Ellen Greenebaum

I-131 dose response for incident thyroid cancers in Ukraine related to the Chornobyl accident.

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case–control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose–response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose–response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43–6.34], and the EAR per 104 PY/Gy was 2.21 (95% CI, 0.04–5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. Conclusions: I-131–related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.

A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Objectives, Design and Methods

Abstract Chornobyl Thyroid Diseases Study Group of Belarus, Ukraine, and the USA. A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Objectives, Design and Methods. Radiat. Res. 161, 481–492 (2004). The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and γ rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly 131I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose–response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.

Malignant granular cell tumor: A case report and review of the recent literature

We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The tumor occurred in the infratemporal fossa of a 30-year-old man, extended to the left orbital base, into the foramen ovale, and invaded the mandible. A granular cell tumor (GCT) was diagnosed by fine-needle aspiration and core needle biopsy of the mass. The patient underwent a radical subtotal debulking procedure followed by radiotherapy. He is alive with recurrent disease 12 months after presentation. Cytologically, the aspirated material was abundantly cellular showing large polygonal cells with ample granular eosinophilic cytoplasm, eccentric nuclei, and often prominent nucleoli. Histologically, the tumor consisted of solid sheets of similar cells that stained strongly with S-100 protein, neuron-specific enolase (NSE), and vimentin. There was moderate nuclear pleomorphism and broad zones of necrosis. Four mitotic figures per 100 high-power field (HPF) were counted. By electron microscopy, the cytoplasm of the tumor cells was filled with lysosomes. Although, some observers advocate that the diagnosis of a MGCT should be reserved for cases in which lymph node and/or distant organ metastasis is evident, we believe malignancy ought to be considered in any GCT with aggressive clinical course defined by persistent local recurrence and destruction of neighboring structures. Nuclear pleomorphism, necrosis, and presence of any mitotic activity should indicate malignancy.

A Screening Study of Thyroid Cancer and Other Thyroid Diseases among Individuals Exposed in Utero to Iodine-131 from Chernobyl Fallout

BACKGROUND Like stable iodine, radioiodines concentrate in the thyroid gland, increasing thyroid cancer risk in exposed children. Data on exposure to the embryonic/fetal thyroid are rare, raising questions about use of iodine 131 (I-131) in pregnant women. We present here estimated risks of thyroid disease from exposure in utero to I-131 fallout from the Chernobyl nuclear accident. METHODS We conducted a cross-sectional thyroid screening study (palpation, ultrasound, thyroid hormones, and, if indicated, fine needle aspiration) from 2003 to 2006. Participants were 2582 mother-child pairs from Ukraine in which the mother had been pregnant at the time of the accident on April 26, 1986, or 2 months after the time during which I-131 fallout was still present (1494 from contaminated areas, 1088 in the comparison group). Individual cumulative in utero thyroid dose estimates were derived from estimated I-131 activity in the mothers thyroid (mean 72 mGy; range 0-3230 mGy). RESULTS There were seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm identified as a result of the screening. Whereas the estimated excess odds ratio per gray for thyroid carcinoma was elevated (excess odds ratio per gray 11.66), it was not statistically significant (P = 0.12). No radiation risks were identified for other thyroid diseases. CONCLUSION Our results suggest that in utero exposure to radioiodines may have increased the risk of thyroid carcinoma approximately 20 yr after the Chernobyl accident, supporting a conservative approach to medical uses of I-131 during pregnancy.

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: pathology analysis of thyroid cancer cases in Ukraine detected during the first screening (1998-2000).

The Ukrainian American Cohort Study evaluated the risk of thyroid disorders in a group of individuals who were younger than age 18 years at the time of the Chornobyl (Chernobyl) accident. In this article, the authors describe the pathology of thyroid carcinomas detected in the first screening.

Metastatic calcification in skin: Exclusive involvement of eccrine sweat ducts. A case report

A remarkable distribution of metastatic calcium in skin involving exclusively the excretory duct of eccrine sweat glands was observed in an adult male with hypercalcemia. An explanation is offered for the unusual distribution of calcium in the skin.

NA Cohort Study of Thyroid Cancer and Other Thyroid Diseases After the Chernobyl Accident : Cytohistopathologic Correlation and Accuracy of Fine-Needle Aspiration Biopsy in Nodules Detected During the First Screening in Ukraine (1998-2000)

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine‐needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown.

Differences in Sonographic Conspicuity According to Papillary Thyroid Cancer Subtype: Results of the Ukrainian–American Cohort Study After the Chornobyl Accident

OBJECTIVE Over time, the histology of papillary thyroid cancers detected in a repeatedly screened population exposed to radiation at Chornobyl (Chernobyl) has shifted from a more aggressive subtype toward less aggressive subtypes. This change may reflect biologic behavior but could also be influenced by the detectability of different subtypes. The study objective was to identify whether there is any relationship between the conspicuity of sonographically detected papillary cancers and histologic subtype. MATERIALS AND METHODS Sonographic images of 84 papillary cancers occurring in young people exposed to radiation at Chornobyl were each given a conspicuity score using a subjective 1-5 scale by four independent expert readers blinded to histologic subtype. The effects of tumor subtype, tumor encapsulation, reader, machine type, and nodule size on sonographic conspicuity were determined using analysis of variance and Spearman correlations. RESULTS Cancer subtype was related to sonographic conspicuity (p < 0.01). The relatively aggressive solid subtype of papillary carcinoma was more conspicuous than the papillary, follicular, and mixed subtypes (p < 0.05). The other subtypes did not differ significantly from each other in conspicuity. Conspicuity was not significantly related to nodule size, degree of encapsulation, age and sex of the subject, or machine type. Although the mean conspicuity score for each reader differed significantly, reliability of conspicuity judgments across readers was fair. CONCLUSION In subjects exposed to radiation from the Chornobyl accident, the solid subtype of papillary carcinoma appears to be more conspicuous on sonography than the other subtypes. Therefore, the change in subtype observed over time in this repeatedly screened population may be influenced by differences in nodule conspicuity.

Isolated sigmoid tuberculosis - Report of a case

PURPOSE: To heighten awareness of colonic tuberculosis (TB) as a once rare disease that is undergoing a resurgence in the United States. METHODS: Report of a case of isolated sigmoid tuberculosis with a brief literature review of the topic. RESULTS: TB can no longer be considered a rare disease in the United States because, in part, of the acquired immunodeficiency syndrome epidemic and because, in part, of increased immigration and lack of containment. The signs and symptoms of colonic TB are nonspecific; therefore, a high index of suspicion must be maintained. Only 20 percent of patients will have associated active pulmonary TB. Colonoscopy with multiple biopsies at ulcer margins should be performed for diagnosis. Tissue should be sent for routine histology and culture and smeared for direct visualization of acid-fast bacilli. If colonic TB is suspected, empiric treatment is warranted, despite negative histology, smear, and culture results. Patients will usually show a dramatic response in one to two weeks. Treatment is solely medical, and all patients should receive a full course of antituberculous chemotherapy. Exploratory laparotomy is necessary if diagnosis is in doubt, when there is concern about a neoplasm, or for complications including perforation, obstruction, hemorrhage, or fistulization. CONCLUSION: An increased awareness of intestinal TB coupled with familiarity of the pathophysiology, diagnostic methods, and treatment should increase the number of cases correctly diagnosed preoperatively and, therefore, improve the outcome of patients with this disease.

Loss of heterozygosity analysis to diagnose adrenal cortical carcinoma

In this issue of Cancer Cytopathology, Abati et al., using the cellular material in fine-needle aspiration (FNA) biopsies, demonstrate the feasibility of detecting loss of heterozygosity (LOH) at the p53 locus on chromosome 17, the putative neuroblastoma tumor suppressor locus on chromosome 1, and at the von Hippel-Lindau locus on chromosome 3 in adrenal cortical carcinomas. The most common mechanism of loss of function of a tumor suppressor gene is mutation of one allele and loss of the other (LOH). This makes it possible to use LOH as a marker of loss of tumor suppressor gene function. With the identification of a large number of repeat sequences of 2, 3, or 4 repeating bases (microsatellites) throughout the genome, whose alleles differ only in the number of repeats, it has become possible over the past few years to use the polymerase chain reaction (PCR) to examine LOH at virtually any locus. This approach technically is simpler than sequencing an entire tumor suppressor gene to look for mutations. Over the past few years, a number of articles have demonstrated the feasibility of determination of LOH at various loci using cellular material obtained by FNA. Tsuda et al. showed LOH on chromosome 16 in FNAs of surgical specimens of 10 of 14 breast carcinomas, with no LOH detected in any of 3 fibroadenomas. Using microdissection of FNA smears, Chuaqui et al. showed LOH at chromosome 11q13 in 10 of 19 breast carcinomas, which demonstrated complete correlation with results obtained from corresponding histologic samples. Abati et al. apply LOH analysis to cellular material from FNAs of adrenal cortical adenomas and carcinomas. This is of clinical interest because the pathologic distinction of adrenal cortical adenomas from carcinomas is a difficult problem, particularly when based on FNA. Prediction of malignant behavior of primary adrenal cortical neoplasms combines clinical and pathologic characteristics such as weight loss, size, growth pattern, and high mitotic rate of the lesion, broad fibrous bands traversing the tumor, and tumor growth at clinical follow-up. Although FNA is used in the triage of nonfunctional 173 CANCER CYTOPATHOLOGY