Tumor metastásico en tejido blando a nivel del sacro secundario a carcinoma de células claras de riñón. Reporte de caso / Metastatic tumor in soft tissue at the level of the sacrum secondary toclear cell carcinoma of the kidney. A case report

Introducción. El cáncer de riñón es la undécima neoplasia maligna más común en los Estados Unidos Mexicanos. El carcinoma de células claras de riñón (CCR) es considerado la estirpe más frecuente y representa el 2-3 % de todos los cánceres a nivel mundial. En el contexto de la enfermedad metastásica, por lo general se identifica un tumor renal primario y las metástasis se localizan en pulmón, hueso, hígado, cerebro y, raramente, en tejidos blandos. Los pacientes con metástasis a tejidos blandos no tienen síntomas en las etapas iniciales y generalmente se identifican sólo cuando las lesiones aumentan de tamaño o durante el estudio de la pieza de resección quirúrgica. Caso clínico. Se presenta el caso de una paciente en la séptima década de la vida, con una metástasis en tejidos blandos de la región sacra, de 10 años de evolución posterior a una nefrectomía secundario a CCR. Resultados. Hallazgos clínicos e imagenológicos de un tumor bien delimitado. Se realizó resección quirúrgica de la lesión, bajo anestesia regional, con extirpación completa. Conclusión. Se recomienda que los pacientes con un sitio metastásico resecable y solitario sean llevados a resección quirúrgica con márgenes libres, como fue el caso de nuestra paciente, por su fácil acceso y ser una lesión única. En el CCR, además de su tratamiento quirúrgico inicial, es indispensable una estrecha vigilancia con examen físico e imágenes transversales, para detectar la presencia de metástasis y con ello evitar tratamientos tardíos.

Introduction. Kidney cancer is the eleventh most common malignancy in the United States of Mexico. Carcinoma renal cell (CRC) is considered the most frequent type and represents 2-3% of all cancers worldwide. In the setting of metastatic disease, a primary renal tumor is usually identified, and metastases are located in the lung, bone, liver, brain, and rarely in soft tissue. Patients with soft tissue metastases do not have symptoms in the initial stages and are generally found only when the lesions increase in size or during the study of the surgical resection piece. Clinical case. In this case, we report a female patient in the seventh decade of life with a soft tissue metastasis located in the sacral region, 10 years after a nephrectomy secondary to CRC. Results. Clinical and radiological findings of a well-defined tumor. Surgical resection of the lesion is performed under regional anesthesia with complete excision. Conclusions. It is recommended that patients with a resectable and solitary metastatic site be candidates for surgical resection with free margins, as was the case with our patient due to its easy access and single lesion. In CRC, in addition to its initial surgical treatment, close surveillance with physical examination and cross-sectional images is essential to monitor the presence of metastases and thus avoid late treatments.

Localización atípica de un lipoblastoma en una niña de 5 años / Atypical location of lipoblastoma in a 5-year-old girl

Se informa de un lipoblastoma perineal en una niña de 5 años localizado en el labio mayor derecho. La lesión aumentó gradualmente en 6 meses. En la ecografía y la resonancia magnética (RM), se observó un tumor heterogéneo sólido limitado con componente graso. Tras su extirpación quirúrgica, el estudio anatomopatológico confirmó un lipoblastoma. El lipoblastoma es un tumor mesenquimatoso benigno poco frecuente de la lactancia y la primera infancia. Los síntomas varían en función de la localización; pueden observarse signos de compresión de los órganos adyacentes. Este tipo de tumores inusuales de los tejidos blandos son más frecuentes en menores de 3 años. Los lipoblastomas se localizan predominantemente en las extremidades, pero también pueden encontrarse en la cabeza y el cuello, el tronco, el mediastino, el riñón, el mesenterio, el retroperitoneo y el perineo. Se debe sospechar su presencia en función de los hallazgos de la ecografía y la RM.

We reported a perineal lipoblastoma in a 5-year-old girl located in the right labia mayor. The lesion gradually increased within 6 months. Ultrasound and magnetic resonance imaging (MRI) showed a limited solid heterogenous tumor with fatty component. After it had been surgically removed, the anatomopathological examination confirmed that it was a lipoblastoma. Lipoblastoma is a rare benign mesenchymal tumor of infancy and early childhood. Symptoms vary depending on localization; signs of compression of adjacent organs may be seen. This type of unusual soft tissue tumors occurred most often in under 3 years old. The localization of lipoblastomas is predominantly in the extremities but may be also found in other sites including the head and neck, trunk, mediastinum, kidney, mesentery, retropritoneum and perineum. The suspicion should be considered according to ultrasound and MRI findings.

Tumores vasculares de interesse odontológico: aspectos clínicos e formas de tratamento / Vascular tumors of dental interest: clinical aspects and forms of treatment

Os hemangiomas são neoplasias benignas dos tecidos moles. São lesões caracterizadas pela proliferação de células endoteliais. Objetivos: O objetivo deste trabalho é demonstrar por meio de uma revisão da literatura os principais hemangiomas de interesse odontológico e suas características clínicas e abordagens terapêuticas. Revisão de literatura: O estudo mostrou prevalência de até 6% na população geral, sendo o tumor mais comum na infância. Essas lesões apresentam rápido crescimento pós-natal, que pode levar meses a dois anos em média, mas geralmente após esse período ocorre sua involução. O diagnóstico é comumente baseado nas características clínicas e na história do paciente. É importante entender que o estudo histopatológico pode ser necessário nos casos em que o diagnóstico é incerto, para diferenciá-lo de outras neoplasias graves. Destacam-se as principais complicações relacionadas a lesões, ulcerações e hemorragias, além de infecções secundárias que podem causar alto índice de morbidade. Assim, é fundamental que o dentista reconheça essas patologias e tenha capacidade para tratá-las. Considerações finais: Foi possível observar que os hemangiomas são manifestações vasculares incomuns para o cirurgião-dentista, porém o profissional deve saber diagnosticá-los e tratá-los. Dentre as áreas acometidas, essas lesões são frequentes na cavidade oral e o tratamento consiste em acompanhamento com intervenções conservadoras(AU)

Hemangiomas are benign soft tissue neoplasms. These are lesions characterized by the proliferation of endothelial cells. Objectives: The objective of this work is to demonstrate through a literature review about the main hemangiomas of dental interest and clinical characteristics and therapeutic approaches. Literature review: The study showed a prevalence of up to 6% in the general population, being the most common tumor in childhood. These lesions presents a rapid postnatal growth, which may take months until two years on average, but usually after this period their involution occurs. The diagnosis is commonly based on clinical characteristics and patient's history. It is important to understand that the histopathological study may be necessary in cases that the diagnostic is uncertainty, in order to differentiate it from other serious neoplasms. Main complications related to injuries, ulceration and hemorrhage can be highlighted, in addition to secondary infections that can cause a high rate of morbidity. Thus, it is essential that dentists recognize such pathologies and be able to treat them. Final considerations: Was possible do observe that hemangiomas are uncommon vascular manifestations for the dental surgeon, however, the professional must know to diagnose and treat them. Among the affected areas, these lesions are frequently seen in the oral cavity and the treatment consists of following up with conservative interventions(AU)

EWSR1-SMAD3 positive fibroblastic tumor: a clinicopathological analysis / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotypes and molecular genetics of EWSR1-SMAD3 positive fibroblastic tumor (ESFT) with an emphasis on differential diagnosis. Methods: The clinicopathological data, immunohistochemical profiles and molecular profiles of 3 ESFT cases diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center from 2018 to 2021were analyzed. The related literature was also reviewed. Results: There were two males and one female. The patients were 24, 12 and 36 years old, respectively. All three tumors occurred in the subcutis of the foot with the disease duration of 6 months to 2 years. The tumors were presented with a slowly growing mass or nodule, accompanied with pain in 1 patient. The tumors ranged in size from 0.1 to 1.6 cm (mean, 1.0 cm). Microscopically, the tumors were located in the subcutaneous tissue with a nodular or plexiform growth pattern. They were composed of cellular fascicles of bland spindle cells with elongated nuclei and fine chromatin. One of the tumors infiltrated into adjacent adipose tissue. There was no nuclear atypia or mitotic activities. All three tumors showed prominent stromal hyalinization with zonal pattern present in one case. Focal punctate calcification was noted in two cases. The immunohistochemical studies showed that tumor cells were diffusely positive for ERG and negative for CD31 and CD34, with Ki-67 index less than 2%. Fluorescence in situ hybridization on the two tested cases identified EWSR1 gene rearrangement. The next generation sequencing analysis demonstrated EWSR1-SMAD3 fusion in all three cases. During the follow up, one patient developed local recurrence 24 months after the surgery. Conclusions: ESFT is a benign fibroblastic neoplasm and has a predilection for the foot, characterized by ERG immunoreactivity and EWSR1-SMAD3 fusion. Local recurrence might occur when incompletely excised. Familiarity with its clinicopathological features is helpful in distinguishing it from other spindle cell neoplasms that tend to occur at acral sites.

Fibromatosis subescapular como causa de escápula alada. Presentación de un caso y revisión bibliográfica / Subscapularis fibromatosis as a cause of winged scapula. Case report and literature review

La escápula alada suele producirse por lesiones neurológicas tanto del nervio espinal como del nervio torácico largo. La aparición a causa de un tumor ventral de la escápula dificulta su diagnóstico inicial. Presentamos el caso de una mujer joven, con limitación para la rotación externa del hombro, sin antecedentes traumáticos conocidos, evolución progresiva e imagen compatible con una lesión de partes blandas dependiente de la aponeurosis del músculo subescapular confirmada por biopsia como un tumor desmoide. Aunque se trata de un tumor benigno y autolimitado, tiene una inquietante alta tasa de recidivas después de la resección, por lo que se dispone de numerosos tratamientos y muchos grupos optan por hacer un seguimiento médico estrecho de los factores pronósticos y las limitaciones funcionales del paciente, con lo que obtienen resultados satisfactorios y, en algunas series, superiores a los del tratamiento quirúrgico. Nivel de Evidencia: IV

Winged scapula is usually caused by neurological injuries to both the spinal nerve and the long thoracic nerve. Its presence as a result of a ventral scapular tumor makes initial diagnosis difficult. We present the case of a young woman with limited external shoulder rotation, no known traumatic history, and images consistent with a soft tissue lesion dependent on subscapular muscle aponeurosis, which was confirmed by biopsy as a desmoid tumor. Although it is a benign, self-limiting tumor, it has an alarmingly high rate of relapse after resection, so many treatments are available, and many teams choose to closely monitor the patient's prognostic factors and functional limitations, obtaining satisfactory outcomes and, in some series, superior to those of surgical treatment. Level of Evidence: IV

Determinación del grado de agresividad tumoral mediante técnicas de inteligencia artificial aplicadas a imágenes de resonancia magnética / Measuring tumor aggressiveness through artificial intelligence

Objetivo: Determinar el grado de agresividad tumoral mediante técnicas de inteligencia artificial utilizando imágenes de resonancia magnética de sarcomas con grado histológico comprobado. Materiales y Métodos: Dos cohortes retrospectivas independientes de pacientes con sarcomas de partes blandas. Para cada paciente de las dos cohortes se adquirieron tres tipos de secuencias de imágenes como indican los protocolos clínicos: potenciadas en T1, en T2 con supresión grasa (T2FS) y STIR. A fin de desarrollar el modelo de inteligencia artificial, se utilizaron 134 imágenes, tanto las de alto grado como las de bajo grado, en T1 y T2 tomando la imagen más representativa del tumor en cualquier corte. Esto se traduce en 36 millones de píxeles que serán analizados por el programa Landing AI. Resultados: La precisión promedio del modelo fue del 84,3% y la sensibilidad, del 73,3%, con un umbral de confianza de 0,66, lo que demuestra inicialmente que se obtuvo un modelo de buena calidad para predecir con imágenes de resonancia magnética el grado de agresividad de un sarcoma de partes blandas antes de la biopsia. Conclusiones: Se presenta un enfoque novedoso para abordar un tipo de enfermedad infrecuente usando técnicas de inteligencia artificial para determinar el grado tumoral en imágenes de resonancia magnética. Según los resultados de nuestro modelo, se lo puede considerar como una segunda opinión experta al realizar los estudios por imágenes antes de la biopsia. Nivel de Evidencia: III

Objective: To determine the degree of tumor aggressiveness by means of artificial intelligence techniques using magnetic resonance images of sarcomas with proven histological grade. Materials and Methods: Two independent cohorts of patients with soft tissue sarcomas (STS) were retrospectively collected. For each patient in the two cohorts, three types of imaging sequences were acquired as indicated by the clinical protocols: T1-weighted (T1), fat-suppressed T2-weighted (FST2) and STIR. For the development of the artificial intelligence model, 134 images were used, both high-grade and low-grade T1 and T2 images, taking the most representative image of the tumor at any slice. This translated into more than 36 million pixels that were analyzed by the Landing AI program. Results: To determine the degree of tumor aggressiveness by means of artificial intelligence techniques using magnetic resonance The model's average accuracy was 84.3%, and its sensitivity was 73.3%, with a confidence threshold of 0.66, indicating that a good quality model was generated for predicting the grade of aggressiveness of an STS prior to biopsy using MRI scans. Conclusions: A novel approach is presented to address a rare pathology using artificial intelligence techniques to determine the tumor grade based on nuclear magnetic resonance images. Based on the results of our model, it can be considered as a second expert opinion when performing imaging studies prior to biopsy. Level of Evidence: III

Angiolipoma sacro. Reporte de un caso / Sacral angiolipoma. A case report

Fundamento: Los angiolipomas son tumores benignos que se presentan en adultos con una localización, preferentemente, en el espacio epidural posterior torácico. Objetivo: Presentar un caso que debutó con un traumatismo axial lumbosacro donde se evidenció una localización poco común de la lesión y sin relación con las estructuras del canal raquídeo. Presentación del caso: Hombre de 25 años que se cayó y debido a ello se le hizo un traumatismo directo en la región sacrococcígea con dolor y aumento de volumen regional, asociado a parestesias glúteas. Los estudios radiológicos evidenciaron una fractura del cóccix y la presencia de una lesión ubicada en las partes blandas, de aspecto redondeado, homogéneo, sólido, de poco más de 50 mm de diámetro. Se le realizó tratamiento quirúrgico que consistió en coccigectomía subperióstica y exéresis macroscópica de la masa. El estudio histológico concluyó el diagnóstico de un angiolipoma. Conclusiones: Los angiolipomas son tumores raros que tienen características radiológicas peculiares, requieren de alta sospecha clínico-imagenológica para indicar los estudios y el tratamiento. La exéresis total es recomendada para evitar la recurrencia y mejorar el pronóstico.

Background: Angiolipomas are benign tumors that appear in adults with special location in the posterior thoracic epidural position. Objective: To present a case that appeared with a lumbosacral axial trauma where a non-common lesion location was evidenced with no relation among the structures of the spinal canal. Case presentation: 25-year-old man who fell down, consequently suffered a painful direct trauma to the sacrococcygeal region and increased regional volume, associated with gluteal paresthesias. Radiological studies showed a fracture of the coccyx and presence of a lesion located in the soft tissues, with a rounded, homogeneous, solid aspect, a little more than 50 mm in diameter. Surgical treatment consisted of subperiosteal coccygectomy and macroscopic excision of the mass. Histological study concluded the diagnosis of an angiolipoma. Conclusions: Angiolipomas are rare tumors with peculiar radiological features, they require high clinical-imaging suspicion for studies and treatment. Total excision is recommended to avoid recurrence and improve prognosis.

Estudio clínico, radiológico y derivación en tumores musculoesqueléticos / Diagnosis and referral of musculoskeletal tumors

Musculoskeletal tumors are uncommon. However, the true burden of all bone and soft tissue tumors of extremities is underestimated. Usually, the diagnosis of sarcomas is missed or delayed. Therefore, an adequate clinical and radiological assessment, along with the awareness and application of simple guidelines for referral to a specialized center, are of utmost importance. These are critical steps for an appropriate diagnosis and treatment of sarcomas, improving their prognosis.

Angioleiomioma en cavidad oral «una neoplasia rara en un sitio poco común¼. Reporte de un caso y revisión de la literatura / Angioleiomyoma in the oral cavity «a rare neoplasm in an unusual site¼. Case report and literature review

El angioleiomioma (AL) es una neoplasia benigna, bien circunscrita y de crecimiento lento, que representa 5% de las neoplasias de tejidos blandos y cuya etiología es desconocida. Se origina del músculo liso, mayormente de las paredes de los vasos sanguíneos; su localización es más frecuente en extremidades, siendo raros en la región de cabeza y cuello, y más aún en cavidad bucal. Histológicamente la lesión se caracteriza por ser un nódulo bien encapsulado con proliferación de fascículos de músculo liso maduro alrededor de la luz de los vasos sanguíneos, cuyas células suelen ser positivas a marcadores de inmunohistoquímica como alfa actina de músculo liso, desmina, HHF35, miosina, calponina y H-caldesmon. El tratamiento actual es la escisión quirúrgica completa con una tasa de recurrencia prácticamente nula. El objetivo es resaltar la importancia del diagnóstico y el manejo correcto de las lesiones intraorales a través de la presentación de un caso clínico de un leiomioma vascular localizado en región nasolabial, además de hacer la revisión de la literatura correspondiente (AU)

The angioleiomyoma (AL) is a benign neoplasm, well circumscribed and slow growing, that represents 5% of the soft tissue neoplasms, whose etiology is unknown. It originates from smooth muscle, mostly from the walls of blood vessels; regarding its location, it more frequently appears in the extremities, being rare in the head and neck region, and even more so in the oral cavity. Histologically, the lesion is characterized by being a well encapsulated nodule with proliferation of mature smooth muscle bundles around the lumen of the blood vessels, whose cells are usually positive for immunohistochemical markers such as alpha smooth muscle actin, desmin, HHF35, myosin, calponin and H-caldesmon. The current treatment is complete surgical excision having zero recurrence rate. The objective of the following article is to educate on the importance of correct diagnosis and management of intraoral lesions through the presentation of a clinical case of a vascular leiomyoma located in the nasolabial region, in addition to reviewing the corresponding literature (AU)

Análise de marcadores sanguíneos em pacientes com osteossarcoma, sarcomas de partes moles e tumor desmóide / Analysis of blood markers in patients with soft tissue sarcoma and desmoid tumor

Introdução: O tumor desmoide (TD) é uma neoplasia rara com altas taxas de recorrência local, composto por células fibroblásticas que se caracterizam pela expressão de moléculas-chave, incluindo o filamento intermediário vimentina, ciclooxigenase-2 (COX-2) e ß-catenina nuclear. Células tumorais circulantes (CTCs) isoladas do sangue periférico de pacientes com sarcomas e outras neoplasias podem ser utilizadas como biomarcadores precoces de invasão e disseminação tumoral. A família dos Receptores do Fator de Crescimento Epidérmico (Epidermal Growth Factor Receptor, EGFR) também podem influenciar no processo de invasão das CTCs, na formação de metástases e na recolonização de seus tumores de origem por meio de um processo de "auto-semeadura do tumor". Objetivo: Nosso objetivo foi identificar CTCs no sangue periférico de pacientes com TD ou sarcomas e avaliar a expressão das proteínas ß-catenina, TGF-ßRI (do Inglês, Transforming Growth Factor-ß Receptor I), COX-2 (Cyclooxygenase2), vimentina, GLUT-1 (Glucose Transporter 1), LGR5 (G-Protein Coupled Receptor 5) e EGFR, e sua correlação com sobrevidas global (SG) e livre de progressão (SLP). Materiais e Métodos: Foi realizado um estudo prospectivo de pacientes com diagnóstico inicial ou TD recidivado com doença mensurável. Para sarcomas, utilizamos amostras coletadas de forma prospectiva e retrospectiva. As amostras de sangue de cada paciente foram processadas e filtradas pelo ISET® (Rarecells, França) para isolamento e quantificação de CTCs. A expressão das proteínas foi analisada por imunocitoquímica (ICC). Para análise molecular das CTCs provenientes de pacientes com TD foi padronizado o método de PCR digital. Resultados: Foram incluídos 18 pacientes com TD, todos com CTCs detectáveis, com níveis que variaram entre 0,5­13 CTCs/mL. Encontramos uma concordância da expressão de ß-catenina em CTCs e tumores primários de 42,8% (6/14) dos casos usando ICC e imunohistoquímica, respectivamente. Nos nossos testes prévios de PCR digital, encontramos cópias mutadas de S45Pro em 4 pacientes (40%) e de S45Phe em apenas um paciente (10%). Em contraste, não foram encontradas mutações Th41Ala. Nas amostras de sarcomas, analisamos 30 amostras e encontramos CTCs em 93% dos pacientes e os níveis variaram de 0-11,25 CTCs/mL. Observamos também que a SG dos pacientes positivos para EGFR (p=0,027) eram inferiores às sobrevidas dos pacientes negativos para as mesmas proteínas. Conclusões: Nosso estudo identificou alta prevalência de CTCs em pacientes com TD e sarcomas. A concordânciada expressão de ß-catenina entre tumor primário e CTCs traz novas perspectivas para avaliar a dinâmica das CTCs no compartimento sanguíneo, abrindo novos caminhos para o estudo da biologia e comportamento do TD. Este é o primeiro estudo a demonstrar a expressão da proteína LGR5 em CTCs de pacientes com diferentes tipos de sarcomas, o que pode abrir novas oportunidades para futuras investigações. O próximo passo é caracterizar CTCs em uma coorte maior de pacientes para entender melhor o papel do LGR5 e das demais proteínas no processo de metástases tumorais em sarcomas. Além disso, esses resultados abrem a possibilidade de usar CTCs para prever a dinâmica do TD no momento da progressão da doença e tratamento. Mais estudos com tamanhos de amostra maiores são necessários para validar nossos achados tanto em TD como em sarcomas

Introduction: Desmoid tumor (DT) is a rare neoplasm with high rates of local recurrence, composed of fibroblast cells that are characterized by the expression of key molecules, including the intermediate filament vimentin, cyclooxygenase-2 (COX-2) and ß-catenin. Circulating tumor cells (CTCs) isolated from the peripheral blood of patients with sarcomas and other neoplasms can be used as early biomarkers of tumor invasion and dissemination. The Epidermal Growth Factor Receptor (EGFR) family can also influence the process of CTC invasion, metastasis formation and recolonization of their tumors of origin through a process of "tumor selfseeding". Objective: Our objective was to identify CTCs in the peripheral blood of patients with TD or sarcomas and to evaluate the expression of ßcatenin proteins, transforming growth factor receptor beta I (TGF-ßRI), COX-2 (cyclooxygenase-2), vimentin, GLUT-1 (Glucose transporter 1), LGR5 (Gprotein coupled receptor 5) and EGFR and their relation with progression free (PFS) and overall suvival (OS). Methods: We performed a prospective study of patients with initial diagnosis or relapsed TD with measurable disease. For sarcomas, we used samples collected prospectively and retrospectively. Blood samples from each patient were processed and filtered by ISET® (Rarecells, France) for isolation and quantification of CTCs. Protein expression was analyzed by immunocytochemistry (ICC). For the molecular analysis of CTCs from patients with TD, the digital PCR method was standardized. Results: Eighteen TD patients were included, all with detectable CTCs, with levels ranging from 0.5­13 CTCs/mL. We found a concordance ofß-catenin expression in CTCs and primary tumors of 42.8% (6/14) of cases using ICC and immunohistochemistry, respectively. In our previous digital PCR tests, we found mutated copies of S45Pro in 4 patients (40%) and of S45Phe in only one patient (10%). In contrast, no Th41Ala mutations were found. In the sarcoma samples, we analyzed 30 samples and found CTCs in 93% of the patients and the levels ranged from 0-11.25 CTCs/mL. We also observed that the OS of EGFR positive patients (p=0.027) were lower than the survival of negative patients for the same proteins. Conclusions: Our study identified a high prevalence of CTCs in patients with TD and sarcomas. The agreement of ß-catenin expression between primary tumor and CTCs brings new perspectives to evaluate the dynamics of CTCs in the blood compartment, opening newavenues for the study of the biology and behavior of TD. This is the first study to demonstrate the expression of LGR5 protein in CTCs from patients with different types of sarcomas, which may open new opportunities for future investigations. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of LGR5 and other proteins in the process of tumor metastases in sarcomas. Furthermore, these results open up the possibility of using CTCs to predict the dynamics of TD at the time of disease progression and treatment. More studies with larger sample sizes areneeded to validate our findings in both TD and sarcomas

Papel do Receptor Lgr5 no Prognóstico e na Biologia de Sarcomas de Partes Moles / Role of the Lgr5 Receptor in the Prognosis and Biology of Soft Tissue Sarcomas

INTRODUÇÃO: Os sarcomas de partes moles (SPM) de alto grau são neoplasias heterogêneas, de prognóstico ruim e que apresentam poucas alternativas de tratamento. A identificação de marcadores de resposta tumoral ao tratamento, prognóstico, e até ao desenvolvimento de novas drogas, é uma busca incessante para um melhor tratamento dos sarcomas. Neste aspecto, o receptor Lgr5 tem um grande potencial em ser um novo alvo molecular, sendo um marcador de células-tronco das criptas intestinais e glândulas mamárias que também atua como um modulador negativo da sinalização da via Wnt/ß-catenina, uma das mais importantes na biologia de sarcomas emerge como um promissor candidato para estudos pré-clínicos, uma vez que já foi demonstrada sua importância em tumores do trato gastrointestinal. Para isso, os modelos de tumor de xenoenxerto derivado do paciente (PDX) representam uma plataforma valiosa para identificar novos biomarcadores e novos alvos, assim como o Lgr5 para avaliar a resposta à terapia e os mecanismos de resistência. OBJETIVO: Este estudo teve como objetivo estabelecer, caracterizar e testar a proteína Lgr5 através de ensaios in vitro e in vivo para desvendar a importância de Lgr5 na biologia de SPM e estabelecer uma estrutura integrada, convergente e translacional para o estudo deste tipo de tumor. MATERIAIS E MÉTODOS: Para a determinação da expressão de Lgr5 foi estabelecida duas coortes de estudo, uma retrospectiva oriunda do Registro Institucional de Sarcomas e uma prospectiva, onde foram convidados pacientes operados na Instituição com o intuito de gerar Patient-derived xenografts (PDX), um modelo-pré-clínico que possui a capacidade de manter as características moleculares dos tumores dos pacientes. Para isso, foram utilizados fragmentos implantados em camundongos imunossuprimidos para gerar esses modelos tumorais derivados de pacientes, além dos estudos funcionais in vitro utilizando linhagens de SPM para análise de perfil de expressão da proteína Lgr5 através de ensaios com imunofluorescência para verificar a capacidade de expressão de Lgr5, citometria de fluxo para verificar o padrão e quantidade de proteína nas amostras analisadas e western blotting para obter um padrão de marcação da proteína Lgr5. Além dos ensaios funcionais para avaliar a participação da proteína na proliferação, se a expressão da proteína interfere no poder migratório das células e tumores de SPM e capacidade de auto renovação, bem como sua associação com os dados clínicos e dados de sobrevida. RESULTADOS: O Registro Institucional retrospectivo conta com mais de 300 pacientes, já o Registro prospectivo com 70 pacientes que derivaram a geração de 33 PDX. Foi observado que pacientes com H-score superior a 20 apresentaram sobrevida global menor em 5 anos em comparação com o H-score de pacientes com valores inferiores a 20. Agora na outra análise feita, o H-score de pacientes com valores superiores a 25 é pior em comparação com os que apresentaram valores inferiores a 25 nos dados de sobrevida livre de doença. Além disso, células que superexpressam a proteína Lgr5 tem maior capacidade migratória (p= 0.02) e uma tendência de aumento na proliferação e auto renovação. Realizamos o teste de implante dessas populações positivas e negativas de Lgr5, separadas previamente por cell sorting. Para isso foram utilizados animais Balb/c Nude. Sugerindo que a expressão da proteína transduzida pode ser modulada por mecanismos compensatórios que precisam ser explorados. CONCLUSÃO: A construção do Registro Institucional de SPM é um grande passo para o melhor compreendimento da biologia dos Sarcomas, além da possibilidade de estudar novos alvos terapêuticos desse tumor raro, uma vez que os estudos e artigos científicos ainda são muito escassos. A geração dos modelos PDX também foi uma estratégia implantada muito bem executada com a geração de 33 PDX de diversos subtipos histológicos. Além da proteína Lgr5 induzir a migração celular a sua expressão está relacionada a um pior prognóstico, uma vez que, quanto maior a expressão de Lgr5 menor é a sobrevida global do paciente.

INTRODUCTION: High-grade soft tissue sarcomas (STS) are heterogeneous neoplasms with a poor prognosis and few treatment alternatives. The identification of tumor response markers to treatment, prognosis, and even the development of new drugs, is an incessant search for a better treatment of sarcomas. In this aspect, the Lgr5 receptor has great potential to be a new molecular target, being a marker of stem cells of the intestinal crypts and mammary glands that also acts as a negative modulator of the signaling of the Wnt/ß-catenin pathway, one of the most important in the biology of sarcomas emerges as a promising candidate for preclinical studies, since its importance in tumors of the gastrointestinal tract has already been demonstrated. To that end, patient-derived xenograft (PDX) tumor models represent a valuable platform to identify new biomarkers and new targets, as does Lgr5 to assess therapy response and resistance mechanisms. OBJECTIVE: This study aimed to establish, characterize, and test the Lgr5 protein through in vitro and in vivo assays to unravel the importance of Lgr5 in the biology of PMS and to establish an integrated, convergent and translational framework for the study of this type of tumor. MATERIALS AND METHODS: To determine the expression of Lgr5, two study cohorts were established, a retrospective one from the Institutional Registry of Sarcomas and a prospective one, in which patients operated on at the Institution were invited to generate Patient-derived xenografts (PDX), a pre-model -clinical that has the ability to maintain the molecular characteristics of patients' tumors. For this, fragments implanted in immunosuppressed mice were used to generate these tumor models derived from patients, in addition to in vitro functional studies using SPM strains to analyze the expression profile of the Lgr5 protein through immunofluorescence assays to verify the ability to express Lgr5, flow cytometry to verify the pattern and amount of protein in the analyzed samples and western blotting to obtain a pattern of labeling of the Lgr5 protein. In addition to functional assays to assess the protein's participation in proliferation, whether protein expression interferes with the migratory power of SPM cells and tumors and self-renewal capacity, as well as its association with clinical data and survival data. RESULTS: The Institutional Retrospective Registry has more than 300 patients, while the Prospective Registry has 70 patients who derived the generation of 33 PDX. It was observed that patients with an H-score greater than 20 had a lower overall survival at 5 years compared to the H-score of patients with values below 20. Now in the other analysis performed, the H-score of patients with values greater than 25 it is worse compared to those who had values less than 25 in the disease-free survival data. Furthermore, cells that overexpress the Lgr5 protein have greater migratory capacity (p=0.02) and a tendency to increase proliferation and self-renewal. We performed the implant test of these positive and negative populations of Lgr5, previously separated by cell sorting. For this, Balb/c Nude animals were used. Suggesting that the expression of the transduced protein can be modulated by compensatory mechanisms that need to be explored. CONCLUSION: The construction of the Institutional Registry of PMS is a big step towards a better understanding of the biology of Sarcomas, in addition to the possibility of studying new therapeutic targets for this rare tumor, since studies and scientific articles are still very scarce. The generation of PDX models was also an implemented strategy very well executed with the generation of 33 PDX of several histological subtypes. In addition to the Lgr5 protein inducing cell migration, its expression is related to a worse prognosis, since the higher the Lgr5 expression, the lower the overall survival of the patient

Osteosarcoma extraesquelético. Presentación de un caso / Extraskeletal osteosarcoma. Case report

El osteosarcoma extraesquelético es un tumor maligno de alto grado que representa menos del 2% de los sarcomas de partes blandas y que afecta principalmente a personas entre la quinta y sexta década de la vida. Típicamente el diagnóstico es tardío, con un período síntomas-diagnóstico extenso, >6 meses en comparación con el del osteosarcoma convencional. Comunicamos el caso de un hombre de 43 años que acudió con una tumoración en la región glútea y el muslo izquierdo de un año de evolución. Luego de estudios complementarios y una biopsia no concluyentes, se procedió a la resección quirúrgica del tumor con márgenes amplios. El estudio histológico de la pieza indicó osteosarcoma extraesquelético. El paciente tuvo una evolución muy buena, sin elementos de recidiva local ni compromiso a distancia luego de 20 meses de seguimiento. Nivel de Evidencia: IV

Extraskeletal osteosarcoma (EOS) is a high-grade malignant tumor that accounts for less than 2% of soft tissue sarcomas and mainly engages people between the fifth and sixth decade of life. It is typically of late diagnosis, with an extensive symptom-diagnosis period greater than 6 months compared to conventional osteosarcoma. We report the case of a 43-year-old patient who presented in our service with a 1-year-old tumor localized in the gluteal and left thigh region. After inconclusive paraclinical studies and biopsy, the tumor was surgically resected with wide margins and diagnosed as EOS after the histological analysis of the piece. The patient showed a very good clinical and paraclinical progression without signs of local or distant recurrence after 20 months of follow-up. Level of Evidence: IV

Pleomorphic hyalinizing angiectatic tumor of the vulva: literature review based on a rare presentation

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft tissues is a rare, non-metastatic tumor of unknown etiology and uncertain behavior, which may recur locally. There are few reports on this condition, and due to the rarity of the disease, its lineage has not yet been fully elucidated. The present study aims to report the case of an unusual entity observed for the first time in vulval topography. A female patient, 83 years old, presented with a tumor in the vulvar region that had evolved for approximately 4 months. Magnetic resonance imaging showed an expansive perineal formation of 8.5 × 3.5 cm, and a hemivulvectomy with a flap rotation was performed. The review of the slides revealed a mesenchymal lesion without significant atypia, which was richly vascularized. In the areas of interest, the immunohistochemical (IHC) study demonstrated positivity for CD34, estrogen, and progesterone receptors; it was negative for the other tested markers. Morphological findings associated with the IHC staining panel supported the diagnosis of PHAT. The main morphological features of PHAT are clusters of ectatic vessels of different sizes that show deposits of subendothelial and intraluminal fibrin. Fusiform and pleomorphic cells randomly arranged in leaves or long fascicles intermingle these vessels. It is essential to recognize this entity and consider it among the differential diagnoses of a mesenchymal lesion, given the wide variety of entities that comprise this group of lesions.

Paratesticular liposarcoma: the clinicopathological features of nineteen cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnoses of paratesticular liposarcoma. Methods: The cases were collected from 2012-2020, from the archives of the Department of Pathology, Peking University Third Hospital, with diagnosis confirmed by histology, immunostaining and FISH tests. Results: Totally 19 patients were enrolled (including 11 in-hospital patients and 8 consultant cases). The patients aged 37-84 years (mean 57 years). The preoperative clinical diagnoses were spermatic cord/inguinal masses (nine patients), scrotal masses (seven patients), and inguinal hernia (three patients). Six lesions recurred after local resection, including one case extending from pelvic liposarcoma. Histologically, there were 10 cases of well-differentiated liposarcoma (WDLPS) and nine cases of dedifferentiated liposarcoma (DDLPS). WDLPSs mostly showed the combined features of lipoma-like, inflammatory and sclerosing subtypes (six patients); the other four WDLPSs had pure lipoma-like subtype features. DDLPSs were low-grade (three patients) or high-grade (six patients), with the morphology resembling myxofibrosarcoma, inflammatory myofibroblastoma, spindle cell sarcoma, pleomorphic undifferentiated sarcoma and pleomorphic liposarcoma. Intense inflammatory cells infiltration was commonly observed in five WDLPSs and two DDLPSs. Ossification was observed in three tumors. Immunohistochemically, the tumors were positive for MDM2 (8/10) and CDK4 (10/10), which were expressed in lipo-differentiating cells, spindle cells in WDLPS, and in dediffferentiated components. S-100 was only expressed by lipocytes (10/10). CD34 expression was positive and diffuse in the stromal cells of WDLPSs and focal or diffuse in dedifferentiated areas (10/10). FISH tests with an MDM2 gene probe were positive (12/12). Conclusions: Paratesticular liposarcoma may be overlooked by both clinicians and pathologists. WDLPS and DDLPS predominate, showing various histologic divergences. The presence of amplification of the 12q14-q15 region (containing the MDM2 and CDK4 genes) is helpful for making the correct diagnosis.

Tumor fibroblástico inguinal superficial positivo para CD34: reporte de un caso y revisión de la literatura / Inguinal superficial cd34-positive fibroblastic tumor: case report and literature review

El tumor fibroblástico superficial de tejidos blandos positivo para antígeno CD34 (CD34) es un tumor raro, de baja frecuencia, que se caracteriza histológicamente por un marcado pleomorfismo, baja actividad mitótica, e inmunoreactividad difusa para CD34. Puede tener un comportamiento similar al de un tumor mesenquimal de malignidad intermedia. Existen sólo 52 casos publicados en la literatura. Se presenta el caso de una paciente de 31 años con una masa en tejidos blandos en región inguinal izquierda, de crecimiento progresivo, de varios meses de evolución dolorosa. La masa fue biopsiada y, con la sospecha de un tumor fibroblástico superficial positivo para CD34, fue posteriormente tratada con una resección ampliada de la lesión y con cobertura del defecto en la piel con un colgajo local de avance de V-Y, con una evolución satisfactoria en su seguimiento postquirúrgico. El reporte de patología confirmó la sospecha diagnóstica de un tumor con reactividad fuerte para CD34, con proteína P53 en 60% a 70%, antígeno Ki67 menor al 15%, sin pérdida de proteína nuclear INI-1, y negatividad para CD31, CD163, AE1AE3, CAM5.2, EMA, CD30, receptores de progestágenos, proteína S100, y desmina, con bordes negativos.

Superficial CD34 (CD34) antigen positive fibroblastic soft-tissue tumor is a rare, lowfrequency tumor, characterized histologically by marked pleomorphism, low mitotic activity, and diffuse immunoreactivity for CD34. It may behave like a mesenchymal tumor of intermediate malignancy. There are only 52 cases published in the literature. We present the case of a 31-year-old patient with a long progressive and painful growth of a soft-tissue lesion in the left inguinal region. The mass was biopsied and, with the suspicion of a superficial CD34-positive fibroblast tumor, it was subsequently treated with an enlarged resection of the lesion and covering the skin defect with a local V-Y advancement flap, with a satisfactory evolution in the postoperative follow-up. The pathology report confirmed the diagnostic suspicion of a tumor with strong reactivity for CD34, with P53 protein in 60% to 70%, Ki67 antigen in less than 15%, without loss of INI-1, and with negativity for CD31, CD163, AE1AE3, CAM5.2, EMA, CD30, progestin receptors, S100 protein and desmin, with negative borders.