Auswahl der wissenschaftlichen Literatur zum Thema „Marine sarcoma“

Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1, and SOD-2. Moreover, TP4-induced mitochondrial hyperpolarization is followed by elevation of mitochondrial ROS. Calcium overload is also triggered by TP4, and cell death can be attenuated by a necrosis inhibitor, ROS scavenger or calcium chelator. In our experiments, TP4 displayed strong anticancer activity in human synovial sarcoma cells by disrupting oxidative status, promoting mitochondrial hyperpolarization and causing calcium overload.

Synovial sarcoma is a rare but highly malignant and metastatic disease. Despite its relative sensitivity to chemotherapies, the high recurrence and low 5-year survival rate for this disease suggest that new effective therapeutic agents are urgently needed. Marine antimicrobial peptide epinecidin-1 (epi-1), which was identified from orange-spotted grouper (Epinephelus coioides), exhibits multiple biological effects, including bactericidal, immunomodulatory, and anticancer activities. However, the cytotoxic effects and mechanisms of epi-1 on human synovial sarcoma cells are still unclear. In this study, we report that epi-1 exhibits prominent antisynovial sarcoma activity in vitro and in a human SW982 synovial sarcoma xenograft model. Furthermore, we determined that calcium overload-induced calpain activation and subsequent oxidative stress and mitochondrial dysfunction are required for epi-1-mediated cytotoxicity. Interestingly, reactive oxygen species (ROS)-mediated activation of extracellular signal-regulated kinase (ERK) plays a protective role against epi-1-induced cytotoxicity. Our results provide insight into the molecular mechanisms underlying epi-1-induced cell death in human SW982 cells.

PURPOSE: To report the activity of the chemotherapeutic agent ecteinascidin-743 (ET-743) in advanced pretreated sarcoma patients observed during a phase I study and a named-patient basis, compassionate use program. PATIENTS AND METHODS: Twenty-nine pretreated, advanced soft tissue sarcoma (STS) and bone sarcoma patients consecutively seen in our centers were included, 12 from a phase I trial and 17 from a compassionate use program cohort. Patients were treated every 3 weeks at either 1,200 μg/m2 (six patients), 1,500 μg/m2 (the recommended dose, 22 patients), or 1,800 μg/m2 (the maximum-tolerated dose, one patient), given as a 24-hour infusion every 3 to 4 weeks. RESULTS: Fifteen men and 14 women were treated. The median patient age was 46 years (range, 16 to 71 years), with a median World Health Organization performance status of 1 (range, 0 to 2). Twenty-five patients had STS, three had osteosarcoma, and one had Ewing’s sarcoma, and all had progressive disease at accrual. Fifteen patients had bulky disease, and 14 had clinical resistance to anthracyclines. A total of 136 treatment cycles were administered (median per patient, five cycles; range, one to 12 cycles). Transient grade 3 and 4 transaminitis was reported in 24% and 5% of cycles, respectively, grade 3 to 4 neutropenia occurred in 32% of cycles, with concomitant sporadic grade 3 to 4 thrombocytopenia in 5.1% of cycles. Grade 2 to 3 asthenia occurred in 21% of cycles. There were two partial responses (PRs) in STS patients and two PRs in osteosarcoma patients. Two minor responses and 10 disease stabilizations were seen. Median duration of response was 10.5 months (range, 2.8 to 15 months), and mean duration of stabilization was 5.2 months. CONCLUSION: ET-743 has activity in advanced, highly pretreated STS and osteosarcoma patients and warrants further trials to establish the extent of its activity in this setting.

Purpose To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. Patients and Methods Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 μg/m2 every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. Results Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean ± standard deviation), 1.04 ± 0.48 ng/mL and 35.6 ± 16.2 L/h/m2, respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. Conclusion ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.

The curiosity and attention that researchers have devoted to alkaloids are due to their bioactivities, structural diversity, and intriguing chemistry. Marine-derived macrocyclic alkaloids (MDMAs) are considered to be a potential source of drugs. Trabectedin, a tetrahydroisoquinoline derivative, has been approved for the treatment of metastatic soft tissue sarcoma and ovarian cancers. MDMAs displayed potent activities that enabled them to be used as anticancer, anti-invasion, antimalarial, antiplasmodial, and antimicrobial. This review presents the reported chemical structures, biological activities, and structure–activity relationships of macrocyclic alkaloids from marine organisms that have been published since their discovery until May 2020. This includes 204 compounds that are categorized under eight subclasses: pyrroles, quinolines, bis-quinolizidines, bis-1-oxaquinolizidines, 3-alkylpiperidines, manzamines, 3-alkyl pyridinium salts, and motuporamines.

10060 Background: Trabectedin, a marine-derived antineoplastic agent, binds to the minor groove of DNA and has previously shown activity in L-sarcomas in single-arm trials. This multicenter, randomized study aimed to characterize the anticancer efficacy with two dosing regimens of trabectedin in pts with treatment-refractory L-sarcomas. Methods: Eligible pts had measurable advanced L-sarcoma, progression despite at least prior A and I, PS 0–1 and adequate organ function. Pts were randomized to IV trabectedin, 1.5 mg/m2, 24h every 3 weeks (q3wk-24h) or 0.58 mg/m2, 3h weekly × 3 on a 28-day cycle (qwk-3h). Primary endpoint is time-to-progression (TTP) and secondary endpoints PFS, overall survival, response, and safety. With 217 events, study provided 90% power to detect a 37% risk reduction in TTP (2-sided 5% significance). Results: 270 pts were randomized as of 5/31/06. Baseline characteristics were comparable: median (range) 2 (1–7) metastatic sites and 2 (1–6) prior regimens; 62% had additional prior agents; 67% had bulky (≥5cm) disease. In the q3wk-24h vs qwk-3h arms median n. cycles were 5 (1–37) vs 2 (1–21); 38% vs 19% received ≥7 cycles. In protocol-specified primary analysis, median (95% CI) TTP was 3.7 (2.1–5.4) vs 2.3 (2.0–3.5) mo [HR: 0.734; p=0.0302] favoring the q3wk-24h arm. Median PFS was 3.3 (2.1–4.6) vs 2.3 (2.0–3.4) mo [HR: 0.755; p=0.0418] and median survival (n=175 events) was 13.8 (12.5–17.9) vs. 11.8 (9.9–13.9) mo [HR: 0.823; p=0.1984]. Benefit from the q3wk-24h arm was more pronounced in pts with central pathology confirmed diagnosis of L-sarcomas. More neutropenia, ↑AST/ALT, emesis and fatigue occurred in the q3wk 24-h. Febrile neutropenia was rare (0.8–1.6%). No cumulative toxicities were noted. Conclusions: Trabectedin can provide clinical benefit to pts with L-sarcoma following failure of all conventional treatment options. Significantly better TTP was noted with the q3wk-24h regimen, although this resulted in somewhat more neutropenia and transaminitis without clinical consequences. No cumulative toxicities were apparent in either arm. Although both dosing regimens are efficacious, there appears to superior disease control with the q3wk-24h arm in this population. [Table: see text]

BALB and Harvey murine sarcoma viruses contain ras transforming genes capable of altering the proliferation and differentiation of cells within the erythroid and lymphoid lineages (W. D. Hankins and E. M. Scolnick, Cell 26:91-97, 1981; J. H. Pierce and S. A. Aaronson, J. Exp. Med. 156:873-887, 1982; E. M. Scolnick et al., Mol. Cell. Biol. 1:68-74). The present studies demonstrate hematopoietic targets of ras-containing viruses within the myeloid lineage. Diffuse colonies were induced by BALB or Harvey marine sarcoma virus infection of murine bone marrow cells. Generally, these colonies were made up of relatively mature macrophages which exhibited increased self-renewal capacity but eventually underwent terminal differentiation in culture. Cells from one BALB murine sarcoma virus-induced colony displayed phenotypic markers of more immature myelomonocytic cells. This colony, designated BAMC1, readily established as a continuous cell line and was highly malignant in vivo. Exposure of these cells to 12-O-tetradecanoylphorbol-13-acetate led to the induction of a more mature myeloid phenotype, which was associated with decreased growth potential in vitro and in vivo. The effects of the inducing agent were not mediated by an alteration in the level of expression of the ras-coded p21 transforming protein. Our present findings extend the spectrum of targets whose growth is altered by ras-containing retroviruses to cells at several stages of differentiation within each of the major hematopoietic lineages.

BALB and Harvey murine sarcoma viruses contain ras transforming genes capable of altering the proliferation and differentiation of cells within the erythroid and lymphoid lineages (W. D. Hankins and E. M. Scolnick, Cell 26:91-97, 1981; J. H. Pierce and S. A. Aaronson, J. Exp. Med. 156:873-887, 1982; E. M. Scolnick et al., Mol. Cell. Biol. 1:68-74). The present studies demonstrate hematopoietic targets of ras-containing viruses within the myeloid lineage. Diffuse colonies were induced by BALB or Harvey marine sarcoma virus infection of murine bone marrow cells. Generally, these colonies were made up of relatively mature macrophages which exhibited increased self-renewal capacity but eventually underwent terminal differentiation in culture. Cells from one BALB murine sarcoma virus-induced colony displayed phenotypic markers of more immature myelomonocytic cells. This colony, designated BAMC1, readily established as a continuous cell line and was highly malignant in vivo. Exposure of these cells to 12-O-tetradecanoylphorbol-13-acetate led to the induction of a more mature myeloid phenotype, which was associated with decreased growth potential in vitro and in vivo. The effects of the inducing agent were not mediated by an alteration in the level of expression of the ras-coded p21 transforming protein. Our present findings extend the spectrum of targets whose growth is altered by ras-containing retroviruses to cells at several stages of differentiation within each of the major hematopoietic lineages.

The marine environment is an excellent source of molecules that have a wide structural diversity and a variety of biological activities. Many marine natural products (MNPs) have been established as leads for anticancer drug discovery. Most of these compounds are alkaloids, including several chemical subclasses. In this review, we focus on the bis-indolyl alkaloid Nortopsentins and their derivatives with antiproliferative properties. Nortopsentins A–C were found to exhibit in vitro cytotoxicity against the P388 murine leukaemia cell line. Their structural manipulation provided a wide range of derivatives with significant anti-tumour activity against human cell lines derived from different cancer types (bladder, colon, gastric, CNS, liver, lung, breast, melanoma, ovarian, pancreatic, prostate, pleural mesothelioma, renal, sarcoma, and uterus). In vivo assays on animal models also proved that Nortopsentins and related bis-indolyl compounds have potent anti-inflammatory activity. These remarks set the foundation for future investigations into the development of new Nortopsentin derivatives as new anticancer and anti-inflammatory agents.

INTRODUÇÃO: O mixofibrossarcoma (MFS) é um dos mais frequentes sarcomas de partes moles (SPM) em idosos que afeta principalmente as extremidades. Historicamente, é um grupo de tumores heterogêneos. Clinicamente está caracterizado por apresentar uma alta incidência de recorrência local (RL) e um conhecimento limitado sobre a sua capacidade de metástase. O índice de RL após a ressecção cirúrgica é relativamente maior quando comparado com outros SPM. Não existe um consenso em como identificar os pacientes com maior risco. O objetivo deste estudo foi analisar os fatores de prognóstico dos pacientes diagnosticados com MFS em uma instituição única. MÉTODOS: Foram analisados retrospectivamente os prontuários de 75 pacientes com diagnóstico confirmado de MFS nas extremidades, que foram submetidos a tratamento cirúrgico, nos últimos 25 anos. Comparamos idade, sexo, tamanho e localização do tumor, grau histológico segundo a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) e o estádio segundo a American Joint Committee on Cancer (AJCC). A média de idade foi 49,7 anos. A localização foi: membro superior (25,4%), membro inferior (66,6%) e pelve (8%). Os pacientes apresentaram baixo, intermediário e alto grau, em: 29,3%, 24% e 46,7% dos tumores, respectivamente. Pelo tamanho foram categorizados em: =/< 5 cm (13,3%), > 5 e <10 cm (42,7%), > 10 e <15 cm (9%) e =/> 15 cm (18,7%). Em total, 26,7% receberam radioterapia pós-operatória. As margens foram livres em 76% e comprometidas em 24%. A análise da regressão de Cox bivariada foi utilizada para determinar as associações entre os fatores clínicos e de tratamento com a RL. RESULTADOS: O tempo médio de seguimento foi 30.7 meses. O 26,7% dos pacientes apresentaram RL. Metástase foi reportada em 27 (36%) pacientes. O local mais comum de metástase foi: pulmão (92,6%) e gânglios linfáticos (18,5%). O tempo médio de sobrevida dos pacientes com metástase foi 21,2 meses. Os fatores preditivos para RL foram: margens comprometidas (hazard ratio 5.47, 95% intervalo de confiança, 2.23-13.40, P < 0.001) e metástase (hazard ratio 10.24, 95% intervalo de confiança, 3.53-26.68, P < 0.001). Os fatores preditivos da sobrevida livre de RL foram: grau histológico, margens comprometidas (hazard ratio 3.18, 95% intervalo de confiança, 1.51-6.70, P =0.001), e metástase (hazard ratio 15.23, 95% intervalo de confiança, 5.57-41.61, P= 0.001). Os fatores preditivos de sobrevida em geral foram: RL (hazard ratio 5.13, 95% intervalo de confiança, 2.15-12.24, P < 0.001), e metástase (hazard ratio 540.97, 95% intervalo de confiança, 5.04-58112.03, P < 0.001). CONCLUSÃO: As margens cirúrgicas comprometidas e a metástase estão diretamente associadas com a RL. O grau histológico do tumor, as margens comprometidas, a RL e a metástase, são fatores de pior prognóstico no MFS
BACKGROUND AND AIMS: Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas (STS) in elderly patients and it primarily affects the extremities. They are a historically heterogeneous group of tumors. The clinical course of MFS is characterized by a high incidence of local recurrences (LR), but knowledge about distant metastasis is sparse. MFS is reported to have a higher risk of LR following definitive surgical excision relative to other STS. There is no agreement on how to identify patients at major risk. The objectives of this study were to analyze the prognostic factors and outcomes of patients with MFS treated at a single institution. METHODS: We retrospectively reviewed the records of 75 patients with pathologically confirmed MFS of the extremities who underwent surgery in the last 25 years. We compared the age, sex, tumor size and location, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade and the American Joint Committee on Cancer (AJCC) stage. Median age was 49.7 years (range, 1 to 88 y). Site of disease was: upper extremity (25.4%), lower extremity (66.6%) and pelvic (8%). Patients had low, intermediate and high-grade, in: 29.3%, 24% and 46.7% of tumors, respectively. Tumors were categorized as =/< 5 cm (13.3%), > 5 and < 10 cm (42.7%), > 10 and < 15 cm (9%) and =/> 15 cm (18.7%). In total, 26.7% received postoperative radiotherapy. All patients underwent surgery. Margins were negative in 76% and positive in 24%. Bivariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR. RESULTS: Median follow-up time was 30.7 months (range, 1.8 to 383.8 m). We found a 26.7% of LR. Distant metastasis was reported in 27 (36%) patients. The most common sites of metastasis were: lung (92.6%) and lymph nodes (18.5%). The overall survival rate in patients with metastasis was 21.2 months (range, 4.8 to 114.8 m). Predictors of LR were: positive margins (hazard ratio 5.47, 95% confidence interval, 2.23-13.40, P < 0.001) and distant metastasis (hazard ratio 10.24, 95% confidence interval, 3.53-26.68, P < 0.001). Predictors of overall survival free of LR were: grade, positive margins (hazard ratio 3.18, 95% confidence interval, 1.51-6.70, P =0.001), and distant metastasis (hazard ratio 15.23, 95% confidence interval, 5.57-41.61, P= 0.001). Predictors of overall survival were grade, LR (hazard ratio 5.13, 95% confidence interval, 2.15-12.24, P < 0.001), and distant metastasis (hazard ratio 540.97, 95% confidence interval, 5.04-58112.03, P < 0.001). CONCLUSION: In this institutional series of MFS, positive margins and distant metastasis were significantly associated with a higher risk of LR. Tumor grade, LR, positive margins and distant metastases were significant predictors of overall survival poor prognosis

碩士
國立中山大學
海洋生物科技暨資源學系研究所
107
Effective bone regeneration strategy and therapy are crucial in view of the aging population trend worldwide. Osteogenesis plays a critical role in bone regeneration. In this study, we aim to identify an osteogenesis-promoting compound using the MC3T3-E1, murine calvarial pre-osteoblast cell line. We then examined osteogenic effects in vivo on a zebrafish development model and rat calvarial defect model. PD-1, the ethyl-acetate extract from Sarcodia ceylanica, upregulated alkaline phosphatase (ALP) activity in MC3T3-E1, whereas OA-4, a pure compound isolated from PD-1, not only similarly enhanced ALP activity, but also exhibited osteogenesis-promoting effects through activation of P38 and extracellular signal-regulated kinases (ERK) signals. OA-4 promoted osteogenic differentiation, and increased the mineralization, as well as exhibiting osteogenesis-promoting effects in vivo. First, 100 M of OA-4 increased the vertebrae calcification on zebrafish larvae. Second, rats with calvarial bone defect subcutaneously injected with OA-4 (1 and 5 mg/kg/day for 28 d) exhibited improved recovery and OA-4 was found through histological analysis to enhance osteogenic protein expression. Our findings indicated that OA-4 is an osteogenesis-promoting compound, and that further exploration of its application of OA-4 in fracture therapy is warranted.

Histopathology is the clinical standard for tissue diagnosis. However, histopathology has several limitations including that it requires tissue processing, which can take 30 minutes or more, and requires a highly trained pathologist to diagnose the tissue. Additionally, the diagnosis is qualitative, and the lack of quantitation leads to possible observer-specific diagnosis. Taken together, it is difficult to diagnose tissue at the point of care using histopathology.

Several clinical situations could benefit from more rapid and automated histological processing, which could reduce the time and the number of steps required between obtaining a fresh tissue specimen and rendering a diagnosis. For example, there is need for rapid detection of residual cancer on the surface of tumor resection specimens during excisional surgeries, which is known as intraoperative tumor margin assessment. Additionally, rapid assessment of biopsy specimens at the point-of-care could enable clinicians to confirm that a suspicious lesion is successfully sampled, thus preventing an unnecessary repeat biopsy procedure. Rapid and low cost histological processing could also be potentially useful in settings lacking the human resources and equipment necessary to perform standard histologic assessment. Lastly, automated interpretation of tissue samples could potentially reduce inter-observer error, particularly in the diagnosis of borderline lesions.

To address these needs, high quality microscopic images of the tissue must be obtained in rapid timeframes, in order for a pathologic assessment to be useful for guiding the intervention. Optical microscopy is a powerful technique to obtain high-resolution images of tissue morphology in real-time at the point of care, without the need for tissue processing. In particular, a number of groups have combined fluorescence microscopy with vital fluorescent stains to visualize micro-anatomical features of thick (i.e. unsectioned or unprocessed) tissue. However, robust methods for segmentation and quantitative analysis of heterogeneous images are essential to enable automated diagnosis. Thus, the goal of this work was to obtain high resolution imaging of tissue morphology through employing fluorescence microscopy and vital fluorescent stains and to develop a quantitative strategy to segment and quantify tissue features in heterogeneous images, such as nuclei and the surrounding stroma, which will enable automated diagnosis of thick tissues.

To achieve these goals, three specific aims were proposed. The first aim was to develop an image processing method that can differentiate nuclei from background tissue heterogeneity and enable automated diagnosis of thick tissue at the point of care. A computational technique called sparse component analysis (SCA) was adapted to isolate features of interest, such as nuclei, from the background. SCA has been used previously in the image processing community for image compression, enhancement, and restoration, but has never been applied to separate distinct tissue types in a heterogeneous image. In combination with a high resolution fluorescence microendoscope (HRME) and a contrast agent acriflavine, the utility of this technique was demonstrated through imaging preclinical sarcoma tumor margins. Acriflavine localizes to the nuclei of cells where it reversibly associates with RNA and DNA. Additionally, acriflavine shows some affinity for collagen and muscle. SCA was adapted to isolate acriflavine positive features or APFs (which correspond to RNA and DNA) from background tissue heterogeneity. The circle transform (CT) was applied to the SCA output to quantify the size and density of overlapping APFs. The sensitivity of the SCA+CT approach to variations in APF size, density and background heterogeneity was demonstrated through simulations. Specifically, SCA+CT achieved the lowest errors for higher contrast ratios and larger APF sizes. When applied to tissue images of excised sarcoma margins, SCA+CT correctly isolated APFs and showed consistently increased density in tumor and tumor + muscle images compared to images containing muscle. Next, variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was further tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. The results indicate that SCA+CT can accurately delineate APFs in heterogeneous tissue, which is essential to enable automated and rapid surveillance of tissue pathology.

Two primary challenges were identified in the work in aim 1. First, while SCA can be used to isolate features, such as APFs, from heterogeneous images, its performance is limited by the contrast between APFs and the background. Second, while it is feasible to create mosaics by scanning a sarcoma tumor bed in a mouse, which is on the order of 3-7 mm in any one dimension, it is not feasible to evaluate an entire human surgical margin. Thus, improvements to the microscopic imaging system were made to (1) improve image contrast through rejecting out-of-focus background fluorescence and to (2) increase the field of view (FOV) while maintaining the sub-cellular resolution needed for delineation of nuclei. To address these challenges, a technique called structured illumination microscopy (SIM) was employed in which the entire FOV is illuminated with a defined spatial pattern rather than scanning a focal spot, such as in confocal microscopy.

Thus, the second aim was to improve image contrast and increase the FOV through employing wide-field, non-contact structured illumination microscopy and optimize the segmentation algorithm for new imaging modality. Both image contrast and FOV were increased through the development of a wide-field fluorescence SIM system. Clear improvement in image contrast was seen in structured illumination images compared to uniform illumination images. Additionally, the FOV is over 13X larger than the fluorescence microendoscope used in aim 1. Initial segmentation results of SIM images revealed that SCA is unable to segment large numbers of APFs in the tumor images. Because the FOV of the SIM system is over 13X larger than the FOV of the fluorescence microendoscope, dense collections of APFs commonly seen in tumor images could no longer be sparsely represented, and the fundamental sparsity assumption associated with SCA was no longer met. Thus, an algorithm called maximally stable extremal regions (MSER) was investigated as an alternative approach for APF segmentation in SIM images. MSER was able to accurately segment large numbers of APFs in SIM images of tumor tissue. In addition to optimizing MSER for SIM image segmentation, an optimal frequency of the illumination pattern used in SIM was carefully selected because the image signal to noise ratio (SNR) is dependent on the grid frequency. A grid frequency of 31.7 mm-1 led to the highest SNR and lowest percent error associated with MSER segmentation.

Once MSER was optimized for SIM image segmentation and the optimal grid frequency was selected, a quantitative model was developed to diagnose mouse sarcoma tumor margins that were imaged ex vivo with SIM. Tumor margins were stained with acridine orange (AO) in aim 2 because AO was found to stain the sarcoma tissue more brightly than acriflavine. Both acriflavine and AO are intravital dyes, which have been shown to stain nuclei, skeletal muscle, and collagenous stroma. A tissue-type classification model was developed to differentiate localized regions (75x75 µm) of tumor from skeletal muscle and adipose tissue based on the MSER segmentation output. Specifically, a logistic regression model was used to classify each localized region. The logistic regression model yielded an output in terms of probability (0-100%) that tumor was located within each 75x75 µm region. The model performance was tested using a receiver operator characteristic (ROC) curve analysis that revealed 77% sensitivity and 81% specificity. For margin classification, the whole margin image was divided into localized regions and this tissue-type classification model was applied. In a subset of 6 margins (3 negative, 3 positive), it was shown that with a tumor probability threshold of 50%, 8% of all regions from negative margins exceeded this threshold, while over 17% of all regions exceeded the threshold in the positive margins. Thus, 8% of regions in negative margins were considered false positives. These false positive regions are likely due to the high density of APFs present in normal tissues, which clearly demonstrates a challenge in implementing this automatic algorithm based on AO staining alone.

Thus, the third aim was to improve the specificity of the diagnostic model through leveraging other sources of contrast. Modifications were made to the SIM system to enable fluorescence imaging at a variety of wavelengths. Specifically, the SIM system was modified to enabling imaging of red fluorescent protein (RFP) expressing sarcomas, which were used to delineate the location of tumor cells within each image. Initial analysis of AO stained panels confirmed that there was room for improvement in tumor detection, particularly in regards to false positive regions that were negative for RFP. One approach for improving the specificity of the diagnostic model was to investigate using a fluorophore that was more specific to staining tumor. Specifically, tetracycline was selected because it appeared to specifically stain freshly excised tumor tissue in a matter of minutes, and was non-toxic and stable in solution. Results indicated that tetracycline staining has promise for increasing the specificity of tumor detection in SIM images of a preclinical sarcoma model and further investigation is warranted.

In conclusion, this work presents the development of a combination of tools that is capable of automated segmentation and quantification of micro-anatomical images of thick tissue. When compared to the fluorescence microendoscope, wide-field multispectral fluorescence SIM imaging provided improved image contrast, a larger FOV with comparable resolution, and the ability to image a variety of fluorophores. MSER was an appropriate and rapid approach to segment dense collections of APFs from wide-field SIM images. Variables that reflect the morphology of the tissue, such as the density, size, and shape of nuclei and nucleoli, can be used to automatically diagnose SIM images. The clinical utility of SIM imaging and MSER segmentation to detect microscopic residual disease has been demonstrated by imaging excised preclinical sarcoma margins. Ultimately, this work demonstrates that fluorescence imaging of tissue micro-anatomy combined with a specialized algorithm for delineation and quantification of features is a means for rapid, non-destructive and automated detection of microscopic disease, which could improve cancer management in a variety of clinical scenarios.

Dissertation

Utilizarea strategiilor didactice interdisciplinare, in scopul stimularii motivatiei elevilor in studiul literaturii, este subiectul cercetarii mele, inscriindu‑se in contextul cercetarilor din Stiintele Educatiei care isi aduc contributia la identificarea activitatilor pedagogice, determinante in angajamentul cognitiv al elevilor si in perseverenta intr‑o sarcina de lucru (Viau, 2014). Marile schimbari ce caracterizeaza societatea secolului XXI, precum digitalizarea si mondializarea, impun didacticii domeniului literaturii o regandire a metodelor si a practicilor sale, cu scopul de a raspunde nevoii reale a elevilor: aceea de a fi pregatiti sa traiasca in lumea de maine. Aceasta situatie necesita o repunere in dezbatere a strategiilor didactice, cu atat mai mult cu cat profesorii, cat si anchetele realizate in domeniul lecturii invoca adesea o motivatie scazuta a elevilor. Mai mult, rezultatele PISA (2015) pozitioneaza Romania pe locul 50 din 65, evidentiind ca aproape 40% dintre elevii romani au dificultati in citirea si intelegerea unui text. Se poate spune ca motivatia reprezinta un „meta‑obiectiv” in educatie, deoarece conditioneaza invatarea. De aceea este important de a intelege ceea ce stimuleaza reusita si perseverenta in studiul unei discipline, in scopul de a oferi elevilor bune conditii de predare si de invatare (Sauve, 2007).

Sarcomas are rare tumours that can arise from bone or a variety of soft tissues in a variety of body sites. Surgery is the treatment mainstay for localized disease. Margins of resection are contingent on accurate histologic diagnosis. Adjuvant chemotherapy is routinely employed in osteosarcoma and Ewing Sarcomas, while it is used only on an individualized basis in high-risk soft tissue sarcoma. Isolated lung metastases from either bone or soft tissue sarcoma are primarily treated by surgery, especially if the disease-free interval is long and the number limited. Otherwise chemotherapy is the first-line therapy and subsequent treatments are decided according to response and disease evolution. Treatment planning should include multidisciplinary consultation to determine optimal therapy, taking into consideration tumour histology, site, and extent of the disease, its natural history and sensitivity to available treatments, surgical challenges and, of course, quality of life.

Sarcomas are rare tumours that can arise from bone or a variety of soft tissues in a variety of body sites. Surgery is the treatment mainstay for localized disease. Margins of resection are contingent on accurate histologic diagnosis. Adjuvant chemotherapy is routinely employed in osteosarcoma and Ewing Sarcomas, while it is used only on an individualized basis in high-risk soft tissue sarcoma. Isolated lung metastases from either bone or soft tissue sarcoma are primarily treated by surgery, especially if the disease-free interval is long and the number limited. Otherwise chemotherapy is the first-line therapy and subsequent treatments are decided according to response and disease evolution. Treatment planning should include multidisciplinary consultation to determine optimal therapy, taking into consideration tumour histology, site, and extent of the disease, its natural history and sensitivity to available treatments, surgical challenges and, of course, quality of life.

Osteogenic sarcoma is the most common primary bone cancer frequently affecting children and teenagers. Despite many years of research, little have the survival rates changed in the last fifty years. Early diagnosis, a complete systemic treatment program with a good tumor response and adequate margins continue to be the main determinants of patients’ prognosis in this disease. Neoadjuvant chemotherapy followed by surgery and subsequent adjuvant systemic treatment remain the standard of care. Numerous reconstruction options available provide these patients better function and improved quality of life.

Chapter 55 discusses malignant chondroid matrix bone tumors. Chondrosarcoma is a malignant bone tumor of cartilage origin. It represents the third most common primary malignant bone tumor, after multiple myeloma and osteosarcoma. Conventional intramedullary chondrosarcoma is its most common subtype, with rarer subtypes that include clear cell, mesenchymal, dedifferentiated, and periosteal chondrosarcoma. Secondary chondrosarcoma represents a lesion that arises in a preexisting benign chondroid lesion (enchondroma or osteochondroma). Chondrosarcomas demonstrate some specific imaging features that can improve diagnostic accuracy and help guide clinical management. Histological grade of central chondrosarcoma usually dictates surgical management. As with other sarcomas, outcome of chondrosarcoma depends on histological grade, surgical margins, and staging.

This chapter discusses eponymous syndromes, including Alice in Wonderland syndrome, Arnold–Chiari malformation, Baker’s cyst, Barrett’s oesophagus, Bazin’s disease, Behçet’s disease, Berger’s disease, Bickerstaff’s brainstem encephalitis, Brown-Séquard syndrome, Brugada syndrome, Budd–Chiari syndrome, Buerger’s disease, Caplan’s syndrome, Charcot–Marie–Tooth syndrome, Churg–Strauss syndrome, Creutzfeldt–Jakob disease (CJD), Crigler–Najjar syndrome, Devic’s syndrome, Dressler’s syndrome, Dubin–Johnson syndrome, Dupuytren’s contracture, Ekbom’s syndrome, Fabry disease, Fanconi anaemia, Felty’s syndrome, Fitz-Hugh–Curtis syndrome, Foster Kennedy syndrome, Friedreich’s ataxia, Froin’s syndrome, Gardner’s syndrome, Gélineau’s syndrome, Gerstmann’s syndrome, Gilbert’s syndrome, Gilles de la Tourette syndrome, Goodpasture’s disease, Guillain–Barré syndrome, Henoch–Schönlein purpura (HSP), Horner’s syndrome, Huntington’s disease, Jervell and Lange-Nielsen syndrome, Kaposi’s sarcoma (KS), Klippel–Trénaunay syndrome, Korsakoff’s syndrome, Langerhans cell histiocytosis, Leriche’s syndrome, Löffler’s eosinophilic endocarditis, Löffler’s syndrome, Lown–Ganong–Levine syndrome, McArdle’s glycogen storage disease (type V), Mallory–Weiss tear, Marchiafava–Bignami syndrome, Marchiafava–Micheli syndrome, Marfan’s syndrome, Meckel’s diverticulum, Meigs’ syndrome, Ménétrier’s disease, Meyer–Betz syndrome, Mikulicz’s syndrome, Milroy disease, Münchausen’s syndrome, Ogilvie’s syndrome, Ortner’s cardiovocal syndrome, Osler–Weber–Rendu syndrome, Paget’s disease of the breast (PDB), Pancoast’s syndrome, Parinaud’s syndrome, Paroxysmal nocturnal haemoglobinuria, Peutz–Jeghers’ syndrome, Peyronie’s disease, Pott’s syndrome, Prinzmetal (variant) angina, Raynaud’s syndrome, Refsum disease, Romano–Ward syndrome, Rotor syndrome, Sister Mary Joseph nodule, Sjögren’s syndrome, Stevens–Johnson syndrome, Sturge–Weber syndrome (SWS), Takayasu’s arteritis, Tietze’s syndrome, Todd’s palsy, Vincent’s angina, Von Hippel–Lindau syndrome, Von Willebrand’s disease (VWD), Wallenberg’s lateral medullary syndrome, Waterhouse–Friderichsen’s (WhF) syndrome, Weber’s syndrome, Wegener’s granulomatosis, Wernicke’s encephalopathy, Whipple’s disease, Zellweger syndrome, Zollinger–Ellison syndrome.

The accessory breast tissue in the axillary region is rare, but as there is breast tissue, there is the possibility of pathological degeneration. With an even greater rarity, breast sarcoma is a diverse group of malignancies derived from mesenchymal tissues. The aim of this report was to describe a case of a young patient with sarcomatous neoplasia in the axillary accessory breast topography. Patient LPMS, 19 years old, female, admitted to the mastology service of the Hospital das Clínicas of the Universidade de São Paulo with a nodule realized in the left axillary region with progressive growth during pregnancy. The patient was healthy with a family history of a maternal aunt with breast cancer at 50 years old. At the clinical examination, she had an extensive tumor affecting the left axillary region measuring 10 cm with clinically negative axilla. Contralateral breast and axilla and supra-/infraclavicular fossas without abnormalities. In the initial mammogram, a hyperdense, oval, and indistinct nodule was found in the left axillary extension, measuring 10.8 cm. In breast magnetic resonance imaging, a heterogeneous mass in the left axillary extension is observed with irregular, lobulated margins, measuring 10.3×10×10.1 cm, heterogeneously and concentric by the contrast. Core biopsy was performed with the result of spindle cell mesenchymal neoplasm. In the systemic staging examinations, there was no evidence of a lesion suspected of distant metastasis. Vincristine 1.5 mg/m2 + Actinomycin D 0.45 mg/kg/day + Cyclophosphamide were prescribed to the patient. After six cycles with no clinical response, it was decided to switch the neoadjuvant chemotherapy to doxorubicin 25 mg/m2 and Ifosfamide 3,000 mg/m2 . After three cycles, the patient remains without a clinical response to neoadjuvant chemotherapy. It was decided to refer the patient to radiotherapy for axillary irradiation on the right, with a subsequent surgical approach. The patient underwent surgery with wide resection of the tumor and axillary lymph nodes. The anatomopathological examination showed sarcoma with immunohistochemistry suggestive of rhabdomyosarcoma measuring 19.3×14.8×14.7 mm with free margins and with sarcoma metastasis in one of the 21 dissected lymph nodes. The patient progresses well postoperatively. Accessory breast tissue has a very rare incidence in the population, with incidence rates of 1–2%. With regard to breast sarcoma, it is a very rare condition. It consists of a heterogeneous group of nonepithelial tumors originating from the mesenchymal tissues of the breast. They account for <1% of all breast malignancies and <5% of all sarcomas. Due to its rarity, current knowledge about breast sarcoma is limited and is mainly based on small retrospectives, case series, or case reports. Angiosarcoma, including secondary angiosarcoma from before breast radiation, is the most frequent type of breast sarcoma. As with other soft-tissue sarcomas, the primary breast sarcoma is associated with genetic conditions such as Li-Fraumeni syndrome, familial adenomatous polyposis, and type 1 neurofibromatosis. Therefore, breast sarcoma treatment generally follows the algorithms derived from trials of soft-tissue sarcomas in the chest wall, as has been done with the reported patient. Surgical treatment is the standard and most accepted treatment for breast sarcoma. The role of chemotherapy for breast sarcoma is also uncertain. There are no prospective studies that specifically assess the benefit of chemotherapy in adjuvant or neoadjuvant settings. Likewise, the benefit of radiotherapy in breast sarcoma is also very doubtful with evidence of benefit in large tumors and with positive margins after surgical resection.

Breast sarcomas are a heterogenous group of malignancies that originate from the breast support stroma. They represent less than 0.1% of all breast neoplasms and less than 5% of all sarcomas. They are more frequent in women and between the fourth and sixth decades. Previous breast cancer treatment and radiotherapy are the main risk factors. The usual clinical presentation is a breast mass, which grows progressively and can reach a large size. They rarely attach themselves to the thorax or infiltrate the skin. Skin changes, when occur, are usually secondary to a large distitute. The tumor is usually well or partially defined, with a firm consistency. Lymph nodes are palpable in up to 25% of cases but tend to be reactional. Imaging findings are nonspecific. For histopathological diagnosis, it is necessary to exclude metaplastic carcinoma, and immunohistochemistry is useful to detect evidence of epithelial origin. Treatment requires resection with wide margins, and mastectomy may be necessary. Hematogenous dissemination occurs, and lymph node interventions should only be performed in the presence of a proven histopathological impairment. There is a trend of improvement in survival with radiotherapy after conservative surgery. After mastectomy, radiotherapy may be beneficial in cases of increased risk of local recurrence (lesions larger than 50 mm, unsuitable margins, and higher grade variants). The role of chemotherapy remains controversial. Liposarcoma, a histological subtype of sarcoma, despite being the second most frequent subtype in soft tissues, rarely occurs in the breast. Liposarcoma encompasses a spectrum, from lesions with essentially benign behavior to frankly malign lesions. Liposarcomas classified as myxoid, pleomorphic, and dedifferentiated have a higher risk of recurrence and metastases. The main differential diagnoses of breast liposarcoma include other breast tumors with lipomatous or liposarcomatous components, fat necrosis, and metaplastic carcinoma. CSSP, 48 years old, female, attended the Mastology Service of the Central Hospital of the Army, referring a breast nodule for 2 months with growth in the period. On clinical examination, a well-defined, mobile oval nodule with firm consistency was observed, measuring 40 mm, with no associated findings. At mammography and ultrasonography, the nodule was oval and circumscribed. Magnetic resonance imaging showed heterogeneous enhancement and a type II curve. A simple mastectomy was performed due to the poor tumor-breast relationship, with a histopathological result of dedifferentiated liposarcoma with areas of myxoid pattern, measuring 40 mm, and free histopathological margins. Adjuvant radiotherapy was indicated due to the diagnosis of dedifferentiated liposarcoma with areas of myxoid pattern.

Introduction: Breast angiosarcoma is a very rare and highly aggressive lesion, with an incidence of 0.5% to 1%. Berg et al. recognized two groups of sarcoma: the first group includes malignant phylloid cysts, lymphomas, and hemangiosarcomas, and the second group includes stromal sarcomas, fibrosarcomas, leiomyosarcomas, histiocytomas, and giant cell sarcoma. Angiosarcomas are lesions of indefinite and friable masses, with a mean age of 35 years. Case Report: A 35-year-old man from Paulo Afonso-PE presents complaining of breast lump. He underwent tumorectomy and confirmed fibroadenoma and phylloids with atypia and mitosis. A battery of tests such as mammography (MMG)/ultrasonography (USG) confirmed the presence of a 1.5-cm nodule in the breast. In addition, a new segmental resection surgery was performed, in which histopathological results confirmed a low-grade malignant phylloid cystosarcoma and demanding margins. The patient was proposed a new surgical of simple mastectomy with immediate reconstruction with silicone implant and latissimus dorsi flap. Finally, the surgery was performed and the histopathological result was the absence of residual neoplastic tissue, with an area of scar fibrosis and typical ductal hyperplasia. After recovery, the patient was referred to clinical oncology and radiotherapy, but both had no indication for adjuvant therapy. After 1 year, the patient returned to perform the symmetry of the opposite breast and reconstruction of the nipple–areola complex. In her follow-up, there were no changes in her examinations. After 2 years, she returned with a breast USG examination, which demonstrated an image nodular 1.5 cm adjacent to breast prosthesis and magnetic resonance imaging suggested the same image. A core was performed, confirming a recurrent malignant variant tumor. The tumor evolved very quickly, and the surgery was performed with an enlarged resection of the entire large and small pectoral and inclusion of the skin. For correction of the deformity, the rotation of the large epiploid with a lower abdominal dermocutaneous flap was used. Conclusion: The use of a technique with the large epiploid to cover the chest wall associated with a lower abdominal dermocutaneous flap presented a good alternative to correct chest wall deformity.

Primary sarcomas of the breast originate from connective tissue and are responsible for less than 1% of all breast malignancies with an incidence of 5 cases per million in the United States. Primary breast angiosarcoma originates in the parenchyma and can secondarily compromise the skin and pectoral muscles in advanced cases. Sarcoma is present more in women between the ages of 14 and 82, mainly in the third and fourth decades of life. At diagnosis, as in other sarcomas, the size is bigger than 5 cm, with a direct correlation with prognosis; because of few data in literature due to its incidence and frequent error and the inespecific clinical and radiological signs, we report a case of breast angiosarcoma in a male patient from the Hospital Santo Antônio/Obras Sociais Irmã Dulce, Salvador, BA. It is the case of a 42-year-old man with a nodule in the upper medial quadrant of the right breast, measuring 2 cm. The mammogram and ultrasound showed a 1.4-cm regular nodule in the upper medial quadrant, BI-RADS 4. The patient underwent a core biopsy with a pathology reporting a chronic inflammatory process and a nonmalignant neoplasia; immunohistochemical positive for CD 68 and LCA and negative for cytokeratin 34beta12, P63, and cytokeratin AE1/AE3. Then, the nodule was excised and the pathology result showed a fusiform cell neoplasia with a positive posterior margin confirmed by immunohistochemical that neoplastic cells were positive for CD34 and CD31, negative for cytokeratin AE1/AE3, and inconclusive to smooth muscle actin with KI-67 <10%, leading to the diagnosis of angiosarcoma. After that, the margins re-excision the pathological staging (American Joint Committee on Cancer) ypT0. No evidence was found for metastases in other sites. The patient is now waiting for radiotherapy for local control benefits. There were 16 fractions in the right breast and a multidisciplinary follow-up. The discussion showed a rare case in the literature in agreement with the 170 cases reported, with a great impact when seen in men since the case reported prevalence in women. In relation to diagnosis, it becomes a challenge, especially in low-grade malignant tumors with multiple tissue pieces and needed the best pathology analysis, which could delay treatment. The inespecific alterations in imaging examinations as well as at tests, such as the presence of fatty tissue in a mammogram, would include hemangiomas and angiolipomas as differential diagnosis contributing to delay in the diagnosis. As treating large tumor resection due to aggressive behavior is recommended, it is a therapeutic option if associated with radiotherapy reducing risk by 20–50%. That was the treatment adopted for the patient described above. This study, besides contributing to the literature on angiosarcoma incidence, also affects the possible presentation in male patients, elevating the diagnostic hypothesis of nodule in the cases of early adequate treatment.

Introduction: Thymomas are rare malignant epithelial neoplasms arising in the thymus. These tumors are commonly located in the prevascular mediastinum but can also be found in other regions of the mediastinum, neck, pulmonary hilum, thyroid gland, lungs, pleura, or pericardium. This disease could be suspected as an incidental finding identified on imaging, local thoracic symptoms or due to a paraneoplastic syndrome. Pleural or pericardial effusions are the most common manifestations of more disseminated disease and may also cause thoracic symptoms. Extrathoracic metastases are seen in fewer than seven percent of patients at presentation, most commonly in the kidneys, extrathoracic lymph nodes, liver, brain, adrenals, thyroid, and bone. Case report: A 66-year-old, white female patient, with previous left mastectomy due to a phyllodes sarcoma in 1997. Diagnosed with malignant thymoma in 2013 and pleural involvement, undergoing systemic chemotherapy and surgery with complete remission of the disease at that time. Two years after, in 2015, presented with disease recurrence in the diaphragm, pleura and lymph nodes, undergoing new surgery, radiotherapy and a second line chemotherapy regimen. Over the years, the disease progressed despite the cancer treatment instituted. In December 2020, the patient presented nodulation in the right breast, with core biopsy suspicion of ductal carcinoma. Undergoing quadrantectomy with lymph node biopsy, with the surgical pathological report finding of thymoma metastasis, resected with free margins. The patient is currently at the 31st pembrolizumab cycle, in good clinical condition.

Dermatofibrosarcoma (DFS) is a rare low-grade fibroblastic mesenchymal tumor derived from the dermis. The lesion accounts for approximately 1% of all soft-tissue sarcomas and less than 0.1% of all malignancies, with an annual incidence of 4.2–4.5 cases per million. It occurs most frequently between the second and fifth decades of life and usually appears in the dermis and subcutaneous tissue. DFS occurs more commonly in the trunk (42%–72%), and breast involvement is uncommon and occurs due to the infiltration of previous dermal involvement. We report a case of a 40-year-old female patient with a history of a violaceous nodulation that was hardened and not adhered to deep planes measuring approximately 5 cm in the inferomedial quadrant of the left breast, whose biopsy was performed in an external unit revealing a DFS. Magnetic resonance imaging of the breast showed a nodule with thickening of the adjacent skin in the aforementioned topography, measuring 3.1×3×2.9 cm, in addition to another nodular image with similar characteristics, compatible with multifocal involvement. She underwent quadrantectomy and immediate reconstruction with a myocutaneous flap of the fat-grafted latissimus dorsi muscle. A surgical specimen containing two nodules, measuring 2.8 and 2.5 cm, respectively, with a result compatible with a DFS with free surgical margins was analyzed. Immunohistochemistry revealed native estrogen and progesterone receptors, positive CD34 in tumor cells, and positive Ki67 in less than 5% of cells. The patient remains under clinical follow-up at our service, with no evidence of recurrence of the lesion, currently with annual consultations for physical examination and checking of breast ultrasound and bilateral mammography examinations.

Introduction: Primary angiosarcoma of the breast (PAOB) is a class of extremely rare sarcomas, with an incidence rate of 1/2,000 cases of breast cancer worldwide. It is more frequent in 20- and 50-year-old women without history of previous cancer and commonly described in the left breast. Clinical presentation can be the same as usual breast cancer and histology can mimic poorly differentiated ductal carcinoma, which is why immunohistochemistry should be performed. Swelling, a feeling of fullness and exponential growth within the breast are frequent complaints, as noted by Kunkiel et al. in their series of case reports. The natural history of PAOB is only partly understood, suggesting that the lesion begins within the mammary parenchyma and then infiltrates skin and subcutaneous tissue nearby. The predominant management has been mastectomy, mainly, or sectorectomy with clear margins in cases of conservative breast surgery. Adjuvant therapies are not associated with improved survival, except for adjuvant chemotherapy in localized tumors of 5 cm or more. Case report: S.O.S., a 32-year-old woman, identified breast asymmetry in 2017, during the lactation period, presence of mild pain and swelling in the left breast. She was admitted to the breast cancer and benign lesions outpatient clinic at Professor Alberto Antunes University Hospital in February 2019. She held a BI-RADS 4 breast magnetic resonance imaging (MRI) in January 2019, which suggestedan irregular mass in the left breast, probably of vasculolymphatic nature; also showed core biopsy in February 2019: low-grade PAOB. In April 2019, she underwent a modified radical mastectomy of the left breast with ipsilateral lymphadenectomy. Due to the large extent of the lesion, an entire cutaneous area of left anterior hemithorax was resected, and thoracoepigastric flap was used to close the left hemithorax. An anatomopathological report diagnosed PAOB grade I. In July 2019, immunohistochemistry corroborated the diagnosis of PAOB with CD31 positive; positive von Willebrand factor (Factor VIII - polyclonal Rabbit) and ki67 positive for 25% of neoplastic cells. In the fourth month after the surgery, the patient started adjuvant radiotherapy, concluding it in October 2019. In post-treatment follow-up, in January 2021, she was referred to the breast reconstruction program, awaiting the procedure until this report was made.