John H. Crosby

Primary leiomyosarcomas of the gastrointestinal tract in the post–gastrointestinal stromal tumor era

Most mesenchymal neoplasms of the gastrointestinal tract are currently classified as gastrointestinal stromal tumors (GIST). Gastrointestinal stromal tumors are diagnosed by immunopositivity for CD117, CD34, and DOG1.1, with or without molecular analyses. According to the World Health Organization classification, the diagnosis of primary leiomyosarcomas of the gastrointestinal tract is so rare that there are no significant data on demographic, clinical, or gross features of this tumor. A comprehensive literature search was performed to identify gastrointestinal leiomyosarcomas. Searches were limited to the past 12 years because definitive tools to differentiate leiomyosarcomas from GIST were introduced in the late 1990s. Cases were included only if convincing data were presented. Six cases of esophageal leiomyosarcoma and 5 cases of gastric leiomyosarcoma were confirmed. Furthermore, 26 cases of leiomyosarcoma of the small bowel, 11 cases of the colon, and 8 cases arising in the rectum were identified. Finally, 28 cases of infantile and adolescent leiomyosarcoma were reviewed. Although survival analysis is precluded by small case numbers and limited survival data availability, the trend identifies that increased size and mitotic activity portends to a worse prognosis in small bowel leiomyosarcomas. Colonic leiomyosarcomas appear to be aggressive tumors, regardless of tumor size and mitotic activity. Rectal leiomyosarcomas present as smaller tumors with favorable prognosis. Leiomyosarcomas in post-GIST era are rare tumors of the gastrointestinal tract with distinctive clinicopathologic characteristics. Owing to different treatment options, it is necessary to accurately differentiate these from GIST, using a combination of histologic appearance, presence of smooth muscle antigens, and absence of specific GIST immunomarkers.

Risk factors for bladder cancer in a cohort exposed to aromatic amines

Occupational and nonoccupational risk factors for bladder cancer were analyzed in a cohort of 1385 workers with known exposure to a potent bladder carcinogen, beta‐naphthylamine. Bladder cancer was approximately seven times (95% confidence interval [CI] = 3.9, 12.4) more likely in exposed rather than nonexposed individuals, yet, otherwise, the groups were generally similar in other exogenous or hereditary risk factors. A total of 13 cases of bladder cancer were identified. After the first year of a screening program involving 380 members of the cohort, 9 of the 13 cases of bladder cancer and 36 persons with atypical bladder cytology, histology, or pathology were compared with 335 noncases for distributions of different variables. Occupational variables were significant in a multivariate model that controlled for age, cigarette smoking history, and source of drinking water. The estimated odds ratio for the association for bladder cancer and the duration of employment, when controlling of these other variables, is 4.3 (95% CI = 1.8, 10.3). In addition to the occupational factors, age was significant in the multivariate analysis. Other potential risk factors, such as consumption of coffee or artificial sweeteners, use of phenacetin, or decreased use of vitamin A were not found to be significantly different in cases and noncases.

The cytologic findings in choroid plexus carcinoma: Report of a case with differential diagnosis

Choroid plexus carcinoma is a rare tumor of the choroid plexus that shows frank cytologic features of malignancy including frequent mitoses, increased cellularity, nuclear pleomorphism, loss of papillary architecture, and necrosis. It occurs predominantly in the pediatric population and is associated with a poor prognosis. We report the cerebrospinal fluid and intraoperative squash preparation cytologic findings of a case of choroid plexus carcinoma arising in the lateral ventricle of a 16‐year‒old girl who developed tumor recurrence in cerebrospinal fluid 6 years after initial resection. To the best of our knowledge, there are only a few reports in the English literature describing the cytologic features of choroid plexus carcinoma. Relevant differentials and the usefulness of ancillary studies in diagnosis are also discussed. Diagn. Cytopathol. 2012.

Interobserver and intraobserver variability in the calculation of the lipid-laden macrophage index: Implications for its use in the evaluation of aspiration in children

The lipid‐laden macrophage index (LLMI) is a semiquantitative test used to evaluate aspiration in children. We assessed the reliability and reproducibility of LLMI by calculating interobserver and intraobserver variability among pathologists, with and without expertise in cytopathology. Forty‐nine bronchoalveolar washes/lavages were blindly reviewed by four reviewers and assigned an LLMI. Three pathologists (two cytopathologists, one pathology fellow) reviewed slides twice and one cytotechnologist reviewed them once. Intraclass correlation coefficient (ICC) with 95% confidence interval (C.I.) was used to measure overall intraobserver and interobserver agreement. Interobserver agreement was also calculated separately for each pair of reviewers. ICC values did not indicate an acceptable level of interobserver agreement among pathologists, with (ICC = 0.67, 95% C.I.: 0.56–0.77) and without (ICC = 0.77, 95% C.I.: 0.61–0.84) the cytotechnologist included in the analysis. An ICC of 0.84 (95% C.I.: 0.78–0.89) indicated an acceptable level of intraobserver agreement among pathologists. When calculated separately for each pair of reviewers, all but two ICC values for interobserver agreement were less than 0.75 (the minimally acceptable value for a reliable clinical measurement), and the lower confidence limit of each of the 95% C.I. was far below the 0.75 cutoff. Using Lins coefficient, intraobserver variability was only acceptable for two pathologists. Our study highlights the lack of precision and subjectivity of the LLMI, as well as the significant inter and intraobserver bias that may occur among experienced and inexperienced pathologists, and cytotechnologists. Clinicians and cytopathologists alike should be mindful of this potential pitfall and interpret LLMI scores with caution. Diagn. Cytopathol. 2010;38:861–865.

Liquid-based Pap Smears as a Source of RNA for Gene Expression Analysis

The Papanicolaou smear has contributed to a decrease in cervical cancer rates in populations that receive regular screening. However, treatment of women with mildly abnormal cells is problematic because the majority of these women do not develop neoplasia. Thus, new techniques for identification of truly precancerous cells are needed. Characterization of cellular gene expression patterns is now possible through microarray techniques that survey the expression of large numbers of genes simultaneously. Here we have assessed the feasibility of combining new microscopic and molecular technologies to determine gene expression patterns in cervical intraepithelial neoplasia grade 3 cells recovered from liquid cytology-based Papanicolaou smear slides. Laser capture microdissection was used to retrieve cervical cells from ThinPrep prepared slides. The quality of RNA recovered from these cells proved suitable for reverse transcription polymerase chain reaction and for T7 RNA polymerase-based linear amplification of messenger RNA. We developed an optimized RNA amplification protocol that permitted microarray gene expression profiling in samples of as few as 20 cervical cells. This approach combining laser capture microdissection, linear RNA amplification, and microarray gene expression analysis will enable comparison of gene expression patterns between cytologically abnormal and normal cells taken from a single slide and may assist in the differential diagnosis of histologically difficult cases.