Fibromatosis-like metaplastic carcinoma of the breast:Two case reports

BACKGROUND Fibromatosis-like metaplastic carcinoma is classified as a rare type of metaplastic carcinoma of the breast by the 2012 WHO pathological and genetic classification criteria for breast tumors,which takes hyperplastic spindle cells as the main component and is often misdiagnosed as benign stromal proliferative lesions or benign mesenchymal tumors of the breast because of its mild morphology.Here,we collected the clinical data of 2 cases of fibromatosis-like metaplastic carcinoma of the breast and performed pathomorphological observation and immunohistochemical staining of the surgically resected specimens.According to the clinical features,imaging features,immunophenotype,diagnosis and differential diagnosis of 2 cases of fibromatosis-like metaplastic carcinoma of the breast,it was further differentiated.CASE SUMMARY Case 1:A 56-year-old postmenopausal female was admitted due to"right breast mass for over 1 year and local ulceration for over 1 mo".Physical examination showed a mass with a diameter of 4.5 cm×5.5 cm palpable at 2.5 cm from the nipple at 1 o'clock in the right breast.The skin on the surface of the mass ruptured about 3 cm,with a small amount of exudation and bleeding,less clear boundary,hard texture,fair activity,without obvious tenderness.No obvious abnormality was palpable in the left breast.No enlarged lymph nodes were palpable in the bilateral axillae and bilateral supraclavicular region.After removing the mass tissue,it was promptly sent to the pathology department for examination.Case 2:Female,52-years-old,premenopausal,admitted due to"right breast mass for more than 3 mo".Physical examination showed a 4.0 cm×4.0 cm diameter mass palpable at 2.0 cm of the nipple in the lower outer 7 o'clock direction of the right breast,with less clear boundary,hard texture,fair activity,no significant tenderness,no palpable significant abnormalities in the left breast,and no palpable enlarged lymph nodes in the bilateral axillae and bilateral supraclavicular region.The mass was resected and sent for pathological examination.Postoperative pathological examination revealed fibromatosis-like metaplastic carcinoma of the breast in both patient 1 and patient 2.No systemic therapy and local radiotherapy were performed after surgery,and no tumor recurrence or metastasis was observed.CONCLUSION Fibromatosis-like metaplastic carcinoma of the breast is a rare subtype of metaplastic carcinoma that is often misdiagnosed,and the diagnosis relies on medical history collection,complete sampling,and full use of immunohistochemical assessment.The risk of lymph node and distant metastasis is low,and the current treatment is based on complete surgical resection.The efficacy of systemic radiotherapy and chemotherapy is not clear.

Priming stimulation modifies synaptic plasticity in the perforant path of hippocampal slice in rat

Objective The potential of all central nervous system synapses to exhibit long term potentiation （LTP） or long term depression （LTD） is subject to modulation by prior synaptic activity, a higher-order form of plasticity that has been termed metaplasticity. This study is designed to examine the plasticity and metaplasticity in the lateral perforant path of rat. Methods Field potential was measured with different priming and conditioning stimulation protocols. Results Ten-hertz priming, which does not affect basal synaptic transmission, caused a dramatic reduction in subsequent LTP at lateral perforant path synapses in vitro, and the reduced LTP lasted for at least 2 h. The LTD was unaffected. The reduction of LTP in the lateral perforant path was also readily induced by applying priming antidromically at the mossy fibers. Conclusion Priming with 10 Hz, which is within a frequency range observed during physiological activity, can cause potent, long-lasting inhibition of LTP, but not LTD. This form of metaplasticity adds a layer of complexity to the activity-dependent modification of synapses within the dentate gyrus.

Introduction to Neural Plasticity Mechanism

In researches that examine neuroplasticity, many studies that are performed directly on isolated neurons in the pyramidal cells of CA1 area (CA1) and slices of the hippocampus indicate that changes occur at the molecular and cellular levels during long-term synaptic potentiation (LTP), and these changes are dependent on N-methyl-D-aspartate (NMDA) acid receptors and/or purinergic receptors. Electrophysiological studies and the chemical induction of LTP of synaptic neurotransmissions provide key evidence that LTP is dependent on the volume of Ca2+ influx through postsynaptic NMDA receptors, in addition to the subsequent activation and autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the increase in the density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on postsynaptic neuronal membranes. The primary peculiarity of LTP in the central nervous system (CNS) excitatory synapses is the synthesis of additional AMPA receptors in the postsynaptic elements. Furthermore, the proteolysis of the extracellular matrix (ECM) has an important role in the synaptic neuroplasticity of the CNS. Proteases from the serine family and metalloproteinases of the extracellular matrix are localized within the synapses and are released into the extracellular space in proportion to the degree of neuronal excitation. These enzymes cause changes in the morphology, shape and size, as well as the overall number of synapses and synthesize new synaptic connections. The proteinases also change the function of receptors, and consequently, the secretions of neurotransmitters from the presynaptic elements are strengthened or weakened.

Repetitive transcranial magnetic stimulation for post-traumatic stress disorder:Lights and shadows

We have read with interest the publication that describes the available data related to the use of neuromodulation strategies for the treatment of posttraumatic stress disorder(PTSD).Despite treatment advances,however,a substantial proportion of PTSD patients receiving psychological and/or pharmacological treatment do not reach an adequate clinical response.In their paper,the authors draw attention to the current understanding of the use of repetitive transcranial magnetic stimulation(rTMS)as a potential treatment for PTSD.Most of the previous studies indeed applied both inhibitory(1 Hz)and excitatory(>1 Hz,up to 20 Hz)rTMS to the right and/or left dorsolateral prefrontal cortex.Despite larger therapeutic effects observed when high-frequency stimulation was applied,the question of which side and frequency of stimulation is the most successful is still debated.The authors also reported on the after-effect of rTMS related to neuroplasticity and identified the intermittent theta burst stimulation as a technique of particular interest because of it showed the most effective improvement on PTSD symptoms.However,although numerous studies have highlighted the possible beneficial use of rTMS protocols for PTSD,the exact mechanism of action remains unclear.In their conclusions,the authors stated that rTMS has been demonstrated to be effective for the treatment of PTSD symptoms.Nevertheless,we believe that further research with homogeneous samples,standardized protocols,and objective outcome measures is needed to identify specific therapeutic targets and to better define significant changes when active and sham stimulation procedures are compared.

Clinicopathological analysis of metaplastic meningioma: report of 15 cases in Huashan Hospital

Objective： Metaplastic meningioma is a rare subtype of benign meningiomas, classified as WHO grade I with well prognosis. Here we presented our experiences on 15 cases of metaplastic meningioma, to investigate the clinicopathological features, therapies and prognosis of these cases. Methods： 15 patients underwent surgical treatment for intracranial metaplastic meningioma between 2001 and 2010 at Neurosurgery Department of Huashan Hospital, Shanghai, China. The clinical data, radiological manifestation, treatment strategy, pathological findings and prognosis of all patients were analyzed retrospectively. Results： Among the 15 cases （10 males and 5 females）, the age ranged from 22 to 74 years old （the mean age was 50.67-year old）. The clinical manifestations include headache, dizziness, seizure attack, vision decrease, and weakness of bilateral lower limbs. All the patients received surgical treatment, combined with radiotherapy in some cases. In the follow-up period, recurrence occurred in 2 cases, of which 1 patient died of other system complications. Conclusions： Metaplastic meningiomas are characterized by focal or widespread mesenchymal differentiation with formation of bone, cartilage, fat, and xanthomatous tissue elements. Surgical removal is the optimal therapy, and the overall prognosis is well. But recurrence may occur in some cases, thus radiotherapy is necessary for such kind of patients.

Metaplastic breast cancer with chondrosarcomatous differentiation combined with concurrent bilateral breast cancer:A case report

BACKGROUND Metaplastic breast carcinoma(MBC)is a rare subtype of invasive breast cancer comprising malignant epithelial and mesenchymal cells.Compared with other invasive breast cancers,MBC is not only histologically distinctly heterogeneous but also has a rapid and aggressive growth pattern,which leads to a significant risk of recurrence and mortality.CASE SUMMARY In this study,we report the case of a patient with a large left breast mass diagnosed with bilateral invasive ductal carcinoma in both breasts after a preoperative core needle aspiration biopsy of the bilateral breast mass.The patient received neoadjuvant chemotherapy and underwent bilateral breast modified radical mastectomy.Postoperative pathology suggested carcinosarcoma with predominantly chondrosarcoma in the left breast and invasive ductal carcinoma(luminal B)in the right breast.As the patient did not achieve complete pathological remission after six cycles of neoadjuvant chemotherapy,we administered six months of intensive capecitabine treatment.Then the patient was switched to continuous treatment with endocrine therapy using letrozole+goserelin,and the patient is currently in stable condition.However,as MBC of the breast is concurrently diagnosed with chondrosarcoma differentiation,our case is sporadic.CONCLUSION Given the variety of immunohistochemical types of bilateral breast cancer,achieving effective chemotherapy should be a key research focus.

Clinicopathological Study of Epithelial Metaplastic Breast Cancer

Introduction: Metaplastic breast cancer (MBC) is a rare pathological type with an incidence rate of not more than 1%, and has been reported to be often detected after its progression and highly malignant with a high proportion of triple negative type tumors, with poor outcomes as compared to IDC [1] [2] [3]. We analyzed clinicopathological characteristics of patients who underwent surgery for epithelial MBC at our department. Patients and Methods: From January 2000 to March 2014, a total of 2120 patients underwent surgery for breast cancer, and MBC was diagnosed in 15 of these patients. Fourteen of the 15 had epithelial MBC and were included in this study. The present study compared clinopathological characteristics of MBC with those of IDC of triple negative type (TN type group) and IDC of non-triple negative type (IDC group). Results: Breast conserving surgery was performed in 7 patients with MBC (50%), a proportion clearly lower than the 64.3% in the IDC group. The mean tumor size was 3.8 cm, which was greater than the 2.13 cm in the TN type group and the 1.7 cm in the IDC group. About nuclear grade, the proportion of grade III was 57.1%, markedly higher than the 38.6% in the TN type group and the 12.6% in the IDC group. All patients were estrogen receptor (ER) and progesterone receptor (PgR) negative;11 patients were TN type tumors and 3 were HER2 type. Conclusion: We studied patients who underwent surgery for epithelial MBC. The examined cases showed clinopathological characteristics of the disease, including large tumors with a highly malignant nature at the initial detection, higher Ki-67 levels, ER and PgR negativity (all cases), mostly TN type, and a high recurrence rate.

Diagnosis and management of Barrett’s metaplasia:What’s new?

Barrett’s esophagus(BE) is a complication of gastroesophageal reflux disease,and a premalignant lesion for esophageal adenocarcinoma(EAC).Observational studies suggest that endoscopic surveillance is associated with the detection of dysplasia and EAC at an early stage along with improved survival,but controversies still remain.The management of patients with BE involves endoscopic surveillance,preventive and clinical measures for cancer,and endoscopic and surgical approaches to treatment.Deciding upon the most appropriate treatment is a challenge.This study presents the results and the effectiveness of these practices.

Male metaplastic breast cancer with poor prognosis:A case report

BACKGROUND Metaplastic breast cancer(MBC)is a rare subtype of breast cancer.They constitute less than 1%of breast cancer cases and are much rarer in males.There are few reports of MBC because of its rarity.MBC,an aggressive type of cancer,is refractory to common treatment modalities of breast cancer and has a poor prognosis.CASE SUMMARY We report a case of MBC in a 78-year-old man.He visited our clinic with a palpable mass on the left breast with no masses in the axillary areas.He had previously undergone robot-assisted laparoscopic radical prostatectomy for prostate cancer,but there was no family history of malignancy.The breast mass was visible on ultrasonography,mammography,and magnetic resonance imaging,and chest computed tomography revealed a lung mass in the posterior basal segment of the right lower lobe.The patient was diagnosed with metaplastic carcinoma on core needle biopsy with lung metastasis.Total mastectomy with sentinel lymph node biopsy and video-assisted segmentectomy of the right lung was performed.However,multiple metastases appeared 3 mo after surgery in the brain,chest,and abdomen,and the patient died 5 mo after the initial diagnosis.CONCLUSION MBC is an aggressive and extremely rare breast cancer type.Further case reports are needed to determine the optimal treatment.

Metaplastic Carcinoma of the Breast: A Clinical Study of 7 Cases from Balochistan

Metaplastic carcinomas of the breast are rare heterogenous neoplasms characterized by adenocarcinoma with dominant areas of spindle cells, squamous and/or other mesenchymal differentiation, that comprise of <5% of all invasive breast cancers. Our objective in this study was to review the pathological features and clinical outcomes for metaplastic carcinoma of breast in breast cancer patients registered in CENAR (Center for Nuclear Medicines and Radiotherapy), Balochistan. Present study was performed on 7 patients affected with metaplastic carcinoma of breast, who were registered patients in CENAR. Informed consent was taken from the patients and BMI was calculated by measuring the height and weight of the patients. Available clinical history obtained by retrieving the patients file and a copy of biopsy report was also obtained from the file. Metaplastic carcinoma of breast was 4.11% of all 170 breast cancer cases registered in CENAR from 2010-2012. Mean age was 40 years ranging from 25 - 50 years. Four subtypes of metaplastic carcinoma of breast were reported in this study;DCIS component was present in one case and mean tumor size was 6.12 cm ranging from 3.5 - 10 cm. Metaplastic carcinomas of breast are rare heterogenous neoplasm with different characteristics, demographics and tumor biology and accounts for almost >5% of all breast cancer cases.

Special Features of Metaplastic Breast Cancer in Tunisian Women

Introduction: Metaplastic breast carcinomas are a rare, heterogeneous group of breast malignancies characterized by an intrinsically aggressive histology and an unfavorable prognosis. Objective: To determine the clinical and pathological characteristics of metaplastic breast cancers in Tunisian patients, and evaluate their impact on its evolution. Methods: A retrospective study of 44 cases of metaplastic cancers archived during a 26-year period in the Cancer Registry of the Tunisian Center. Results: The frequency of metaplastic cancer was 0.97%. Mean age at diagnosis was 55.4 years (range 26 - 84). Average time to diagnosis was 5.5 months. Average clinical tumor size was 4.95 cm (range 1.5 - 15). Axillary ipsilateral adenopathy was present at diagnosis in 45.9%. The clinical stages IIB (31.8%) and IIA (22.7%) predominated. Squamous metaplasia was the most common (68%) followed by the heterologous mesenchymal subtype. Ganglionic invasion was histologically proven in 17 cases, of which 77% had only adenocarcinomatous contingents. Absence of hormone receptor expression and HER2 overexpression predominated. Primary surgery was carried out in 95% of cases. Average follow-up was 40 months (range 2 - 135). Average overall survival (OS) was 74 months, 63% at 5 years and 60% at 10 years. Average progression free survival (PFS) was 29 months (range 3 - 129), 38% at 5 years and 32% at 10 years. Factors significantly influencing OS and PFS were histological lymph node involvement (p = 0.001 and p = 0.002 respectively). Conclusion: Metaplastic breast cancer observed in Tunisian women constitutes a histological type with an unfavorable prognosis whose improvement requires a more adapted therapeutic strategy.

Metaplastic meningioma with pure and extensive cartilaginous transformation: A diagnostic dilemma

Meningiomas are the most common extra-axial central nervous system tumours and often discovered in the middle to late adult life and especially in women. About 85%-90% of meningiomas are benign, 5%-10% are intermediate-grade, and 3%-5% are malignant. Metaplastic meningioma is a rare subtype of WHO Grade I meningioma histologically characterized by the presence of mesenchymal components. The presence of pure and extensive cartilaginous differentiation in meningiomas is extremely rare and remains a diagnostic dilemma. We report, perhaps the first case of this entity in a 52-year-old woman and discuss the pathogenesis, the imaging features and the histopathologicals data.

Electric-Induced Cycloelimination for Simulating Structural Plasticity in Organic Nociceptors

Continuous lifelong acquisition,updating,and finetuning of knowledge and skills is of crucial significance for the survival of humans.However,current neuromorphic devices exhibit obvious catastrophic forgetting when restimulated by new information.This remains a challenge for neuromorphic devices and artificial intelligence to achieve continuous learning.Herein,we propose an electric-induced cycloelimination strategy to realize an organic transistor nociceptor that can simulate synaptic and structural plasticity.The system benefits from the ring-opening characteristics of cross-linked poly(vinyl cinnamate)under a strong pulse voltage,during which new energy-level trap states are formed.The prepared organic transistor nociceptors exhibit both structural and synaptic plasticity.They simulate the characteristics of human nociceptors,including threshold,relaxation,sensitization,and maladaptation behavior.For the first time,we have simulated and explored the structural plasticity behavior in organisms based on electronic devices.More remarkably,the transistor nociceptors realize the reinput of information without forgetting the initial informa tion.The strategy developed for the preparation of organic transistor nociceptors provides insights for addressing the catastrophic forgetting in the lifelong learning of intelligent neuromorphic devices.

Bioinformatics analysis of human kallikrein 5 (KLK5) expression in metaplastic triple‐negative breast cancer

Background:Metaplastic breast carcinoma(MBC)is a rare breast cancer subtype;most cases are triple‐negative breast cancers(TNBCs)and are poorly responsive to conventional systemic therapy.Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered.We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.Methods:Differentially expressed genes(DEGs)in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407.The GSE76275 data set and The Cancer Genome Atlas(TCGA)database were used to screen DEGs in TNBC and non‐TNBC.Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology(GO)analysis of DEGs.Online databases,including UALCAN,GEPIA,HPA,Breast Cancer Gene‐Expression Miner,and quantitative PCR and western blot,were used to examine KLK5 messenger RNA and protein expression in breast cancer.Analysis of KLK5‑associated genes was performed with TCGA data,and the LinkedOmics database was used to detect the genes co‐expressed with KLK5.STRING(Search Tool for the Retrieval of Interacting Genes)and Cytoscape were used to screen for hub genes.Kaplan‑Meier plotter was used for survival analysis.Results:KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC.The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC.KEGG and GO analyses revealed that epithelial‐to‐mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1and DSG3 influence metaplastic TNBC progression. Prognosis analysis showedthat only low expression of KLK5 in metaplastic TNBC had clinical significance.Conclusion: Our research indicated that KLK5 may be a pivotal moleculewith a key role in the mechanism of tumorigenesis in metaplastic TNBC.