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Primary cutaneous gamma-delta T-cell lymphoma (CGD-TCL) is a rare cutaneous lymphoma. Panniculitis-like T-cell lymphoma (SPTCL) has a better prognosis than CGD-TCL. SPTCL is sometimes associated with autoimmune disease. A 64-year-old Japanese female with a history of dermatomyositis presented with subcutaneous nodules on the upper extremities and exacerbated dermatomyositis. A skin biopsy showed lobular panniculitis, a vacuolar interface change, and a dermal mucin deposit. Fat cells rimmed by neoplastic cells, fat necrosis, and karyorrhexis were observed. The atypical lymphoid cells showed CD3+, CD4−, CD8+, granzyme B+, CD20−, and CD56−. Polymerase chain reaction analysis demonstrated a T-cell receptor rearrangement. The patient was initially diagnosed with SPTCL, so the dose of prednisone was raised from 7.5 to 50 mg daily (1 mg/kg). After one month, erythematous nodules regressed, and muscle symptoms improved. Subsequently, prednisone was tapered, and cyclosporin A was added. After one year, the patient remained symptom-free and continued taking 7.5 mg prednisone and 100 mg cyclosporin A daily. Afterward, we immunostained skin samples with antibodies against TCR-ß and δ and found positive TCR-δ and negative TCR-ß. Therefore, we corrected the diagnosis to CGD-TCL, although the clinical course and the presence of dermatomyositis were reminiscent of SPTCL.

Abstract Background A balloon occlusion technique is suggested for use in cryobiopsy for interstitial lung diseases because of the bleeding risk. However, it may interfere with selection of the involved bronchus for peripheral pulmonary lesions (PPLs). A two-scope technique, in which two scopes are prepared and hemostasis is started using the second scope immediately after cryobiopsy, has also been reported. This study aimed to evaluate the safety and diagnostic utility of transbronchial cryobiopsy using the two-scope technique for PPLs. Methods Data of patients who underwent conventional biopsy followed by cryobiopsy using the two-scope technique for PPLs from November 2019 to March 2021 were collected. The incidence of complications and risk factors for clinically significant bleeding (moderate to life-threatening) were investigated. Diagnostic yields were also compared among conventional biopsy, cryobiopsy, and the combination of them. Results A total of 139 patients were analyzed. Moderate bleeding occurred in 25 (18.0%) patients without severe/life-threatening bleeding. Although five cases required transbronchial instillation of thrombin, all bleeding was completely controlled using the two-scope technique. Other complications included two pneumothoraces and one asthmatic attack. On multivariable analysis, only ground-glass features (P

Angiosarcoma is a malignant mesenchymal tumor characterized by the presence of vascular endothelial cells. Although rare, angiosarcoma developing in the mammary glands has a poor prognosis. We report a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer. A 78-year-old woman noticed a tumor in her right breast and visited our hospital. The patient had undergone breast-conserving surgery and axillary lymph node dissection from the right breast 12 years before the visit. The tumor was diagnosed as T4bN0M0, stage IIIB. Anastrozole was administered as postoperative adjuvant therapy for 5 years; the patient also received 50-Gy whole-breast radiation therapy after surgery. Physical examination during her visit revealed an elevated lesion with blue purpura around the nipple in the right breast. We performed breast ultrasound and detected a well-defined 19.6 × 16.4 × 10.7 mm hypoechoic tumor in the left subareolar area. The patient underwent core needle biopsy (CNB). Based on the CNB specimen findings, she was suspected to experience late local recurrence after surgery. Therefore, she underwent total mastectomy after breast-conserving surgery. A dark-red tumor sized 18 × 12 mm was found in a specimen from the nipple. The pathological diagnosis of the specimen revealed short spindle-shaped tumor cells with strong nuclear pleomorphism and a significant interstitial fibrosis. Immunohistochemistry using D2-40 and CD31 antibodies showed irregular luminal proliferation at the anastomosis, infiltration into the surrounding tissue, and massive necrosis, thereby leading to the diagnosis of breast angiosarcoma. We have reported a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer.

Abstract Multiple primary lung cancers (MPLCs) harbour various genetic profiles among the tumours, even from individuals with same non-intrinsic risk factors. Paired mutational analyses were performed to obtain a census of mutational events in MPLC and assess their relationship with non-intrinsic risk factors. Thirty-eight surgical specimens from 17 patients diagnosed as MPLC were used. Extracted DNAs were sequenced for somatic mutations in 409 cancer-associated genes from a comprehensive cancer panel. We statistically analysed the correlation between each driver mutation frequency and non-intrinsic risk factors using Fisher's exact test, and whether genetic mutations occurred concomitantly or randomly in MPLC using an exact test. Comprehensive genetic analyses suggested different mutation profiles in tumours within the same individuals, with some exceptions. EGFR, KRAS, TP53, or PARP1 mutations were concomitantly detected in some MPLC cases. EGFR mutations were significantly more frequent in never or light smokers and females. Concomitant EGFR or KRAS mutations in MPLCs were significantly more frequent than expected by chance (P = .0023 and .0049, respectively) suggesting a more prominent role of non-intrinsic risk factors in EGFR and KRAS mutations than other mutations, which occurred more randomly. Concomitant EGFR or KRAS mutations were particularly prominent in never or light smokers and males.

Introduction: Multiple primary lung cancers (MPLCs) occur in common carcinogenetic risks such as lifestyle, biological aging, immune responses, hormones, and metabolism. Although MPLCs harbor various genetic profiles within the same individuals, differences in the tumor microenvironment (TME) are unclear. We investigated the impact of genetic aberrations, non-intrinsic factors, and pathological subtypes on tumor immunity. Materials and Methods: In total, 73 surgically resected specimens from 32 patients with MPLC were analyzed. PD-L1 expression in tumor cells (TCs) and immune cells (ICs), CD3-positive tumor-infiltrating lymphocytes (TILs), CD8/CD3 ratios, and FOXP3-positive TILs that compose TMEs were evaluated by immunohistochemistry and classified on a score of 0–2. 38 tumors were sequenced for somatic mutations in 409 cancer-associated genes. Results: Females and never or light smokers had a higher incidence of PD-L1-negative tumors and a higher concordance rate. PD-L1 positivity in TCs and ICs was significantly less frequent in EGFR-mutated than in wild-type tumors. Differences in the score of TMEs were observed between the KRAS-mutated-only tumor and the KRAS and TP53-co-mutated tumors, and between the KRAS-mutated-only tumor and the KRAS and STK11-co-mutated tumors. Significantly more FOXP3-high TILs were observed in invasive pathological subtypes than in non-invasive ones. Conclusion: Comparing TMEs among MPLCs revealed that non-smokers or light smokers and females were unlikely to express PD-L1 regardless of tumor site and confirmed that the EGFR mutations and co-occurring KRAS and STK11 or TP53 mutations were associated with TME. Pathological subtypes may impact the efficacy of immune therapy due to their potential correlations with regulatory T cells.

Adenoid cystic carcinomas (ACCs) are malignant tumors that most often occur in the salivary glands and bronchi, with occurrence in the breast being rare. ACCs of the breast reportedly give rise to few lymph node metastases or distant metastases and have a favorable prognosis. A 56-year-old woman with a left breast mass identified by mammographic screening was examined at our institute. Breast ultrasound revealed a sharply marginated, hypoechoic mass 12.7 × 9.4 × 8.7 mm in size in the upper outer quadrant of the left breast, and a vacuum-assisted biopsy (VAB) was performed at the mass site. Pathological examination of the VAB specimen revealed atypical cells with a cribriform growth pattern, and mucosal fluid surrounding tumor nests and within tumor ducts. The area around the tumor nests and inside of tumor ducts were also positively stained with alcian blue. These findings, we reached a pathological diagnosis of ACC. The preoperative diagnosis was stage I (cT1N0M0) triple-negative left breast cancer. Surgery consisted of breast-conserving surgery and sentinel node biopsy. The excised specimen was a 15.0 × 12.1 × 9.7 mm mass with a greyish white cut surface. Pathological examination of the excised specimen revealed a so-called adenoid cystic pattern. Results from immunohistochemical staining were identical to those from a VAB specimen, as they were estrogen receptor-negative, progesterone receptors-negative, and human epidermal growth factor receptor 2-negative, with low Ki67 expression. The final diagnosis, given the above findings, was left breast cancer (ACC) pT1N0M0 stage I triple-negative subtype.

The Chinese water pine Glyptostrobus pensilis is the sole surviving species of the genus Glyptostrobus. It is endemic to southern China, central Vietnam, and eastern Laos, and today it is nearly extinct in the wild. Forest community characteristics and population structure of G. pensilis in China have remained unknown up to now. We investigated six swamp forest stands and analyzed their forest community characteristics (i.e. vertical stratification, species composition, and diversity) and population structure, including the frequency distribution of DBH (diameter at breast height) and age-classes as found in Fujian Province, southeastern China.The vertical stratifications of all the forest stands were rather simple. The remaining wild specimens ranged from roughly 15 to some 357 years for an average of ca. 85 years, with only a few individuals less than 20 years old. Compared with the stands and populations of G. pensilis in Vietnam, the taxonomic compositions of the stands in the two regions were different, except for the dominant species-G. pensilis. The Shannon–Wiener index showed the overstory of each stand had much lower diversity (0.26 on average) in Fujian Province than that (1.97 on average) in Vietnam, whereas the diversity indices were about the same (around 2.41) for the understories in the two regions. Furthermore, we discovered 18 G. pensilis seedlings at the study sites in Fujian Province. This discovery demonstrates that G. pensilis regeneration is extremely poor and its populations are declining, although these populations are relatively healthier than those in Vietnam. Keywords: Age-class, Fujian Province, Glyptostrobus, Regeneration, Relict plant, Vietnam

Pure mucinous breast carcinoma with micropapillary pattern (MUMPC) was proposed as a new histopathological variant of pure mucinous carcinoma (PMC) with tumor cells forming a micropapillary architecture. The Classification of Tumours of the Breast by the World Health Organization, however, does not differentiate MUMPC as a distinct subtype. There is currently no consensus whether tumors that exhibit these features are classified as PMC or invasive micropapillary carcinoma (IMPC) with associated mucin production. A 45-year-old woman was examined for a tumor in her left breast. Upon physical examination, an elastic hard mass of around 5 cm along with accompanying skin flare and ulceration was palpated in the upper outer quadrant of the left breast. Mammary ultrasonography revealed a clearly marginated hypoechoic tumor of 55.0 × 46.9 × 37.0 mm in size in the upper outer quadrant of the left breast. A vacuum-assisted biopsy (VAB) was performed in the same site and histopathological diagnosis of PMC was made. Contrast-enhanced magnetic resonance imaging (MRI) showed a T1W1 low-intensity signal and a T2W1 high-intensity signal at the primary focus, ring enhancement of the tumor margin, and stranding enhancement inside the tumor. A preoperative diagnosis of left breast cancer (PMC), cT4bN1M0, stage IIIB, luminal B-like was made. We performed a simple mastectomy with axillary lymph node dissection. A 55.0 × 48.1 × 37.1 mm tumor with the gelatinous cut surface was excised. Histopathological examination of the excised specimen revealed mucin lake formation in the tumor containing clusters of atypical cells. The atypical cells showed swollen, irregular nuclei and a papillary growth pattern that lead to the diagnosis of MUMPC.

Background Tumor spread through alveolar spaces (STAS) is a recently described invasive pattern associated with the prognosis and recurrence of lung adenocarcinoma. This study was performed to determine whether the presence and distance of STAS can be predicted by the immunohistochemical intensity of SLX, a well‐known cell adhesion protein. Methods In total, 245 patients with pathological stage I lung adenocarcinoma who underwent lobectomy with radical mediastinal lymph node dissection were identified from 1998 to 2012. Recurrence‐free survival (RFS) was compared between patients stratified by STAS and the immunohistochemical intensity of SLX in the main tumor. Patients were divided into three groups based on the intensity of SLX staining: high (n = 108), moderate (n = 48), and low (n = 89). Results STAS was observed in 71 patients (29.0%). Patients with STAS had significantly poorer five‐year RFS (67.1%) than those without STAS (84.8%). Although no relationship was observed between the existence of STAS and SLX intensity, the distance between STAS cells and the main tumor was significantly shorter in the moderate group (median 0.9 mm, range: 0.2–1.2 mm) than in the other two groups (median 1.2 mm, range: 0.4–5.0 mm). The five‐year RFS rates in the high, moderate, and low groups were 80.0%, 96.0%, and 75.8%, respectively. Multivariate analysis revealed that pathological stage, lymphatic/vascular invasion, and SLX intensity were independent predictors of recurrence. Conclusion SLX staining cannot predict the presence of STAS; however, it can predict the distance between STAS and the main tumor in stage I lung adenocarcinoma.

Abstract Background Alveolar soft part sarcoma (ASPS) is an extremely rare neoplasm that tends to occur in the lower limbs of children and adolescents. Metastatic breast tumors constitute 0.5–2.0% of all malignant mammary neoplasms, and cases of ASPS with mammary metastases are very rare. Case presentation Three years ago, an 11-year-old girl presented to the hospital with pain in the right jaw after becoming aware of a mass in the right cheek. After detailed examination, the patient was diagnosed with ASPS with the primary tumor in the right cheek and multiple lung metastases, and chemotherapeutic treatment was initiated. One year later, accumulation of fluorodeoxyglucose (FDG) was observed in the right front of the skull (standardized uptake value (SUV)-max 2.8) and left breast (SUV-max 2.4) using FDG-positron emission tomography (PET) / computed tomography (CT). Ultrasonography revealed the mammary tumor as a hypoechoic, internally heterogeneous mass measuring 22.4 × 16.2 × 21.1 mm with a rich blood supply. Using pathological findings of core-needle biopsy, we diagnosed it as ASPS. Based on the above information, we made a diagnosis of ASPS with left mammary and cranial metastases. Due to chemoresistance, surgical excision was selected as the mode of treatment; resection of the metastatic cranial bone was performed first, and partial mastectomy of the left breast was performed in two stages. Postoperative conditions were good, and we are currently performing regular follow-ups (visual palpation every 3 months and semi-annual mammary gland ultrasonography). Conclusions We have reported an extremely rare case of ASPS with mammary metastasis with some reference-based discussion. In our case, disease control was obtained by a combination of drug therapy and surgical treatment.

Background and study aims Eosinophilic gastrointestinal disorders are classified into eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis according to the site of eosinophilic infiltration. Although well established in eosinophilic esophagitis, endoscopic findings in eosinophilic gastritis and eosinophilic gastroenteritis with regard to gastric lesions have not been clearly described. The aim of this study was to identify endoscopic findings of gastric lesions associated with eosinophilic gastrointestinal disorders. Patients and methods Out of 278 patients with eosinophilic gastrointestinal disorders, 18 had eosinophilic gastritis or eosinophilic gastroenteritis confirmed by biopsy; their endoscopic images were analyzed retrospectively. The association between endoscopic findings and number of eosinophils in the gastric mucosa was investigated. Results Erythema was most frequently observed (72 %), followed by ulcers (39 %), discoloration (33 %), erosions (28 %), nodularity (28 %), and polyps (28 %). There were several unique endoscopic findings such as submucosal tumor-like deep large ulcers in three patients, antral Penthorum-like appearances (small nodules radially lined toward the pyloric ring) in three patients, “muskmelon-like appearances” (discolored mucosa-composed mesh pattern) in three patients, multiple white granular elevations in two patients, cracks (appearance of furrows similar to those in eosinophilic esophagitis) in five patients, and antral rings in one patient. No significant association was observed between endoscopic findings and number of gastric eosinophils. Conclusions Several unique endoscopic findings of gastric lesions were observed in patients with eosinophilic gastritis or eosinophilic gastroenteritis. Submucosal tumor-like ulcers, antral Penthorum-like appearances, muskmelon-like appearances, and cracks might be associated with eosinophilic gastrointestinal disorders.

East Asia contains “relict” plant species that persist under narrow climatic conditions after once having wider distributions. Here, using distribution records coupled with ecological niche models, the authors identify long-term stable refugia possessing past, current and future climatic suitability favoring ancient plant lineages.

Abstract Background Ovarian serous borderline tumor/atypical proliferative serous tumor (SBT/APST) is characterized by presenting at an early stage and much longer survival than high-grade serous carcinoma. Given that the prognosis of ovarian SBT/APST with no invasive features is excellent, remote relapse after surgery can pose a diagnostic pitfall. Bone metastasis as transformed low-grade carcinoma is an extremely rare initial presentation of recurrence in patients whose primary tumor was confined to the ovaries. Case presentation A 55-year-old Japanese woman who had undergone surgery for a right ovarian tumor 13 years previously presented with right-lateral chest pain and neurologic abnormalities in the lower limbs. Computed tomography (CT) scan and magnetic resonance imaging revealed an irregular mass in the right arch of the 12th thoracic vertebra, extending through the intervertebral foramen and into surrounding soft tissue, the maximum diameter of the whole mass being 78 mm. Pathological examination of a CT-guided needle biopsy of the paraspinal lesion demonstrated papillary cell clusters with blunt nuclear atypia and psammomatous calcification that were positive for PAX8, estrogen receptor, and WT1, but negative for thyroglobulin on immunohistochemical testing, and of a P53 non-mutational pattern. On clinicopathologic review, the previous 13- × 11- × 9-cm ovarian tumor was an intracystic and exophytic papillary growth without surface involvement; it had ruptured intraoperatively. Microscopically there was serous epithelium with minimal cytologic atypia proliferating in hierarchical branches with no invasive foci or micropapillary components. The tumor was confined to the right ovary with no peritoneal implants. Neither primary nor metastatic tumor harbored KRAS/BRAF mutations according to polymerase chain reaction using formalin-fixed paraffin-embedded tissues. We concluded that, after a 13-year disease-free interval, the paraspinal lesion was bone metastasis of low-grade carcinoma originating from the ovarian SBT/APST. The patient received radiotherapy for the paraspinal lesion followed by administration of paclitaxel and carboplatin plus bevacizumab and remains alive 168 months after the initial surgery. Conclusions Pathologists and radiologists should not exclude late recurrence of ovarian SBT/APST when bone metastases are suspected, even when neither peritoneal nor lymph node involvement are detected. Long-term surveillance of women with ovarian serous tumors with no invasive features is recommended.

Abstract Background “Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. Methods A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry. Results There were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p

Abstract Background The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators. Methods The subjects consisted of 30 patients who received the TPD regimen. The expression levels of estrogen receptor, progesterone receptor, Ki67, CD8, forkhead box protein (FOXP) 3, programmed death (PD) 1, programmed death ligand (PD-L) 1, CD163, phosphatase and tensin homolog and lymphocyte activation gene 3 were evaluated in biopsy specimens, by immunostaining. Results CD8+, CD8/FOXP3 ratio (CFR)high and PD-L1− group had significantly longer PFS than the CD8−, CFRlow and PDL1+ group (p = 0.045, log-rank) (p = 0.007, log-rank) (p = 0.040, log-rank), respectively. The CFRhigh group had significantly better OS than the CFRlow group (p = 0.034, log-rank). In the univariate analysis, CD8+, CFRhigh groups extended PFS significantly (p = 0.027, hazard ratio [HR] = 0.162) (p = 0.008, HR = 0.195), respectively. The receiver operating characteristic (ROC) analyses showed that the results for CFR [area under the curve (AUC): 0.708] were better than those for other factors (AUC: CD8 = 0.681, FOXP3 = 0.639, PD1 = 0.528, PD-L1 = 0.681). Conclusions This study shows with the TPD regimen, a high CFR leads to a high ORR and long PFS in HER2-positive breast cancer. CFR, therefore, may be one of the important prognostic factors for this disease.

Abstract Background Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Previously, the differences between these two progression types did not affect the determination of treatment strategies since both PPL and PNM are classified as progressive disease based on the response evaluation criteria in solid tumors (RECIST) diagnostic criteria. On the other hand, tumor infiltrating lymphocytes (TILs) are effective when used as indicators for monitoring the immune tumor microenvironment (iTME) in the cancer host, and TILs play an important role as biomarkers in predicting prognosis and therapeutic effects. This study focused on the progression types of cancer in patients undergoing eribulin chemotherapy. In addition, the iTME in individuals with PPL and PNM was evaluated using TILs as a marker. Methods Of the 52 patients with locally advanced or metastatic breast cancer who underwent chemotherapy with eribulin, 40 remained in the study, and 12 patients were dropout cases. The antitumor effect was evaluated based on the RECIST criteria using version 1.1. TILs were defined as the infiltrating lymphocytes within tumor stroma and were expressed in proportion to the field investigated. In PPL cases, the high-TIL group was considered as type I and the low-TIL group was classified as type II. In PNM cases, the high-TIL group was considered as type III and the low-TIL group was classified as type IV. Results In 19 cases, individuals with type I progression had significantly longer progression free survival and overall survival (OS) compared to those with type III progression (p = 0.040, p

Abstract Background Clinically amyopathic dermatomyositis with anti-Melanoma Differentiation-Associated gene 5 (MDA5) antibody often presents with severe interstitial lung disease. Although serum ferritin level is known to reflect interstitial lung disease activity, there are few case reports describing this association. Case presentation A 58-year-old man was referred to our outpatient clinic with a 3-week history of cough and respiratory distress. He had erythema over the V area of the neck and a Gottron’s sign. Chest computed tomography revealed diffuse ground-glass opacities and reticular shadows in both lungs. Test for anti-MDA5 antibody was positive. After admission, he received triple combination therapy (methylprednisolone pulse therapy, tacrolimus, and cyclophosphamide). However, his respiratory condition worsened as the serum ferritin level increased. Despite no apparent deterioration on chest radiography, he ultimately died due to respiratory failure. Conclusions In this case, triple combination therapy was not effective for the patient’s respiratory condition. The serum ferritin level was correlated with disease activity and was more useful than chest radiography for monitoring clinical status.

Abstract Background The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses can be evaluated with tumor-infiltrating lymphocytes (TILs), which has frequently been verified clinically. On the other hand, residual cancer burden (RCB) evaluation has been shown to be a useful predictor of survival after neoadjuvant chemotherapy (NAC). In this study, RCB and TILs evaluations were combined to produce an indicator that we have termed “RCB-TILs”, and its clinical application to NAC for breast cancer was verified by subtype-stratified analysis. Methods A total of 177 patients with breast cancer were treated with NAC. The correlation between RCB and TILs evaluated according to the standard method, and prognosis, including the efficacy of NAC, was investigated retrospectively. The RCB and TILs evaluations were combined to create the “RCB-TILs”. Patients who were RCB-positive and had high TILs were considered RCB-TILs-positive, and all other combinations were RCB-TILs-negative. Results On multivariable analysis, being RCB-TILs-positive was an independent factor for recurrence after NAC in all patients (p < 0.001, hazard ratio = 0.048), triple-negative breast cancer (TNBC) patients (p = 0.018, hazard ratio = 0.041), HER2-positive breast cancer (HER2BC) patients (p = 0.036, hazard ratio = 0.134), and hormone receptor-positive breast cancer (HRBC) patients (p = 0.002, hazard ratio = 0.081). Conclusions The results of the present study suggest that RCB-TILs is a significant predictor for breast cancer recurrence after NAC and may be a more sensitive indicator than TILs alone.

Abstract Background Adrenocoricotrophic hormone (ACTH) – independent bilateral adrenocortical macronodular hyperplasia (AIMAH) is a rare cause of Cushing’s syndrome, and is characterized by bilateral adrenal hyperplasia. However, Primary aldosteronism (PA) is a relatively common adrenal disease. Case presentation A 56-year-old man who has been treated hypertension and diabetes mellitus was detected low plasma potassium level with an elevated level of plasma aldosterone concentration and bilateral adrenal swelling. Endocrinological examinations showed autonomous secretion of cortisol and aldosterone, with suppression of plasma ACTH level and renin activity. A selective adrenal venous sampling demonstrated that left adrenal gland was responsible for aldosterone hypersecretion. He was diagnosed preclinical Cushing’s syndrome due to ACTH – independent bilateral adrenocortical macronodular hyperplasia (AIMAH) associated with aldosterone producing adenoma of the left adrenal gland. A laparoscopic left adrenalectomy was performed. Conclusion The resected adrenal specimen histologically consisted with a diagnosis of AIMAH. Moreover, tiny cell clusters positive immunostaining for aldosterone synthase was revealed. This is a rare case of AIMAH accompanied by preclinical Cushing’s syndrome and primary aldosteronism.

Abstract Background Phyllodes tumor is a rare breast mass. Most phyllodes tumors are benign, but occasionally some show malignancy. Even if the tumors are benign, they can easily show recurrence. Case presentation We report a case of a 48-year-old Asian woman, who had previously undergone a tumorectomy of her left breast 12 years before, with a pathological diagnosis of fibroadenoma. Five years after the initial tumorectomy, the patient presented with an abnormally enlarged left breast. A biopsy determined the growth to be a phyllodes tumor; subsequently, a partial mastectomy was conducted. However, the patient’s left breast showed rapid enlargement in the next 5 months. The treating physicians suspected a relapse and subsequently consulted with our hospital. The breast mass was resected at our institution. After this surgery, the patient had repeated episodes of relapse and underwent four additional operations. Since then, the patient has not had any additional relapse so far. Conclusions We present a case of a phyllodes tumor with multiple episodes of relapse. Although phyllodes tumors commonly show relapse, this case was unique because of the number of episodes of relapse. This case highlights the need to carry out tumorectomy with adequate margins with subsequent careful observation to check for relapse.

Abstract Background The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated if variables such as tumor expression of β-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy. Methods The subjects included 52 patients with MBC who underwent chemotherapy with eribulin. The expression levels of Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor (HER) 2, Ki67, β-tubulin class III, GSTP-1 and TLE-3 were evaluated using immunostaining employing needle biopsy specimens. Results Patients with TLE3-negative tumors displayed significantly poorer outcomes regarding progression-free survival than patients with TLE3-positive tumors when prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions was analyzed (p = 0.011, log-rank). In contrast, no such difference in prognosis was found in a comparison of TLE-3 positive/negative patients in the group of all patients (p = 0.433, log-rank) or of patients with non-TNBC lesions (p = 0.659, log-rank). Based on a univariate analysis of 22 TNBC cases, a better progression-free survival correlated significantly with a positive TLE3 expression in the tumor (p = 0.025). A multivariate logistic regression analysis including 22 patients with TNBC also showed that a positive TLE3 expression significantly correlated with a better progression-free survival (p = 0.037). Conclusions Our findings suggest that TLE3 is a useful marker for predicting the therapeutic effect of eribulin chemotherapy for TNBC.

Abstract Background Circulating tumor cells (CTCs) are linked to metastatic relapse and are regarded as a prognostic marker for human cancer. High expression of plakoglobin, a cell adhesion protein, within the primary tumor is positively associated with CTC clusters in breast cancer. In this study, we investigated the correlation between plakoglobin expression and survival of breast cancer. Methods We evaluated 121 breast cancer patients treated with neoadjuvant chemotherapy. Expression of plakoglobin was identified by immunohistochemical staining in the cell membrane. We also examined the relation between the expression of plakoglobin and E-cadherin, an epithelial–mesenchymal transition (EMT) marker. Results Patients with high plakoglobin expression had significantly worse distant-metastasis-free survival (DMFS) (P = 0.016, log rank). Plakoglobin expression had no correlation with pathological complete response rate (P = 0.627). On univariate analysis with respect to distant metastasis, high plakoglobin expression showed worse prognosis than low plakoglobin expression [P = 0.036, hazard ratio (HR) = 3.719]. Multivariate analysis found the same result (P = 0.013, HR = 5.052). In addition, there was a significant relationship between the expression of plakoglobin and E-cadherin (P = 0.023). Conclusions Plakoglobin expression is an independent prognostic factor in patients with breast cancer, particularly for DMFS, and this is related to EMT.

Background: Alectinib is an oral drug developed for the treatment of patients with fusion gene encoding echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we present the case of a patient treated with alectinib who developed a hypersensitivity reaction with successful rechallenge treatment. Case Presentation: A 39-year-old woman who was a passive smoker was referred to Osaka City University Hospital for the evaluation of a skin event caused by treatment for NSCLC with the fusion gene EML4-ALK. The skin reaction was observed on the anterior chest, upper arms, and ear auricles on day 11 of treatment with oral alectinib. The skin event presented as widely distributed erythematous macules that were confluent, indicating a severe and life-threatening form. The skin lesions started to resolve after the initiation of treatment with 40 mg prednisolone. After regrowth of the tumor, she received a rechallenge program for alectinib for 2 weeks; thereafter, alectinib treatment was successfully reinitiated. Conclusion: To the best of our knowledge, we present the first case in which alectinib, which binds to the adenosine triphosphate site of EML4-ALK, induced erythema multiforme. Moreover, successful readministration of alectinib through our rechallenge program has not been reported so far.

Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively.Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.

In the original version of this Article, an incorrect sample size was provided for the number of relict species (443 instead of 442) and the number of relict forests (423 instead of 422). These errors have been corrected in both the PDF and HTML versions of the Article.

The peripheral blood platelet-lymphocyte ratio (PLR) has been proposed as an indicator for evaluating systemic inflammatory responses in cancer-bearing patients. While some reports suggest a correlation between PLR and prognosis, few studies have examined the relationship between PLR and sensitivity to chemotherapy. We conducted a study on whether PLR could serve as a predictor of the therapeutic effects of neoadjuvant chemotherapy (NAC).PLR was evaluated in 177 breast cancer patients treated with the NAC 5-fluorouracil, epirubicin and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between PLR and prognosis, and between PLR and the efficacy of NAC, were evaluated retrospectively.The low PLR group had significantly more patients > 56 years old (p = 0.001) and postmenopausal women (p = 0.001) than the high PLR group. The low PLR group also had a higher pathologic complete response (pCR) rate (p = 0.019). On examining the correlation with prognosis, the low-PLR group was found to have significantly longer disease-free survival (p = 0.004) and overall survival (p = 0.032) than the high PLR group. Multivariate analysis also revealed that lymph node metastasis (p = 0.043, hazard ratio = 4.40) and a high PLR (p = 0.005, hazard ratio = 2.84) were independent, unfavorable prognostic factors.For patients with breast cancer treated with NAC, a low PLR indicated high chemotherapy sensitivity, suggesting that PLR could serve as a predictive marker of the therapeutic effect of NAC.

Species assembly in ground beetle (Coleoptera: Carabidae) communities in local microhabitats was studied in a forest. The following questions were addressed: are there important filters that sort the species in the assemblages? If so, what is the specific nature of these filters? In order to address these questions rarefaction analysis was used to determine whether ground beetle species are distributed non-randomly. Next, the nature of filters was determined by analyzing (1) the community matrix and searching for the consequences of competitive exclusion and (2) species-environmental relations. Rarefaction analysis revealed that the species composition is filtered: species richness was less than expected and there were fewer than expected congeneric species coexisting at high beetle population densities. However, community matrix and body size analyses did not detect significant competition among the beetle species and the matrix was significantly nested. Species-environmental analyses indicated that the ground beetle assembly was strongly linked to ground vegetation. It is concluded that spatial distribution of ground beetles across local communities in this forest habitat is determined more by local environmental conditions than competition, and ground beetles do not interact strongly among themselves so that competitive effects do not play an important role in their distribution except at high beetle population densities.

A rare coniferous Tertiary relict tree species, Thuja sutchuenensis Franch, has survived in the Daba Mountains of southwestern China. It was almost eliminated by logging during the past century. We measured size and age structures and interpreted regeneration dynamics of stands of the species in a variety of topographic contexts and community associations. Forest communities containing T. sutchuenensis were of three types: (1) the Thuja community dominated by T. sutchuenensis, growing on cliffs; (2) the Thuja-Quercus-Cyclobalanopsis community dominated by T. sutchuenensis, Quercus engleriana and Cyclobalanopsis oxyodon, along with Fagus engleriana and Carpinus fargesiana, on steep slopes; (3) the Thuja-Tsuga-Quercus community dominated by T. sutchuenensis, Tsuga chinensis, and Quercus spinosa, on crest ridges. The established seedlings/saplings were found in limestone crevices, on scarred cliff-faces, cliff-edges, fallen logs, canopy gaps and forest margins. The radial growth rate was 0.5-1.1 mm per year. Its growth forms were distorted. It had strong sprouting ability after disturbances. The T. sutchuenensis population thrives on cliffs where there is little competition from other species because of harsh conditions and rockslide disturbances. It is shade-intolerant but stress-tolerant. Its regeneration has depended on natural disturbances.

Neoadjuvant chemotherapy (NAC) is a standard care regimen for patients with breast cancer. However, the pathologic complete response (pCR) rate remains at 30%. We hypothesized that a cancer stem cell marker may identify NAC-resistant patients, and evaluated CD133 and ALDH1 as a potential surrogate marker for breast cancer. The aim of this study was to find a surrogate maker to predict chemosensitivity of NAC for breast cancer.A total of 102 patients with breast cancer were treated with NAC consisting of epirubicin followed by paclitaxel. Core needle biopsy (CNB) specimens and resected tumors were obtained from all patients before and after NAC, respectively. Chemosensitivity and prognostic potential of CD133 or ALDH1 expression was evaluated by immunohistochemistry. Clinical CR (cCR) and pCR rates were 18% (18/102) and 29% (30/102), respectively. Forty-seven (46%) patients had CD133-positive tumors before NAC, and CD133 expression was significantly associated with a low pCR rate (p=0.035) and clinical non-responders. Multivariate analysis revealed that CD133 expression was significantly (p=0.03) related to pCR. Recurrence was more frequent in patients with CD133-positive tumors (21/47, 45%) than that in patients with CD133-negative tumors (7/55, 13%). The number of patients with CD133-positive tumors (62%) after NAC was higher than that (46%) before NAC. Furthermore, most patients with CD133-positive tumors before NAC maintained the same status after NAC.CD133 before NAC might be a useful marker for predicting the effectiveness of NAC and recurrence of breast cancer after NAC.