悪性腸腰筋症候群（malignant psoas syndrome: MPS）は腸腰筋への悪性腫瘍の浸潤により第1～4腰神経領域の疼痛を特徴とする，同側股関節の伸展時痛を呈する症候群である．症例は76歳，女性．左乳癌術後再発に対して化学療法中であったが，右下肢痛のため通院困難となり，再発治療開始後4年6カ月に精査加療目的で入院となった．MPSによる右下肢痛に対して，NSAIDs，アセトアミノフェン，オピオイド，鎮痛補助薬，放射線治療を開始し，症状改善傾向であった．しかし，入院中に癒着性イレウスで緊急手術を施行，廃用と乳癌多発転移の進行により，訪問診療を導入し自宅退院，退院25日後に自宅で死亡した．MPSの報告は少なく，その原因は医療従事者の間で認知度が低い可能性が指摘されている．MPSは腹部臓器の癌患者で頻度が高いが，今回われわれは悪性腸腰筋症候群を呈した乳癌の1例を経験したので報告する．

Purpose We hypothesized that innate immune response pathways might be involved in thyroid carcinogenesis. To investigate this hypothesis, we aimed at analyzing the expression of several receptors and molecules in the innate immune system in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) tissues. Methods Of the surgically resected specimens, 11 ATC tissues, 25 PTC tissues, and 8 nodular hyperplasia (NH) tissues were selected and examined for the expression of toll-like receptor (TLR) 2, TLR3, TLR4, TLR5, TLR7, TLR9, the myeloid differentiation primary response gene 88 (MyD88), and toll-interleukin-1 receptor domain-containing adaptor inducing INF-β (TRIF) by immunohistochemistry (IHC). Results Several TLRs were expressed in each tissue. TLR3 was strongly expressed in all tissues. In contrast, TLR4 was not detected in any tissues. While TLR5 was moderately expressed in NH but significantly reduced in PTC and ATC, TLR9 was absent in NH tissue but moderately expressed in both PTC and ATC. On MyD88 expression, no significant difference was found between PTC and ATC. TRIF was significantly upregulated in PTC and ATC compared to NH. Surprisingly, PTC and ATC tissues exhibited similar expression patterns of TLRs, MyD88, and TRIF. Conclusion These data suggest the involvement of the innate immune system in both PTC and ATC. Specifically, TLR3-mediated TRIF activation was confirmed in PTC and ATC. This provides new insight into thyroid carcinogenesis.

BACKGROUND Dermatomyositis (DM) is occasionally associated with malignancy, which is so-called cancer-associated myositis. The cancer screening in patients with dermatomyositis is an important clinical issue. That is because malignant disease underlying dermatomyositis is potentially life-threatening. Transcriptional intermediary factor 1γ (TIF1γ) antibodies (anti-TIF1γ Abs) are one of the myositis-specific autoantibodies, which are investigated as potential predictors of malignancy in patients with dermatomyositis. However, the etiology of anti-TIF1γ Abs generations in various cancer patients is not known. CASE REPORT A 70-year-old male patient was admitted for muscle pain and weakness in both legs. Erythematous on the face, eruption, and a V sign were also observed. Laboratory tests showed the elevation of creatine kinase, myoglobin, and aldolase. He was diagnosed as dermatomyositis. Cancer screening was performed, and esophageal cancer was detected in the lower esophagus. Despite the symptoms of dermatomyositis were improved with steroid, methotrexate, and radical esophagectomy, he died with esophageal cancer 3 years after the onset of dermatomyositis. TIF1γ is frequently overexpressed in cancer tissues. Therefore, some cancer patients without dermatomyositis could be positive for anti-TIF1γ Abs. We retrospectively analyzed anti-TIF1γ Abs in cancer patients (n=131). However, the screening of anti-TIF1γ Abs in cancer patients without dermatomyositis (n=130) showed there were no seropositive patients. Only this cancer-associated myositis patient was positive for anti-TIF1γ Abs. CONCLUSIONS Our result suggested the generation of anti-TIF1γ Abs is specific for cancer associated myositis, not for tumorigenesis.

Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options. While rationally-derived regimens are emerging from the results of recent gene profiling studies, TNBC is an angiogenesis-dependent malignancy, and antiangiogenic therapies have been examined energetically in this field. Antiangiogenic agents in combination with chemotherapeutic platinum compounds have shown some benefit in recent randomized control studies for the treatment of TNBC. These combinations could be more safe and efficacious in patients, when pharmacotherapy schedule is modified taking into account its tolerability.

PURPOSE:Paget disease of the breast is a rare cancer that originates from the nipple-areolar complex. It is often overlooked and misdiagnosed as benign chronic eczema of the nipple. We aimed to retrospectively verify whether blood flow analysis using Doppler sonography was useful for detecting the presence of Paget disease. METHODS:In this retrospective study, 12 patients with pathologically proven unilateral nipple eczematous lesions (seven with Paget disease and five with simple dermatitis) were included. Nipple blood flow signal was observed using Doppler sonography, and the detected blood flow signals were quantified using digitally recorded images. Quantified blood flow ratio and pathologically examined capillary density were evaluated between affected and unaffected nipples. Findings of mammography, grayscale sonography, and contrast-enhanced magnetic resonance imaging (CE-MRI) were reviewed. RESULTS:In patients with Paget disease, Doppler effects in the affected nipple were more clearly visible than those in the unaffected nipple. These effects were sufficiently visible to identify Paget disease. No obvious effects were observed in the affected and unaffected nipples of simple dermatitis. The quantified blood flow ratio and pathologically examined capillary density were significantly higher for the Paget lesion than those for the non-Paget lesion. The sensitivity of CE-MRI and Doppler sonography was markedly correlated, revealing blood flow changes in the nipple lesions of Paget disease. CONCLUSION:Doppler sonography visualized the proliferation of blood vessels in Paget lesions. The visualization of increased nipple blood flow using Doppler sonography is a simple and low-cost method that provides useful data for identifying Paget disease during routine medical care.

BACKGROUND:Breast cancer-related lymphedema often causes cellulitis and is one of the most common complications after breast cancer surgery. Streptococci are the major pathogens underlying such cellulitis. Among the streptococci, the importance of the Lancefield groups C and G is underappreciated; most cases involve Streptococcus dysgalactiae subspecies equisimilis. Despite having a relatively weak toxicity compared with group A streptococci, Streptococcus dysgalactiae subspecies equisimilis is associated with a mortality rate that is as high as that of group A streptococci in cases of invasive infection because Streptococcus dysgalactiae subspecies equisimilis mainly affects elderly individuals who already have various comorbidities.CASE PRESENTATION:An 83-year-old Japanese woman with breast cancer-related lymphedema in her left upper limb was referred to our hospital with high fever and acute pain with erythema in her left arm. She showed septic shock with disseminated intravascular coagulation. Blood culture showed positive results for Streptococcus dysgalactiae subspecies equisimilis, confirming a diagnosis of streptococcal toxic-shock syndrome. She survived after successful intensive care.CONCLUSIONS:To the best of our knowledge, this case represents the first report of Streptococcus dysgalactiae subspecies equisimilis-induced streptococcal toxic-shock syndrome in a patient with breast cancer-related lymphedema. Breast cancer-related lymphedema is a common problem, and we must pay attention to invasive streptococcal soft tissue infections, particularly in elderly patients with chronic disease.

Eight years after surgical treatment for breast cancer, serum p53 antibody levels suddenly increased in a 67-year-old woman without recurrent signs of cancer. Early esophageal squamous cell carcinoma was detected by endoscopic screening. After endoscopic submucosal dissection was completed, serum p53 antibody levels decreased to be in the normal range. Serum p53 antibody monitoring can be helpful for early detection of not only recurrence of primary carcinoma but also development of metachronous carcinoma. This case is the first to monitor the changing titers of serum p53 antibody at the early phase of esophageal cancer progression into lamina propria mucosae until the disappearance of tumor cells.

Second-generation ultrasound contrast agents have enabled real-time, detailed ultrasound (US) imaging of blood flow, and Sonazoid is one of these agents. Sonazoid-enhanced ultrasound (CEUS) of the breast has been shown to have higher diagnostic accuracy of malignancy than contrast-enhanced MRI (MRI). There have been efforts to qualitatively evaluate CEUS using time-intensity curves (TIC). The setting of region of interest (ROI) is important in the evaluation of CEUS using TIC. However, the time changes are constant and independent of ROI setting or CEUS conditions. This study examined the relation between therapeutic effects of neoadjuvant chemotherapy (NAC) and the time to peak (TTP) using CEUS. The subjects were 25 women with locally advanced breast cancer. There were 8 women with luminal type, 3 with luminal HER2 type, 7 with HER2 enrich type, and 7 with triple negative type. The NAC regimen was 4 courses of FEC, followed by 4 courses of Doc±trastuzumab (Tr). The therapeutic effect was based on histological effects in surgical specimens and on the reduction of maximum tumor diameter (Diameter) determined by MRI performed before and after NAC. For histological effects, the patients were divided into a group with near pCR or pCR (Effective group) and a group with worse results (Ineffective group). CEUS was performed a total of 4 times, approximately every 8 weeks from initiation until completion of NAC. An examination was performed on the relation of the changes in TTP with the reduction of Diameter and with histological effects. The reduction of Diameter was correlated, albeit weakly, with the TTP change only between the first and second times (correlation coefficient: 0.382). However, there was no significant difference. The TTP change between the first and third times showed a significant relation with the Effective group (p value=0.0225). There was no significant difference by subtype, but there was a significant relation with HER2-positive patients who received Tr (p value=0.0357). A relation of TTP change was observed with reduction in Diameter and with the histological effect.

Triple-negative breast cancer (TNBC) is aggressive, with high risk of visceral metastasis and death. A substantial proportion of patients with TNBC is associated with BRCA mutations, implying that these tumors are sensitive to DNA-damaging agents. We report successful treatment of a metastatic TNBC in a woman with a BRCA2 germline mutation using combined bevacizumab/paclitaxel/carboplatin (BPC) therapy. The patient was pregnant and had liver metastases, and a complete clinical response was sustained for approximately 5 years. Mastectomy was performed during the 29th week of pregnancy, and the baby was later delivered by caesarean section. Subsequently, multiple metastases in both liver lobes were detected using computed tomography and magnetic resonance imaging and the patient was treated with a BPC regimen, which led to complete disappearance of metastatic lesions in the liver. No additional treatment was provided, and after 5 years the patient consented to direct sequencing of BRCA2 and a 6781delG mutation was identified. At the most recent (5-year) follow-up, the patient was alive with good quality of life and no evidence of metastases.This finding suggests that BPC therapy might be considered a good therapeutic option for the treatment of metastatic TNBC in a woman with a BRCA2 germline mutation.

INTRODUCTION:Invasive lobular carcinomas have an increased propensity for distant metastases, particularly to the peritoneum, ovaries, and uterus. In contrast, distant metastases of nonpalpable lobular carcinomas are extremely rare, and the causes of underlying symptoms of primary carcinomas remain unclear. We report a case of an asymptomatic invasive lobular carcinoma with a primary mammary lesion in a patient with rectal stenosis.CASE PRESENTATION:A 69-year-old Japanese woman presented to our hospital for treatment of constipation. Although rectal stenosis was confirmed, thorough testing of her lower digestive tract did not identify its cause. Thus, an exploratory laparotomy and tissue biopsy was performed, and the presence of an invasive lobular carcinoma was confirmed. Subsequent breast examinations showed that the invasive lobular carcinoma that led to the rectal stenosis was a metastatic lesion from a primary lesion of the breast duct. As the present breast lobular carcinoma was asymptomatic and nonpalpable, we did not initially consider metastatic breast cancer as a cause of her symptoms, and the final diagnosis was delayed.CONCLUSIONS:Peritoneal metastasis from nonpalpable invasive lobular carcinomas is very rare. However, breast cancer metastasis should be considered when carcinomatous peritonitis is present in a patient with an unknown primary cancer.

The thymus is composed of multiple stromal elements comprising specialized stromal microenvironments responsible for the development of self-tolerant and self-restricted T cells. Here, we investigated the ontogeny and maturation of the thymic vasculature. We show that endothelial cells initially enter the thymus at E13.5, with PDGFR-β(+) mesenchymal cells following at E14.5. Using an allelic series of the thymic epithelial cell (TEC) specific transcription factor Foxn1, we showed that these events are delayed by 1-2 days in Foxn1 (Δ/Δ) mice, and this phenotype was exacerbated with reduced Foxn1 dosage. At subsequent stages there were fewer capillaries, leaky blood vessels, disrupted endothelium - perivascular cell interactions, endothelial cell vacuolization, and an overall failure of vascular organization. The expression of both VEGF-A and PDGF-B, which are both primarily expressed in vasculature-associated mesenchyme or endothelium in the thymus, were reduced at E13.5 and E15.5 in Foxn1 (Δ/Δ) mice compared with controls. These data suggest that Foxn1 is required in TECs both to recruit endothelial cells and for endothelial cells to communicate with thymic mesenchyme, and for the differentiation of vascular-associated mesenchymal cells. These data show that Foxn1 function in TECs is required for normal thymus size and to generate the cellular and molecular environment needed for normal thymic vascularization. These data further demonstrate a novel TEC-mesenchyme-endothelial interaction required for proper fetal thymus organogenesis.

男性乳腺に発生した明細胞汗腺腫を経験したので報告する．症例は38歳男性．右乳腺の血性乳頭分泌と腫瘤を主訴に来院した．診察所見は右乳輪下に径1.5cm，境界明瞭かつ可動性良好な楕円形腫瘤を触知し，乳頭分泌は淡血性で単孔性であった．マンモグラフィー所見は境界明瞭な腫瘤性陰影として，超音波所見は拡張乳管内に存在する内部エコー不均一な腫瘤として描出された．針生検所見より皮膚付属器由来の新生物が示唆され，外科生検で乳腺発生の明細胞汗腺腫と診断した．検索しえた乳房発生の明細胞汗腺腫は，本邦および海外で30例．これら既報例からその臨床的特徴を検討すると，乳癌に比し男性発生頻度が高く，発症年齢に特異的分布はなく，乳輪近傍に好発する嚢胞性病変である傾向があった．

目的：一般に乳癌術前化学療法（neoadjuvant chemotherapy: NAC）の臨床的効果判定は病変の最大径の変化によってなされるが，内部の壊死や瘢痕組織の残存により正確にとらえられない症例もある．そこで我々は，Sonazoid®造影超音波（以下，CEUS）を加えることでより正確な効果判定が可能であるか，またどのようなCEUS所見に注目するべきか検討した．対象と方法：対象は2007年7月‐2010年7月に当院でNAC後に手術を施行した乳癌患者のうち，NAC前後にCEUSを行った20症例22結節．Sonazoid®懸濁液0.0075 ml/kgを静脈内投与．投与後1分間の動画とMicro Flow Imagingをもとに，腫瘤内部の染影を染影なし／非腫瘤部と同程度の染影／非腫瘤部よりやや強い染影／非腫瘤部より明らかに強い染影／評価不能の5段階に，腫瘤周囲の染影および腫瘤内部の不染域を無／有／評価不能の3段階に分類し，NACの組織学的効果判定と比較検討した．結果と考察：NAC前にみられた腫瘤内部および周囲の染影がNAC後に低下する傾向がみられ，組織学的効果判定の高い群でその傾向はより強くみられた．腫瘤内部の不染域に関しては組織学的効果判定と一定の傾向はみられず，単に不染域の有無だけでなく，腫瘤サイズの変化や染影部分の状態なども加味しながら評価する必要があると考えられた．結論：CEUSにより腫瘤内部と周囲の染影を評価することで，NACの効果を評価できる可能性が示唆された．

A 39-year-old premenopausal nulliparous woman presented with severe pain in her right breast, bleeding and pus-like discharge, and a deep ulcer approximately 18 cm in diameter.Contralateral breast metastasis, bilateral axillary lymph node metastases, and multiple lung and bone metastases were detected on computed tomography.Five years previously she had undergone surgery for ovarian cancer and had prematurely discontinued adjuvant chemotherapy because of side effects. Following the administration of pain control, the patient received trastuzumab(Tr)plus vinorelbine(VNR)for her breast cancer as first-line therapy to avoid hair loss.The ulcer on her right chest wall underwent complete epithelialization and the patient's performance status improved from 3 to 0.The pus-like discharge, pain, bleeding, and odor from the breast resolved completely, and 5 months later, her quality of life had improved.The lung metastases also resolved completely.No adverse affects, including hematotoxicity and hair loss, were seen until treatment failure 12.5 months later. Second-line and third-line treatments were performed, but brain metastases developed, and the patient's overall condition deteriorated because of the development of ileus of unknown etiology.She died 21 months later.The patient received all therapies on an outpatient basis. Combination therapy using Tr and VNR is superior in safety and tolerability, and has been considered an option for first-line treatment of metastatic, locally advanced HER2-positive breast cancer.

目的：乳腺疾患に対して第二世代超音波造影剤Sonazoid®を用いた造影超音波を行い，その特徴と意味を検討した．対象と方法：造影超音波が行われ，組織診断が確定した乳癌97病変と良性30病変を検討対象とした．Sonazoid®は混濁液として0.0075 mg/kgを静脈内投与し，Pulse Subtraction low Mechanical index modeやMicro flow imagingで観察した．結果と考察：微小気泡の共鳴信号を高い時間空間分解能で画像化する造影超音波により，微細な染影や細かい血管走行の描出が可能であった．染影は病変内部の不均一性を反映し，病変周囲に限局した染影は浸潤性発育に伴う腫瘍血管の存在を示し浸潤癌に特徴的な所見であった．血管走行は病変の発育形態を反映し，良性病変では多数の分枝を持つのに対し，悪性病変では分枝に乏しい走行を示した．結論：乳腺造影超音波では病変の微細な構造を観察することが可能であった．