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Franco Bertoni

Publications and source records attributed to Franco Bertoni.

At least 19 recordsLinked to original sources
PubMed2004

Osteosarcoma associated with hyperparathyroidism.

The fourth case in the literature is presented of a patient with the rare association of hyperparathyroidism and osteosarcoma. A 56-year-old woman presented with hyperparathyroidism and a lesion in the tibia. Initial diagnosis was brown tumor. Histology, however, revealed osteosarcoma, and the patient was treated accordingly. The experimental induction of osteosarcoma by parathormone in rodent studies makes this finding alarming, considering the increasing use of parathormone in the treatment of osteoporosis. The mechanism by which osteosarcoma is induced in humans cannot be explained based on current knowledge of mechanisms of action of parathyroid hormone.

Bone Neoplasms↗
PubMed2004

Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma.

BACKGROUND: Investigation of the relation between primary tumor and metastatic disease is necessary for the identification of predictive factors for postrecurrence survival (PRS) in patients with recurrent osteosarcoma. METHODS: Cellular levels of P-glycoprotein, ErbB-2, p53, and Bcl-2 expression were evaluated in primary tumor biopsy and metachronous pulmonary metastasis specimens from 19 patients with high-grade osteosarcoma. Results were analyzed for differences between primary tumor and pulmonary metastases and for correlations between expression patterns and survival. RESULTS: Positive staining in lung metastases was noted in 68%, 53%, 32%, and 84% of patients for P-glycoprotein, ErbB-2, p53, and Bcl-2, respectively. These percentages were higher than those observed in primary tumor specimens for all genetic markers evaluated, with a significant difference in the percentage of patients with positive staining for P-glycoprotein (68% vs. 32%; P = 0.05) and a near-significant difference in the percentage of patients with positive staining for Bcl-2 (84% vs. 53%; P = 0.08). Patients with ErbB-2 expression in the primary tumor were more likely to have multiple metastases and shorter recurrence-free intervals compared with patients in whom ErbB-2 expression was not observed, whereas differences in P-glycoprotein, p53, and Bcl-2 expression were not related to differences in metastatic pattern. PRS was influenced by p53 expression levels in pulmonary metastases, with patients who had negative staining for p53 having a significantly better PRS rate relative to patients with positive staining for p53 (3-year PRS rate: p53-negative, 64%; p53-positive, 17%; P = 0.008). CONCLUSIONS: In the current study of patients with high-grade osteosarcoma, most patients exhibited increased cellular expression of P-glycoprotein, ErbB-2, and Bcl-2 in recurrent pulmonary metastases compared with primary tumor. Further studies aimed at investigating the relation between altered p53 expression in lung metastases and postrecurrence survival are recommended.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Molecular analysis of p53, MDM2 and H-ras genes in low-grade central osteosarcoma.

Low-grade central osteosarcoma is an uncommon form that is characterized by a long premorbid history, and is compatible with prolonged survival after treatment. However, molecular abnormalities are rare in low-grade central osteosarcomas, whereas p53 mutations occur in approximately 20% of conventional high-grade osteosarcomas. In this study, 21 cases of low-grade central osteosarcoma were analyzed for mutations of the p53 gene, amplification of the MDM2 gene, and mutations of the H-ras gene using formalin-fixed, paraffin-embedded materials. We also examined the expression of p53, MDM2, and p21WAF1 protein immunohistochemically and assessed the proliferation activities using the monoclonal antibody MIB-1. One case (4.7%) showed strong p53 immunoreactivity, whereas p53 gene mutations were not detected at all. Seven cases (33.3%) showed immunoreactivity for MDM2 protein. As for gene alterations, MDM2 amplification was found in four cases (19.0%). p21WAF1 expression was detected in 12 cases (57.1%). MIB-1-LI showed very low levels in all the cases and no significant correlation with p53 or MDM2 immuno-reactivity. None of the tumors showed H-ras mutations. In conclusion, the number of p53 gene alterations in low-grade central osteosarcomas is lower than that in conventional high-grade osteosarcomas. MDM2 alterations and p21WAF1 expression might be involved in the tumorigenesis of low-grade central osteosarcomas.

Adolescent↗
PubMed2004

Leiomyosarcoma of the spermatic cord: a light and ultrastructural description of one case.

A case of leiomyosarcoma arising in the spermatic cord is described. A 83-year-old man required medical care for an irreducible inguinal hernia. The patient underwent herniorraphy and transinguinal radical orchiectomy. Macroscopically, the spermatic cord was enlarged by a gray-tan and ill-defined neoplasm measuring 4 x 4 x 3 cm. Histologically, this proliferation was composed of atypical spindle cells with blunted end nuclei and eosinophilic cytoplasm. Immunohistochemistry and ultrastructure confirmed the smooth muscle nature of the neoplastic cells. The diagnosis of leiomyosarcoma of the spermatic cord was made. To improve the assignment of this rare lesion to its specific anatomic location, we analyzed the immunohistochemical and ultrastructural characteristics of the smooth muscle tumoral cells and in particular those of the intracellular filament aggregates.

Actins↗
PubMed2004

Central low-grade osteosarcoma with pagetoid bone formation: a potential diagnostic pitfall.

Central low-grade osteosarcoma is an uncommon form of osteosarcoma, which is often difficult to distinguish from benign bone lesions. We reviewed the radiographic studies, the histologic material and the clinical records of two patients with central low-grade osteosarcoma that closely simulated the histologic appearance of Paget's disease of bone. The patients were two women aged 46 and 53 years. Radiologically, they presented a large ill-defined densely sclerotic lesion involving the proximal tibia. Both lesions only focally presented the conventional histologic appearance of central low-grade osteosarcoma, with a proliferation of fibroblast-like cells embedded in a dense collagenous stroma and irregular anastomosing tumor bone trabeculae. The most striking feature was the presence of extremely thickened irregular plates of bone with an irregular mosaic pattern of cement lines that closely resembled that of Paget's disease of bone. One patient, who had been initially treated for Paget's disease for 7 years, experienced disease progression. At resection of proximal tibia, there was evidence of dedifferentiation to high-grade osteosarcoma. After 2 months, she developed local recurrence that was treated with above-knee amputation, followed by chemotherapy. She died with multiple lung metastases 4 months later. The other patient is alive 9 months after wide tumor resection. These cases further expand the spectrum of central low-grade osteosarcoma, and underscore the diagnostic difficulties in separating central low-grade osteosarcoma from benign bone diseases, which may lead to delay in diagnosis, inadequate treatment, and eventually to dedifferentiation. Recognition of this variant of central low-grade osteosarcoma is based on the aggressive radiologic appearance and on adequate tumor sampling for histologic examination.

Bone Neoplasms↗
PubMed2004

Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature.

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.

Adolescent↗
PubMed2004

Hemangioendothelioma of the spine.

A review of the patient files from our institution's oncology department showed that between 1950 and 2000, 11 patients were diagnosed with hemangioendothelioma of the spine, a rare, low-grade malignant vascular tumor. After reevaluation of the diagnoses by orthopaedic oncologists and pathologists, three patients were excluded; therefore eight patients formed the study group. The eight lesions were located in the thoracic (three) or lumbar spine (five, one in each vertebral level). Computed tomography scans revealed expansile lytic process. All lesions involved the vertebral body, but only one was diffuse with spinous process involvement. Treatment included: external beam irradiation alone (one patient), curettage and external beam irradiation (one patient), laminectomy and external beam irradiation (two patients), anterior resection only (two patients), and anterior resection with postoperative external beam irradiation (two patients). Patients without spinal stabilization had chronic low back pain; no patient with spinal stabilization had such pain. One patient who had surgical resection and radiation therapy had a radiation-induced sarcoma develop after 4 years. One patient who was treated with radiation therapy alone had a metastatic lung lesion develop. No other patient had tumor recurrence or progression. Therefore, patients with hemangioendothelioma of the spine may be treated with radiation therapy alone, surgery alone, or a combination thereof. However, because the number of patients in the current series was small, no definitive recommendations regarding treatment may be made. Resection of large lesions and stabilization of vertebral collapse may decrease back pain.

Adult↗
PubMed2004

Simultaneous osteosarcoma lung metastasis and second primary lung cancer.

Second malignant neoplasms (SMNs) after treatment of children and adolescent cancers have been extensively studied. Lung cancer as an SMN is rare in all type of primary cancer in children and in osteosarcoma as well. The authors reviewed all cases of osteosarcomas treated at their institution from 1975 to 2000 and found 22 cases of SMN, only 1 involving lung cancer. The authors describe this latter case, a 17-year-old girl with a localized osteosarcoma of the tibia who developed simultaneously lung metastases of osteosarcoma and a primitive lung adenocarcinoma only 18 months from the diagnosis. Lung cancer is unusual in youths as a primary malignancy or as a second primary malignancy. The occurrence of a primitive lung cancer together with lung metastases from osteosarcoma is even more unusual, and examination of all new lung nodules is highly recommended.

Adenocarcinoma↗
PubMed2004

An isolated vertebral metastasis of urachal adenocarcinoma.

We describe a case of urachal adenocarcinoma arising in a 30-year-old woman. The patient underwent partial cystectomy. Three years later, she presented with an isolated metastasis to a thoracic vertebra, which was treated by vertebral corporectomy. Histologic findings are described, and the clinical findings, management, and metastatic patterns of this rare tumor, as well as the differential diagnosis on a biopsy specimen, are discussed.

Adenocarcinoma, Mucinous↗
PubMed2004

Fibrous dysplasia with degenerative atypia: a benign lesion potentially mistaken for sarcoma.

Fibrous dysplasia is a benign disorder of bone in which proliferating fibrous tissue replaces the bony spongiosa. Cytologic atypia is generally not considered a feature of this proliferating tissue. We present a case of fibrous dysplasia with marked atypical nuclear changes consistent with degenerative or regressive changes. A 42-year-old man presented with an osteolytic lesion of the right iliac bone. Histologic study demonstrated a fibro-osseous lesion with woven bone trabeculae and bland-looking fibrous tissue. Several areas showed atypical cells with enlarged pleomorphic nuclei and bizarre features. There was no change in the nuclear-cytoplasmic ratio nor were mitotic figures identified. The differential diagnosis is discussed. When radiographic and other histologic findings suggest fibrous dysplasia, the atypical nuclear changes should not, by themselves, alter the diagnosis.

Adult↗
PubMed2004

Role of surgery in local treatment of Ewing's sarcoma of the extremities in patients undergoing adjuvant and neoadjuvant chemotherapy.

Although more and more patients with Ewing's sarcoma of bone (ESB) are being treated by surgery, the relative role of surgery and radiotherapy in the local treatment of this tumor has yet to be determined. Because the outcome of ESB may differ according to the anatomical site of the tumor, results reported in the literature, which generally refer to series with tumors located in all sites, may be selection biased. Therefore, we have retrospectively evaluated patients with ESB exclusively in the extremity and locally treated by surgery or radiotherapy. Two hundred and sixty-eight patients treated at Rizzoli 1979-1996 for non-metastatic ES of the extremities were assessed. Chemotherapy was administered according to four sequentially activated protocols. One hundred and thirty-six patients were treated by surgery, 70 by surgery and radiotherapy, and 60 patients by radiotherapy. Two patients underwent only chemotherapy. The follow-up range was 5-23 years (mean 13 years). One hundred and fifty-two patients remained continuously free of disease, 108 relapsed, 2 died of chemotherapy toxicity and 6 developed a second malignancy. The 5-year event-free survival (EFS) and overall survival (OS) were respectively 62 and 69%. Although patients of all groups were matched for possible risk factors, the rates of 5-year EFS and local control were significantly lower in patients treated with radiotherapy compared to patients treated by surgery or surgery and radiotherapy (48% vs 66%, p=0.002; 80% vs 94%, p=0.0001). Furthermore, in group 3 there were 6 secondary malignancies. Our results indicate that surgery should always be considered in the local treatment of ES of the extremities. Postoperative radiation therapy must be added in case of inadequate surgical margins.

Adolescent↗
PubMed2004

Quantitative assessment of HER2/neu expression by real-time PCR and fluorescent in situ hybridization analysis in low-grade osteosarcoma.

Low-grade osteosarcoma is a rare variant of osteosarcoma. Although malignant, it must be distinguished from conventional osteosarcomas because of its excellent prognosis. Numerous published papers have described the expression of HER2/neu oncogene in osteosarcoma as a poor prognostic factor; however their results are discordant. To address the expression of HER2/neu and to validate the assessment methods of amplification of the HER2/neu oncogene, the authors have employed quantitative real-time PCR and fluorencent in situ hybridization analysis (FISH) in 21 low-grade osteosarcomas. We calculated the quantification of HER2/neu oncogene amplification as the ratio of measured HER2/neu gene/beta-globin reference gene in real-time PCR. All 21 cases had amplified signals in the quantitative real-time PCR. However, in the FISH analysis, HER2/neu oncogene amplification was only identified in 26% (5/19). The exact reasons for the discordance between these two methods are unknown; however, variable histological features might play a potential role. In conclusion, as our study showed amplification of HER2/neu oncogene in low-grade osteosarcoma, we assume that expression of HER2/neu is not a poor prognostic factor in low-grade osteosarcoma.

Base Sequence↗
PubMed2003

Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor.

BACKGROUND: In primary central high-grade osteosarcoma, a number of distinct subtypes have been identified, but little is known about the response to chemotherapy. METHODS: The authors investigated whether the subtypes correlated with histologic response to chemotherapy in 1058 patients with osteosarcoma of the extremities who were treated with neoadjuvant chemotherapy over the last 20 years. The tumors were classified as osteoblastic (70%), chondroblastic (13%), fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had localized disease and 147 had resectable lung metastases. RESULTS: The response to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and telangiectatic (80%) tumors and significantly lower in chondroblastic tumors (43%). Prognosis was significantly correlated with the histologic subtypes. The 5-year overall survival rate was significantly higher (P = 0.0001) in fibroblastic (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic subtype, the 5-year overall survival rate was significantly higher (P = 0.0001) in good responders P = 0.0001 (68%) than in poor responders (52%). CONCLUSIONS: The authors concluded that the histologic subtype of primary central high-grade osteosarcoma of the extremity was strictly correlated with histologic response to chemotherapy and probably, as a consequence, also with prognosis. Further studies are needed to establish whether these results justify a specific therapeutic approach based on the histologic subtype of the tumor.

Adolescent↗
PubMed2003

Malignancy in giant cell tumor of bone.

BACKGROUND: The term malignant giant cell tumor embraces multiple entities and therefore can be confusing. The goals of the current study were to define the clinicopathologic and histologic features of malignancy in giant cell tumors and to clarify the terminology. METHODS: The authors reviewed all cases from the Rizzoli Institute (Bologna, Italy) of primary (PMGCT) and secondary (SMGCT) malignancy in giant cell tumors. PMGCT is a high-grade sarcoma that arises side by side with benign giant cell tumors. SMGCT is a high-grade sarcoma that occurs at the sites of previously treated giant cell tumors of bone. RESULTS: The authors report 5 PMGCTs and 12 SMGCTs; half of the SMGCTs were postradiation sarcomas. Patient age ranged from 20 to 68 years (median, 62 years) for PMGCT and from 30 to 77 years (median, 40 years) for SMGCT. The average latent period between diagnosis of giant cell tumor and diagnosis of SMGCT was 9 years (range, 3-15 years) for patients with postradiation SMGCT and 19 years (range, 7-28 years) for patients with SMGCT resulting from spontaneous transformation. The histologic classification of high-grade sarcomas in the PMGCT group was osteosarcoma in four cases and malignant fibrous histiocytoma in one case. In the SMGCT group, the histologic classification was osteosarcoma in nine cases, fibrosarcoma in two cases, and malignant fibrous histiocytoma in one case. The outcomes associated with all malignancies in giant cell tumors were poor, with the worst outcome associated with postradiation SMGCT. CONCLUSIONS: Malignancies in giant cell tumors of bone always are high-grade sarcomas with a poor prognosis. These lesions must be distinguished from benign giant cell tumors of bone. SMGCT usually is easy to diagnose upon malignant clinicoradiographic presentation. In contrast, PMGCT often mimics giant cell tumors both clinically and radiographically. In addition, upon histologic examination, PMGCT shows areas of conventional giant cell tumor, which can lead to difficulties in making the correct diagnosis.

Adult↗
PubMed2003

C-kit receptor expression in Ewing's sarcoma: lack of prognostic value but therapeutic targeting opportunities in appropriate conditions.

PURPOSE: Autocrine/paracrine stimulation of c-kit has been recently observed in Ewing's sarcoma (ES) cell lines. In this study, we tested the prognostic and therapeutic role of the receptor in this tumor. METHODS: One hundred one ES tumor biopsies were evaluated for the expression of c-kit by the avidin-biotin-peroxidase procedure. Effectiveness of STI-571 (Gleevec; Novartis, Basel, Switzerland), a selective inhibitor of specific tyrosine kinases, was analyzed with respect to in vitro growth and migration inhibition, as single agent or in combination with doxorubicin. RESULTS: Approximately 30% of patients expressed c-kit in their primary tumors. No significant association between the expression of the receptor and the clinical outcome was observed. In vitro growth of ES cell lines showing high levels of c-kit demonstrated limited inhibition by exposure to STI-571 (10 micromol/L is required to obtain 40% to 50% of growth inhibition). A decrease of stem-cell factor-mediated ES cell migration was also found. The drug acted additively with doxorubicin in inhibiting ES cell growth. CONCLUSION: The negative prognostic findings and the limited in vitro therapeutic activity of STI-571 indicate that the putative aberrant signaling provided by c-kit overexpression may be dispensable for ES development and unlikely to constitute a critical therapeutic target. Accordingly, the dose of STI-571 required to give a significant ES growth inhibition is much higher than for those tumors in which mutations of c-kit constitute a relevant pathogenetic event. Nevertheless, in the subset of ES patients showing a high level of c-kit expression, the activity of the drug may be exploited in combination with standard therapy.

Antineoplastic Agents↗
PubMed2003

Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival.

PURPOSE: To identify factors that influence postrelapse survival (PRS) in patients with nonmetastatic osteosarcoma of the extremity. PATIENTS AND METHODS: One hundred sixty-two patients with recurrent osteosarcoma of the extremity were retrospectively reviewed. The first-line treatment included surgery of the primary lesion and chemotherapy with methotrexate, doxorubicin, cisplatin, and ifosfamide. RESULTS: The projected 5-year PRS rate was 28%. Patients who had complete surgery of recurrence had a 5-year PRS of 39%, whereas for those who did not have complete surgery, PRS was 0% at 3 years (P <.0001). In the latter group, PRS was not influenced by site of recurrence and relapse-free interval (RFI), although it was influenced (P =.006) by the use of second-line chemotherapy (PRS, 53% at 12 months for patients who received chemotherapy v 12% for those who did not). In patients who had complete surgery, PRS was influenced by site of relapse (5-year PRS, lung 44%, other 19%; P <.06), RFI (5-year PRS at < or = 24 months, 20%; at > 24 months, 60%; P <.0001), and number of lung metastases (5-year PRS, two or fewer nodules, 59%; more than two nodules, 14%; P <.0001) but not by the use of a second-line chemotherapy treatment. CONCLUSION: RFI, site of metastases, and number of pulmonary nodules are the main prognostic factors for PRS in osteosarcoma. Complete surgery of recurrence is pivotal in the strategy of treatment. Patients with unresectable recurrence benefit from second-line chemotherapy, whereas our data do not support a generalized use of chemotherapy after complete surgery of first recurrence.

Adolescent↗
PubMed2003

Value of P-glycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities.

PURPOSE: To evaluate the prognostic value of P-glycoprotein and clinicopathologic parameters in a large series of high-grade osteosarcoma (OS) patients treated at the Rizzoli Institute. PATIENTS AND METHODS: With the use of immunohistochemistry, P-glycoprotein was assessed in 149 patients with primary, nonmetastatic, high-grade OS who were homogeneously treated with chemotherapy protocols based on doxorubicin, high-dose methotrexate, and cisplatin and the addition of ifosfamide in the postoperative phase. RESULTS: P-glycoprotein positivity was found in 47 of 149 cases (32%) and was significantly associated with a higher incidence of relapse and a worse outcome, as was age younger than 12 years and tumor volume greater then 150 mL at diagnosis. Multivariate analysis further confirmed the prognostic value of these parameters, which all were independent adverse prognostic factors. Event-free survival and proportional hazards regression analyses confirmed that overexpression of P-glycoprotein at clinical onset is the most important adverse prognostic factor for high-grade OS patients treated with these chemotherapy protocols. CONCLUSION: Increased P-glycoprotein levels, together with tumor volume and age, should be taken into consideration to identify, at time of diagnosis, subgroups of OS patients with a higher risk of recurrence. This subgroup identification will constitute the basis for drawing individualized treatment protocols on the basis of risk evaluation, with the aim of using more aggressive chemotherapy, or combination chemotherapy with other adjuvants, only in those patients for which more aggressive regimens are strictly necessary and warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗