Omer Gorgun

Brain metastasis in pediatric extracranial solid tumors: survey and literature review

Objectives: Brain is a rare site of metastasis in most extracranial pediatric solid tumors. The aim of this study is to investigate the incidence, treatment, prognosis of brain metastasis in extracranial pediatric malignant tumors in a single institution and to review the literature.Methods: From September 1989 to December 2002, 1100 children ≤16 years of age with extracranial solid tumors including lymphomas were diagnosed and treated in the Division of Pediatric Oncology, Oncology Institute, Istanbul University. Patients with parenchymal metastases in the brain were assessed.Results: Sixteen (10 female, 6 male) of 1100 patients (1.45%) with extracranial solid tumors developed brain metastases. The median age of the patients was 10.5 (1–16) years. The diagnosis was sarcomas in 12 patients: 5 osteosarcomas, 4 Ewing’s sarcoma family tumors, 1 rhabdomyosarcoma, 1 clear cell sarcoma of the soft tissue, 1 alveolar soft part sarcoma. Two patients had Wilms’ tumor and two had germ cell tumors. Four patients (25%) had brain metastasis at diagnosis. Twelve (75%) developed brain metastasis during therapy or relapse at a median duration of 16 (1–70) months from initial diagnosis. All patients had metastases to various sites, mostly lung, at the time the brain metastases were detected. Treatment included surgery, followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 1, S and RT in 1, S in 1, RT and CT in 6, RT in 1, CT in 1 and no treatment in 5. Only one patient with alveolar soft part sarcoma is alive with disease 20 months from diagnosis of brain metastasis. All other patients died at a median time of 2 months (2 days–6 months) from the time of brain metastasis.Conclusions: Children with metastatic cancer who develop headaches or any other neurologic symptom should be investigated for possible brain metastasis. Although, the outcome for these patients is dismal in this series and in the literature; reports of long term survival in a few cases with Wilms’ tumor, osteosarcoma and alveolar soft part sarcoma who had isolated brain metastasis, suggest that a subset of patients may benefit from therapy.

Ependymal tumors in childhood

Ependymal tumors are classified as ependymoma (benign or low grade) versus anaplastic ependymoma (malignant or high grade). Ependymomas represent 5–10% of intracranial neoplasm in children. In this study, demographic data and the treatment results of pediatric patients with ependymal tumors, treated in a single institute, is reported.

Hypertrophic osteoarthropathy and intrathoracic Hodgkin disease of childhood.

BACKGROUND Hypertrophic osteoarthropathy (HOA), well known in adults, is rarely encountered in children. The clinical features include clubbing of the fingers and toes, arthritis, and painful periosteal new bone formation of the tubular bones. The association of malignant disorders with HOA is more common in adults than in children. CASE In this paper, a 12-year-old boy with intrathoracic Hodgkin disease and HOA is presented and four other children with HOA and Hodgkin disease in the literature reviewed. DISCUSSION The presence of HOA has been thought to be a bad prognostic sign, but complete remission of Hodgkin disease and regression of clinical signs and symptoms of HOA were attained in our patient after chemotherapy and radiotherapy, and continue during 9 months post-therapy follow-up. CONCLUSIONS HOA accompanying a malignant tumor in children is very rare. Only 5 cases have been associated with Hodgkin disease, including the present boy. It is important that patients with symptoms of HOA and an intrathoracic mass be examined carefully to rule out a malignancy.

Malignant Ovarian Germ Cell Tumors A Single-Institution Experience

Objective:To evaluate the clinicopathologic prognostic factors in malignant ovarian germ cell tumors. Methods:We reviewed the medical records of 70 patients treated from 1990 to 2006 at our center. Clinical data including demographics, stage, surgery, chemotherapy, survival, menses status, and fertility were collected from patients’ charts. Results:Median age was 22 years (range, 9–68). The histologic subtypes included 36 dysgerminomas, 11 yolk sac tumors, 3 immature teratomas, 1 embryonal carcinomas, and 19 mixed types. The most striking clinicopathologic finding was a history of concomitant immunosuppressant therapy, which was observed in 2 patients. Two patients had contralateral sex-cord tumors at presentation and follow-up. During a median follow-up period of 4.6 years, 11 patients had recurrence. The median time to recurrence was 8 months (6–28 months). Recurrences appeared in the abdominopelvic cavity in 9 out of 11 patients. Only one could be salvaged with second-line chemotherapy. Cumulative survival rate was 97% and 60% in patients with dysgerminoma and nondysgerminoma, respectively. Nondysgerminoma histology and residual tumor after surgery were unfavorable prognostic factors (P < 0.001 and P = 0.015). Fertility-sparing surgery was as effective as radical surgery among all eligible patients. Of patients with known menstrual status, 96% had regular menses. Of the 8 patients who opted for conception among these patients, 7 delivered healthy infants. Conclusions:Nondysgerminomas have an aggressive clinical course. New treatment strategies are needed for eradication of abdominopelvic disease at initial diagnosis and recurrent setting. Occurrence of malignant ovarian germ cell tumors may be associated with immunosuppression in some patients. Sex-cord stromal tumors may present with bilateral involvement. It is possible to maintain fertility after fertility-sparing surgery followed by chemotherapy.

Rhabdomyosarcoma of the biliary tree

A 14-year-old girl was admitted to a local university hospital with complaints of right upper abdominal pain that had lasted for 1 year and abdominal distention for 1 week. On physical examination the abdomen was found to be distended and the liver was 2 cm below the right costal margin. Complete blood count, biochemistry and serum alpha-fetoprotein levels were found to be within normal limits. A sonogram and computed tomography (CT) of the abdomen revealed an enlarged liver with a mass of heterogeneous structure with cystic areas and septations. The chest X-ray and CT of the thorax and whole body bone scan were normal. The patient underwent laparotomy. Upon surgical examination, a 20 × 25 × 30 cm mass in the liver filled with hemorrhagic and necrotic material was observed. Partial right lobectomy and cholecystectomy were performed. No other intraabdominal mass was seen. Histopathologic examination revealed an infiltration consisting of loose myxoid and hypercellular areas. The cells were round or spindle shaped with scant cytoplasms. There were also cells with prominent eosinophilic cytoplasms characteristic of rhabdomyoblasts. Focal areas of pleomorphic cells were observed. Tumor necrosis was prominent. In some parts of the tumor, the surface was covered by a layer of cuboidal cells (bile duct epithelium) and beneath this epithelium there was a dense cellular zone, the so-called ‘cambium layer’. Immunohistochemical studies revealed a positive reaction for desmin and vimentin in tumoral cells. Pathologically, the tumor was consistent with a botryoid RMS of the intrahepatic bile ducts (Fig. 1). A sampled lymph node was reactive and the gallbladder was normal. Surgical margins were microscopically negative. The patient was referred to the Oncology Institute, Istanbul University, for further treatment and follow up. She was diagnosed as a group I rhabdomyosarcoma. Chemotherapy consisting of vincristine (1.5 mg/m 2 on day 1), actinomycin-D (45 μ g/kg on day 1), and cyclophosphamide (2 g/m 2 on day 1) (VAC) with mesna protection was initiated. Vincristine had to be abandoned due to severe neurotoxicity (drop-foot) at week 6. Actinomycin-D and cyclophosphamide was administered every 3 weeks for the first 12 weeks and at weeks 16, 20, 23, 29, 32, 38, 41, 47, and 50. The courses of chemotherapy were uneventful except grade 2–3 anemia, grade 2–3 neutropenia, trombocytopenia and drop-foot. On radiotherapy consultation, it was decided not to administer radiotherapy because a complete removal of the tumor with negative margins could be achieved. Chemotherapy was terminated at the end of 1 year. The patient is alive with no evidence of disease 40 months after termination of chemotherapy.

A Modified Protocol with Vincristine, Topotecan, and Cyclophosphamide for Recurrent/Progressive Ewing Sarcoma Family Tumors

Purpose: Topotecan has recently been used in the treatment of pediatric cancer. We evaluated our experience with the modified combination of vincristine, topotecan, and cyclophosphamide (VTC) given in 3 days, in children with recurrent Ewing sarcoma. Method: Children received vincristine (1.5 mg/m2/1st day), cyclophosphamide (600 mg/m2/day × 2 days) + mesna, and topotecan (1 mg/m2/day × 3 days) every 21 days. Result: A total of 118 courses of VTC were given to 13 patients. One patient received VTC both at first and at second relapse. Thus, 14 relapse episodes in 13 patients were evaluated. After three courses of VTC chemotherapy (CT), two achieved complete response (CR), five achieved partial response, thus an objective response was attained in 7/14 (50%) episodes. Two patients had stable disease and two patients progressed. In three episodes, CR was achieved by surgery before CT. One of them had a second relapse and attained CR with VTC. Median time from diagnosis to relapse was 23 months (5–45 months). Site of relapse was local in four patients, and metastatic in 10 episodes of nine patients. Seven patients are alive, three with no evidence of disease and four alive with disease; six have died of disease. Local treatment was used in 11 episodes. The toxicity of the VTC combination was limited mainly to the hematopoietic system. Conclusion: In conclusion, the modified VTC protocol in 3 days every 3 weeks seems to be effective and tolerable in children and adolescents with recurrent/progressive Ewing sarcoma.

Spontaneous pneumothorax in children with osteosarcoma: report of three cases and review of the literature.

Abstract Spontaneous pneumothorax is a rare manifestation of primary lung cancer or metastasis. It is estimated that < 1% of all cases of spontaneous pneumothorax are tumor-associated and metastatic osteogenic or soft-tissue sarcomas are associated most commonly with pneumothorax especially in the setting of cytotoxic chemotherapy or radiotherapy. In this article, we report three pediatric cases with osteosarcoma that developed spontaneous pneumothorax during chemotherapy with a review of the literature. Two of them had lung metastasis at the time of the detection of pneumothorax and the remaining patient was found to have a bronchopleural fistula. SPx is an emergency situation and early diagnosis and management can improve prognosis and quality of life of the patient however the optimal management has yet to be determined.

Granulocyte colony-stimulating factor in neutropenic, pediatric solid tumor patients following chemotherapy.

Granulocyte colony-stimulating factor (G-CSF) has been used to reduce the duration and/or degree of neutropenia of different etiologies in recent years. In this study, experience with the use of G-CSF (Neupogen, Roche) after 123 courses of highly myelosuppressive chemotherapy administered to 31 (20 female, 11 male) patients with pediatric solid tumors is reported. G-CSF was initiated at a white blood cell (WBC) count of 918 +/- 452/microL (100-2000), at a dose of 7.6 +/- 2.3 micrograms/kg/d (5-14) subcutaneously for 5.2 +/- 2.4 days (2-18). G-CSF was given for afebrile neutropenia after 82 and for febrile neutropenia after 41 courses. Only in two episodes where G-CSF was given for afebrile neutropenia, fever developed. The average hospitalization period for febrile neutropenia was 9.8 +/- 3.3 days (5-20). Chemotherapy could be given on scheduled time and dosage in 90% of the courses in which G-CSF was used for afebrile neutropenia. G-CSF was well tolerated. Bone pain was observed in two patients and urticaria in one patient. In conclusion, G-CSF increased the WBC count effectively, there were only two febrile episodes in 82 courses in children receiving G-CSF for afebrile neutropenia, it was well tolerated, and it was found to be feasible for use in a developing country.

Breast Metastases in Children and Adolescents With Rhabdomyosarcoma: A Large Single-Institution Experience and Literature Review

Introduction: Breast metastasis is rare in childhood malignancies. Soft tissue sarcomas, especially rhabdomyosarcomas (RMS), and hematologic neoplasms, such as lymphomas, are the most common tumors that metastasize to the breast, albeit rare. Materials and Methods: All cases with breast metastasis within a cohort of 200 RMS patients followed in our institution during 1990 to 2014 were assessed retrospectively and the literature was reviewed. Results: There were 3 adolescent female patients with breast metastasis. All had alveolar histology. The primary tumors were in the parameningeal sites, extremities, and the perineum, respectively. Two patients had breast metastasis at diagnosis, and 1 during follow-up. In 1 breast lesion, there was a complete response to chemotherapy, and in another there was no response to chemotherapy, and the patient underwent radical mastectomy. In the third patient, there was partial response, and lesions progressed. All patients died with recurrent/progressive disease, 2 with no recurrence in the breast. In the English literature, there are 70 cases including our cases. All but 1 involve female patients, all adolescents, most have alveolar histology and poor prognosis. All had chemotherapy, whereas some had surgery and/or radiotherapy for local treatment. Conclusion: Breast metastasis should be considered in adolescent female patients with RMS. Optimal management is not clear. Besides chemotherapy, mastectomy and radiotherapy should be considered on a case basis.

Interferon-α for unresectable progressive and symptomatic plexiform neurofibromas.

Neurofibromas are the most common manifestations of neurofibromatosis type-1. They occasionally cause pain or progressive loss of function due to nerve compression. Optimal treatment approach is still challenging and the current treatment results are not satisfactory. Four cases of plexiform neurofibromas with various clinical presentations and an addendum to a previously published report on a patient who had relief from pain and/or regression of tumor volume after treatment with interferon-&agr; 2a are presented.