Long-term effects of radiation exposure among adult survivors of childhood cancer: results from the childhood cancer survivor study

In the last four decades, advances in therapies for primary cancers have improved overall survival for childhood cancer. Currently, almost 80% of children will survive beyond 5 years from diagnosis of their primary malignancy. These improved outcomes have resulted in a growing population of childhood cancer survivors. Radiation therapy, while an essential component of primary treatment for many childhood malignancies, has been associated with risk of long-term adverse outcomes. The Childhood Cancer Survivor Study (CCSS), a retrospective cohort of over 14,000 survivors of childhood cancer diagnosed between 1970 and 1986, has been an important resource to quantify associations between radiation therapy and risk of long-term adverse health and quality of life outcomes. Radiation therapy has been associated with increased risk for late mortality, development of second neoplasms, obesity, and pulmonary, cardiac and thyroid dysfunction as well as an increased overall risk for chronic health conditions. Importantly, the CCSS has provided more precise estimates for a number of dose-response relationships, including those for radiation therapy and development of subsequent malignant neoplasms of the central nervous system, thyroid and breast. Ongoing study of childhood cancer survivors is needed to establish long-term risks and to evaluate the impact of newer techniques such as conformal radiation therapy or proton-beam therapy.     

The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions

This study presents data on 3,011 pleural and peritoneal effusion specimens that were examined over a three-year period (1982 to 1984). Totals of 812 (44%) of 1,846 pleural and 423 (36%) of 1,165 peritoneal specimens were positive for malignant cells. While 535 patients had malignant pleural effusions, 254 patients had malignant peritoneal effusions, and 57 had both malignant pleural and peritoneal effusions. The most common primary neoplasms causing malignant pleural effusions were carcinomas of breast (24%) and lung (19%) and lymphoreticular neoplasms (16%). The most common primary neoplasms causing malignant peritoneal effusions were carcinomas of ovary (32%) and breast (13%) and lymphoreticular neoplasms (7%). There was an average interval of more than 30 months between the histologic diagnosis of the primary neoplasm and the diagnosis of malignant effusions in patients with carcinoma of breast, lymphoreticular neoplasm and malignant melanoma. The average time until death following the diagnosis of a malignant effusions was five months or less, except for patients with carcinoma of the breast and carcinoma of the ovary. One hundred twenty-five patients (15%) presented with malignant effusions caused by neoplasms of unknown primary sites. The most common primary neoplasms that were later diagnosed were, in decreasing order of frequency, carcinoma of the ovary, carcinoma of the lung and lymphoreticular neoplasms.     

Pet birds as an independent risk factor for lung cancer: case-control study.

OBJECTIVE--To test the hypothesis that exposure to pet birds increases risk of developing lung cancer. DESIGN--Case-control study. Computerised interviews were used to assess previous exposure to pets and other risk factors for lung cancer. SETTING--Three major hospitals treating respiratory disease in former West Berlin. SUBJECTS--All people newly diagnosed as having primary malignant neoplasm of the trachea, bronchi, or lung who were 65 or younger and control subjects matched for age and sex from the general population of former West Berlin. 279 cases and 635 controls qualified for the study; 239 cases and 429 controls participated. MAIN OUTCOME MEASURES--Odds ratio of developing lung cancer according to whether or not pet birds were kept and the duration of keeping pet birds. RESULTS--In addition to the risk of lung cancer imposed by smoking, passive smoking, and occupational exposure to carcinogens, an increased relative risk of 2.14 (95% confidence interval 1.35 to 3.40) was found among people exposed to pet birds. The adjusted odds ratio for exposures longer than 10 years was 3.19 (1.48 to 8.21). CONCLUSIONS--Avian exposure seems to carry a risk of lung cancer. Until the pathogenesis is understood, long term exposure to pet birds in living areas should be avoided, especially among people at high risk of developing lung cancer.     

Local radiation dose and solid second malignant neoplasms after childhood cancer in Germany: a nested case–control study

Radiotherapy (RT) has been associated with the development of solid second malignant neoplasms (SMNs) in childhood cancer survivors. The aim of this study was to analyse the effect of cumulative doses of previous RT received at the SMN body region, at all other body regions and at body regions adjacent to the SMN, on the risk of developing a solid SMN. A total of 190 cases diagnosed with a solid second malignant neoplasm in 1980–2002 were matched with 368 controls with single neoplasm from the database of the German Childhood Cancer Registry (GCCR) (33,809 patients at cut-off date). The GCCR registers approximately 97 % of all childhood malignancies which occur at an age of less than 15 years in Germany since 1980. It was found that 147 (77.4 %) cases had received RT compared to 208 (56.6 %) controls with cumulative focus doses from 8 to 110 Gy. Fifty per cent of the SMNs and 60 % of RT affected the head region. RT was shown to increase the risk of a solid second tumour within the body region of radiation by 5.3 % per Gy (odds ratio 1.053; 95 % confidence interval 1.036–1.071). With increasing age at diagnosis and with more recent treatment eras, this effect decreased. Cumulative RT doses received at all other body regions or only at body regions adjacent to the SMN did not show an additional effect on the risk of developing an SMN. It is thus concluded that RT is the main risk factor for the development of SMNs within the irradiated body region. Late effects surveillance of former patients should give special attention to the originally irradiated parts of the body.     

Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation.

OBJECTIVE--To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin''s disease. DESIGN--Cohort study. SETTING--The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS--2846 patients first treated for Hodgkin''s disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES--Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin''s disease and of second primary non-Hodgkin''s lymphomas. RESULTS--113 second primary cancers occurred. Relative risk of cancer other than Hodgkin''s disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin''s lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin''s lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION--The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin''s disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin''s disease.     

Further follow up of mortality and incidence of cancer in men from the United Kingdom who participated in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes.

OBJECTIVES--To study the long term effects of participation in the United Kingdom''s atmospheric nuclear weapon tests and experimental programmes and to test hypotheses generated by an earlier report, including the possibility that participation in tests caused small hazards of leukaemia and multiple myeloma. DESIGN--Follow up study of mortality and cancer incidence. SUBJECTS--21,358 servicemen and civilians from the United Kingdom who participated in the tests and a control group of 22,333 non-participants. MAIN OUTCOME MEASURES--Numbers of deaths; standardised mortality ratios; relative risks of mortality from all causes and 27 types of cancer. RESULTS--During seven further years of follow up the numbers of deaths observed in participants were fewer than expected from national rates for all causes, all neoplasms, leukaemia, and multiple myeloma (standardised mortality ratios 0.86, 0.85, 0.57, and 0.46); death rates were lower than in controls (relative risks 0.99, 0.96, 0.57, and 0.57; 90% confidence intervals all included 1.00). In the period more than 10 years after the initial participation in tests the relative risk of death in participants compared with controls was near unity for all causes (relative risk 0.99 (0.95 to 1.04) and all neoplasms (0.95 (0.87 to 1.04)); it was raised for bladder cancer (2.69 (1.42 to 5.20)) and reduced for cancers of the mouth, tongue, and pharynx (0.45 (0.22 to 0.93)) and for lung cancer (0.85 (0.73 to 0.99)). For leukaemia mortality was equal to that expected from national rates but greater than in controls for both the whole follow up period (1.75 (1.01 to 3.06)) and the period 2-25 years after the tests (3.38 (1.45 to 8.25)). CONCLUSION--Participation in nuclear weapon tests had no detectable effect on expectation of life or on subsequent risk of developing cancer or other fatal diseases. The excess of leukaemia in participants compared with controls seems to be principally due to a chance deficit in the controls, but the possibility that participation in the tests may have caused a small risk of leukaemia in the early years afterwards cannot be ruled out.     

Relationship between serum Se concentration in dogs and incidence of some disease conditions

The aim of the study was to determine if there is a relationship between serum selenium concentration in dogs and their health, and to assess the relationship between selenium concentration and morphological parameters of blood. Mean serum selenium concentration in dogs ranged from 0.169 to 0.273 mg/ml. Dogs diagnosed with malignant neoplasm had a significantly lower mean concentration of serum selenium compared to healthy dogs and those from the groups studied. The present study showed no statistically significant differences in Se serum content according to sex, age, and food type. Dogs diagnosed with malignant neoplasm had a significantly lower mean serum selenium concentration compared to healthy dogs and those from the other groups analysed, namely with hip dysplasia, allergy and fractures and with non-malignant tumour. Healthy dogs were characterized by the highest mean serum selenium concentration, significantly higher compared to dogs with non-malignant tumour, malignant neoplasm, allergy and fractures. Low levels of selenium contribute to the incidence of neoplasms and allergies and increase the risk of bone fractures in dogs. Additional laboratory tests should be conducted when certain diseases are diagnosed to determine Se concentration in dogs, thus making it possible to take preventive measures or therapeutic action.     

Cancer incidence and stage at diagnosis among people with psychotic disorders: Systematic review and meta-analysis

Research regarding the incidence of cancer among people with psychotic disorders relative to the general population is equivocal, although the evidence suggests that they have more advanced stage cancer at diagnosis. We conducted a systematic review and meta-analysis to examine the incidence and stage at diagnosis of cancer among people with, relative to those without, psychotic disorders. We searched the MEDLINE, EMBASE, PsycINFO, and CINAHL databases. Articles were included if they reported the incidence and/or stage at diagnosis of cancer in people with psychotic disorders. Random effects meta-analyses were used to determine risk of cancer and odds of advanced stage cancer at diagnosis in people with psychosis, relative to those without psychotic disorders. A total of 40 articles were included in the review, of which, 31 were included in the meta-analyses. The pooled age-adjusted risk ratio for all cancers in people with psychotic disorders was 1.08 (95% CI: 1.01–1.15), relative to those without psychotic disorders, with significant heterogeneity by cancer site. People with psychotic disorders had a higher incidence of breast, oesophageal, colorectal, testicular, uterine, and cervical cancer, and a lower incidence of skin, prostate, and thyroid cancer. People with psychotic disorders also had 22% higher (95% CI: 2–46%) odds of metastases at diagnosis, compared to those without psychotic disorders. Our systematic review found a significant difference in overall cancer incidence among people diagnosed with psychotic disorders and people with psychotic disorders were more likely to present with advanced stage cancer at diagnosis. This finding may reflect a need for improved access to and uptake of cancer screening for patients diagnosed with psychotic disorders.     

The changing pattern of neoplastic disease in Canadian Eskimos.

The records of the two main referral centres for the western and central Arctic were reviewed for Eskimo patients with cancer diagnosed between 1949 and 1974 inclusive. To these were added the records for the past 6 years of patients from the eastern Arctic, giving the toatal of 180 histologically proved cases of malignant disease. Athe data were analysed for prevalence, relative frequency, geographic distribution and changes with time of the various neoplasms. Salivary gland and renal neoplasms have in recent years been displaced by cancer of the lung and uterine cervix as the most common malignant tumours in Canadian Eskimos. The prevalence of lung cancer in Eskimo women, particularly of the central Artic, is striking. Cancer of the nasopharynx kept the same relative position during early and late years of the survey period. Breast cancer is still uncommon in Eskimos. Lactation rather than gestation history appeared to be an important protective factor. Cases of cervical cancer outnumbered those of breast cancer by 18 to 4, in sharp contrast to the relative proportions of these tumours in all Canadian women.     

Thyroid Bethesda reporting category, ‘suspicious for papillary thyroid carcinoma’, pitfalls and clues to optimize the use of this category

A. Mahajan, X. Lin and R. Nayar Thyroid Bethesda reporting category, ‘suspicious for papillary thyroid carcinoma’, pitfalls and clues to optimize the use of this category Objective: The Bethesda System of Reporting Thyroid Cytopathology classifies the indeterminate categories based on their differing risks of malignancy, as atypia of undetermined significance (AUS), follicular neoplasm/suspicious for follicular neoplasm (FLUS) and suspicious for malignancy. The vast majority of cases of the last category are suspicious for papillary thyroid carcinoma (PTC). The aim of the present study was to identify the pitfalls and clues to improve the usage of the suspicious category as well as improve its outcome of malignancy. Methods: We reviewed the cytological features on air dried Diff‐Quik® and alcohol‐fixed Papanicolaou smears from 54 thyroid fine needle aspirates (FNAs) with surgical follow‐up that were originally diagnosed as suspicious. Procedure data/specimen adequacy was correlated and follow‐up histology reports were reviewed after our cytological review was completed. Incidental PTC that was not the target of the FNA was excluded from the calculations for correlation. Results: In our cytological review, we retained a diagnosis of suspicious in 18 of the 54 cases and the remaining 36 were re‐categorized as follows: 6 malignant, 10 neoplasm (which is used in our centre instead of FLUS) and 20 AUS. The reasons for overcall of suspicious cases included pseudopapillae, syncytial sheets, nuclear grooves and pinpoint nucleoli in chronic lymphocytic thyroiditis and Hürthle cell neoplasms, and intranuclear inclusions in parathyroid adenoma, hyalinizing trabecular adenoma and mesenchymal repair. The primary reasons for undercall of PTC as suspicious included cystic aspirates with minor features of PTC such as histiocytoid cells, bubblegum colloid, syncytial sheets and cellular swirls. Cases with cytoplasm similar to Hürthle cells were also noted to cause difficulty in accurate classification. Conclusions: Recognition of these pitfalls and clues can help improve diagnosis, patient treatment and consequently reduce the number of unnecessary thyroidectomies.     

Necrosis in thyroid nodules after fine needle aspiration biopsy. Report of two cases

Two cases of infarction of thyroid neoplasms following fine needle aspiration (FNA) biopsy are reported. Histologic study of a 2.5 x 2.5 cm nodule excised 18 days after FNA had diagnosed a Hürthle-cell neoplasm showed mainly necrotic debris and granulation tissue. While FNA made the diagnosis of a papillary carcinoma in the second case, which had had an FNA biopsy of the same nodule six years earlier, most of the nodule was fibrotic and necrotic. These two cases demonstrate the potential problems in such cases: (1) post-FNA infarction may obscure the nature of a cytologically diagnosed neoplasm, making histologic confirmation difficult, and (2) FNA of an infarcted nodule may have difficulties in obtaining diagnostic material, potentially resulting in a false-negative diagnosis. Review of the literature on thyroid infarction shows it to be a rare event, with most reported cases occurring after FNA biopsy of a neoplasm. The finding of necrosis and fibrosis in an aspirate or surgical specimen should thus suggest the presence of a neoplasm.     

Intraductal papilloma of the salivary gland. A report of two cases with diagnosis by fine needle aspiration biopsy

BACKGROUND: Intraductal papillomas are rare, benign tumors most commonly encountered in minor salivary glands. They are cystic, solitary neoplasms that arise from ductal epithelium and produce painless swellings. CASES: Two cases arose in major salivary glands. The first case was a superficial, firm mass at the superior edge of the parotid, cytologically evocative of an adnexal tumor. A firm, submandibular mass in the second case was diagnosed as a papillary neoplasm. Fluid was aspirated from both cases. Three-dimensional epithelial clusters, some with a papillary configuration and histiocytes, were the main cellular components. The majority of cells showed oncocytic differentiation; however, benign-appearing ductal cells in honeycomb sheets were also present. The first case also had occasional cells suggestive of sebaceous differentiation. The excised lesions were unilocular cystic papillary neoplasms consistent with intraductal papilloma; focal sebaceous differentiation was noted in the first case. CONCLUSION: Awareness of the cytologic features of intraductal papilloma of the salivary glands should prompt its inclusion in the differential diagnosis of papillary lesions of the head and neck.     

Risk of testicular cancer after vasectomy: cohort study of over 73,000 men.

OBJECTIVE--To confirm or refute reports that vasectomy may increase the risk of cancers of the testis and prostate. DESIGN--Computerised record linkage study of cohort of men with vasectomy and comparison of cancer rates with those in the whole Danish population; manual check of all records of patients with testicular and prostate cancer diagnosed within the first year of follow up. SETTING--Denmark 1977-89. SUBJECTS--Cohort of 73,917 men identified in hospital discharge and pathology registers as having had a vasectomy for any reason during 1977-89. MAIN OUTCOME MEASURES--Observed incidences of testicular, prostate, and other cancers up to the end of 1989. RESULTS--The overall pattern of cancer incidence in the study cohort was similar to that expected nationally. No increased incidence in testicular cancer was observed (70 cases; standardised morbidity ratio 1.01 (95% confidence interval 0.79 to 1.28)). The incidence during the first year of follow up was also close to that expected (nine cases; standardised morbidity ratio 0.80 (0.36 to 1.51)). The incidence of prostate cancer was not increased (165 cases; standardised morbidity ratio 0.98 (0.84 to 1.14)). CONCLUSIONS--The incidence of testicular cancer in men with vasectomy is no higher than in other men. Vasectomy does not cause testicular cancer and does not accelerate the growth or diagnosis of pre-existing testicular neoplasms. Data concerning a causal relation between vasectomy and prostate cancer were inconclusive.     

Relative risks of radiation-associated cancer: comparison of second cancer in therapeutically irradiated populations with the Japanese atomic bomb survivors

In this paper the radiation-associated relative risks of second primary cancer incidence in groups treated for first primary cancer by radiotherapy are compared with radiation-associated relative risk estimates in the Japanese atomic bomb survivor cancer incidence data. For four cancer sites, namely lung cancer, bone cancer, ovarian cancer and leukaemia, the relative risks in the comparable (age at exposure, time since exposure, sex matched) subsets of the Japanese data are significantly greater than those in the majority of second cancer studies. Even when the differences between the relative risks in the Japanese atomic bomb survivors and the medical series do not approach conventional levels of statistical significance, relative risks tend to be higher in the Japanese data than in the second cancer studies. At least for leukaemia, the discrepancy between the Japanese and second cancer risks can be largely explained by cell- sterilisation effects. There are few indications of modification of radiation-associated second cancer relative risk among those treated with adjuvant chemotherapy, nor are there strong indications of modification of radiation- associated relative risk by heritable genetic factors. If anything, there is evidence that second cancer relative excess risks are lower among those patients with cancer-prone disorders than among non-susceptible patients. However, the higher underlying cancer risk in some of these medically exposed populations should also be considered, in particular for those with cancer-prone conditions, so that the absolute excess risk is sometimes higher than in the Japanese data. Received: 14 May 1999 / Accepted in revised form: 17 September 1999     

Cancer morbidity and mortality among the liquidators of the Chernobyl accident: estimation of radiation risks

The work focuses on the results of the analysis of the cancer incidence among the Chernobyl emergency workers residing in Russia during 1991-2001. The analysis is based on the data for the cohort of male emergency workers from 6 regions of Russia including 55718 persons with documented external radiation doses in the range of 0.001-0.3 Gy who worked within the 30-km zone in 1986-1987. The mean age at exposure for these persons was 34.8 years old and the mean external radiation dose 0.13 Gy. In this cohort 1370 cases of solid cancer were diagnosed. Three follow-up periods were considered: 1991-1995, 1996-2001 and 1991-2001. The second follow-up period was chosen to allow for a minimum latency period of 10 years. Risk assessments were performed for two control groups: the first control group ("external") represented incidence rates for corresponding ages in Russia in general and the second control group ("internal") consisted of emergency workers. The estimated standardized incidence ratio (SIR) is in good agreement with that of the control within 95% CI. The values of the excess relative risk per unit dose 1 Gy (ERR/Gy) for solid malignant neoplasms have been estimated to be 0.33 (95% CI: -0.39, 1.22) (internal control) for the follow-up period 1991-2001 and 0.19 (95% CI: -0.66, 1.27) for 1996-2001. The analysis of cancer morbidity was carried out for the cohort of 29003 emergency workers who took part in liquidation of the consequences of the Chernobyl accident from 26 April 1986 to 25 April 1987. It was shown that the excess relative risk of cancer deaths per unit dose 1 Sv (ERR/Sv) is equal to 1.52 (95% CI: 0.20, 2.85).     

Risk of prostate cancer among cancer survivors in the Netherlands

BackgroundIn parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting.MethodsData from the Netherlands Cancer Registry were used to estimate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for prostate cancer as second primary cancer. The effect of time since first cancer diagnosis, specific first cancer sites, age, and pelvic radiotherapy was taken into account.ResultsOut of 551,553 male patients diagnosed with a first primary cancer between 1989 and 2008, 9243 patients were subsequently diagnosed with prostate cancer. Overall, cancer survivors showed an increased risk (SIR 1.3, 95% CI 1.2–1.3) of prostate cancer. The increased prostate cancer risk was limited to the first year of follow-up for the majority of the specific first cancer sites. More than 10 years after the first cancer diagnosis, only melanoma patients were at increased risk (SIR 1.5, 95% CI 1.2–1.9), while patients with head or neck cancers were at decreased risk (SIR 0.7, 95% CI 0.5–0.9) of being diagnosed with prostate cancer. Patients who underwent primary pelvic radiotherapy for their first cancer had a decreased risk of prostate cancer in the long term (SIR 0.5, 95% CI 0.4–0.6).ConclusionsOur data showed that cancer survivors have an increased prostate cancer risk in the first year following a first cancer diagnosis, which is most likely the result of active screening or incidental detection.     

Prediction of Mortality Using On-Line,Self-Reported Health Data: Empirical Test of the Realage Score

Objective

We validate an online, personalized mortality risk measure called “RealAge” assigned to 30 million individuals over the past 10 years.

Methods

188,698 RealAge survey respondents were linked to California Department of Public Health death records using a one-way cryptographic hash of first name, last name, and date of birth. 1,046 were identified as deceased. We used Cox proportional hazards models and receiver operating characteristic (ROC) curves to estimate the relative scales and predictive accuracies of chronological age, the RealAge score, and the Framingham ATP-III score for hard coronary heart disease (HCHD) in this data. To address concerns about selection and to examine possible heterogeneity, we compared the results by time to death at registration, underlying cause of death, and relative health among users.

Results

The RealAge score is accurately scaled (hazard ratios: age 1.076; RealAge-age 1.084) and more accurate than chronological age (age c-statistic: 0.748; RealAge c-statistic: 0.847) in predicting mortality from hard coronary heart disease following survey completion. The score is more accurate than the Framingham ATP-III score for hard coronary heart disease (c-statistic: 0.814), perhaps because self-reported cholesterol levels are relatively uninformative in the RealAge user sample. RealAge predicts deaths from malignant neoplasms, heart disease, and external causes. The score does not predict malignant neoplasm deaths when restricted to users with no smoking history, no prior cancer diagnosis, and no indicated health interest in cancer (p-value 0.820).

Conclusion

The RealAge score is a valid measure of mortality risk in its user population.     

Clinical and cytologic features of papillary neoplasms of the breast

OBJECTIVE: To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.     

Analysis of a historical cohort of Chinese tin miners with arsenic, radon, cigarette smoke, and pipe smoke exposures using the biologically based two-stage clonal expansion model.

Hazelton, W. D., Luebeck, E. G., Heidenreich, W. F. and Moolgavkar, S. H. Analysis of a Historical Cohort of Chinese Tin Miners with Arsenic, Radon, Cigarette Smoke, and Pipe Smoke Exposures Using the Biologically Based Two-Stage Clonal Expansion Model. Radiat. Res. 156, 78-94 (2001).The two-stage clonal expansion model is used to analyze lung cancer mortality in a cohort of Yunnan tin miners based on individual histories with multiple exposures to arsenic, radon, cigarette smoke, and pipe smoke. Advances in methodology include the use of nested dose-response models for the parameters of the two-stage clonal expansion model, calculation of attributable risks for all exposure combinations, use of both a fixed lag and a gamma distribution to represent the time between generation of the first malignant cell and death from lung cancer, and scaling of biological parameters allowed by parameter identifiability. The cohort consists of 12,011 males working for the Yunnan Tin Corporation, with complete exposure records, who were initially surveyed in 1976 and followed through 1988. Tobacco and arsenic dominate the attributable risk for lung cancer. Of 842 lung cancer deaths, 21.4% are attributable to tobacco alone, 19.7% to a combination of tobacco and arsenic, 15.8% to arsenic alone, 11% to a combination of arsenic and radon, 9.2% to a combination of tobacco and radon, 8.7% to combination of arsenic, tobacco and radon, 5.5% to radon alone, and 8.7% to background. The models indicate that arsenic, radon and tobacco increase cell division, death and malignant conversion of initiated cells, but with significant differences in net cell proliferation rates in response to the different exposures. Smoking a bamboo water pipe or a Chinese long-stem pipe appears to confer less risk than cigarette use, given equivalent tobacco consumption.     

Cancer molecular epidemiology: new horizons of prophylaxis

Perspectives of malignant neoplasm prophylaxis based on molecular biology achievements are discussed. Gene variants critical to development of hereditary cancer syndromes, genes modulating malignant neoplasm development risk without hereditary cancer syndrome development, and genes determining tendency of individuals for different malignant neoplasm progress risk increasing lifestyle factors are examined. Molecular epidemiology by using large scale population analysis of cancerogenesis linked genetic polymorphisms prevalence allows determination of risk groups at the most earlier stages of cell transformation or even before the onset of cell malignization and development of goal-based prophylaxis measures based on polymorphism and corresponding cancer type. Epidemiologic analysis of this type allows for earlier diagnostics in risk groups, therapy efficacy increase, disability decrease. Specific therapy on molecular level may be possible in the future.