Expresión Inmunohistoquímica de Ki-67 en Lesión Central de Células Gigantes / Immunohistochemical Expression of Ki-67 in Central Giant Cell Lesion

RESUMEN: La lesión central de células gigantes (LCCG) es una lesión osteolítica benigna que en algunos casos presenta un comportamiento agresivo, con recidiva y mal pronóstico. Ki-67 es una proteína nuclear cuya función general es la regulación de la proliferación celular. Este marcador es utilizado para el reconocimiento de células en proliferación y como herramienta de pronóstico en el diagnóstico de neoplasias. El objetivo de este estudio fue cuantificar la inmunoexpresión de Ki-67 en las diferentes poblaciones celulares de las LCCG y analizar su asociación con las características clínicas, demográficas y radiográficas. Se evaluó la inmunoexpresión de Ki-67 de 17 casos de LCCG en dos poblaciones celulares: células gigantes multinucleadas (CGM) y células mesenquimatosas estromales (CME). El análisis estadístico se efectuó con el programa SAS 9.0 y SPSS versión 23.0, con un nivel alfa impuesto de P<0,05. Las CME mostraron inmunoexpresión promedio de 9,4 % y las CGM de 0,65 %. No se encontró relación estadísticamente significativa entre las características clínicas, demográficas y radiográficas de las LCCG y la inmunoexpresión de Ki-67. La expresión de Ki-67 en CME sugiere que esta población se encuentra en constante actividad celular y que las LCCG son lesiones dinámicas y en constante proceso de diferenciación.

ABSTRACT: The central giant cell lesion (CGCL) is a benign osteolytic lesion which in some cases presents an aggressive behavior with recurrence and poor prognosis. Ki67 is a nuclear protein whose general function is the regulation of cell proliferation. This marker is used to identify proliferating cells and as a prognostic tool in the diagnosis of neoplasms. The aim of this study was to quantify the immune expression of Ki-67 in the different cell populations of CGCL and analyze its association with clinical, demographic and radiographic characteristics. The Ki-67 immune expression of 17 cases of LCCG was evaluated in two cell populations: multinucleated giant cells (CGM) and stromal mesenchymal cells (SMC). The statistical analysis was carried out with SAS 9.0 and SPSS version 23.0, with an alpha tax level of P <0.05. The CME showed average immune expression of 9.4 % and the CGM of 0.65 %. No statistically significant relationship was found between the clinical, demographic and radiographic characteristics of the CGCL and the immune expression of Ki-67. The expression of Ki-67 in CME suggests that this population is in constant cellular activity, and that the CGCL are dynamic lesions in a continuous differentiation process.

Comparación de inmunoexpresión de receptores CD68 en células gigantes y mononucleadas en lesiones central y periférica de células gigantes de los maxilares / A comparison of immunoexpression of CD68 receptors in giant cell and mononuclear cells of central and peripheral giant cell lesions of the jaws

Introducción: La lesión central (LCCG) y periférica (LPCG) de células gigantes de los maxilares, son lesiones reactivas con comportamiento clínico diferente. Objetivo: Comparar la inmunoexpresión de CD68 en células gigantes (CGm) mononucleares (CMn) en lesiones central y periférica de los maxilares. Material y métodos: Se evaluaron 35 casos de LCCG y 24 de LPCG en bloques de parafi na que podían ser procesadas para la expresión del anticuerpo CD68. La inmunoexpresión se valoró en el citoplasma de ambas poblaciones celulares, obteniendo proporciones; la inmunoexpresión se categorizó en intensa, moderada, leve. Las proporciones se compararon con χ2, siendo signifi cativo p ≤ 0.05. Resultados: Para las CGm de LCCG, CD68 se expresó en una proporción de 96 versus 84.2% LPCG (p < 0.005). La proporción de la tinción de la expresión intensa y moderada fue más frecuente en las LCCG (p = 0.032). Las proporciones entre las CMn 59.3% LCCG versus 18.6% en la LPCG (p < 0.001). Hubo diferencia en intensidad de CD68, en las CMn de LCCG fue mayor (p = 0.002). Conclusiones: La alta expresión de CD68 en las CGM y CMn en la lesión central y periférica confi rma su fenotipo de macrófago. Las diferencias entre las proporciones y la tinción a CD68 refl eja mayor actividad fagocítica posiblemente relacionada con el comportamiento clínico (AU)

Introduction: Central (CGCL) and Peripheral (PGCL) giant cell lesions of jaws are reactive lesions displaying diff erent behavior patterns. Objective: To compare CD68 immunoexpression between CGCL and PCGL in giant multinucleated and mononuclear cells. Material and methods: 35 CGCL and 24 PGCL were retrieved from paraffi n-embedded biopsy, as well as the feasibility to analyze CD68 immunoexpression. The immunoexpression was analyzed in cytoplasm both cell populations cellular, for and staining intensity was categorized as intense, moderate or faint. Proportions were compared by χ2, making a p ≤ 0.05 value signifi cate. Results: In 96% of CGCL's in GMCs displayed CD68, as compared to 84.2% in PGCL, (p < 0.005). The proportion of stained cells, intense to moderate staining was more frequent in CGCL (p = 0.032). The proportion CD68 was expressed in 59.3% or CGCL mononuclear cells, as compared to 18.6% in PGCL, (p < 0.001). There was diff erence in staining CD68 intensity between mononuclear cells in CGCL, (p = 0.002). Conclusions: The high CD68 expression frequency in GMCs and mononuclear cells in central and peripheral GCL confi rm a macrophage phenotype; a more intense staining in CGML and GMCs suggests a more active phagocytic activity, and possibility underline the diff erent clinical behavior (AU)

Brown Tumour of Hyperparathyroidism, a benign latency in the jaws: A Review of Literature. Literature.

Background: To inculcate awareness about the importance of thorough screening of the patients presenting with giant cell lesions in the jaw bones for clinical, biochemical and radiological features of hyperparathyroidism. Material and Methods: The history, physical examination, laboratory values, imaging and pathologic findings are described in a 32-year-old woman, presenting with brown tumour lesion in mandible, due to primary hyperparathyroidism. A systematic review of published literature from PubMed is added, which highlights the importance of a thorough diagnostic workup and selection of appropriate treatment modality. Results: In the case presented, after Parathyroid adenoma excision, within thirty minutes, the serum values of Parathormone and Calcium returned to normalcy and spontaneous regression of the brown tumour was noted. Also, the review of literature emphasized the need for systemic investigations of suspected giant cell jaw lesions and established that parathyroidectomy can be considered the primary treatment modality for brown tumours of the jaw due to hyperparathyroidism. Conclusion: Radiolucent lesions of the jaws showing giant cells on histopathology should raise suspicion of hyperparathyroidism. This case emphasizes the importance of a detailed systemic investigation for all lesions in the maxillofacial region.

Recurrent Peripheral Giant Cell Granuloma: A Case Report.

Abstract: Peripheral Giant Cell Granuloma is a non-neoplastic, tumor-like, reactive lesion occurring exclusively on gingiva/alveolar crest. It is thought to arise from the periodontal ligament or periosteum. Clinically, it bears resemblance to pyogenic granuloma, peripheral ossifying fibroma and many other peripheral soft tissue lesions seen in the oral cavity, thereby making histopathology mandatory for the diagnosis of this lesion. The lesion although being relatively common still carries a lot of ambiguity. The ambiguity is in terms of its etiology, growth potential, biological behavior (recurrence), histogenesis of its cells as well as its treatment. The entity further holds significance because of its notorious behavior and its high tendency to recur. The present paper describes a case report on recurrent peripheral giant cell granuloma with a comprehensive insight of the literature on its clinical and histological aspects. Special attention has been given on the histogenesis of its cells and treatment of this lesion.

FASN expression, angiogenesis and lymphangiogenesis in central and peripheral giant cell lesions

Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) are non-neoplastic proliferative processes of the jaws. PGCL is a reactive process induced by irritant local factors and CGCL is an intra-osseous lesion of unknown etiology. Both lesions exhibit similar histologic features showing abundant mononuclear cells, admixed with a large number of multinucleated giant cells and a rich vascularized stroma with extravasated erythrocytes, hemosiderin deposition, and blood-filled pools. Recent studies have linked fatty acid synthase (FASN) with angiogenesis. Objective: To evaluate angiogenesis and lymphangiogenesis and their relationship with FASN expression in CGCL and PGCL. Material and Methods: Thirteen CGCL and 14 PGCL of the jaws were selected for immunoexpression of FASN; CD34 and CD105 (to assess blood microvessel density [MVD] and microvessel area [MVA]); and D2-40 (to assess lymphatic MVD and MVA). Results: Within PGCL and CGCL, MVD-CD34 was signifcantly higher than MVD-CD10S, followed by MVD-D2-40. Moreover, a signifcantly higher number of FASN-positive multinucleated giant cells than mononuclear cells were observed. Between PGCL and CGCL, only MVD-CD34 and all MVA were signifcantly higher in PGCL. Positive correlation between MVA-CD10S with FASNpositive mononuclear cells in both lesions was observed. Conclusions: Our results show both lesions exhibiting similar levels of FASN expression and neoangiogenesis, suggesting constitutive processes that regulate tissue maintenance. .

Lesión híbrida conformada por una lesión central de células gigantes y un fibroma osificante central: reporte de un caso y revisión de la literatura / Hybrid lesión composes by a central giant cell lesion and central ossifying fibroma: a case report and review of literature

Las lesiones híbridas son entidades poco frecuentes conformadas por elementos histopatológicos de distintas lesiones, la asociación de un Fibroma Osificante Central (FOC) con una Lesión Central de Células Gigantes (LCCG) es un ejemplo de ellas y representa el tipo más frecuentemente reportado en la literatura con diez casos hasta la fecha. A continuación presentamos el caso de una paciente de 24 años de edad, quien es referida al servicio de clínica estomatológica de la Facultad de Odontología, por presentar un aumento de volumen en la zona mandibular derecha que ocasiona asimetría facial, al examen intrabucal se observó una lesión tumoral de aproximadamente 2,5 cms. de diámetro y recubierta por mucosa bucal sana, que se extendía desde el canino inferior derecho hasta el segundo premolar del mismo lado (de 43 al 45). La paciente refiere una evolución de 3 meses y aparición posterior a un trauma. Se indican pruebas hematológicas y de vitalidad pulpar de los dientes involucrados, tomografía computarizada y biopsia Incisional, la cual concluye: LCCG asociada a FOC. Se trata con recesión quirúrgica total previo tratamiento endodóntico de los dientes involucrados y después de dos años la paciente se mantiene libre de recidiva. El reporte de este tipo de lesiones híbridas permitirá entender mejor en el futuro su comportamiento y a su vez brindar el tratamiento más adecuado a estos pacientes.

Hybrid lesions are rare entities formed by histopathological elements of different lesions, the association of a Central Ossifying Fibroma (COF) with a Central Giant Cell Lesion (CGCL) is an example of them and represents the most frequently reported type in the literature, only ten cases to date. We present the case of a 24 years female patient, who is referred to the dental clinic service to present a swelling in the right mandibular region causing facial asymmetry, the intra oral examination revealed a 2,5 cm lesion covered with healthy oral mucosa which extended from the distal aspect of lower right canine to the right second bicuspid, with 3 months evolution and associated to a trauma. Haematological tests, pulp vitality of involved teeth, CT scan and incisional biopsy were indicated, concluding a diagnosis of COF associated to CGCL. The decision was made to go for the surgical approach of the lesion with previous endodontic treatment of involved teeth and after two years the patient remains free of recurrence. The report of this type of hybrid lesions helps to understand their behavior and guides to the best treatment for these patients.

Clinical and imagiological findings of central giant cell lesion and cherubism

Cone beam computed tomography (CBCT) is the best examination for bone lesions of the maxilla, allowing the dentist to evaluate precisely the behavior and components of the lesion and their relationship to the surrounding structures. Central giant cell lesion and cherubism are histologically very similar lesions. Therefore clinical and radiological examinations are fundamentally important for the diagnosis. The aim of this paper is to report two cases diagnosed as central giant cell lesions and cherubism using CBCT. This imaging modality was very important for the diagnosis of the lesions presented in the current study. It also allowed observing precisely the limits of the lesions, the components, the behavior and the exact relationship to adjacent structures.

A tomografia computadorizada de feixe cônico (TCFC) é o melhor exame para lesões ósseas da maxila, permitindo que o dentista possa avaliar com mais confiabilidade o comportamento, os componentes da lesão, e sua relação com estruturas adjacentes. A Lesão central de células gigantes e o querubismo são patologias muito semelhantes histologicamente, portanto, exames clínicos e radiológicos são de fundamental importância para o diagnóstico. O objetivo deste trabalho é relatar dois casos diagnosticados usando TCFC, um de lesões centrais de células gigantes e um de querubismo. Esta modalidade de imagem foi muito importante para o diagnóstico das patologias apresentadas neste estudo. Também permitiu observar com mais confiabilidade os limites das lesões, os componentes, o comportamento e a relação exata com as estruturas adjacentes.

Lesão periférica de células gigantes recorrente: relato de caso / Recurrent peripheral giant cell lesion: case report

Lesão periférica de células gigantes é um processo proliferativo não neoplásico reativo à irritaçãolocal ou trauma. Apresenta-se como uma lesão bem circunscrita, que acomete a mucosa alveolar egengiva, podendo comprometer os tecidos ósseos adjacentes, causando mobilidade dentária. O examemicroscópico dessa lesão revela uma massa não encapsulada de tecido, contendo um grande númerode células do tecido conjuntivo e de células gigantes multinucleadas em um padrão estrutural,constituído de nódulos focais de células gigantes, separados por septos fibrosos. Tecido hemorrágico,hemossiderina, células inflamatórias e osso neoformado ou material calcificado também podem serencontrados ao longo do tecido conjuntivo. A associação de extensas lesões periféricas de célulasgigantes a fatores bucais ou sistêmicos ainda não é claramente estabelecida. O objetivo deste trabalhoé o de relatar um caso de lesão periférica de células gigantes recorrente. O correto diagnóstico eo adequado tratamento culminaram em resultados satisfatórios e completa resolução do caso, semindícios de recidivas. Este trabalho apresenta uma revisão atual sobre essa entidade, além de discutir sobre os fatores relacionados à sua etiologia.

Peripheral giant cell lesion is a non-neoplastic proliferative process reactive to the local that has anirritation or a trauma. Presents as well-circumscribed lesion confined to the alveolar and gingivalmucosa, may compromise the bone tissue adjacent causing tooth mobility. On histologic evaluation,the lesion is a noncapsulated mass of tissue containing a large number of young connective tissuecells and multinucleated giant cells in an architectural pattern of giant cells? focal nodules, separatedby fibrous septa. Hemorrhage, hemosiderin, inflammatory cells, and newly formed bone or calcifiedmaterial may also be seen throughout the cellular connective tissue. The association of large peripheralgiant cell?s lesions to oral or systemic factors is also unclear. The purpose of this work is to presenta case of peripheral giant cell?s lesion recurrence. The correct diagnosis and treatment culminatedin a totally satisfactory result and complete resolution of the case, without recurrences. This paperpresents a review on the current entity, and discusses the factors related to its etiology.

Clonality analysis of giant cell lesions of the jaws

Despite the importance of clonality to understand the pathogenesis and progression of tumors, it has not been investigated yet in giant cell lesions of the jaws. The aim of this study was to analyze the clonality of peripheral giant cell lesions (PGCL) and central giant cell lesions (CGCL) of the jaws. Six samples of PGCL and 5 samples of CGCL were analyzed in this study using the polymorphic human androgen receptor locus (HUMARA) assay. Three out of the 5 samples of the CGCL and 3 out of 6 samples of PGCL exhibited a monoclonal pattern. Our findings demonstrate that some giant cell lesions of the jaws are clonal, which indicate that these lesions may have a common genetic mechanism of development. Further studies are necessary to better elucidate the molecular mechanisms involved in the pathogenesis of such lesions.

Apesar da importância que a clonalidade das lesões tem para o entendimento da patogênese e progressão dos tumores, ainda não foi feita essa investigação em lesões de células gigantes dos maxilares. O objetivo desse trabalho foi analisar a natureza clonal de lesões periféricas de células gigantes (LPCG) e de lesões centrais de células gigantes (LCCG). Foram analisadas nesse estudo 6 amostras de LPCG e 5 amostras de LCCG, sendo todas elas provenientes de pacientes do sexo feminino. Para essa investigação foi utilizado o método baseado na região polimórfica do exon um do gene humano para oreceptor de andrógeno (HUMARA). Três das 5 amostras de LCCG e 3 das 6 amostras de LPCG exibiram um padrão monoclonal. Nossos resultados demonstram que algumas lesões de células gigantes dos maxilares apresentam uma natureza monoclonal indicando que essas lesões podem ter um mecanismo genético comum de desenvolvimento. Outros estudos são necessários para uma maior compreensão dos mecanismos moleculares envolvidos na patogênese dessas lesões.

Estudo comparativo da atividade proliferativa celular do fibroma ossificante periférico e da lesão de células gigantes periférica / Comparative study of the proliferative activity of the peripheral giant cells lesion and of peripheral ossifying fibroma

Foi realizado um estudo clínico retrospectivo descritivo e histoquímico de casos do fibroma ossificante periférico (FOP) e da lesão de células gigantes periférica (LCGP), coletados aleatoriamente no arquivo do Serviço de Diagnóstico Histopatológico da Universidade de Passo Fundo. O objetivo do trabalho foi comparar as atividades proliferativas celulares dessas lesões, visando o estabelecimento de uma conduta terapêutica adequada para cada uma das enfermidades. Os dados referentes ao sexo, idade, raça, localização da lesão e ocorrência de recidiva foram analisados e, o número de regiões organizadoras nucleolares (NORs) por núcleo de células ovóides foi determinado por meio do método de impregnação pela prata (Ag-NOR). Os resultados obtidos para o FOP foram de prevalência da lesão em mulheres (70%) da raça branca (60%) com média de idade de 28,11 anos, maior ocorrência da lesão na maxila anterior e índice de recidiva de 30%. O número médio de NORs foi de 1,72 para cada núcleo. Já para a LCGP, o sexo feminino também atingiu 70%, porém a média de idade foi de 42,90 anos e 100% dos pacientes pertenciam à raça branca. A ocorrência da lesão foi maior na região mandibular anterior e apresentou um índice de 20% de recidiva. Nesta lesão, o número médio de NORs foi de 1,93 por núcleo. Contudo, nos testes de correlação, nenhuma das características clínicas apresentou associação com o número médio de NORs por núcleo e a comparação desse número médio por núcleo nas LCGPs e nos FOPs não mostrou diferença significativa entre os grupos.

A retrospective clinical descritive and histochemical study envolving cases of periferic bone fibroma and of periferic giant cell lesion, randomly collected from the archives of Histophatologic Diagnostic Service of University of Passo Fundo was made. The objective of this work was to compare the proliferating cellular activities of these lesions, aiming the establishment of an adequate therapeutic conduct to each one of the disorders. The datas referring to the gender, age, race, position of the lesion and recurrence occurrence were analized and considered and the NORs’ numbers by egg-shaped cells’ nucleus were analized through the impregnation of silver method (Ag-NOR), getting as a result of periferic bone fibroma, 70% women, with an age average of 28.11 years old, where 60% of the pacients were white, and with the lesion’s position more often being on the front upper jaw, with the recurrence’s index up to 30%. The NORs’ average number was of 1.72 to each nucleus. On the periphery giant cell lesion, the female gender had also achieved 70%, however the age’s average was of 42.90 and 100% were white. The occurrence of the lesion was higher on the front inferior jaw and had showed a recurrence’s index of 20%. The NORs’ average of this lesion was 1.93 to each nucleus. Nevertheless, on the correlation’s tests none of these clinic characteristics showed a connection with the higher average’s number of NORs by nucleus and the comparison of NORs average’s number by nucleus on periphery bone fibroma and periphery giant cell lesion did not show a significant difference between the groups.

A case report; Brown tumor of the maxilla and mandible in association with primary hyperparathyroidism