Abstract
Fine-needle aspiration (FNA) cytology is a safe, rapid, and cost-effective diagnostic procedure that is widely used for evaluating lesions at virtually any site in the human body. In order to provide valuable information that enables oncologists to make optimal therapeutic decisions, the use of ancillary studies as diagnostic adjuncts in cytology is often required. Ancillary studies allow us to document a lesion to be neoplastic or nonneoplastic, benign or malignant, primary or metastatic malignancy, and the possible primary origin of a metastatic neoplasm. In addition, some tests may provide prognostic and predictive information and assess eligibility of the patient for certain targeted therapies. Immunocytochemistry is the most commonly used ancillary method on cytology specimens; flow cytometric immunophenotyping is a very useful adjunct for the diagnosis of hematopoietic neoplasms. Recently, advances in molecular biology and biomedical research have had a major impact on the practice of pathology including cytology. As a result, cytogenetic and molecular studies have been increasingly applied in daily practice. It is noteworthy that ancillary test results should be evaluated in concert with cytologic features, clinical and radiologic findings to avoid erroneous interpretation. This chapter outlines the utility of immunocytochemistry, flow cytometric, cytogenetic, and molecular studies in the cytologic diagnosis of neoplastic lesions including their indications, sample requirements, reliability and limitations.
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Chu P, Wu E, Weiss LM (2000) Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 13:962–972
Gyure KA, Morrison AL (2000) Cytokeratin 7 and 20 expression in choroid plexus tumors: utility in differentiating these neoplasms from metastatic carcinomas. Mod Pathol 13:638–643
Wang NP, Zee S, Zarbo RJ et al (1995) Coordinate expression of cytokeratins 7 and 20 defines unique subsets of carcinomas. Appl Immunohistochem 3:99–107
Moldvay J, Jackel M, Bogos K et al (2004) The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathol Oncol Res 10:85–88
Dabbs DJ, Abendroth CS, Grenko RT et al (1997) Immunocytochemistry on the Thinprep processor. Diagn Cytopathol 17:388–392
Guiter GE, Gatscha RM, Zakowski MF (1999) ThinPrep vs. conventional smears in fine-needle aspirations of sarcomas: a morphological and immunocytochemical study. Diagn Cytopathol 21:351–354
Leung SW, Bedard YC (1996) Immunocytochemical staining on ThinPrep processed smears. Mod Pathol 9:304–306
Mehta P, Battifora H 1993 How to do multiple immunostains when only one tissue slide is available. The “peel and stick” method. Appl Immunohistochem 1:297–298
Miller RT, Kubier P (2002) Immunohistochemistry on cytologic specimens and previously stained slides (when no paraffin block is available). J Histotechnology 25:251–257
Sherman ME, Jimenez-Joseph D, Gangi MD (1994) Immunostaining of small cytologic specimens. Facilitation with cell transfer. Acta Cytol 38:18–22
Gong Y, Joseph T, Sneige N (2005) Validation of commonly used immunostains on cell-transferred cytologic specimens. Cancer 105:158–164
Wolff AC, Hammond ME, Schwartz JN et al (2007) American society of clinical oncology/college of american pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145
Goldstein NS, Ferkowicz M, Odish E et al (2003) Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol 120:86–92
Nizzoli R, Bozzetti C, Crafa P et al (2003) Immunocytochemical evaluation of HER-2/neu on fine-needle aspirates from primary breast carcinomas. Diagn Cytopathol 28:142–146
Gong Y, Symmans WF, Krishnamurthy S et al (2004) Optimal fixation conditions for immunocytochemical analysis of estrogen receptor in cytologic specimens of breast carcinoma. Cancer 102:34–40
Gong Y, Han E, Guo M et al (2010) Stability of estrogen receptor status in breast carcinoma: a comparison between primary and metastatic tumors with regard to disease course and intervening systemic therapy. Cancer 117(4):705–713
Jimenez-Heffernan JA, Vicandi B, Lopez-Ferrer P et al (2001) Value of fine needle aspiration cytology in the initial diagnosis of Hodgkin’s disease. Analysis of 188 cases with an emphasis on diagnostic pitfalls. Acta Cytol 45:300–306
Gong Y, Caraway N, Gu J et al (2003) Evaluation of interphase fluorescence in situ hybridization for the t(14;18)(q32;q21) translocation in the diagnosis of follicular lymphoma on fine-needle aspirates: a comparison with flow cytometry immunophenotyping. Cancer 99:385–393
Katz RL (1991) Cytologic diagnosis of leukemia and lymphoma values and limitations. Clin Lab Med 11:469–499
Damle RN, Wasil T, Fais F et al (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 94:1840–1847
Del Poeta G, Maurillo L, Venditti A et al (2001) Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 98:2633–2639
Verstovsek G, Chakraborty S, Ramzy I et al (2002) Large B-cell lymphomas: fine-needle aspiration plays an important role in initial diagnosis of cases which are falsely negative by flow cytometry. Diagn Cytopathol 27:282–285
Chen HI, Akpolat I, Mody DR et al (2006) Restricted kappa/lambda light chain ratio by flow cytometry in germinal center B cells in hashimoto thyroiditis. Am J Clin Pathol 125:42–48
Jorgensen JL (2005) State of the art symposium: flow cytometry in the diagnosis of lymphoproliferative disorders by fine-needle aspiration. Cancer 105:443–451
Beck RC, Stahl S, O’Keefe CL et al (2003) Detection of mature T-cell leukemias by flow cytometry using anti-T-cell receptor V beta antibodies. Am J Clin Pathol 120:785–794
Morice WG, Kimlinger T, Katzmann JA et al (2004) Flow cytometric assessment of TCR-Vbeta expression in the evaluation of peripheral blood involvement by T-cell lymphoproliferative disorders: a comparison with conventional T-cell immunophenotyping and molecular genetic techniques. Am J Clin Pathol 121:373–383
Galindo LM, Garcia FU, Hanau CA et al (2000) Fine-needle aspiration biopsy in the evaluation of lymphadenopathy associated with cutaneous T-cell lymphoma (mycosis fungoides/sezary syndrome). Am J Clin Pathol 113:865–871
Katz RL, Hirsch-Ginsberg C, Childs C et al (1991) The role of gene rearrangements for antigen receptors in the diagnosis of lymphoma obtained by fine-needle aspiration. A study of 63 cases with concomitant immunophenotyping. Am J Clin Pathol 96:479–490
Barr FG (2004) Diagnostic applications of chromosomal translocations in bone and soft tissue sarcomas. Expert Rev Mol Diagn 4:579–582
Beatty BG, Bryant R, Wang W et al (2004) HER-2/neu detection in fine-needle aspirates of breast cancer: fluorescence in situ hybridization and immunocytochemical analysis. Am J Clin Pathol 122:246–255
Gu M, Ghafari S, Zhao M (2005) Fluorescence in situ hybridization for HER-2/neu amplification of breast carcinoma in archival fine needle aspiration biopsy specimens. Acta Cytol 49:471–476
Moore JG, To V, Patel SJ et al (2000) HER-2/neu gene amplification in breast imprint cytology analyzed by fluorescence in situ hybridization: direct comparison with companion tissue sections. Diagn Cytopathol 23:299–302
Tomas AR, Praca MJ, Fonseca R et al (2004) Assessing HER-2 status in fresh frozen and archival cytological samples obtained by fine needle aspiration cytology. Cytopathology 15:311–314
Sauter G, Lee J, Bartlett JM et al (2009) Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 27:1323–1333
Gong Y, Booser DJ, Sneige N (2005) Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma. Cancer 103:1763–1769
Tapia C, Savic S, Wagner U et al (2007) HER2 gene status in primary breast cancers and matched distant metastases. Breast Cancer Res 9:R31
Xiao C, Gong Y, Han EY et al (2011) Stability of HER2-positive status in breast carcinoma: a comparison between primary and paired metastatic tumors with regard to the possible impact of intervening trastuzumab treatment. Ann Oncol 22:1547–1553
Gong Y, Gilcrease M, Sneige N (2005) Reliability of chromogenic in situ hybridization for detecting HER-2 gene status in breast cancer: comparison with fluorescence in situ hybridization and assessment of interobserver reproducibility. Mod Pathol 18:1015–1021
Gong Y, Sweet W, Duh YJ et al (2009) Chromogenic in situ hybridization is a reliable method for detecting HER2 gene status in breast cancer: a multicenter study using conventional scoring criteria and the new ASCO/CAP recommendations. Am J Clin Pathol 131:490–497
Gong Y, Sweet W, Duh YJ et al (2009) Performance of chromogenic in situ hybridization on testing HER2 Status in breast carcinomas with chromosome 17 polysomy and equivocal (2+) herceptest results: a study of two institutions using the conventional and new ASCO/CAP scoring criteria. Am J Clin Pathol 132:228–236
Tanner M, Gancberg D, Di Leo A et al (2000) Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am J Pathol 157:1467–1472
Kim GY, Oh YL (2004) Chromogenic in situ hybridization analysis of HER-2/neu status in cytological samples of breast carcinoma. Cytopathology 15:315–320
Lin F, Shen T, Prichard JW (2005) Detection of Her-2/neu oncogene in breast carcinoma by chromogenic in situ hybridization in cytologic specimens. Diagn Cytopathol 33:376–380
Vocaturo A, Novelli F, Benevolo M et al (2006) Chromogenic in situ hybridization to detect HER-2/neu gene amplification in histological and ThinPrep-processed breast cancer fine-needle aspirates: a sensitive and practical method in the trastuzumab era. Oncologist 11:878–886
Alkan S, Lehman C, Sarago C et al (1995) Polymerase chain reaction detection of immunoglobulin gene rearrangement and bcl-2 translocation in archival glass slides of cytologic material. Diagn Mol Pathol 4:25–31
Belaud-Rotureau MA, Parrens M, Carrere N et al (2007) Interphase fluorescence in situ hybridization is more sensitive than BIOMED-2 polymerase chain reaction protocol in detecting IGH-BCL2 rearrangement in both fixed and frozen lymph node with follicular lymphoma. Hum Pathol 38:365–372
Buno I, Nava P, Alvarez-Doval A et al (2005) Lymphoma associated chromosomal abnormalities can easily be detected by FISH on tissue imprints. An underused diagnostic alternative. J Clin Pathol 58:629–633
Kishimoto K, Kitamura T, Fujita K et al (2006) Cytologic differential diagnosis of follicular lymphoma grades 1 and 2 from reactive follicular hyperplasia: cytologic features of fine-needle aspiration smears with Pap stain and fluorescence in situ hybridization analysis to detect t(14;18)(q32;q21) chromosomal translocation. Diagn Cytopathol 34:11–17
Richmond J, Bryant R, Trotman W et al (2006) FISH detection of t(14;18) in follicular lymphoma on papanicolaou-stained archival cytology slides. Cancer 108:198–204
Ahmed SM, Salgia R (2006) Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer. Respirology 11:687–692
Billah S, Stewart J, Staerkel G et al (2011) EGFR and KRAS mutations in lung carcinoma: molecular testing by using cytology specimens. Cancer cytopathol 119:111–117
Kulmala SM, Syrjanen S, Shabalova I et al (2004) Human papillomavirus testing with the hybrid capture 2 assay and PCR as screening tools. J Clin Microbiol 42:2470–2475
Day SP, Hudson A, Mast A et al (2009) Analytical performance of the investigational use only cervista HPV HR test as determined by a multi-center study. J Clin Virol 45(1):S63–S72
Arentsen HC, de la Rosette JJ, de Reijke TM et al (2007) Fluorescence in situ hybridization: a multitarget approach in diagnosis and management of urothelial cancer. Expert Rev Mol Diagn 7:11–19
Assersohn L, Gangi L, Zhao Y et al (2002) The feasibility of using fine needle aspiration from primary breast cancers for cDNA microarray analyses. Clin Cancer Res 8:794–801
Ayers M, Symmans WF, Stec J et al (2004) Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 22:2284–2293
Pusztai L, Ayers M, Stec J et al (2003) Gene expression profiles obtained from fine-needle aspirations of breast cancer reliably identify routine prognostic markers and reveal large-scale molecular differences between estrogen-negative and estrogen-positive tumors. Clin Cancer Res 9:2406–2415
Sotiriou C, Powles TJ, Dowsett M et al (2002) Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer. Breast Cancer Res 4:R3
Symmans WF, Ayers M, Clark EA et al (2003) Total RNA yield and microarray gene expression profiles from fine-needle aspiration biopsy and core-needle biopsy samples of breast carcinoma. Cancer 97:2960–2971
Gong Y, Yan K, Lin F et al (2007) Determination of oestrogen-receptor status and ERBB2 status of breast carcinoma: a gene-expression profiling study. Lancet Oncol 8:203–211
Cheung CC, Carydis B, Ezzat S et al (2001) Analysis of ret/PTC gene rearrangements refines the fine needle aspiration diagnosis of thyroid cancer. J Clin Endocrinol Metab 86:2187–2190
Cohen Y, Rosenbaum E, Clark DP et al (2004) Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules. Clin Cancer Res 10:2761–2765
Gustafson KS, Furth EE, Heitjan DF et al (2004) DNA methylation profiling of cervical squamous intraepithelial lesions using liquid-based cytology specimens: an approach that utilizes receiver-operating characteristic analysis. Cancer 102:259–268
Pu RT, Laitala LE, Alli PM et al (2003) Methylation profiling of benign and malignant breast lesions and its application to cytopathology. Mod Pathol 16:1095–1101
Pu RT, Laitala LE, Clark DP (2006) Methylation profiling of urothelial carcinoma in bladder biopsy and urine. Acta Cytol 50:499–506
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Gong, Y. (2014). Ancillary Studies on Neoplastic Cytologic Specimens. In: Nayar, R. (eds) Cytopathology in Oncology. Cancer Treatment and Research, vol 160. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38850-7_2
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DOI: https://doi.org/10.1007/978-3-642-38850-7_2
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