High neutrophil incorporation rate of ascitic fluid cytology as an indicator of cancerous ascites

Fujimori,Misa; Tsuchihashi,Haruyo; Fujimori,Shumpei; Kobayashi,Sayaka; Nomi,Yuri; Hirato,Junko; Oyama,Tetsunari; Fukuda,Toshio; Saio,Masanao

doi:10.3892/ijo.2020.5118

High neutrophil incorporation rate of ascitic fluid cytology as an indicator of cancerous ascites

Authors:
- Misa Fujimori
- Haruyo Tsuchihashi
- Shumpei Fujimori
- Sayaka Kobayashi
- Yuri Nomi
- Junko Hirato
- Tetsunari Oyama
- Toshio Fukuda
- Masanao Saio
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Affiliations: Laboratory of Histopathology and Cytopathology, Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma 371‑8514, Japan, Department of Pathology, Public Tomioka General Hospital, Tomioka, Gunma 370‑2316, Japan, Department of Pathology, Gunma University Hospital, Maebashi, Gunma 371‑8514, Japan
Published online on: September 3, 2020 https://doi.org/10.3892/ijo.2020.5118
Pages: 1214-1222

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Abstract

The cell‑in‑cell phenomenon (CiCP) involves the incorporation of a viable cell by other cells (host cells) and includes two concepts: Emperipolesis and cell cannibalism. The former involves the incorporation of hematopoietic cells as the incorporated cells, while the latter involves cell incorporation by tumor cells as host cells. A total of 239 peritoneal cavity fluid cytology specimens were evaluated for CiCP and the number of singly detectable nuclei (SDN) were measured by examining virtual slide image files. The rates of CiCP‑positive cases (RCPCs) and CiCP emergence rate (CER)/SDN were significantly higher in ascites samples than in peritoneal washing samples (P<0.0001 and P=0.0026, respectively), although the numbers of SDN were not significantly different between the groups (P=0.8063). Both the RCPCs and CER/SDN were significantly higher in tumor‑positive specimens than in tumor‑negative specimens (P=0.0220 and P=0.0312, respectively), although the numbers of SDN were not significantly different between the samples (P=0.2471). Most of the incorporated cells were lymphocytes and the host cells were macrophages; however, the rate of neutrophil incorporation (NI) by host cells in the total CiCP cells in a sample was significantly higher in tumor‑positive specimens than in tumor‑negative specimens (P=0.0288). NI was mainly performed via emperipolesis by macrophages, with only six examples not by macrophages observed among all CiCP samples. The threshold NI rate/total CiCP (NI/CiCP) between tumor‑positive and tumor‑negative groups was 11.1% (P=0.0115). Using this threshold, the peripheral blood leukocyte count was significantly higher in the high‑NI/CiCP group than in the low‑NI/CiCP group (P=0.0022). The present findings revealed novel aspects of less frequently observed CiCP in ascitic fluid cytology by utilizing combined manual and computer assisted image analysis evaluation of samples. Notably, the present study indicated the importance of increased NI as an indicator of cancerous ascites.

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1	Lewis W: The engulfment of living blood cells by others of the same type. Anatomical Record. 31:43–49. 1925. View Article : Google Scholar
2	Humble JG, Jayne WH and Pulvertaft RJ: Biological interaction between lymphocytes and other cells. Br J Haematol. 2:283–294. 1956. View Article : Google Scholar : PubMed/NCBI
3	Gupta N, Jadhav K and Shah V: Emperipolesis, entosis and cell cannibalism: Demystifying the cloud. J Oral Maxillofac Pathol. 21:92–98. 2017. View Article : Google Scholar : PubMed/NCBI
4	Rastogi V, Sharma R, Misra SR, Yadav L and Sharma V: Emperipolesis-a review. J Clin Diagn Res. 8:ZM01–ZM02. 2014.PubMed/NCBI
5	Samii K and Pasteur E: Images in hematology. Emperipolesis Am J Hematol. 59:641998. View Article : Google Scholar
6	Rosai J and Dorfman RF: Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol. 87:63–70. 1969.PubMed/NCBI
7	Foucar E, Rosai J and Dorfman R: Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Review of the entity. Semin Diagn Pathol. 7:19–73. 1990.PubMed/NCBI
8	Singhal N, Handa U, Bansal C and Mohan H: Neutrophil phagocytosis by tumor cells-a cytological study. Diagn Cytopathol. 39:553–555. 2011. View Article : Google Scholar
9	Kale A: Cellular Cannibalism. J Oral Maxillofac Pathol. 19:7–9. 2015. View Article : Google Scholar : PubMed/NCBI
10	Bansal C, Tiwari V, Singh U, Srivastava A and Misra J: Cell cannibalism: A cytological study in effusion samples. J Cytol. 28:57–60. 2011. View Article : Google Scholar : PubMed/NCBI
11	Sharma N and Dey P: Cell cannibalism and cancer. Diagn Cytopathol. 39:229–233. 2011.PubMed/NCBI
12	Fais S: Cannibalism: A way to feed on metastatic tumors. Cancer Lett. 258:155–164. 2007. View Article : Google Scholar : PubMed/NCBI
13	Richards DM and Endres RG: How cells engulf: A review of theoretical approaches to phagocytosis. Rep Prog Phys. 80:1266012017. View Article : Google Scholar : PubMed/NCBI
14	Koss L and Melamed M: Fundamental concepts of neoplasia: Benign tumor and cancer. Koss's diagnostic cytology and its histopathologic bases. Koss L and Melamed M: Lippincott Williams & Wilkins; Philadelphia: pp. 143–179. 2006
15	Al-Abbadi M: Warthin's tumor. Salivary gland Cytology. Al-Abbadi M: Wiley-Blackwell; Hobokwnm NJ: pp. 69–75. 2011, View Article : Google Scholar
16	Kini S: Gonads (Ovaries ans Testis). Color atlas of diagnosis in exfoliative and aspiration cytopathology. Wolters Kluwer/Lipponcott Williams & Wilkins; Philadelphia, PA: pp. 852–869. 2011
17	Saxena S, Beena KR, Bansal A and Bhatnagar A: Emperipolesis in a common breast malignancy. A case report Acta Cytol. 46:883–886. 2002. View Article : Google Scholar
18	Rane SR, Parkhi M, Vishwasrao S and Nakate L: Non-Hodgkin's lymphoma with extensive emperipolesis mimicking Rosai-Dorfman disease: A rare case report. Indian J Pathol Microbiol. 62:319–322. 2019. View Article : Google Scholar : PubMed/NCBI
19	Meykler S, Baloch ZW and Barroeta JE: A case of marginal zone lymphoma with extensive emperipolesis diagnosed on pleural effusion cytology with immunocytochemistry and flow cytometry. Cytopathology. 27:70–72. 2016. View Article : Google Scholar
20	Lopes LF, Bacchi MM, Coelho KI, Filho AA and Bacchi CE: Emperipolesis in a case of B-cell lymphoma: A rare phenomenon outside of Rosai-dorfman disease. Ann Diagn Pathol. 7:310–313. 2003. View Article : Google Scholar : PubMed/NCBI
21	Pinto D and Schmitt F: Current applications of molecular testing on body cavity fluids. Diagn Cytopathol. Mar 30–2020.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
22	Renshaw AA: Quality improvement in cytology: Where do we go from here? Arch Pathol Lab Med. 135:1387–1390. 2011. View Article : Google Scholar : PubMed/NCBI
23	Ministry of Education Culture, Sports, Science and Technology, and Ministry of Health, Labor and Welfare: Ethical guidelines for medical and health research involving human subjects. https://www.mhlw.go.jp/file/06-Seisakujouhou-10600000-Daijinkanboukousei-kagakuka/0000080278.pdfuri. Accessed March 31, 2015.
24	Smith P and Gray W: Cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix. Diagnostic Cytopathology. Gray W and Kocjan G: Churchill Livingstone Elsevier; London: pp. 609–644. 2010, View Article : Google Scholar
25	Nakazato Y, Maeshima AM, Ishikawa Y, Yatabe Y, Fukuoka J, Yokose T, Tomita Y, Minami Y, Asamura H, Tachibana K, et al: Interobserver agreement in the nuclear grading of primary pulmonary adenocarcinoma. J Thorac Oncol. 8:736–743. 2013. View Article : Google Scholar : PubMed/NCBI
26	Grilley-Olson JE, Hayes DN, Moore DT, Leslie KO, Wilkerson MD, Qaqish BF, Hayward MC, Cabanski CR, Yin X, Socinski MA, et al: Validation of interobserver agreement in lung cancer assessment: Hematoxylin-eosin diagnostic reproducibility for non-small cell lung cancer: The 2004 World Health Organization classification and therapeutically relevant subsets. Arch Pathol Lab Med. 137:32–40. 2013. View Article : Google Scholar
27	Lindauer K, Bartels T, Scherer P and Kabiri M: Development and validation of an image analysis system for the measurement of cell proliferation in mammary glands of rats. Toxicol Pathol. 47:634–644. 2019. View Article : Google Scholar : PubMed/NCBI
28	Gordon S: Alternative activation of macrophages. Nat Rev Immunol. 3:23–35. 2003. View Article : Google Scholar : PubMed/NCBI
29	Mantovani A, Sozzani S, Locati M, Allavena P and Sica A: Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 23:549–555. 2002. View Article : Google Scholar : PubMed/NCBI
30	Yunna C, Mengru H, Lei W and Weidong C: Macrophage M1/M2 polarization. Eur J Pharmacol. 877:1730902020. View Article : Google Scholar : PubMed/NCBI
31	Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P and Mantovani A: Macrophage polarization in tumour progression. Semin Cancer Biol. 18:349–355. 2008. View Article : Google Scholar : PubMed/NCBI
32	Lewis CE and Pollard JW: Distinct role of macrophages in different tumor microenvironments. Cancer Res. 66:605–612. 2006. View Article : Google Scholar : PubMed/NCBI
33	Leek RD, Landers RJ, Harris AL and Lewis CE: Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J Cancer. 79:991–995. 1999. View Article : Google Scholar : PubMed/NCBI
34	Lissbrant IF, Stattin P, Wikstrom P, Damber JE, Egevad L and Bergh A: Tumor associated macrophages in human prostate cancer: Relation to clinicopathological variables and survival. Int J Oncol. 17:445–451. 2000.PubMed/NCBI
35	Ohno S, Ohno Y, Suzuki N, Kamei T, Koike K, Inagawa H, Kohchi C, Soma G and Inoue M: Correlation of histological localization of tumor-associated macrophages with clinico-pathological features in endometrial cancer. Anticancer Res. 24:3335–3342. 2004.PubMed/NCBI
36	Hanada T, Nakagawa M, Emoto A, Nomura T, Nasu N and Nomura Y: Prognostic value of tumor-associated macrophage count in human bladder cancer. Int J Urol. 7:263–269. 2000. View Article : Google Scholar : PubMed/NCBI
37	Mäkitie T, Summanen P, Tarkkanen A and Kivelä T: Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci. 42:1414–1421. 2001.PubMed/NCBI
38	Farinha P, Masoudi H, Skinnider BF, Shumansky K, Spinelli JJ, Gill K, Klasa R, Voss N, Connors JM and Gascoyne RD: Analysis of multiple biomarkers shows that lymphoma-associated macro-phage (LAM) content is an independent predictor of survival in follicular lymphoma (FL). Blood. 106:2169–2174. 2005. View Article : Google Scholar : PubMed/NCBI
39	Ko SY, Ladanyi A, Lengyel E and Naora H: Expression of the homeobox gene HOXA9 in ovarian cancer induces peritoneal macrophages to acquire an M2 tumor-promoting phenotype. Am J Pathol. 184:271–281. 2014. View Article : Google Scholar :
40	Law AMK, Valdes-Mora F and Gallego-Ortega D: Myeloid-derived suppressor cells as a therapeutic target for cancer. Cells. 9:5612020. View Article : Google Scholar :
41	Mukaida N, Sasaki SI and Baba T: Two-faced roles of tumor-associated neutrophils in cancer development and progression. Int J Mol Sci. 21:34572020. View Article : Google Scholar :
42	Schupp J, Krebs FK, Zimmer N, Trzeciak E, Schuppan D and Tuettenberg A: Targeting myeloid cells in the tumor sustaining microenvironment. Cell Immunol. 343:1037132019. View Article : Google Scholar
43	Li TJ, Jiang YM, Hu YF, Huang L, Yu J, Zhao LY, Deng HJ, Mou TY, Liu H, Yang Y, et al: Interleukin-17-producing neutrophils link inflammatory stimuli to disease progression by promoting angiogenesis in gastric cancer. Clin Cancer Res. 23:1575–1585. 2017. View Article : Google Scholar
44	Li S, Cong X, Gao H, Lan X, Li Z, Wang W, Song S, Wang Y, Li C, Zhang H, et al: Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells. J Exp Clin Cancer Res. 38:62019. View Article : Google Scholar : PubMed/NCBI
45	Wang SC, Chou JF, Strong VE, Brennan MF, Capanu M and Coit DG: Pretreatment neutrophil to lymphocyte ratio independently predicts disease-specific survival in resectable gastroesophageal junction and gastric adenocarcinoma. Ann Surg. 263:292–297. 2016. View Article : Google Scholar :
46	Ock CY, Nam AR, Lee J, Bang JH, Lee KH, Han SW, Kim TY, Im SA, Kim TY, Bang YJ, et al: Prognostic implication of anti-tumor immunity measured by the neutrophil-lymphocyte ratio and serum cytokines and angiogenic factors in gastric cancer. Gastric Cancer. 20:254–262. 2017. View Article : Google Scholar
47	Araki K, Ito Y, Fukada I, Kobayashi K, Miyagawa Y, Imamura M, Kira A, Takatsuka Y, Egawa C, Suwa H, et al: Predictive impact of absolute lymphocyte counts for progression-free survival in human epidermal growth factor receptor 2-positive advanced breast cancer treated with pertuzumab and trastuzumab plus eribulin or nab-paclitaxel. BMC Cancer. 18:9822018. View Article : Google Scholar : PubMed/NCBI