症例は51歳,女性.右乳房C域に腫瘤を触知し,マンモグラフィと超音波検査で同部位に管状陰影を認めたが,穿刺吸引細胞診にて確定診断が得られず,経過観察とした.1年後,腫瘤は右乳房A域に移動していた.針生検にて寄生虫疾患を疑い,外科的切除を実施,Spirometra属裂頭条虫のプレロセルコイドを確認して乳房弧虫症と確定診断した.初回切除から3年後,2回目切除から1年6カ月後に,同側乳房内に再発をきたした.再発の原因として,初診から外科的切除まで1年間を要し,その間にプレロセルコイドが遊走したことが推察された.乳房弧虫症の本邦報告は自験例を含めて17例と稀である.弧虫症では,時間経過とともにプレロセルコイドの遊走をきたし,虫体の完全切除が困難となる可能性があるため,画像診断で弧虫症を疑った場合は,直ちに外科的切除を考慮すべきである.

症例は52歳，女性．右乳腺葉状腫瘍の診断で乳房部分切除術を行い，術後診断は悪性葉状腫瘍であった．初回手術から8カ月後に乳房内再発をきたし乳房切除術を，乳房切除術から7カ月後に局所再々発をきたし腫瘍摘出術を実施し，術後診断はいずれも悪性葉状腫瘍だった．腫瘍摘出術から9年5カ月後（初回手術から10年8カ月後），右腋窩腫瘤が出現した．画像上は内部に広基性充実性部分を伴う嚢胞性病変で，穿刺吸引細胞診で組織型を確定できない悪性細胞を認め，葉状腫瘍の再発を疑い，腫瘍摘出術を行った．病理組織学的検査の結果，悪性葉状腫瘍と診断した．腋窩腫瘍摘出後1年を経過して再発は認めていない．長い無病期間後の再発であること，腋窩腫瘍の局在が深胸筋膜より浅い層に存在したことより，乳腺悪性葉状腫瘍が腋窩異所性乳腺から異時性発生したと考えられ，本邦に同様の報告はなく，極めて稀な症例である．

e12030 Background: A cosmetic outcome is one of the most important goals of surgical treatment of breast cancer. We began performing nipple-sparing mastectomy (NSM) in 1978. NSM is a controversial procedure because of its association with surgical complications and recurrence. We herein review the safety of the NSM surgical technique, compare the recurrence and prognosis of NSM with those of standard mastectomy (MT) and breast-conserving surgery (BCS), and compare the recurrence and prognosis of NSM with and without reconstruction. Methods: We retrospectively analyzed 723 patients with early-stage breast cancer who underwent NSM, including 93 patients who underwent reconstruction and 630 patients who did not undergo reconstruction, from 1985 to 2007. Our surgical method of NSM involved creation of a thick skin flap to avoid surgical complications including nipple necrosis. We compared the outcome of NSM with that of 100 patients who underwent MT and 259 patients who underwent BCS. No patients who underwent NSM or MT received radiotherapy. We compared the local recurrence rate (LRR), disease-free survival (DFS), and overall survival (OS) among all patients who underwent NSM, MT, and BCS. Results: (1) In the NSM group, the numbers of patients with stage 0, 1, 2A, and 2B cancer were 21, 320, 253, and 129, respectively. No nipple necrosis occurred during the 114-month follow-up period. In total, 6.7% of patients in the NSM group developed local recurrence, including 3.3% at the nipple and 3.4% at the skin flap. There were no significant differences among the NSM, MT, and BCS groups in LLR (6.7%, 4.0%, and 4.2%, respectively), 10-year DFS (88%, 90%, and 87%, respectively), or 10-year OS (92%, 91%, and 97%, respectively). (3) There were also no significant differences between patients with and without reconstruction in LLR (7.5% and 6.5%, respectively), 10-year DFS (91% and 88%, respectively), or 10-year OS (95% and 92%, respectively). Conclusions: Our data show that NSM without radiotherapy may be considered as an alternative option for mastectomy when BCS is inapplicable in patients with early-stage breast cancer.

Recent reports have suggested that nipple-sparing mastectomy (NSM) is a potential alternative to mastectomy (MT). The aim of our study was to investigate the oncological and technical outcomes of NSM compared with MT using long-term follow-up data. A total of 932 patients between April 1985 and March 2004 were enrolled in our study. Among them, 788 patients received NSM, whereas 144 patients received the routine mastectomy. The median follow-up time was 78 months. No significant difference in the probability of local recurrence between the NSM cohort and the MT cohort was found (8.2 vs. 7.6 %, p = 0.81). The rate of nipple-areola complex (NAC) relapse was low (3.7 %), and all of the nipple and/or areola recurrence cases were treated with NAC removal. Furthermore, nipple and/or areola recurrence was associated with a significantly better prognosis than that of skin flap recurrences and local lymph node recurrences. For the 21-year disease-free survival and the 21-year overall survival, no significant difference between the NSM and MT cohorts was observed. There was no occurrence of nipple necrosis in our trial. This was the first study to investigate the long-term follow-up of NSM in a large Japanese population. We reported the NSM could be performed without nipple necrosis and is oncologically as safe as mastectomy without radiotherapy. Therefore, we suggest that NSM without radiotherapy is a potential alternative to mastectomy for breast cancer patients for both outcome and aesthetic benefits.

We report an 89-year-old patient with recurrent hormone-responsive breast cancer who presented with pleural, skin and bone metastases. Nineteen years previously, she had undergone a mastectomy and then for 16 years received adjuvant hormone therapy. The patient was orally administered a combination therapy of anastrozole, UFT and cyclophosphamide. A remarkable response was seen after 5 months, and no side effects were observed. The patient became well and the treatment was continued without relapse at 8 months. Oral anti-cancer treatments in combination with hormone therapy appear to have few side effects and might be an effective treatment option for recurrent breast cancer patients.

We report a postmenopausal recurrent breast cancer patient with triple negative disease who presented with right recurrent nerve palsy. Nine years previously, she had undergone a mastectomy. FDG-PET scan revealed neck lymph node metastases from the breast cancer. The recurrent nerve palsy was thus considered to have been caused by the lymph node metastases. The patient was orally administered DMpC (doxifluridine, medroxyprogesterone acetate and cyclophosphamide) combination therapy. This resulted in a remarkable response after five months, with the recurrent nerve palsy completely disappearing at six months. No side effects from the treatment were observed. The patient was well and the treatment was being continued without relapse at nine months. Oral anti-cancer treatments such as DMpC appear to have few side effects and might be an effective treatment option for recurrent breast cancer patients with triple negative disease.

There is a growing body of evidence indicating that calcitonin (CT) and its receptor (CTR) is involved in cell growth, differentiation and tissue development. Using laser capture microdissection (LCM) and real-time reverse transcription polymerase chain reactions (RT-PCR), we have investigated CTR mRNA expression in 60 primary breast cancers, including 14 pairs of matched cancers and unaffected ductal epithelia from the same patients. Our results demonstrate that CTR mRNA was constantly expressed in normal ductal epithelium and in breast cancer. In the 14 cases where matched samples were available, a decrease in CTR mRNA expression was found in 9 breast cancers (64.3%), an increased CTR expression in 2 cases (14.3%) and no significant change in 3 cases (21.4%). In 60 cases of primary breast cancers, decreased CTR expression was found in 44 (73.3%), increased CTR expression was detected in 10 cases (16.7%) and no change was observed in 6 cases (10%). Decreased CTR expression was found more often in cases with lymph node metastasis (p = 0.0498) and lymphatic invasion (p = 0.0179). Also there was a decreased CTR expression in cases with an extensive intraductal component (p = 0.0543) and a high nuclear grade (p = 0.1934), although this was not statistically significant. Overall, we conclude that CTR mRNA was constantly expressed in unaffected ductal epithelium, whereas decreased CTR mRNA expression was frequently found in breast cancers, particularly in cases with lymph node metastasis and lymphatic invasion. These results suggest that CTR might be of great potential significance in breast cancer progression.

The axillary arch of Langer is the most common muscular variation in the axilla. Recognition of anatomic variations is important for surgeons to perform safe axillary surgery. We describe a case of a woman with breast cancer, in whom sentinel lymph node biopsy was successfully performed and the presence of this anomaly preoperatively diagnosed by magnetic resonance axillography.

We describe a woman with metastatic breast cancer treated with multiple rounds of prior cytotoxic and endocrine therapies, who presented with ipsilateral diaphragmatic paralysis. The use of anastrozole, a highly selective nonsteroidal aromatase inhibitor (1 mg daily), successfully induced remission of metastatic tumors in our patient, who is partially recovering from diaphragmatic paralysis.

We have reported that magnetic resonance axillography (MR-axillography) is the best method for assessing lymph node size and representing the relation of the lymph node to normal anatomy.

The Fragile Histidine Triad (FHIT) Gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a tumor suppressor gene involved in different tumor types. Abnormalities of the FHIT locus were found in many established cancer cell lines and tumors including breast cancer. In sporadic breast cancer, loss of heterozygosity within the FHIT gene has been observed at different frequencies and has been correlated with tumor progression. Aberrant FHIT transcripts have been reported in breast cancer. Furthermore, Fhit protein loss is correlated with prognosis. We summarized the research advances of FHIT genetic, epigenetic change and aberrant Fhit protein expression in breast cancer. Fhit protein may be a novel prognostic factor for breast cancer. FHIT gene therapy may potentially be clinically useful for treatment of breast cancer, suggesting further research involving FHIT introduction should be performed in breast cancer.

目的:乳癌における悪性度の術前評価が治療の決定に必要とされている. われわれは日常細胞診断業務に使っている乳腺穿刺吸引細胞の塗沫標本を用いて乳癌の悪性度を評価することを目的として細胞診Grade分類を試みた.方法:218例の浸潤性乳管癌から得られた術前穿刺吸引塗沫標本のパパニコロウ染色標本を用いた. その細胞像から, 背景の壊死の有無細胞の大きさ, N/C比, 核の大きさ, 核クロマチンの形状, 核クロマチンの濃度, 核の大小不同の7項目について0, 1～3に数値化, 評価しその和の6～19をスコアと命名した. それらをさらに3群に分け, I～IIIに分類した. これを細胞診のGradeと命名した.成績:われわれが行った細胞学的Gradeは組織学的なGradeと相関があり, リンパ節転移の有無とも相関があった. また免疫組織学的染色におけるER陽性との間には負の相関がみられた. Ki-67における増殖能の指標とも正の相関を示した.結論:乳腺穿刺吸引細胞材料を用いた細胞診Grade分類は日常の診断業務とともに臨床に有用な情報を提供することができる.

背景:術前の穿刺吸引細胞診で, 腫瘍細胞が孤立散在性に出現した乳腺乳管内乳頭腫の1例を経験したので報告する.症例:患者は40歳女性. 左乳房B領域に直径1cmの嚢胞性腫瘤が認められた. 穿刺吸引細胞診は疑陽性であったため生検が施行された. 細胞診では, 採取された細胞量は多く, ほとんど孤立散在性に出現していた. 細胞質広く, 赤色顆粒を有する大型細胞, 紡錘形細胞, N/C比高く, 核濃染性の小円形細胞など, 多種多様な細胞像であった. 免疫細胞化学的に, 大型細胞はEMA陽性, 小円形細胞等はa smooth muscle actin (a-SMA) 陽性であった. 組織像では, 拡張した乳管の中に乳管内乳頭腫が多量の凝固壊死巣と連続してみられた. 出血梗塞を合併した乳管内乳頭腫と診断された.結論:乳管内乳頭腫の細胞診では, 乳頭状集を形成するのが一般的特色である. しかし, 出血性梗塞を起こしたときには孤立散在性細胞が出現し, 癌と紛らわしいことがある.

A tumor suppressor gene, retinoic acid receptor (RAR) β2, has been mapped to chromosome 3p24, a region where loss of heterozygosity (LOH) has been observed commonly in carcinomas of various tumor tissues. RAR β2 expression is reduced or lost in many malignant tumors including breast cancer, however, whether LOH accounts for the loss of expression of RAR β2 in breast cancer is unknown. We, therefore, assessed LOH on chromosome band 3p24 to correlate it with RAR β2 expression and other established prognostic parameters in 52 breast carcinomas. Based on three microsatellites, D3S 1283, D3S 1293 and D3S 1286, all of the tumors were informative, of these, 12 (23%) exhibited LOH. RAR β2 expression was lost in 42% (19/45) of these samples. We found that LOH on chromosome band 3p24 was not correlated with loss of RAR β2, but correlated with higher histological grade, p53-positivity, and loss of estrogen and progesterone receptors. Our findings suggest that LOH of the RAR β2 gene does not account for the frequent loss of RAR β2 expression in breast cancer but the genomic structural alteration at or close to the RAR β2 gene locus are likely to be associated with tumor progression and/or loss of hormonal dependency.

BACKGROUND:Grading of carcinomas is an estimation of differentiation. Nuclear grading is the cytological evaluation of tumor nuclei in comparison with the nuclei of normal mammary epithelial cells. Because nuclear grading does not involve an assessment of the growth pattern of the tumor, it applies not only to invasive ductal carcinoma but also to other subtypes of breast carcinoma.METHODS:A total of 215 primary breast carcinomas obtained from the Affiliated Kihoku Hospital of Wakayama Medical College were enrolled in our present study. Nuclear grade was evaluated according to the criteria of the National Surgical Adjuvant Study of Breast Cancer (NSAS-B) protocol. Immunohistochemistry was also performed to determine Bcl-2, p53, c-erbB-2, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues for all cases.RESULTS:Thirty-two (14.9%) of the patients were graded as 1,124 (57.7%) as 2, and 59 (27.4%) as 3. Nuclear grade displayed a negative correlation with Bcl-2 expression (r=-0.308, p<0.0001), and a positive correlation with c-erbB-2 overexpression (r= 0.172, p=0.0117) and tumor proliferative index labeling by MIB-1 (r=0.485, p<0.0001).CONCLUSIONS:These results imply that nuclear grade is related to the characteristics of tumor biology, indicating that the morphology and biology of breast cancer are tightly linked. Our present results also suggest that adding the nuclear grade to the pathological diagnosis of invasive breast carcinoma may be clinically useful for predicting tumor behavior, for example aggressiveness, and for prognostication.

BACKGROUND:Surgical sampling for assessing axillary status has not been considered as a well defined surgical procedure. We have reported that MRI is a good instrument for assessing lymph node size and identifying lymph node position. We also developed a mathematical model that takes into consideration the size of axillary lymph nodes, and retrospectively determined the number and size of the axillary lymph nodes that need to be sampled from level I-II to achieve a greater than 90% probability of metastasis detection after surgical sampling, with the future aim of using MR-axillography to assess lymph node size.METHODS:One thousand nine hundred and thirty four lymph nodes from 102 level I-II dissections performed on T1 and T2 breast cancer patients with nodal metastases were examined histologically and the greatest long-axis dimension on histologic slides was measured.RESULTS:This model permitted determination of the cutoff level necessary for an expected probability of detection of metastasis of over 90%. The cutoff level, regardless of tumor size, is a maximum of 6 nodes removed from level I-II in which the greatest long-axis measurement is greater than or equal to 6 mm. The cutoff level in patients with macrometastatic nodes is a maximum of 3 or 4 nodes in which the long-axis dimensions are greater than or equal to 9 or 7 mm, respectively, removed from level I-II.CONCLUSIONS:This model showed that surgical sampling on the basis of lymph node size might have good potential to detect lymph nodes metastases.

BACKGROUND:Angiogenesis plays an important role in the growth and metastasis of solid tumors. Several angiogenic factors have been identified, and thymidine phosphorylase (TP) is thought to be one such factor. To date, little information is available on the relationship between TP and other clinicopathological variables.METHODS:Formalin-fixed, paraffin-embedded materials from 116 primary breast carcinomas were used. The expression of TP, estrogen receptor, Bcl-2, Bax, p53, c-erbB-2 and MIB-1 was examined by immunohistochemical methods.RESULTS:Nuclear and/or cytoplasmic TP expression was observed in the neoplastic cells, and accentuation of TP was often present at the infiltrating tumor edge and intraductal spread region. Tumor cell TP expression was significantly inversely correlated with histological grade (p< 0.05) and positively correlated with Bcl-2 expression, but no association with other tumor variables was found.CONCLUSIONS:TP is associated with Bcl-2 expression and tumor differentiation in breast cancer. TP may be a new prognostic parameter for breast cancer.