Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing.

Next-generation sequencing has revealed mutations in several bone-related lesions and was recently used to uncover the genetic basis of giant cell lesions of the jaws (GCLJ). Consistent with their benign nature, GCLJ show a low tumor mutation burden. They also harbor somatic, heterozygous, mutually exclusive mutations in TRPV4, KRAS, or FGFR1. These signature mutations occur only in a subset of lesional cells, suggesting the existence of a 'landscaping effect', with mutant cells inducing abnormal accumulation of non-mutant cells that form the tumor mass. Osteoclast-rich lesions with histological similarities to GCLJ can occur in the jaws sporadically or in association with genetically inherited syndromes. Based on recent results, the pathogenesis of a subgroup of sporadic GCLJ seems closely related to non-ossifying fibroma of long bones, with both lesions sharing MAPK pathway-activating mutations. In this review, we extrapolate from these recent findings to contextualize GCLJ genetics and we highlight the therapeutic implications of this new information. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Immunohistochemical features of giant cell ependymoma of the filum terminale with unusual clinical and radiological presentation.

BACKGROUND: Giant cell ependymoma of the filum terminale is a rare variant, generally manifested as a well-circunscribed intradural mass with an indolent biological behavior. CASE PRESENTATION: We describe the case of a 48-year-old Mexican female who non-relevant past medical history, that developed a GCE of the filum terminale. Magnetic resonance imaging and computed tomography revealed the presence of an intra-axial tumor extending from L3 to L5 with extra-medullary invasion. Therefore the tumor was considered unresectable and only incisional biopsy was obtained, establishing the tentative diagnosis of a poorly differentiated neoplasia. A second evaluation of the case revealed the presence of numerous non-cohesive pleomorphic giant cells with intranuclear inclusions and broad eosinophilic cytoplasm, alternating with intermediate size cells with round, hyperchromatic nuclei and forming a perivascular pseudo-rosettes pattern. The ependymal phenotype was supported by light microscopy and corroborated by immunohistochemistry analysis. The patient was subsequently treated with radiotherapy 54Gy. She is alive after a 27-month follow-up, with residual disease, difficulty ambulating and pain. CONCLUSIONS: GCE of filum terminale may have an atypical clinical and radiological presentation, albeit with invasive characteristics and anaplasia on histologic analysis. However, its biological behavior is indolent and associated to longer survival. Due to the presence of giant cells, the differential diagnosis of other primary neoplasias at that site were considered, including paraganglioma, malignant peripheral nerve sheath tumors as well as metastatic malignant melanoma, adrenal carcinoma, thyroid gland carcinoma and urothelial carcinoma, that may all harbor giant cells.

Histochemical analysis of collagen fibers in giant cell fibroma and inflammatory fibrous hyperplasia.

OBJECTIVE: The aim was to investigate collagen fibers in giant cell fibroma, inflammatory fibrous hyperplasia, and oral normal mucosa. MATERIALS AND METHODS: Sixty-six cases were stained with picrosirius red. The slides were observed under polarization, followed by the measurement of the area and the percentage of the type I and type III collagens. The age and gender were obtained from the clinical records. RESULTS: No differences could be observed in both the area and percentage of the type I and type III collagens within the categories of lesions and normal mucosa. In the giant cells fibroma, a greater area and percentage of type I collagen could be identified in individuals of less than 41.5 years (p<0.05). CONCLUSION: The distribution of type I and type III collagen fibers in the studied lesions followed a similar pattern to that observed in the normal mucosa, indicating a normal collagen maturation process of type III to I. The study supports that multinucleated and stellate cells of the giant cell fibroma appear to be functional within collagen types III and I turnover. The greater amount of type I collagen identified in giant cell fibroma in individuals of less than 41.5 years reinforce the neoplastic nature of lesion.

Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor.

A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue

Abstract: Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology.

Tumor de células gigantes de vaina tendinosa en paquete adiposo de Hoffa: reporte de caso / Giant cell tumor of tendon sheath in Hoffa´s fat pad. Case report

Se presenta un caso de gonalgia aguda atraumática de causa tumoral localizada paquete adiposo de Hoffa en un paciente pediátrico. Se realizó resección en bloque con asistencia artroscópica. El diagnóstico de tumor de células gigante de vaina tendinosa fue confirmado mediante histopatología. Nivel de evidencia: V...

We report a case of acute atraumatic knee pain due to a soft tissue tumor in Hoffa’s fat pad in a pediatric patient. An arthroscopically assisted en bloc resection was performed. The diagnosis of giant cell tumor of tendon sheath was confirmed through histopathology study. Level of Evidence: V...

Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue.

Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology.

Ressecção alargada no tratamento do dermatofibrossarcoma protuberante / Extended resection for treatment of dermatofibrosarcoma protuberans

INTRODUÇÃO: Dermatofibrossarcoma Protuberante (DFSP) é um tumor de pele raro e de malignidade intermediária, com baixo potencial metastático, mas alta taxa de recorrência após tratamento cirúrgico. O tratamento clássico é a ressecção alargada, com margens variáveis. Muitos trabalhos descreveram os resultados da cirurgia micrográfica de Mohs no tratamento desta afecção. O objetivo deste estudo retrospectivo é verificar se a ressecção alargada constitui um método confiável no tratamento do DFSP. MÉTODO: Entre agosto de 1968 e setembro de 2013, 31 lesões foram ressecadas em 30 pacientes com DFSP. Todos os pacientes foram submetidos à excisão cirúrgica radical, com remoção de 3 cm de tecido sadio nas margens laterais e com a margem profunda incluindo uma estrutura anatômica não infiltrada pelo tumor. Os seguintes aspectos foram estudados: gênero, idade, local da lesão, tratamento prévio e características peculiares da proservação. RESULTADOS: Dezenove (63,3%) pacientes eram do sexo masculino e 11 (37,7%), do feminino. A média de idade da apresentação foi de 40,9 anos. As lesões estavam localizadas em tronco (61,3%), cabeça (22,6%), membros superiores (6,4%), membros inferiores (6,4%) e pescoço (3,3%). Tratamento prévio não foi observado em 58,1% dos pacientes. Um paciente (3,3%) evoluiu com recidivas e óbito, em decorrência do tratamento cirúrgico; três (10,0%) faleceram por outras causas. CONCLUSÕES: A ressecção alargada com margens de 3 cm, com remoção de estrutura anatômica sadia, constitui método eficiente no tratamento do DFSP.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare skin tumor with intermediate malignancy and low metastatic potential, but a high recurrence rate after surgical treatment. The classical treatment is extended resection with varying margins. Many studies have described Mohs micrographic surgery for treatment of this disease. This retrospective study was to verify if extended resection is a reliable DFSP treatment method. METHOD: A total of 31 lesions were resected in 30 patients with DFSP between August 1968 and September 2013. All patients underwent radical surgical excision, with removal of 3 cm of healthy tissue on the lateral margins and with deep margin including an anatomical structure without tumor infiltration. Analyzed patient characteristics included sex, age, tumor site, previous treatment, and peculiar characteristics observed during the follow-up period. RESULTS: Nineteen (63.3%) patients were male and 11 (37.7%) female. Their average age at tumor presentation was 40.9 years. The tumors were located on the trunk (61.3%), head (226%), upper limbs (6.4%), lower limbs (6.4%), and neck (3.3%). No previous treatment was reported in 58.1% of the patients. One patient (3.3%) developed recurrence and died due to the surgical treatment; three patients (10.0%) died from other causes. CONCLUSIONS: Extended resection with 3-cm margins and removal of healthy anatomical structures is an effective treatment for DFSP.

Giant cell tumors of bone: nonsurgical factors associated with local recurrence.

OBJECTIVE: To determine the rate of giant cell tumor (GCT) recurrence and evaluate the factors associated with its recurrence in patients who underwent surgery and submitted to only one adjuvant method. METHODS: Forty-one patients (22 female, 19 male; mean age: 34.22 ± 9.70 years) with GCT, who underwent surgical and one adjuvant treatment, were evaluated after a mean follow-up period of 40.17 ± 22.08 months. The average tumor size was 8.51 ± 3.69 cm. The tumors in 18 patients (43.9%) were grade II and in 23 patients (56.1%) grade III, according to the system developed by Campanacci et al. The surgical margin was intralesional resection and curettage in 60.9% of the patients, and marginal or wide resection in 39.1%. RESULTS: Nine (22%) of the 41 patients had recurrence. None of the gender (p=0.436), age (p=0.310), site of the tumor (p=0.940), surgical margins (p=0.400) and the type of the filling material (PMMA or autograft) (p=0.680) had an association with recurrence. However, Campanacci grade III (p=0.028) and the size of the tumor (p=0.034) was associated with the recurrence. CONCLUSION: Tumor size and tumor grade III according to the Campanacci system appear to be risk factors for local recurrence after the local resection of GCT.

Condiloma acuminado gigante (tumor de Buschke-Lowenstein): presentación de un caso / Giant acuminated condiloma (Bushke-Lowenstein tumor): case report

El condiloma gigante del pene o tumor de Buschke-Lowenstein, es un tumor epitelial benigno de origen viral y sexualmente transmisible, que en raros casos puede malignizar. Su histología se caracteriza por papilomatosis y acantosis endo y exofítica. Existen diferentes tratamientos del tumor, pero el más efectivo es la resección quirúrgica radical para evitar recidivas y malignización. Describir y documentar un caso de un condiloma acuminado gigante o tumor de Buschke-Lowenstein. Revisaremos la bibliografía existente sobre este tipo de tumor. Paciente masculino de 51 años de edad con lesiones vegetantes de 6 años de evolución, que se extienden desde la región perianal a perineal y ambas regiones inguinales, escroto y base de pene, a quien se le realizó resección quirúrgica amplia de la lesión. El estudio anatomopatológico reporta condiloma acuminado gigante, con inflamación crónica severa sobre agregada, el paciente mantiene resultados funcionales y estéticos muy satisfactorios después de la cirugía. El tumor de Buschke-Lowenstein es un condiloma acuminado gigante que se presenta con más frecuencia en hombres, benigno, cuyas lesiones clínicas son mayores de 10 cm, por lo que el tratamiento de elección debe ser siempre quirúrgico.

The giant condyloma of the penis or denominated Buschke-Lowenstein tumor is a benign epithelial tumor of viral origin and its sexually transmissible, in rare cases can become transformation to malignant. Histology is characterized by papillomatosis and acanthosis endophytic and exophytic. There are different treatments of the tumor, but the most effective of them is the radical surgical resection to prevent recurrences and the malignant transformation of the lesion. To describe and document a case view of us in our institution of giant condyloma acuminatum or Buschke-Lowenstein tumor. We will review the existent literature on this type of tumor. Male patient 51 years old with vegetative lesions of 6 years of evolution, extending from the perineal and per anal region to groins, the scrotum and the penis base, who underwent extensive surgical resection treatment. The pathology reports giant condyloma acuminatum with severe chronic inflammation, actually the patient maintains satisfactory functional and aesthetic results after the surgery. The Buschke-Lowenstein tumor is a giant condyloma acuminated it´s occurs more often in men, benign clinical lesions which are greater than 10 cm, so the treatment of choice should always be the surgical.

Epidemiology of bone tumors in Mexico City: retrospective clinicopathologic study of 566 patients at a referral institution.

A retrospective analysis of all bone tumors accessioned at a large referral center (Instituto Nacional de Rehabilitacion) in Mexico City between 2000 and 2005 is presented. A total of 6216 biopsies and surgical resection specimens were reviewed during this period, of which 566 corresponded to bone tumors. Benign bone tumors accounted for 71.6% of cases and malignant bone tumors for 28.4%. The tumors affected men in 53.7% of cases and women in 46.3% of cases, with an average age at presentation of 25 years. The femur was the most common location of the tumors (39.9%), followed by the tibia (17.7%) and humerus (11.8%). The commonest malignant bone tumors were osteosarcoma (46.6%) and chondrosarcoma (8.7%). Of malignant bone tumors, 18.6% corresponded to metastases of carcinomas from internal organs and 8.1% were multiple myeloma. The most common benign bone tumor was osteochondroma (43.7%) followed by giant cell tumor of bone (14.6%) and enchondroma (10.1%). The age distribution showed a peak in children and adolescents comprised predominantly of benign lesions and a second peak in young adults that corresponded to malignant bone tumors (principally osteosarcoma). Malignant bone tumors most often involved the femur, vertebra, and tibia. Our results parallel the findings previously reported in the world literature and show a similar distribution and epidemiology as in other developed and underdeveloped countries. Geographic location does not appear to represent a risk factor for any particular type of bone tumor and does not affect the age distribution, location, or histopathologic type of the lesions.

Tratamiento quirúrgico del tumor de células gigantes: análisis de 20 años de experiencia / Surgical treatment of giant cell tumors: 20 years experience

Giant cell tumor (GCT) is a benign, locally aggressive lesion that primarily affect the long bones epiphyses, which represents 5-9 percent of the bone primary tumors. The purpose of this study is to show the Instituto Traumatológico‘s orthopaedic oncology group experience in the treatment of GCT and suggest a scheme of treatment according to Campanacci’s stage. For which a retrospective study was done, that include 112 patients treated from 1987 to 2007. The average time of follow-up was 9, 2 years, most frequent location was the knee region (69 percent). 85 patients (76 percent) were in stage 3 of Campanaci’s classification. We used different surgical alternatives from basic curettage to resection plus reconstruction with prostheses or aloprostheses. Post surgical complications were seen in 16 patients(14 percent). In the follow-up we had 8 pseudoarthrosis, 7 osteosintesis material failure and 3 allograft fractures. Local recurrence was seen in 15 patients (13,3 percent). 3 cases presented pulmonary metastases (2,6 percent). Mean functional evaluation, using Musculo Skeletal Tumor Society (MSTS) score, was 25, 6 points.

El Tumor de Células Gigantes (TCG) óseo es una neoplasia benigna, localmente agresiva, representa entre el 5-9 por ciento de los tumores óseos primarios. El objetivo del estudio fue revisar la experiencia de nuestra Institución en el tratamiento quirúrgico de esta neoplasia y sugerir un esquema de tratamiento según la etapa de Campanacci. Para esto se realizó un estudio retrospectivo que incluyó 112pacientes tratados desde el año 1987 hasta 2007. El tiempo promedio de seguimiento fue de 9,2 años, el tumor se ubicó alrededor de la rodilla en 78 pacientes (69 por ciento). 85 casos (76 por ciento) se encontraban en etapa III de Campanacci. Utilizamos distintas alternativas quirúrgicas desde el curetaje simple a la resección más reconstrucción con prótesis o aloinjerto. Dieciséis pacientes (14 por ciento) presentaron complicaciones post operatorias. A largo plazo hubo 8 pseudoartrosis, 7 fallas del material de osteosíntesis y 3 fracturas del aloinjerto. Recidivaron 15 pacientes (13,3 por ciento). Tres casos presentaron metástasis pulmonares (2,6 por ciento). La evaluación funcional promedio con la escala de la Musculo Skeletal Tumor Sociaty (MSTS) realizada al año del post operatorio, fue de 25,6 puntos.

Displasia fibrosa óssea da maxila: relato de caso

Introdução: A displasia fibrosa óssea(DFO) é uma lesão pseudoneoplásica benigna de etiologia ainda desconhecida, que aparece sob três padrões clínicos característicos, ocasionalmente superpostos. Há a forma monostótica, que atinge um único osso, a poliostótica, acomentendo vários ossos, mas nunca todos, e a poliostótica associada às pigmentações cutâneas tipo café com leite e anormalidades endócrinas, especialmente na puberdade precoce, devido ao acometimento dos ossos da face e crânio, geralmente causando deformidade, é doença de particular interesse pelo otorrinolaringologista. Será descrito um caso de portador de DFO monostótica, com diagnóstico confirmado pelo exame anatomopatológico. Relato de caso: Paciente de quarenta anos de idade, sexo masculino, cor branca, natural do Estado de Santa Catarina, procurou o Serviço de otorrinolaringologia e Cirurgia Crânio-maxilo-facial do Hospital Angelina Caron, em setembro de 2006, tendo como queixa principal, um aumento da hemiface direita, que iniciou aos doze anos de idade com evolução lenta, apresentando no momento dificuldade para adaptar a prótese dentária superior. O exame clínico nos mostrou um paciente hígido, sem patologia de base com aumento da hemiface direita na região de maxila e zigoma direitos. O exame tomográfico evidenciou aumento da densidade e volume ósseo envolvendo a hemimaxila, osso zigomático e seio maxilar direitos, com abaulamento superior de soalho orbitário direito justificando o diagnóstico de displasia fibrosa óssea monostótica. Em fevereiro de 2007, o paciente foi submetido a cirurgia para reparação funcional, onde foi realizada osteoplastia de rebordo alveolar de maxila direita por acesso intrabucal. O material removido foi enviado para exame histopatológico, confirmando o diagnóstico inicial de displasia fibrosa monostótica...

Genomic gains of COL1A1-PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans.

Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1-PDGFB in pure GCF and GCF/DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells.

[Giant cell collagenoma of the bulbar conjunctiva]. / Colagenoma de células gigantes de conjuntiva bulbar.

PURPOSE/METHODS: To report a rare case of a tumor in a conjunctival location, a giant cell collagenoma. Tissue was stained with hematoxylin-eosin, periodic acid-Schiff, and Masson's trichromic stain and studied by immunohistochemistry. RESULTS/CONCLUSION: The clinical and histopathologic features of conjunctival giant cell collagenoma are similar to characteristics of the same tumor occurring in other parts of the body. This is the first report of this tumor in the eye.