Over expression of CDK4 and MDM2 in a patient with recurrent ALK-negative mediastinal inflammatory myofibroblastic tumor: A case report.

RATIONALE: The diagnosis of anaplastic lymphoma kinase (ALK)-negative inflammatory myofibroblastic tumors (IMT) remains challenging because of their morphological resemblance with spindle cell sarcoma with myofibroblastic characteristics. PATIENT CONCERNS: A 69-year-old female patient presented with loco-regional recurrent IMT several times within 8 years after primary treatment and neck lymph node metastasis 3.5 years after last recurrence. DIAGNOSIS: The primary, recurrence, and lymph node metastasis lesions were diagnosed as ALK-negative IMTs based on the histopathological features. INTERVENTIONS: Biopsy samples were obtained during repeated surgeries and evaluated for genomic alterations during first and recurrent presentations. The evaluation was done using pathway-driven massive parallel sequencing, and genomic alterations between primary and recurrent tumors were compared. OUTCOMES: Copy number gains and overexpression of mouse double minute 2 homolog (MDM2) and cyclin dependent kinase 4 (CDK4) were observed in the primary lesion, and additional gene amplification of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), Succinate Dehydrogenase Complex II subunit C (SDHC), and thyroid stimulating hormone receptor (TSHR) Q720H were found in the recurrent tumors. Metastases to the neck lymph node were observed 3.5 years after recurrence. LESSONS: Our results indicated genetic evolution in a microscopically benign condition and highlighted the importance of molecular characterization of fibro-inflammatory lesions of uncertain malignant potential.

Successful role of adjuvant radiotherapy in a rare case of tracheal inflammatory myofibroblastic tumor: a case report.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare benign cancer that can express a more aggressive phenotype related to the genetic mutation of the anaplastic lymphoma kinase receptor (ALK). Involvement of trachea is extremely rare and due to the clinical and radiologic nonspecificity, the definitive diagnosis is based on the histologic evaluation of tissue specimens. Total surgical excision is curative and chemotherapy or radiotherapy has been employed in the treatment of unresectable tumors or as adjuvant therapies. CASE PRESENTATION: The case described here is being reported because of the rare tracheal location and the atypical treatment approach used for an ALK-positive IMT. A 7-week pregnant woman voluntary interrupted pregnancy and underwent total surgical excision that resulted to have close margins. Although ALK-positive expression indicated the use of ALK inhibitors, she refused any type of adjuvant therapy that could affect ovarian function. Thus, 3D conformational external beam radiotherapy was performed with a daily dose of 180 cGy, 5 times per week, up to 45 Gy at the level of trachea. A total of 62 months of follow-up showed and no signs of disease recurrence or late radiation therapy-related toxicity. CONCLUSIONS: This report describes an extremely rare case of a tracheal IMT, underlying the key role of radiotherapy as adjuvant treatment able to definitively cure IMT, limiting systemic chemotherapy-related toxicity.

Results of the phase II EORTC 22971 trial evaluating combined accelerated external radiation and chemotherapy with 5FU and cisplatin in patients with muscle invasive transitional cell carcinoma of the bladder.

INTRODUCTION: We prospectively evaluated concomitant radiotherapy and chemotherapy for advanced bladder cancer in a phase II EORTC trial to test whether it could be further studied as a potential treatment of bladder cancer. PATIENTS AND METHODS: Patients up to 75 years of age with invasive transitional-cell carcinoma of the bladder up to 5 cm, stage pT2 to pT3b, N0M0, without residual macroscopical tumour after transurethral excision were eligible. Radiotherapy consisted of 2 fractions of 1.2 Gy daily up to 60 Gy delivered in a period of 5 weeks. During the first and the last week, cisplatin 20 mg/m(2)/day and 5 FU 375 mg/m(2)/day were given concomitantly. RESULTS: The study was interrupted early due to poor recruitment. Nine patients of the originally 43 planned were treated. Mean age was 63 years. Five patients had tumour stage pT2, 1 stage pT3a and 3 stage pT3b. All patients completed radiotherapy and chemotherapy as scheduled. Only one grade 3 and no grade 4 toxicity was seen. All patients were evaluated 3 months after treatment: eight patients had no detectable tumour and one had para-aortic lymph nodes. During further follow-up, a second patient got lymph node metastases and two patients developed distant metastases (lung in the patient with enlarged lymph nodes at the first evaluation and abdominal in one other). Those three patients died at respectively 19, 14, and 18 months after registration. Late toxicity was limited and often temporary. After 26 to 57 months of follow-up, no local recurrences were seen. Six patients remained alive without disease. DISCUSSION: Despite the small cohort, this combination of concomitant chemotherapy and accelerated hyperfractionated radiotherapy for invasive bladder cancer seemed to be well tolerated and to result in satisfactory local control with limited early and late toxicity. It could therefore be considered for study in further clinical trials.

[Clinical analysis of imflammatory myofibroblastic tumor of the nasal cavity and paranasal sinus].

OBJECTIVE: To investigate the clinical features, therapeutic methods and therapeutic efficacy of imflammatory myofibroblastic tumor(IMT)of the nasal cavity and paranasal sinuses. METHOD: Clinical data of 14 cases diagnosed as IMT by pathology were retrospectively analyzed. There were 8 males and 6 females,age ranging from 18 to 77 years. 12 cases of them were treated by surgery while 2 cases received postoperative radiotherapy. RESULT: All cases were operated. All the patients were followed up for a period of 1 to 7 years after operation and two cases were proved low grade IMT pathologically. Eight cases survived with no recurrence until the last follow-up and 6 cases relapsed, of which 4 cases died and 2 were alive with tumor. CONCLUSION: IMT of the nasal cavity and paranasal sinuses is very rare. The diagonosis of IMT is based on pathology and immunohistochemistry. Proper diagnosis is essential to avoid mutilating and disfiguring surgical procedures. Radical excision is still the first choice of treatment for IMT of the nasal cavity and paranasal sinuses. Chemotherapy and radiotherapy may not be helpful to prevent recurrence after operation. Due to high recurrence rate, long-term follow up is necessary after operation.

Non conventional fractionation in radiotherapy of the musculo-skeletal sarcomas.

In 1989 we started an accelerated hyperfractionated schedule of radiotherapy (two 1.6 Gy daily fractions) in standard risk localized Ewing's sarcoma of bone, with the aim at reducing late effects in young patients and at improving disease control through a better integration of treatment modalities. From 1991, the same schedule was used in preoperative radiotherapy of adult soft tissue sarcomas of the extremities: the main purpose was to reduce the time to surgery and to evaluate surgical complications in comparison with a previous experience of hypofractionated radiotherapy (one 3 Gy daily fraction). From 1991 to 1997, 76 patients with Ewing's sarcoma and 24 patients with soft tissue sarcoma were treated at our Institution. Results and complication rates are analyzed in comparison with historical data. In Ewing's sarcoma, a correct evaluation of improvement in local control was difficult because of changing treatment policy (bulky disease was not included in the present series). Late effects, as evaluated in patients with a minimum follow-up of 3 years, occurred with similar incidence, but at higher total dose levels in patients treated with accelerated hyperfractionation. In patients with soft tissue sarcomas, incidence of surgical complications is reduced as compared to historical experience. Major problems of wound healing were seen in association with intraoperative brachitherapy boost.

[Nonspecific symptoms due to gastrointestinal stromal tumors]. / Aspecifieke klachten bij gezwellen van de maag-darmwand.

Three patients, two women aged 64 and 52 years and one man aged 78 years, had non-specific symptoms and they had signs of a tumour at imaging examination. Immunohistochemical study of operation preparations led to the diagnosis of 'gastrointestinal stromal tumour' (GIST). It is important to consider the possibility of a GIST at surgery, because the potential malignancy requires a resection with free margins.

Low-grade myofibroblastic sarcoma of the larynx: a rare entity with review of literature.

Mesenchymal neoplasms of the larynx are rare and make up approximately 0.3% to 1.0% of all malignancies at this location. Low grade myofibroblastic sarcoma (LGMS) of larynx is a rare entity. We describe a rare case of LGMS of larynx who presented with complaint of hoarseness of voice. The patient was treated with total laryngectomy plus partial pharyngectomy followed by post-operative radiotherapy. Histopathologically, the lesion was composed of spindle cells that manifested variable cellular anaplasia and expressed smooth muscle actin (SMA) and focally S-100.One of the resection limits was involved so patient was given post-operative radiotherapy. The patient is alive and disease free 14 months after surgery. The characteristic clinical, histopathological features and treatment of this case are described with a literature review.

Adjuvant radiotherapy for recurrent granular cell tumor.

Granular cell tumor (GCT) is a rare neoplasm traditionally treated with surgical excision alone. However, recurrences and metastases of GCT have been reported. The authors review the literature and report the case of a 33-year-old black woman with a large, recurrent GCT. The patient was treated with adjuvant radiation therapy and followed without evidence of recurrence. Adjuvant radiotherapy may have a role in the treatment of certain GCT thought, by clinical or pathologic criteria, to be at high risk for recurrence or metastasis, especially in those cases where extensive surgical excision would produce unacceptable morbidity.

Sarcoma after injection of intramuscular iron.

Two cases are presented of sarcomata arising at the site of previous iron dextran injections. One of the tumours showed a histological pattern associated with iron dextran administration in animal experiments.

A pilot study investigating intraoperative electron beam irradiation in the treatment of ovarian malignancies.

Intraoperative electron beam radiation therapy (IOEBRT) in the treatment of ovarian malignancies was investigated at the Clement O. Miniger Radiation Oncology Center (COMROC). Nine patients were operated in the COMROC IOEBRT operating amphitheater and five were found to have disease sufficiently limited to allow for IOEBRT. The patients' ages ranged from 13 to 80 (median 53) years. Five patients had serous cystadenocarcinoma, one papillary adenocarcinoma, one mixed germ cell tumor, one squamous cell carcinoma, and one granular cell tumor of the ovary. The median survival of the non-IOEBRT group was 13 (range 12-29) months, while the IOEBRT group's median survival was 14 (range 18-46) months. All of the patients tolerated IOEBRT well without addition to the surgical morbidity.

Lymphoma presenting as an intramuscular mass.

BACKGROUND: Resection of an intramuscular mass without tissue diagnosis can lead to unnecessary surgery. METHOD: During a 4.5-year period 19 previously healthy patients referred with an undiagnosed soft tissue tumour were found to have intramuscular non-Hodgkin's lymphoma. In seven patients this was the only focus of disease (Stage IE). Patients were treated with chemotherapy or radiotherapy alone or in combination. RESULTS: After mean follow-up of 43 months all of the patients with stage IE lymphoma are alive and disease free. CONCLUSION: Primary intramuscular non-Hodgkin's lymphoma has a good prognosis. The importance of a tissue diagnosis by needle core biopsy is emphasized.