Malignização primária no tumor de células gigantes: um estudo de caso

CONTEXT: Primary malignancy in giant cell tumor (PMGCT) is rare. It is defined as a high-grade sarcoma originating in a giant cell tumor (GCT) and seems to behave less aggressively than its secondary counterpart does. CASE REPORT: This report presents the case of a 39-year-old female with pain in her left shoulder for one month. Radiography showed a pathological fracture of the proximal humerus associated with an osteolytic lesion. Histopathological analysis showed typical areas of GCT juxtaposed with a sarcomatous component. CONCLUSIONS: PMGCT seems to behave less aggressively than secondary malignancy in GCT, and it may simulate its more common benign counterpart clinically and radiographically. However, it requires a more aggressive type of treatment.CONTEXTO: Malignização primária no tumor de células gigantes (MPTCG) é rara. Ela é definida como um sarcoma de alto grau originário de um tumor de células gigantes que parece ser menos agressivo que o tipo secundário. RELATO DE CASO: Relatamos um caso de uma paciente de 39 anos de idade, com dor no ombro esquerdo há um mês. A radiografia mostrou uma fratura patológica do úmero proximal associada a uma lesão osteolítica. O exame histopatológico revelou típicas áreas de tumor de células gigantes justapostas por um componente sarcomatoso. CONCLUSÃO: MPTCG parece se comportar menos agressivamente que a neoplasia secundária do tumor de células gigantes (TCG), e pode simular o TCG, que é mais comum, tanto clínica como radiograficamente. Entretanto, exige tratamento mais agressivo

Malignant transformation of a recurrent giant cell tumor of bone with lung metastasis: a case report

Giant cell tumors (GCT) are benign tumors with potential for aggressive behaviour and capacity to metastasize. It is a locally destructive tumor that occurs predominantly in long bones of adolescents and young adults in the epiphysis. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi-nucleated giant cells with homogenous distribution. There are varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favour an intralesional approach that preserves anatomy of bone. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Malignant transformation without radiotherapy exposure, is an uncommon event, occurring in less than 1% of giant cell tumors of bone. Here we reported a case of recurrent GCT of tibia that at the time of final recurrence was found to have undergone malignant transformation over a period of 6 years following several limb salvaging procedures. Concurrent metastases were found in the lung, but these were non-transformed GCT following which the patient has undergone above knee amputation

A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases

Giant cell tumor (GCT) of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated sarcomas. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT

Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy

Giant cell tumor of bone (GCTB) is an intermediate bone tumor that rarely undergoes malignant transformation. Secondary malignant GCTB (SMGCTB) is defined as a lesion in which high‑grade sarcoma occurs at the site of previously treated GCTB. The present study retrospectively reviewed the medical records of patients with GCTB treated at Okayama University Hospital between April 1986 and April 2020. The clinicopathological and histological features of patients with SMGCTB without prior radiotherapy were investigated. A total of three patients (4%) with SMGCTB were detected, and the tumor sites were the distal ulna, distal femur and sacrum. Two of the patients had been treated with curettage and bone graft, and one had been treated with denosumab. In all cases, the lesions were made up of two components, the conventional GCTB component and the malignant component. The Ki67 labeling index was higher in the malignant components of SMGCTB and metastatic lesions compared with that in primary and recurrent conventional GCTB, or the conventional GCTB component of SMGCTB. Moreover, p53 expression was higher in these same components in patients who underwent curettage and bone grafting; however, there was no difference in the patient that received denosumab treatment. In this patient, clinical cancer genomic profiling revealed loss of CDKN2A, CDKN2B and MTAP expression. All three patients developed distant metastasis. The patients with SMGCTB in the ulna and femur died 13 and 54 months after detection of malignant transformation, respectively. The patient with SMGCTB in the sacrum received carbon‑ion radiotherapy to the sacrum and pazopanib; the treatment was effective and the patient was alive at the last follow‑up 3 years later. In conclusion, p53 may be associated with malignant transformation in GCTB. Future studies should investigate the association of between denosumab treatment and malignant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB

The significance of expression proliferation factors and cell cycle regulation proteins in giant cell tumor of bone

Gigantocelularni tumor kosti (GCTB) je primarni koštani tumor koga karakteriše prisustvo dve ćelijske populacije: džinovske ćelije tipa osteoklasta i monojedarne stromalne ćelije koje predstavljaju pravu neoplastičnu tumorsku komponentu. Biološko ponašanje GCTB je nepredvidivo. Terapija izbora za gigantocelularni tumor kosti je hirurška. Međutim, pojava recidiva nakon hirurške intervencije je opisana kod značajnog broja pacijenata i kreće se od 10 do 25%. Postoji veliki broj studija koje se bave analizom biološkog ponašanja GCTB, pre svega sa ciljem predviđanja nastanka recidiva. One su veoma značajne jer ukazuju da GCTB sa agresivnijim biološkim ponašanjem zahteva i agresivniji terapijski pristup. Naše istraživanje se odnosi na određivanje različitih kliničko-radiološko-patohistoloških parametara koji bi mogli uticati na predikciju biološkog ponašanja GCTB, odnosno predviđanje pojave recidiva. Izdvajanjem i jasnim definisanjem karakteristika tumora koje bi mogle ukazivati na povećan rizik za ponovnu pojavu GCTB, nakon hirurške terapije, moglo bi eventualno opravdati i ekstenzivnost/agresivnost terapijskog pristupa. Ciljevi: Gigantocelularni tumor kosti je benigni tumor, koji i danas ima nepredvidljivo ponašanje, morfološko i kliničko. U cilju preciznijeg utvrđivanja ponašanja tumora i utvđivanja novih prognostičkih faktora, postavili smo sledeće ciljeve: 1. Utvrđivanje korelacije ekspresije Ki-67, p53 i Ciklin D1 u tkivu gigantocelularnog tumora kosti sa biološkim ponašanjem ovog tumora (pojavom rest-recidiva ili pojavom plućnih metastaza). 2. Utvrđivanje korelacije ekspresije Ki-67, p53 i Ciklin D1 u tkivu gigantocelularnog tumora kosti sa kliničko-patološkim prognostičkim parametrima (klinička GTM, Enneking-ova klasifikacija). Metodologija: Ova teza je izvedena kao studija preseka, u koju je uključeno 164 pacijenata kojima je u periodu od 1964-2008. god. na Institutu za patologiju Medicinskog fakulteta u Beogradu dijagnostikovan gigantocelularni tumor kosti, a koji su operisani na Institutu za Ortopedsko-hirurške bolesti „Banjica“. Kriterijumi za uključenje u studiju bili su: patohistološki verifikovan gigantocelularni tumor kosti...Giant cell tumor of bone (GCTB) is a primary bone tumor, characterized by the presence of two cell populations: osteoclast-like giant cells and mononuclear stromal cells, which are, in fact, the real neoplastic tumor component. Biological behavior of the GCTB is unpredictable. Apart from the locally aggressive growth followed by the destruction of bone tissue and propagation in the surrounding soft tissue, as well as frequent incidence of fractures and relapses, the occurrences of pulmonary metastases are also reported. The therapy of choice for giant cell tumor of bone is surgical. However, the recurrence after surgical intervention is found in significant number of patients, i.e. at a rate of 10 to 25%. A large number of studies deal with analyzing the biological behavior of GCTB, primarily in order to predict the recurrence. Those studies are of great importance, since they imply that GCTB with a more aggressive biological behavior also requires a more aggressive therapeutic approach. Our research refers to determining various clinical, radiological and pathohistological parameters which may have an influence on predicting the biological behavior of GCTB, i.e. on predicting the incidence of relapses. Detecting and clearly defining the tumor characteristics which could indicate an increased risk of GCTB recurrence after surgical therapy might account for the extensiveness/aggressiveness of therapeutic approach. Objective: Giant Cell Tumor of Bone is a benign tumor, which still has an unpredictable behavior, morphology and clinical. In order to precisely determine the behavior of the tumor and the determining of new prognostic factors, we set the following objectives: 1. Establishing correlations expression Ki-67, p53 and Cyclin D1 in the tissues of giant cell tumor of bone with the biological behavior of this tumor (the appearance of rest-relapse or emergence of pulmonary metastases). 2. Establishing correlations expression of Ki-67, p53 and Cyclin D1 in the tissues of giant cell tumor of bone with clinicopathological prognostic parameters (clinical GTM, Enneking's classification)..

Cimentoplastia associada a radioterapia no tratamento de lesões osteolíticas do esqueleto apendicular em canídeos

Dissertação de Mestrado Integrado em Medicina VeterináriaO presente estudo incidiu numa amostra de 3 canídeos, respectivamente diagnosticados com quisto aneurismático ósseo, osteossarcoma e tumor de células gigantes, ao nível do esqueleto apendicular. O mesmo teve como objectivos: 1) descrever o tratamento multimodal de lesões osteolíticas apendiculares em canídeos, envolvendo cimentoplastia (pela técnica percutânea guiada por tomografia computorizada [TC] ou pela técnica após curetagem das lesões), combinada com radioterapia por megavoltagem de electrões e com outra terapêutica adjuvante, considerada como adequada em cada caso; 2) descrever complicações e efeitos secundários; 3) sugerir correcções às técnicas propostas; 4) estudar a eficiência de tais protocolos no alívio da dor e no controlo local das referidas lesões e a sua influência no decurso da doença, baseados no período de seguimento dos casos clínicos descritos, o qual compreendeu 72 a 406 dias. As técnicas e o tratamento multimodal propostos foram simples, bem-sucedidos e seguros nos casos descritos. O protocolo multimodal foi bem tolerado por todos os canídeos e as complicações e efeitos secundários da terapêutica aplicada foram mínimos. Em resposta ao tratamento, foi registado alívio completo da dor nos 3 pacientes, que se prolongou por todo o período de seguimento. Adicionalmente, as lesões foram consideradas como radiologicamente estacionárias até ao fim do período de seguimento em 2 canídeos. Contudo, um terceiro paciente sofreu fractura patológica 396 dias após o início do tratamento. Do conhecimento do autor, este constitui o primeiro estudo no âmbito da Medicina Veterinária, no qual foi descrito o tratamento multimodal, envolvendo cimentoplastia e radioterapia por megavoltagem, em lesões osteolíticas apendiculares, que não exclusivamente osteossarcomas, e a técnica de cimentoplastia percutânea guiada por TC. Adicionalmente, é o primeiro estudo em Medicina Veterinária, em que foram descritas as técnicas radioterapia em quistos aneurismáticos ósseos e em tumores de células gigantes.ABSTRACT - CIMENTOPLASTY COMBINED WITH RADIATION THERAPY IN THE TREATMENT OF APPENDICULAR OSTEOLYTIC LESIONS IN DOGS - The current study used a sample of 3 dogs, diagnosed respectively with an aneurysmal bone cyst, an osteosarcoma and a Giant Cell Tumor, at the appendicular skeleton, and aimed to: 1) describe the multimodal treatment of appendicular osteolytic lesions, using cementoplasty (by Computed Tomography (CT)-guided percutaneous technique or by the technique following curettage) combined with electrons megavoltage radiation therapy and other adjuvant therapy, considered pertinent in each case ; 2) report the complications and adverse side effects of the treatment; 3) suggest corrections of the proposed techniques; 4) study the efficiency of the treatment in enhancing pain relief and local control of the lesions and its influence in the course of the disease, based on the follow-up period of the reported cases, which ranged from 72 till 406 days. The techniques and the multimodal treatment described were simple, well-succeeded and safe in the reported cases. The multimodal protocol was well tolerated in all patients and the complications and adverse side effects were minimal. The treatment achieved complete pain relief, which remained till the end of the follow-up period in all patients. Moreover, the lesions were considered radiologically stable during the whole follow-up period in 2 dogs. However, one patient experienced pathologic fracture 396 days after the beginning of the treatment. To the author’s knowledge, this is the first study in veterinary medicine reporting the mentioned multimodal treatment in other appendicular osteolytic lesions than osteosarcoma, and describing the CT-guided percutaneous cementoplasty. This is also the first study describing the radiation therapy techniques for aneurysmal bone cysts and giant cell tumors in veterinary medicine