material. Indeed, Tawfik et al. [37] have described the use of WSI on cell blocks prepared from residual gynecological Pap samples. Based on 1,110 Pap test slides prepared and analyzed using WSI, the sensitivity reported by these authors was comparable to standard LBC-prepared slides and highly specific for identifying low-grade intraepithelial lesions and high-grade squamous intraepithelial lesions. Given that cell blocks are somewhat comparable to surgical pathology specimens, they may have potential for WSI diagnostic use.
Tissue microarrays (TMAs), a high-throughput, faster, and more economical method for comparative IHC or molecular analyses, are generally derived from surgical pathology specimens. They are constructed by removing cylindrical cores of tissue from separate “donor” FFPE blocks, which are then assembled together in a single “recipient” paraffin block. Since cytology microarrays [38] have been constructed largely from cells, they may not afford the same advantages associated with TMAs derived from FFPE blocks. With adequately cellular cell blocks, however, there is an opportunity to create cytology-derived FFPE TMAs [39] and accordingly perform high-throughput analyses on cytology specimens, which may sometimes represent the only sample available from patients.
Clinicians and cytologists are sometimes faced with cytology samples that are non-diagnostic or inadequate for ancillary testing, which hinders appropriate patient management. This may result from various factors, including the nature of the lesion targeted for FNA, operator skill, and inadequate cellularity on the cell block. To improve the diagnostic yield, manufacturers of needles, especially for endoscopic ultrasound-guided procedures, have developed larger-gauge needles with new needle tip designs that extract “micro-cores.” The procedure and sample represent a hybrid – the motion to obtain the tissue fragments is the same as FNA biopsies, yet the needle size and design produce a “micro-core.” These samples typically contain mini tissue fragments in a core-shaped fragment of partially clotted blood. These FNA-derived micro-core biopsies represent a cross-roads between cytology and histology. There is some debate regarding the best method and laboratory ideally equipped to manage such specimens – either as cytology cell blocks or as histology biopsies. Since these samples, in addition to having visible tissue fragments, also contain cells dispersed in blood and liquid media, they are better managed by cytology procedures that will capture all of the cells by centrifugation and then allow them to be processed as a cell block. The larger fragments that can be easily handled with forceps can be placed directly into a cassette in a manner similar to grossing core biopsies or combined in the cell block. In cases where two blocks are created, one using centrifugation and the other without centrifugation, they are still best handled by the same (cytology) laboratory and assigned the same laboratory accessioning number to avoid discrepant reporting and redundant ancillary testing. Unfortunately, there is no standardized protocol to manage these newer specimens. With suboptimal management of such specimens and lack of communication concerning the added value of capturing more cells within a cell block, cytology risks losing these specimens to surgical pathology, which may result in loss of the important background cellular component of the sample, inferior quality of the final product, and thus substandard quality of the final diagnosis and patient care.
Conclusion
A plethora of old and new methods are available for routinely preparing cell blocks in cytology practice. However, to date no single method has been widely adopted by all cytology laboratories. Several steps can be undertaken to enhance the cellularity of cell blocks, some which occur at the point-of-care, including better operator skill, enhanced specimen adequacy, proper triage, and dedicated passes for cell block [19], and others which can be implemented in cytology and histology laboratories. Despite ongoing development of new and improved cell block techniques, the production and optimal utilization of cell blocks remains a work in progress that requires standardization. This is important because without assured adequate cellularity in cell blocks, the tendency will be to continually move towards competing specimens such as core-needle biopsies or hybrid cytology-histology samples.
References
1Xing W, Hou AY, Fischer A, Owens CL, Jiang Z: The Cellient automated cell block system is useful in the differential diagnosis of atypical glandular cells in Papanicolaou tests. Cancer Cytopathol 2014;122:8–14.
2Calabretto ML, Giol L, Sulfaro S: Diagnostic utility of cell-block from bronchial washing in pulmonary neoplasms. Diagn Cytopathol 1996;15:191–192.
3Collins GR, Thomas J, Joshi N, Zhang S: The diagnostic value of cell block as an adjunct to liquid-based cytology of bronchial washing specimens in the diagnosis and subclassification of pulmonary neoplasms. Cancer Cytopathol 2012;120:134–141.
4Mathew EP, Nair V: Role of cell block in cytopathologic evaluation of image-guided fine needle aspiration cytology. J Cytol 2017;34:133–138.
5Bahrenburg L: On the diagnostic results of the microscopical examination of the ascitic fluid in two cases of carcinoma involving the peritoneum. Cleve Med Gazz 1896;11:274–278.
6Saqi A: The state of cell blocks and ancillary testing: past, present, and future. Arch Pathol Lab Med 2016;140:1318–1322.
7Crapanzano JP, Heymann JJ, Monaco S, Nassar A, Saqi A: The state of cell block variation and satisfaction in the era of molecular diagnostics and personalized medicine. Cytojournal 2014;11:7.
8Varsegi GM, Shidham V: Cell block preparation from cytology specimen with predominance of individually scattered cells. J Vis Exp 2009;29:1316.
9La Fortune KA, Randolph ML, Wu HH, Cramer HM: Improvements in cell block processing: the cell-gel method. Cancer 2017;125:267–276.
10Kulkarni MB, Desai SB, Ajit D, Chinoy RF: Utility of the thromboplastin-plasma cell-block technique for fine-needle aspiration and serous effusions. Diagn Cytopathol 2009;37:86–90.
11Sung S, Sireci A, Remotti H, Hodel V, Mansukhani M, Fernandes H, Saqi A. Plasma Thrombin Cell Blocks: Potential Source of DNA Contamination. Cancer Cytopathology. In press.
12Zanini C, Gerbaudo E, Ercole E, Vendramin A, Forni M: Evaluation of two commercial and three home-made fixatives for the substitution of formalin: a formaldehyde-free laboratory is possible. Environ Health 2012;11:59.
13Cahill L: Best practices in cytopathology for cell blocks survey results. ASC Bulletin, American Society of Cytopathology. Volume LI, Number 2, 2014.
14Yang GC, Wan LS, Papellas J, Waisman J: Compact cell blocks. Use for body fluids, fine needle aspirations and endometrial brush biopsies. Acta Cytol 1998;42:703–706.
15Yung RC,
