute and chronic GVHD occurred in 7 and 4 patients, respectively. Clinical evidence for TMA was detected in 2 patients, while chronic kidney disease developed in all patients. The main histopathological findings were diffuse endothelial injury in glomeruli, peritubular capillaries (PTCs), and small arteries. In addition, all cases showed glomerulitis, renal tubulitis, and peritubular capillaritis with infiltration of CD3+ T cells and TIA-1+ cytotoxic cells, suggesting that GVHD occurred during the development of TMA. Diffuse and patchy C4d deposition was noted in glomerular capillaries and PTCs, respectively, in 2 biopsy and 2 autopsy cases, suggesting the involvement of antibody-mediated renal endothelial injury in more than 50% of renal TMA cases. In conclusion, the kidney is a potential target of chronic GVHD that may induce the development of HSCT-associated TMA. Importantly, some cases are associated with chronic humoral GVHD.

Evaluation of sentinel lymph node biopsy in clinically node-negative breast cancer.

BACKGROUND: In patients with clinically node-negative breast cancer, diagnosed with palpation and several types of imaging examination, sentinel lymph nodes accurately predict the status of the other axillary nodes, which determine the nature of subsequent adjuvant treatment. In addition, compared with axillary lymph node dissection, sentinel-node biopsy results in less postoperative morbidity, including pain, numbness, swelling, and reduced mobility in the ipsilateral arm. METHODS: We analyzed the validity of the sentinel node biopsy procedure using dual-agent injection of blue dye and radioactive colloid performed in our hospital from May 2006 through March 2010. A total of 258 breasts of 253 patients were studied. Simultaneous axillary lymph node dissection was performed only if rapid intraoperative diagnosis identified metastasis in sentinel lymph nodes. The identification rate, accuracy, provisional false-negative rate, which was calculated with data from all 65 patients whose sentinel lymph nodes had metastasis, and axillary recurrence rate of sentinel node biopsy were calculated. RESULTS: The sentinel node identification rate was 99.2%, and the accuracy of sentinel lymph node status was 98.0%. The provisional false-negative rate was 7.7%. During an observation period averaging 24 months, axillary recurrence was observed in only 1 of 256 cases (0.4%), and there were no cases of parasternal recurrence. In patients who underwent sentinel-node biopsy without axillary lymph node dissection, there was no obvious morbidity. CONCLUSION: Our sentinel-node biopsy procedure yielded satisfactory results, which were not inferior to the results of previous clinical trials. Thus, we conclude our sentinel-node biopsy procedure is feasible. If the efficacy and safety of sentinel-node biopsy are confirmed in several large-scale randomized controlled trials in Europe and the United States, sentinel-node biopsy will become a standard surgical technique in the management of clinically node-negative breast cancer.

An accurate diagnosis of Noguchi classification is possible after the modification of preoperative biopsy-induced fibrosis.

PURPOSE: After computed-tomography-guided needle biopsy (CTNB), the lung may undergo iatrogenic fibrosis (post-CTNB fibrosis), which can be misdiagnosed as tumor-induced fibrosis. The purpose of the study was to examine if an accurate evaluation of pulmonary adenocarcinoma can be made using the Noguchi classification (type A or B vs. type C), even after CTNB. MATERIALS AND METHODS: The subjects were 71 patients with primary pulmonary adenocarcinoma of 20 mm or less that had been resected surgically after CTNB. Twenty-four patients who did not undergo a preoperative biopsy served as controls. Resected specimens were stained with hematoxylin-eosin (HE) and elastic-fiber staining for a precise observation of fibrosis. RESULTS: The period from CTNB to surgery ranged from 12 to 153 days. Post-CTNB fibrosis consisted primarily of collagen fibers with a few thin elastic fibers observed only with high magnification, which was able to distinguish post-CTNB fibrosis in 39 of 48 patients (81.3%) with bronchioloalveolar carcinoma (BAC) lesions (types A/B/C) and in 6 of 23 patients (26.1%) without BAC lesions (types D/E/F/E + F), showing a significant difference (p <0.0001). In the control group, no lesions that resembled post-CTNB fibrosis were observed. CONCLUSION: An evaluation of pulmonary adenocarcinoma by Noguchi classification can be accurately performed even after CTNB.

A new reporting form for breast cytology.

The Cytology and Core Needle Biopsy Subcommittee, organized under the Rules Committee of the Japanese Breast Cancer Society, has prepared a new form for breast cytology reports. This reporting form consists of "diagnostic categories" and "recommendations." The "diagnostic category" is either "specimen inadequacy" or "specimen adequacy." The judgment on "specimen adequacy" is subdivided into four categories: "normal or benign," "indeterminate," "suspicious for malignancy," and "malignant." The "recommendation" indicates descriptions of cytological features and estimated histological type of tumor (these descriptions should be as detailed as possible). On the basis of an analysis of cytological data from 3,439 cases performed before preparing this form, the subcommittee has attached the following recommended goals to this form: (1) the percentage of "specimen inadequacy" should be 10% or less of all samples, (2) the percentage of "indeterminate" samples should be 10% or less of all "specimen adequacy" cases, and (3) 90% or more of "suspicious for malignancy" cases should be diagnosed as "malignant" in a subsequent histological examination. We hope that modification of this form, if it requires revision in the future, will be evidence-based, as was the process for compiling this set of rules.

Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel.

PURPOSE: The Y-box binding protein 1 (YB-1) regulates expression of P-glycoprotein encoded by the MDR1 gene. There have been no previous studies regarding the involvement of YB-1 in the development of resistance to paclitaxel. The present study was done to examine how paclitaxel affects the localization and expression of YB-1 in breast cancer. EXPERIMENTAL DESIGN: We evaluated the expression and localization of YB-1 and P-glycoprotein in breast cancer tissues obtained from 27 patients before and after treatment with paclitaxel. The effect of paclitaxel on localization of cellular YB-1 was examined by using GFP-YB-1. Interaction of YB-1 with the Y-box motif of the MDR1 promoters was studied by electrophoretic mobility shift assay. The effects of paclitaxel on MDR1 promoter activity were examined by luciferase assay. RESULTS: Of 27 breast cancer tissues treated with paclitaxel, nine (33%) showed translocation of YB-1 from the cytoplasm to the nucleus together with increased expression of P-glycoprotein during the course of treatment. Twelve breast cancer tissues (44%) showed neither translocation of YB-1 nor increased expression of P-glycoprotein. Nuclear translocation of YB-1 was correlated significantly with increased expression of P-glycoprotein (P=0.0037). Confocal analysis indicated that paclitaxel induced nuclear translocation of green fluorescent fused YB-1 in MCF7 cells. Furthermore, binding of YB-1 to the Y-box of MDR1 promoter was increased in response to treatment with paclitaxel. In addition, MDR1 promoter activity was significantly up-regulated by paclitaxel in MCF7 cells (P<0.001). CONCLUSIONS: The results of the present study suggested that YB-1 may be involved in the development of resistance to paclitaxel in breast cancer.

MRI of the breast: comparison of MRI signals and histological characteristics of the same slices.

The development of MRI with high spatial resolution and a special breast coil has contributed to more-accurate diagnosis of breast tumor, such as determination of morphologic characteristics including internal architecture of the breast lesion. To clarify how individual MRI findings reflect the pathological findings, we made slices of resected breast lesions identical to those obtained with axial MRI and compared them respectively according to histological subtype of tumors. In this article, we present MRI findings on the basis of histopathological evidence. In general, fibroadenomas (FA) show a well-defined border on contrast-enhanced fat-suppressed T1-weighted images (CFT1). However, a subtype of fibroadenoma, mastopathic type, with a poorly defined border on CFT1 and carcinoma-like enhancement, is similar to cancer on MRI. Scirrhous carcinomas take either of two patterns on dynamic MRI, i.e., homogeneous enhancement or thick irregular peripheral ring enhancement. The latter type shows central fibrosis zones histologically. Papillotubular carcinoma shows a spotted pattern on dynamic MRI. The low-enhancement areas within the spotted pattern reflect parenchyma between clusters of cancer. Solid-tubular carcinoma shows thin peripheral enhancement on dynamic MRI and linear high signal on CFT1. This finding of CFT1 corresponds to infiltration of lymph cells and fibroblast cells in the adjacent zone. Invasive lobular carcinoma shows nonmass lesions and a slow gradual enhancement pattern. Mucinous carcinomas show high signal intensity on T2-weighted images because of mucin and reveal gradual enhancement. The ill-defined border of mucinous carcinoma on CFT1 is useful to distinguish it from FA.

Electron microscopic findings for diagnosis of breast lesions.

The normal mammary gland can be roughly divided into the large duct close to the nipple and the terminal duct located within the lobulus. Both the large duct and the terminal duct are composed of epithelial cells and myoepithelial cells. The epithelial cells can be divided into light and dark cells using electron density. Heterochromatin is the predominant type of chromatin found in normal mammary glands. The cytoplasm of myoepithelial cells contains a number of fine filaments that possess dense patches. The myoepithelial cells of the large duct have a large process with a crablike appearance that protrudes from the cytoplasm. The myoepithelial cells of the terminal duct, by contrast, assume a relatively flat form and are approximately parallel to the epithelial-stromal junction. If the nuclei of the epithelial cells of normal mammary glands and benign breast lesions are compared with those of malignant breast lesions, the latter are primarily oval or circular in shape whereas the former often show marked notches. The predominant chromatin is heterochromatin in noncancer cells and euchromatin in cancer cells. The intracytoplasmic lumen (ICL) can be roughly divided into two types. The ICL is frequently seen in breast cancers, especially scirrhous carcinoma and lobular carcinoma. Invasive ductal carcinoma can be divided into three types: papillotubular carcinoma, solid-tubular carcinoma, and scirrhous carcinoma. Scirrhous carcinoma can be divided into two subtypes: scirrhous carcinoma in the broader sense of the term (characterized by scirrhous invasion of the stroma by papillotubular carcinoma or solid-tubular carcinoma), and scirrhous carcinoma in the narrower sense of the term (characterized by linear or cluster-like invasion of the stroma without forming ducts). Ultrastructural characteristics of scirrhous carcinoma in the narrow sense are bright cytoplasm (seen in most cells) and euchromatin (seen in all cells of this type of carcinoma). In cases of papillotubular carcinoma, solid-tubular carcinoma, and scirrhous carcinoma in the broad sense, euchromatin is predominant but sporadic cells with heterochromatin are also seen. Adenoid cystic carcinoma and carcinoid tumor of the breast are histological types of breast carcinoma that show characteristic features under an electron microscope. Ultrastructurally, the former shows a pseudocyst and true lumen whereas the latter presents numerous neuroendocrine granules within the cytoplasm. Breast carcinoma shows several ultrastructural characteristics that are useful in differential diagnosis. Therefore, it is advisable to take electron microscopic findings into account when evaluating or diagnosing breast lesions.

Can cytological findings predict intraductal spread of breast cancer? Histopathological case-control study.

An important predictive factor for local recurrence after breast-conserving therapy is the state of the surgical margin. In order to obtain a negative surgical margin, the present case-control study was conducted to determine whether the extent of ductal spread can be estimated from the information obtained by fine-needle aspiration (FNA). Samples from 69 cases of extensive ductal spread (EDS) in which it was thought that cancer cells had remained in the residual breast when the lumpectomy was performed with 2 cm margins, were retrieved and compared with 62 cases having almost the same clinical and pathological tumor size. The cases of EDS included a significantly larger number of papillotubular carcinomas (37%vs 13%, P = 0.004) and displayed a high nuclear atypia (42%vs 26%, P = 0.001). We could estimate the same tendency with cytological studies. Cancer cells with cohesive papillary-like clusters suggesting papillotubular carcinoma and with a large nuclear diameter were significantly more numerous in cases of EDS (P < 0.01). In conclusion, EDS can be determined by estimating histological type via cytodiagnosis and measuring the nuclear diameter of cancer cells.