Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma.

The incidences of some childhood cancers have been shown to fit a two-mutation hypothesis for cancer initiation. According to this hypothesis, the first mutation can be either germinal or somatic while the second is always somatic. A probabilistic model involving the mean number of tumors per genetically susceptible individual is developed as a function of age and is compared with age incidence data for retinoblastoma. The change in the mean number of tumors with time is interpreted in terms of the growth of retinal cells. In patients who are not genetically susceptible, the times of occurrence of the first and second somatic mutations can be inferred from a comparison of familial and non-familial unilateral case incidences. The total incidences of hereditary and nonhereditary forms of retinoblastoma are related to germinal and somatic mutation rates. The even distribution of certain childhood cancers throughout the world suggests that their incidences are determined by spontaneous mutation rates rather than by local environmental mutagenic carcinogens.     

X-ray sensitivity of diploid fibroblasts from patients with hereditary or sporadic retinoblastoma.

Fibroblasts derived from patients with hereditary retinoblastoma appear to be more sensitive to the lethal effects of x-rays than do fibroblasts from patients with sporadic retinoblastoma or normal controls. A defect in DNA repair is postulated to account for the high incidence of second tumors in these patients. Retinoblastoma appears to be an interesting model for the study of genetic susceptibility to the development of spontaneous or radiation-induced tumors.     

Mutation and Cancer: Statistical Study of Retinoblastoma

Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells.The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye.This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.     

The incidence of second primary tumors in thyroid cancer patients is increased, but not related to treatment of thyroid cancer

OBJECTIVE: The aim of the present study is to assess the prevalence of second primary tumors in patients treated for thyroid cancer. Furthermore, we wanted to assess the standardized risk rates for all second primary tumors, but especially for breast cancer, as data in the literature indicate an excessive risk in differentiated thyroid cancer (DTC) patients for this tumor. Materials and methods: We included consecutive patients, who received ablation treatment with I-131 at the Leiden University Medical Center between January 1985 and December 1999 (n = 282). The mean period of follow-up was 10.6 +/- 4.1 years. RESULTS: Thirty-five of the 282 patients (12.4%) had a second primary tumor (SPT), either preceding or following the diagnosis of thyroid cancer. Five other patients had three primary tumors, including DTC. As a result, 40 additional tumors were found in this group, revealing an overall prevalence of 14.2%. Twenty tumors (7.1%) preceded the thyroid cancer with a mean interval of 5.7 years (range: 0.5-22.0 years), whereas 20 tumors (7.1%) occurred after this tumor with a mean interval of 6.7 years (range: 1.0-15.0 years). In 13 female patients, breast cancer was found as SPT. The standardized incidence rate (SIR) for all cancers after the diagnosis of DTC in this study population was not increased (1.13; confidence interval (CI): 0.68-1.69). However, we found an increased SIR of 2.26 (CI: 1.60-3.03) for all cancers either following or preceding DTC, which is mainly caused by a SIR of 3.95 (CI: 2.06-6.45) for breast cancer. CONCLUSION: Patients with DTC have an overall increased standardized incidence rate for second primary tumors, but not for second primary tumors following I-131 therapy. These findings suggest a common etiologic and/or genetic mechanism instead of a causal relation.     

Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years

We assessed the risk of second brain tumors in a cohort of patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. Four hundred and twenty-six patients (United Kingdom residents) with pituitary adenomas received radiotherapy at the Royal Marsden Hospital (RMH) between 1962 and 1994. They were followed up for 5749 person-years. The cumulative incidence of second intracranial tumors and systemic malignancy was compared with population incidence rates through the Thames Cancer Registry and the National Health Service Central Register (previously OPCS) to record death and the potential causes. Eleven patients developed a second brain tumor, including five meningiomas, four high grade astrocytomas, one meningeal sarcoma, and one primitive neuroectodermal tumor. The cumulative risk of second brain tumors was 2.0% [95% confidence interval (CI), 0.9-4.4%] at 10 yr and 2.4% (95% CI, 1.2-5.0%) at 20 yr, measured from the date of radiotherapy. The relative risk of second brain tumor compared with the incidence in the normal population was 10.5 (95% CI, 4.3-16.7). The relative risk was 7.0 for neuroepithelial and 24.3 for meningeal tumors. The relative risks were 24.2 (95% CI, 4.8-43.5), 2.9 (95% CI, 0-8.5), and 28.6 (95% CI, 0.6-56.6) during the intervals 5-9, 10-19, and more than 20 yr after radiotherapy (four cases occurred >20 yr after treatment). There was no evidence of excess risk of second systemic malignancy. An additional 10-yr update confirmed our previous report of an increased risk of second brain tumors in patients with pituitary adenoma treated with surgery and radiotherapy. The 2.4% risk at 20 yr remains low and should not preclude the use of radiotherapy as an effective treatment option. However, an increased risk of second brain tumors continues beyond 20 and 30 yr after treatment.     

Prognostic factors and survival in patients with hereditary hemochromatosis and cirrhosis.

OBJECTIVES: The survival of treated, noncirrhotic patients with hereditary hemochromatosis is similar to that of the general population. Less is known about the outcome of cirrhotic hereditary hemochromatosis patients. The present study evaluated the survival of patients with hereditary hemochromatosis and cirrhosis. METHODS: From an established hereditary hemochromatosis database, all cirrhotic patients diagnosed from January 1972 to August 2004 were identified. Factors associated with survival were determined using univariate and multivariate regression. Survival differences were assessed using the Kaplan-Meier life table method. RESULTS: Ninety-five patients were identified. Sixty patients had genetic testing, 52 patients (87%) were C282Y homozygotes. Median follow-up was 9.2 years (range 0 to 30 years). Nineteen patients (20%) developed hepatocellular carcinoma, one of whom was still living following transplantation. Cumulative survival for all patients was 88% at one year, 69% at five years and 56% at 20 years. Factors associated with death on multivariate analysis included advanced Child-Pugh score and hepatocellular carcinoma. Patients with hepatocellular carcinoma were older at the time of diagnosis of cirrhosis (mean age 61 and 54.6 years, respectively; P=0.03). The mean age at the time of diagnosis of hepatocellular carcinoma was 70 years (range 48 to 79 years). No other differences were found between the groups. CONCLUSIONS: Patients with hereditary hemochromatosis and cirrhosis are at significant risk of developing hepatocellular carcinoma. These patients are older when diagnosed with carcinoma and may have poorer survival following transplantation than patients with other causes of liver disease. Early diagnosis and treatment of hereditary hemochromatosis by preventing the development of cirrhosis may reduce the incidence of hepatocellular carcinoma in the future.     

Management of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is responsible for 13.4% of the total deaths attributable to thyroid cancer in human beings and research on MTC over the last 40 years has identified the RET proto-oncogene as a very relevant component of development of both sporadic and hereditary MTC. An activating germline RET proto-oncogene mutation responsible for a multiple endocrine neoplasia syndrome type 2 (MEN2) or a familial hereditary MTC syndrome is carried by 25% to 35% of patients with MTC. The recognition of RET proto-oncogene mutations by genetic sequencing has allowed us to differentiate hereditary from sporadic MTC, so that it is now possible to identify and treat children at risk for this disease before development of metastasis. Thanks to this discovery, we can now establish the association of MTC with other tumors in the context of MEN2 syndrome; determine adequate follow-up, prognosis, and treatment for patients with hereditary disease; and use this information to develop new therapies against both sporadic and hereditary MTCs.     

Treatment of solid tumors following allogeneic bone marrow transplantation

Second solid tumors are well known late complications after bone marrow transplantation. Treatment strategies are ill defined. We retrospectively evaluated treatment and outcome in a single institution. From August 1974 to July 1996, six solid tumors were observed in five of 387 patients 2 to 13 years after BMT, corresponding to a probability of developing a second solid tumor of 9% (1-17%, 95 CI) at 15 years: these comprised endometrial carcinoma, carcinoma of the thyroid gland, cervical carcinoma, sarcoma of the small intestine, osteosarcoma of the tibia and ovarian carcinoma. All five patients were treated as intensively as they would be without a history of BMT. At last follow-up four of the five patients were alive and without signs of tumor. We postulate that second solid tumors after BMT should be treated as de novo tumors. Early detection based on consequent clinical follow-up of the transplant patients might explain the relatively good outcome.     

Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983

Second malignant neoplasms are a serious complication after successful treatment of childhood acute lymphoblastic leukemia (ALL). With improvement in survival, it is important to assess the impact of contemporary risk-based therapies on second neoplasms in ALL survivors. A cohort of 8831 children diagnosed with ALL and enrolled on Children's Cancer Group therapeutic protocols between 1983 and 1995 were observed to determine the incidence of second neoplasms and associated risk factors. The median age at diagnosis of ALL was 4.7 years. The cohort had accrued 54 883 person-years of follow-up. Sixty-three patients developed second neoplasms, including solid, nonhematopoietic tumors (n = 39: brain tumors n = 19, other solid tumors n = 20), myeloid leukemia or myelodysplasia (n = 16), and lymphoma (n = 8). The cumulative incidence of any second neoplasm was 1.18% at 10 years (95% confidence interval, 0.8%-1.5%), representing a 7.2-fold increased risk compared with the general population. The risk was increased significantly for acute myeloid leukemia (standardized incidence ratio [SIR] 52.3), non-Hodgkin lymphoma (SIR 8.3), parotid gland tumors (SIR 33.4), thyroid cancer (SIR 13.3), brain tumors (SIR 10.1), and soft tissue sarcoma (SIR 9.1). Multivariate analysis revealed female sex (relative risk [RR] 1.8), radiation to the craniospinal axis (RR 1.6), and relapse of primary disease (RR 3.5) to be independently associated with increased risk of all second neoplasms. Risk of second neoplasms increased with radiation dose (1800 cGy RR 1.5; 2400 cGy RR 3.9). Actuarial survival at 10 years from diagnosis of second neoplasms was 39%. Follow-up of this large cohort that was treated with contemporary risk-based therapy showed that the incidence of second neoplasms remains low after diagnosis of childhood ALL.     

Second malignancies after Hodgkin's disease: the Munich experience

 The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974–1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic relation to the field of previous radiotherapy. Taken together, in our patient population, we observed all three categories of SM (solid tumors, leukemias, NHL). The risk for second leukemias is lower than in previous studies, whereas the risk of second NHL is somewhat higher. We confirm that splenectomy is a possible risk factor for SM. Even after correction for the age-specific cancer incidence, treatment intensity is associated with the development of second malignant tumors. Continued follow-up is mandatory after treatment for HD. Since the prognosis of most SM is unfavorable, early recognition and prevention are of the utmost importance. Received: November 20, 1998 / Accepted: May 10, 1999     

Quadruple cancer,including triple cancers in the head and neck region

Multiple primary tumors are not rare: they are encountered in 3-5% of malignant tumors. They are particularly frequent in the head and neck [20]. They are most often met with secondary malignant tumors; triple tumors occur in only 0.5%, quadruple tumors in 0.3% of malignant tumors. The possibility of developing a second metachronous cancer 5 years after undergoing treatment of the initial head and neck cancer is approximately 22%. Multiple metachronous tumors often appear 3-4 years after the observation of the primary tumor, or even after 5-10 years in the case of laryngeal tumors. The frequency of multiple primary tumors in the head and neck region supports the "field cancerization" theory, according to which the inducing agents (primarily smoking and alcohol consumption) can initiate the tumorous degeneration at a number of sites in the oropharyngeal region. The authors report on a case in whom surgery for bladder tumor was followed 101 months later by tumor development in the region of the head and neck: 3 such tumors were treated within a period of 21 months. The histologic result on the bladder tumor was transitiocellular carcinoma, while the latter ones were squamous cell carcinomas. Three of the tumors were treated effectively (no local recurrence or metastasis developed), but the fourth led to the death of the patient. The literature on multiple tumors of the head and neck is reviewed, and possible etiologic factors are discussed. It is pointed out that, besides primary and secondary prevention, close observation of these patients is required, repeated panendoscopy of the upper aerodigestive tract and genetic examinations are recommended.     

Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin's disease: long-term analysis of risk factors and outcome

The survival of patients with Hodgkin's disease has dramatically improved over the past 30 years because of advances in treatment. However, concern for the risk of long-term complications has resulted in a number of trials to evaluate reduction of therapy. The consequences of these trials on recurrence, development of long-term complications, and survival remain unknown. One major consequence of successful treatment of Hodgkin's disease is the development of second malignant neoplasms. We sought to determine the factors most important for development of second tumors in pathologically staged and treated Hodgkin's disease patients followed for long intervals to provide background information for future clinical trials and guidelines for routine patient follow-up. Between April 1969 and December 1988, 794 patients with laparotomy staged (PS) IA-IIIB Hodgkin's disease were treated with radiation therapy (RT) alone or combined radiation therapy and chemotherapy (CT). There were 8,500 person-years of follow-up (average of 10.7 person-years per patient). Age and gender-specific incidence rates were multiplied by corresponding person-years of observation to obtain expected numbers of events. Observed to expected results were calculated by type of treatment, age at treatment, sex, and time after Hodgkin's disease. Absolute (excess) risk was expressed as number of excess cases per 10,000 person-years. Seventy-two patients have developed a second malignant neoplasm. Eight patients developed acute leukemia, 10 had non-Hodgkin's lymphoma (NHL), and 53 patients developed solid tumors at a median time of 5 years, 7.25 years, and 12.2 years, respectively, after Hodgkin's disease. One patient developed multiple myeloma 16.5 years after Hodgkin's disease. The relative risk (RR) of developing a second malignancy was 5.6. The absolute excess risk per 10,000 person-years (AR) of developing a second malignancy was 69.6 (7.0% excess risk per person per decade of follow-up). The highest RR occurred for the development of leukemia (RR = 66.2), however because of the low expected risk, the AR was only 9.3. The RR of solid tumors after Hodgkin's disease was lower (4.7); however, the AR was greater (49) than for acute leukemia. Among the solid tumors, breast, gastrointestinal, lung, and soft tissue cancers had the highest absolute excess risks. The risk for developing breast cancer after Hodgkin's disease was greatest in women who were under the age of 25 at treatment. The most significant risk factor for the development of both leukemia and solid tumors was the combined use of radiation therapy and chemotherapy. The RR following RT alone was 4.1 (AR = 51.1); for RT + CT (initially or at relapse) the RR was 9.75 (P < 0.05, nonoverlapping confidence limits, AR = 123.9). Survival following development of a second malignancy was poor in patients with leukemia, gastrointestinal tumors, lung cancer, and sarcoma. Survival from other malignancies including NHL and breast cancer was more encouraging. Second malignant neoplasms are a major cause of late morbidity and mortality following treatment for Hodgkin's disease. The most significant risk factor for the development of second tumors is the extent of treatment for Hodgkin's disease. Recommendations are presented for both prevention and early detection of these tumors.     

Hereditary non-polipomatous colorectal cancer: hereditary predisposition, diagnosis and prevention

BACKGROUND: Colorectal cancer is the third in frequency and the second in mortality in developed countries. In Brazil, it is among the six more common malignant neoplasias. About 20% of colorectal tumors have some hereditary component. AIM: This study presents a review of genetic and clinic aspects, as well as diagnosis and prevention of the hereditary non-polipomatous colorectal cancer, that is the more frequent form of hereditary colorectal cancer. This approach is important because, currently there are possibilities of management, prevention and surveillance specific to individuals at-risk for hereditary non-polipomatous colorectal cancer that can lead to a great improvement in patients' survival and their at-risk relatives.     

Model for the incidence of embryonal cancers: application to retinoblastoma.

The two-mutation theory of cancer initiation hypothesizes that some cancers originate after two successive mutations, of which the second mutation is always somatic and the first mutation may be germinal (hereditary cases) or somatic (nonhereditary cases). A quantitative model using the Poisson distribution is developed for ages at diagnosis for hereditary and nonhereditary cases. This model relates age-specific incidence data explicitly to the number of divisions of embryonal cells and to rates of somatic mutations per cell division. A good fit is obtained when the model is applied to data on ages at diagnosis for one such embryonal tumor, retinoblastoma.     

Alterations of <Emphasis Type="Italic">RB1</Emphasis> gene in embryonal and alveolar rhabdomyosarcoma: special reference to utility of pRB immunoreactivity in differential diagnosis of rhabdomyosarcoma subtype

PURPOSE: Rhabdomyosarcoma (RMS), which is the most common pediatric soft tissue sarcoma, is classified into two major histologic subtypes, embryonal RMS (ERMS) and alveolar RMS (ARMS). RMS is occasionally reported to be the second neoplasm of hereditary retinoblastoma. Osteosarcoma is known as the most common second neoplasm of hereditary retinoblastoma, and tumorigenesis of osteosarcoma has been proven in previous studies to be related to the RB gene (RB1) alteration. Therefore, there might be a correlation between the tumorigenesis of RMS and RB1 alteration. METHODS: We examined the RB protein (pRB) expression and RB1 alteration such as allelic imbalance (gain or loss) and homozygous deletion, using immunohistochemistry, microsatellite makers, and quantitative real-time PCR in 57 sporadic RMS. RESULTS: Allelic imbalance was more frequently detected in ERMS (13/27), than in ARMS (3/20) (P = 0.04). Homozygous deletion on the protein-binding pocket domain of RB1 was found in 6 of 27 ERMS and in 2 of 20 ARMS (P = 0.24). Furthermore, immunohistochemical pRB labeling indexes (LI) in 31 ERMS (median value, 31%) were significantly reduced in comparison with those observed in 26 ARMS (median value, 85%) (P < 0.0001). CONCLUSIONS: Our results support the assertion that tumorigenesis of RMS may be associated with RB1 alteration especially in ERMS, as previously reported for osteosarcoma. As for the RB pathway, each subtype of RMS may have a different tumorigenesis. In addition, immunohistochemical pRB LI may have the potential to be a useful ancillary tool in the differential diagnosis of RMS subtypes.     

Percutaneous cryoablation for pulmonary nodules in the residual lung after pneumonectomy: report of two cases

Lung cancers in the residual lungs of patients who have undergone pneumonectomies are often unresectable, primarily because of the risks of overt pulmonary function losses. Percutaneous cryoablation of lung tumors is a potentially minimally invasive technique that has recently been used in the treatment of lung cancers and metastatic lung tumors. Here, we present two patients who had previously undergone pneumonectomies, in whom lung cancers in the residual lungs were treated by cryoablation. In both patients, the procedures were performed safely without any complications, such as airway bleeding, hemothoraces, or pneumothoraces. The changes in pulmonary functions after the procedures were minimal: % vital capacity (-1% and -4%), and %FEV(1) (-1% and +10%) in the first and second patients, respectively. The performance statuses were maintained at zero in both patients after cryoablation. In the first patient, local control has been maintained for 4 years. In the second patient, local control was maintained for 2 years until the patient died of distant metastases. This is, to our knowledge, the first reported case of lung cryoablation in residual lungs of patients who have previously undergone pneumonectomies. Application of percutaneous cryoablation may represent a new treatment option for lung tumors in patients who have previously undergone pneumonectomies.     

Bilateral breast cancer

The aim of this study was to evaluate the clinical and pathological features of breast cancer patients with bilateral breast cancer and to assess the impact of the second breast cancer on their prognosis. Thirty six breast cancer patients with bilateral (metasynchronous) cancer were treated in Greatpoland Cancer Center from 1983 to 1995. It constituted 4.1% of all breast cancer patients treated in those years. 5-year survival rates were compared with clinical data (age, clinical stage, histological diagnosis), methods of treatment and length of interval between occurring of both tumors. Five year survival of patients treated for second breast cancer was 55.6% (20/36), disease-free survived--15/36 (41.7%). 5-year survival rate was greater in group of patients with clinical stage T1 or T2 (69.6%, 16/23) than in group with T3 or T4 (30.8%, 4/13) (p=0.009). In group of 20 patients without nodal involvement (N0) 5 years survived 75.0% of patients (15/20), in group with N1--11.1% (1/9) (p=0.01). Length of interval between both breast tumors influenced 5-year survival rate. In group of patients with interval longer than 5 years, 5-year survival rate was 73.9% (17/23), in group of patients with interval shorter than 2 years--0% (0/6) (p=0.002). No correlations were observed between survival rate and age, histological diagnosis, methods of treatment.     

Medullary thyroid carcinoma (MTC)--clinical and molecular aspects on the basis of own experience

In our clinic 19615 patients were operated over 25 years on for goiter. Malignant thyroid neoplasms were found in 1049 (5.3%) patients including 875 (83.4%) women and 174 (16.6%) men. Sixty two adult patients (42 women and 20 men were operated on for medullary thyroid carcinoma (MTC). Thyroid cancer was diagnosed in this group pre or intraoperatively in 44 (71%) patients and postoperatively, on histologic examination, in 18 (29%) patients. These patients were reoperated. Radical operations (total thyroidectomy with regional lymph node removal) were conducted in 43 (69.3%) patients and palliative ones in 19 (30.7%) patients. After MTC surgery, MEN 2A (MTC and an adrenal tumor) were diagnosed by means of imaging techniques (USG, CT) in 6 (9.7%) patients. All adrenal tumors were unilateral. Five of these patients were operated, and pheochromocytoma was confirmed by histopathologic examination. Two years after the MTC operation, 1 women was lost to follow-up. After a year, she was admitted to hospital for severe hypertension and died of cerebral hemorrhagia. Pheochromocytoma was revealed by autopsy. All patients were treated complementarily after the MTC operation. Different combinations of teleradiotherapy, chemotherapy and substitutive doses of levothyroxine were used. Ten (23.2%) of 43 patients operated radically were reoperated 1-3 years after the first operation due to loco-regional tumor recurrence. Radical reoperations were performed in 4 patients, and palliative ones in 6. Over a 0.5-23-year follow-up period, 26 (41.9%) patients died, including 20 of cancer, and 6 of other reasons. Four out of 36 living patients have clinical or biochemical symptoms of neoplastic disease. The follow-up period of MEN 2 patients operated on ranged from 1 to 6 years. Up to now, no tumor in the second adrenal gland has been diagnosed in any of these patients. Genetic (molecular) tests performed in 31 out of 36 living patients revealed mutations of RET gene in 4 (12.9%).     

Challenge of the two neural tumors: neuroblastoma and retinoblastoma

Fifty cases of neuroblastoma and 29 retinoblastoma patients who had additional chemotherapy were analyzed retrospectively. Male:Female ratio were 1:1 and 0.8:1, the ages ranged from birth to 14 years (4 +/- 3.42 year) for neuroblastoma, and one month to 5.5 years (2.4 +/- 1.4 year) for retinoblastoma. More than 70%-90% of them came in advanced stages. The treatment consisted of surgical resection, enucleation or exenteration if feasible. Radiation therapy and chemotherapy were given as specific and palliative measures. All of the neuroblastoma who were younger than 8 months old survived long-term. Various chemotherapeutic agents did not seem to effect the outcome of the advanced cases of these two diseases. The retinoblasts did not seem to be sensitive to MTX and Ara-C. Thio-tepa intrathecally seems to be worth trying. Since these two tumors are not sensitive to treatment and are still a great challenge to the developed countries, awareness of the diseases, early diagnosis and early treatment are appropriate approaches for the developing countries.     

Intrathoracic extramedullary hematopoietic tumor in hemoglobin H disease.

We report a Chinese patient with hemoglobin H (Hb H) disease who developed intrathoracic extramedullary hematopoiesis (EMH) 17 years following splenectomy for a blunt abdominal injury. The patient initially presented with extreme hyperbilirubinemia and multiple intrathoracic tumors. Hb H disease was diagnosed after investigation, and the marked jaundice, which declined gradually after supportive treatment, was attributed to his chronic hemolysis superimposed on an acute hepatitis C virus infection. A biopsy of the intrathoracic tumors revealed an EMH. Intrathoracic EMH, which is usually encountered in patients with beta-thalassemia and hereditary spherocytosis, has never been reported in Hb H disease. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with asymptomatic intrathoracic tumor to avoid unnecessary surgical interventions.