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Because few studies have assessed the accuracy of lung cancer histologic diagnoses reported by state cancer registries, we examined whether the Iowa Surveillance, Epidemiology, and End Results Cancer Registry (i.e., the Iowa Cancer Registry)-reported lung cancer histologic diagnoses were reliable. We investigated agreement between lung cancer histologic types reported for 413 patients with lung cancer by the Iowa Cancer Registry and those obtained through an independent review of diagnostic slides. Among lung cancer histologic types, small-cell carcinoma had the highest sensitivity (94.1%, 95% confidence interval [CI] = 85.6% to 98.4%), positive predictive value (94.1%, 95% CI = 85.6% to 98.4%), negative predictive value (98.8%, 95% CI = 96.9% to 99.7%), and highest percent exact agreement (98.0%, 95% CI = 96.6% to 99.4%). The lowest sensitivity (21.9%, 95% CI = 9.3% to 40.0%) and positive predictive value (23.3%, 95% CI = 9.9% to 42.3%) were noted for large-cell carcinoma, probably because other more specific features of adenocarcinoma or squamous carcinoma were absent. Adenocarcinoma had the lowest specificity (84.4%, 95% CI = 79.0% to 88.9%), negative predictive value (85.2%, 95% CI = 79.9% to 89.6%), and percent exact agreement (82.9%, 95% CI = 79.2% to 86.6%). Samples collected by cytologic examination (odds ratio [OR] = 2.4, 95% CI = 1.1 to 5.2) or biopsy examination (OR = 2.2, 95% CI = 1.1 to 4.2) were more likely to be misclassified than samples obtained via resection. Thus, the histologic type obtained by the Iowa Cancer Registry is reasonably reliable, but independent slide review is needed for precise histologic typing of lung cancer.

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BACKGROUND AND PURPOSE: We have examined a new technique for the thermal treatment of prostate cancer involving the percutaneous placement of small magnetic alloy rods into the gland in a procedure analogous to the placement of permanent brachytherapy seeds. When the patient and the implanted rods are placed in an extracorporeal alternating magnetic field, the rods heat and can produce tissue necrosis. The rods are temperature self-regulating and produce temperatures no higher than their preprogrammed regulation value. The rods are biocompatable permanent implants, comprised of cobalt and palladium. MATERIALS AND METHODS: We examined rods that heat to 55 degrees, 60 degrees, and 70 degrees C. Patients are treated for 1-hour sessions and easily have multiple sessions. RESULTS: Isolated rods produced little or asymmetrical necrosis. However, arrays of 70 degrees C rods placed within 1 cm of each other caused consistent necrosis between the rods. The temperature at the edge of the array dropped off quickly, and therefore, the rods can be placed within 2 mm of the capsule even posteriorly near the rectum. CONCLUSIONS: Arrays of high-temperature rods can be employed for tissue ablation, while lower-temperature arrays could be used to produce hyperthermia in order to achieve synergism with adjuvant radiation therapy. The technique is applicable in an outpatient setting.

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Exposure to high concentrations of radon progeny (radon) produces lung cancer in both underground miners and experimentally exposed laboratory animals. To determine the risk posed by residential radon exposure, the authors performed a population-based, case-control epidemiologic study in Iowa from 1993 to 1997. Subjects were female Iowa residents who had occupied their current home for at least 20 years. A total of 413 lung cancer cases and 614 age-frequency-matched controls were included in the final analysis. Excess odds were calculated per 11 working-level months for exposures that occurred 5-19 years (WLM(5-19)) prior to diagnosis for cases or prior to time of interview for controls. Eleven WLM(5-19) is approximately equal to an average residential radon exposure of 4 pCl/liter (148 Bq/m3) during this period. After adjustment for age, smoking, and education, the authors found excess odds of 0.50 (95% confidence interval: 0.004, 1.81) and 0.83 (95% percent confidence interval: 0.11, 3.34) using categorical radon exposure estimates for all cases and for live cases, respectively. Slightly lower excess odds of 0.24 (95 percent confidence interval: -0.05, 0.92) and 0.49 (95 percent confidence interval: 0.03, 1.84) per 11 WLM(5-19) were noted for continuous radon exposure estimates for all subjects and live subjects only. The observed risk estimates suggest that cumulative ambient radon exposure presents an important environmental health hazard.

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We describe the first systematic survey of pathology laboratories serving Iowans to assess attitudes concerning assistance with cancer research efforts. Previous reports suggested that pathologists are reluctant to loan slides and/or paraffin tissue blocks for research purposes because of potential loss or damage, medicolegal concerns, or lack of compensation for time and effort spent in retrieving materials. In this study, we obtained survey responses from laboratory directors of 54 of the 56 pathology laboratories serving Iowans. The survey covered issues related to the availability of research materials, reimbursement for the retrieval of materials, and turnaround time for returning borrowed materials. Contrary to previous reports, we found that the laboratory directors surveyed were willing to loan slides and blocks for research purposes, provided that confidentiality is maintained, that the materials are handled properly and returned in a timely manner, and that compensation is provided.

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The authors describe a patient with a long-standing history of systemic lupus erythematosus and leukopenia who received multiple intermittent doses of recombinant granulocyte colony-stimulating factor (G-CSF) and who underwent splenectomy because of a clinical impression of sequestration of granulocytes by the spleen. Histologic evaluation of the spleen revealed marked granulocytic hyperplasia with an increase in immature myeloid precursors, morphologically indistinguishable from a myeloid leukemic infiltrate. A postsplenectomy bone marrow aspirate and biopsy revealed a normocellular bone marrow with active hematopoiesis and trilineage maturation. The bone marrow aspirate cultured cells showed no numeric or structural chromosomal abnormality. Extramedullary hematopoiesis after receipt of G-CSF was previously reported, but, to our knowledge, ours is the first report of morphologic changes virtually identical to a leukemic infiltrate in spleen after G-CSF treatment. We describe the histologic and immunohistochemical findings in the spleen, compare our observations with those of others reported in the literature, and postulate a possible mechanism for this phenomenon.

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STUDY OBJECTIVE: To describe the wide variation of histologic characteristics produced by electrosurgical burns. DESIGN: Retrospective analysis. SETTING: University-associated teaching hospital. SUBJECTS: Pigs and dogs. INTERVENTIONS: Various power settings were employed with both monopolar and bipolar electrodes to incur electrosurgical damage. Animals were followed for up to 96 hours after injury. MEASUREMENTS AND MAIN RESULTS: Histologic analysis yielded characteristics of electrosurgical damage including areas of complete necrosis and coagulation, perivascular changes, endothelial damage, and hyperchromic pyknotic nuclei. White cell infiltration was seen only at the margin of necrotic zones of coagulation. CONCLUSION: The wide spectrum of histology from electrosurgical burns is primarily a result of the area that is sampled. Surgeons should actively investigate any postsurgical complications involving electrosurgery to obtain a definitive cause.

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Reports suggest that it is possible and useful to classify T1 (Stage A) carcinomas of the urinary bladder into subgroups dependent on the depth of invasion as defined by the muscularis mucosae (MM). In an attempt to evaluate the reproducibility of these findings, we reviewed the slides from 77 cases of T1 bladder cancer diagnosed in 1983 in Iowa residents. The cases were identified through a statewide cancer registry. Slides and pathology reports were obtained from the original laboratories. Two pathologists independently evaluated each case, most (74 cases) of which were transurethral resections, for the presence or absence of MM and three levels of invasion (lamina propria, MM, and submucosa). Disagreements were resolved by simultaneous review resulting in a consensus diagnosis. Because of the population-based source, tissue had been obtained by multiple urologists and processed in multiple laboratories, resulting in noticeable variation in quality of material. Interobserver agreement for the level of invasion was poor between the two pathologists (kappa = 0.22; 95% C.I. = 0.08-0.36). Consensus resulted in 34 cases (44.2%) invasive to the lamina propria, 23 (29.9%) to the MM, and 11 (14.3%) to the submucosa. The level was indeterminate in nine (11.7%). All of the 77 cases were followed until death or 1993-95, with 57 patients dying during this interval. There were no significant differences in survival for each level of invasion (lamina propria, MM, submucosa) and the indeterminate cases, as determined by either consensus or individual observer evaluation. Our findings suggest that microstaging of early invasive bladder cancer is technically difficult and, at least in cases derived from various urologists and laboratories, does not yield a prognostically significant separation.

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Second malignant neoplasms were evaluated among 32,251 women with ovarian cancer, including 4,402 10-year survivors, within the nine population-based registries of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (1973-1992) and the Connecticut Tumor Registry (1935-1972). Overall, 1,296 second cancers occurred against 1,014 expected [observed/expected (O/E), 1.28; 95% confidence interval (CI), 1.21-1.35]. Sites contributing 25 or more excess cancers included leukemia (O/E, 4.17; O, 111; 95% CI, 3.43-5.03) and malignancies of colon (O/E, 1.33; O, 188; 95% CI, 1.15-1.54), rectum (O/E, 1.43; O, 76; 95% CI, 1.13-1.79), breast (O/E, 1.18; O, 404; 95%, CI 1.07-1.30), and bladder (O/E, 2.07; O, 65; 95% CI, 1.59-2.63). Ocular melanoma (O/E, 4.45; O, 8; 95% CI, 1.92-8.77) was also significantly increased. Second cancer risk was high during all follow-up intervals, and cumulative risk at 20 years was 18.2%, compared with a population expected risk of 11.5%. Statistically significant relationships existed between serous adenocarcinoma of the ovary and breast cancer (O/E, 1.29; 95% CI, 1.06-1.56) and mucinous ovarian adenocarcinoma and rectal cancer (OE/E, 1.95; 95% CI, 1.09-3.22). Secondary leukemia appeared linked with antecedent chemotherapy, whereas radiotherapy was associated with cancers of connective tissue, bladder, and possibly pancreas. Genetic and reproductive factors predisposing to ovarian cancer may have contributed to the elevated risk of breast and colorectal neoplasms and possibly ocular melanoma. Thus, excess malignancies following ovarian cancer represent complications of curative therapies and/or underlying susceptibility states that have etiological and clinical ramifications.

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Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant mesenchymal tumor characterized by local invasion and recurrence. Fewer than 50 cases have been reported in the pediatric population. We reviewed our experience in the treatment of children with DFSP to define clinical and pathological characteristics. Seven pediatric patients were included in the study (mean age, 11.7 yr). Clinically, the tumors were described as firm nodules fixed to the skin but mobile over the deep fascia, with slow, progressive growth. Diagnosis was made by excisional biopsy in 6 patients and punch biopsy in 1 patient. Six of 7 patients had positive margins after the diagnostic procedure. Pathologically, diagnosis was based on histology, with confirmation by CD34 staining. Definitive surgical therapy consisted of wide local excision (1-3 cm margins) in 5 patients and Moh's micrographic resection in 2 patients. There have been no local recurrences or distant metastases, with a mean follow-up of 15.1 months. Pathological and clinical diagnostic criteria for the pediatric population are reviewed, and treatment options are discussed.

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BACKGROUND: Site-specific cancer frequencies and incidence rates are reported regularly by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, but not by histologic type within site. This report reviews data for 160,977 histologically or cytologically confirmed invasive and in situ cancers of the female genital tract. METHODS: Data were supplied by the SEER program for histologically confirmed cases of uterine corpus, uterine cervix, ovary, vulva, vagina, fallopian tube, and placental cancers diagnosed between 1973 and 1987. Histologic types were reviewed for race, age at diagnosis, incidence, stage, and survival. RESULTS: There were 89,943 invasive and 71,034 in situ neoplasms. Squamous carcinoma was the most common invasive malignancy of the cervix (77.1%), vulva (74.4%), and vagina (70.8%). Adenocarcinoma was the most frequent malignancy in the uterine corpus (81.5%) and ovary (86.6%), with these percentages reaching 91.6% for corpus and 86.9% for ovary if adenosquamous carcinoma and adenocarcinoma with squamous metaplasia are included. Cervical carcinoma in situ accounted for 91.0% of all in situ cancers. In situ cancers made up 78.5% of all cervical cancers, 35.1% of vaginal cancers, and 50.4% of vulvar cancers. CONCLUSIONS: There are dominant histologic groups in each female genital tract site that are largely responsible for incidence and survival statistics. Within the groups, however, there are subtypes with differing features. Epidemiologic studies may provide more definite information by considering the effect of these subtypes in examining risk factors.

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This article describes a case of a laparoscopic injury and the ensuing litigation. Data from the hospital report and the testimony of witnesses are presented. In the next issue of this Journal, the results of the jury finding will be presented as Part II.

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Atheroemboli-associated inflammatory type polyps localized to a portion of the sigmoid colon occurred in a 68-year-old diabetic man presenting with a 2-year history of bloody diarrhea and abdominal pain. The patient underwent segmental resection of the sigmoid colon. The specimen contained 15 polyps ranging from 0.3 to 1.9 cm in greatest dimension, localized to an 8-cm length of sigmoid colon. The polyps had an edematous submucosa with a superficially ulcerated mucosa. Microscopically, arterioles within the submucosa of the polyps contained organized atheroemboli. The overlying mucosa was largely replaced by granulation tissue, with foci of coagulation necrosis present in residual mucosa. The remainder of the bowel was unremarkable. The histologic diagnosis of atheroembolization to the gastrointestinal tract is difficult, requiring the inclusion of submucosa with atheroemboli in the biopsy tissue. Ischemic ulcers and erosions as well as inflammatory polyps related to atheroemboli may require deeper biopsy for etiologic diagnosis.

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We tested a newly developed bipolar sphincterotome. Monopolar and bipolar sphincterotomes were employed to cut small bowel smoothly and hemostatically. The bipolar instrument required 17.1 watts while the monopolar required 29.2 watts; these values are significantly different at p = 0.005. Bipolar sphincterotomies were performed via open surgical access on eight dogs. The animals were allowed to recover and were followed for 6 weeks. There was no evidence of stenosis or common duct dilation at autopsy, and serum alkaline phosphatase and bilirubin were within normal limits. Both sphincterotomes were used to cut tissue in vitro and histological examination displayed no evidence of thermal injury at the return electrode site of the bipolar sphincterotome. The lower power levels required by the bipolar sphincterotome may decrease procedure complications.

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We report the case of a 45-year-old burned man (55% total body surface area full-thickness burn) who developed symptomatic cytomegalovirus infection during cyclosporine (CSA) therapy (3 mg/kg orally) for skin transplantation. During the sixth hospital week the patient developed signs compatible with CMV infection, and CMV was recovered from the urine and sputum. Examination of skin biopsy specimens from the transplanted cadaver allograft revealed inclusion bodies compatible with CMV infection, and CMV antigens were detected by immunohistochemical testing. The CMV infection of the skin was confirmed by recovery of infectious virus and by detection of CMV nucleic acids using in situ hybridization with a biotinylated HCMV DNA probe. Restriction enzyme analysis of a urine CMV isolate and two isolates from skin demonstrated differences in DNA patterns, suggesting that the patient was infected simultaneously with two different CMV strains.

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A slide review of diagnostic pathologic tissue obtained from 364 bladder cancer cases, identified through the Iowa Surveillance, Epidemiology, and End Results (SEER) Program in 1983, classified 97 (26.6%) of these cases as invasive bladder cancers. These findings contrasted sharply with the Iowa SEER Program classification that coded 289 (79.4%) of these cases as invasive bladder cancers. These results were validated further by the hazard ratio of 4.54 (95% confidence interval, 2.57 to 8.03) among invasive relative to noninvasive bladder cancer cases when the slide review findings were used. In contrast, the hazard ratio was only 1.70 (95% confidence interval, 0.76 to 3.79) when the Iowa SEER Program findings were used. The traditional method used by the National Cancer Institute's SEER Program to deal with this problem is described and its implications are discussed.

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The energy required and tissue damage in bipolar and monopolar polypectomy snares were compared in a canine model. The bipolar snare required an average of 34 joules of energy, whereas the monopolar snare required 228 joules to cut the same diameter of gastric mucosa tended into a polypoid structure (p = 0.0005). The reduced energy delivered to the tissue from the bipolar procedure resulted in only 32% average depth of damage to the underlying gastric wall, whereas the monopolar procedure caused an average 69% (p = 0.001). Surgically created polyps required 247 joules and 69 joules for corresponding monopolar and bipolar polypectomy (p = 0.001). The decreased energy required and the correspondingly reduced damage caused to the underlying bowel wall by the bipolar snare should reduce the incidence of perforation and post-polypectomy syndrome. The bipolar snare completes a local circuit about the snare, eliminating the return electrode and, consequently, the possibility of any return electrode burns. The bipolar snare thus provides an added safety margin during polypectomy.

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The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed.

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Antigen receptor gene rearrangement studies have been applied to gastrointestinal (GI) lymphoid proliferations in only a limited number of cases, and their use and contribution to the diagnosis and characterization of GI lymphomas is unknown. We retrospectively studied 17 cases of primary GI lymphoma using fresh/frozen tissue with a combination of immunophenotypic and genotypic techniques. The vast majority of the neoplasms were B-cell lymphomas (88%) with rare T-cell tumors. The most common B-cell immunophenotype was IgM-kappa (40%), while five of the B-cell lymphomas (33%) lacked surface light chain immunoglobulin. Immunophenotypic evidence of histiocytic differentiation was not identified. Clonality was confirmed in 59% (10/17) of the neoplasms by immunophenotyping and 88% (15/17) by antigen receptor gene rearrangement studies. All of the 15 B-cell lymphomas (100%) demonstrated clonally rearranged immunoglobulin gene rearrangement. The two lymphomas with T-cell immunophenotypes did not demonstrate T-cell receptor beta-chain gene rearrangement. Antigen receptor gene rearrangement data can be useful and may even be necessary in certain cases for the proper classification and/or diagnosis of GI lymphoid proliferations.

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