Journal of Cytology
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ORIGINAL ARTICLE  
Year : 2011  |  Volume : 28  |  Issue : 2  |  Page : 57-60
Cell Cannibalism: A cytological study in effusion samples


1 Department of Pathology, Eras Medical College and Hospital, Lucknow, India
2 CSMMU, Lucknow, India

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Date of Web Publication12-May-2011
 

   Abstract 

Background: Cytological examination of effusion fluid is a relatively easy and quick method for the diagnosis of primary or secondary malignancy.
Aims: To analyze the cytological significance of cell cannibalism in malignant effusion samples.
Materials and Methods: A retrospective review of 100 cases of malignant effusion was done. These 100 cases included 50 cases of contiguous, local spread to pleural/ascitic fluid. The remaining 50 cases were of disseminated malignancy. Effusions due to hematolymphoid malignancies were excluded. Smears from these cases were assessed for the presence of cell cannibalism, tumor cell within a tumor cell.
Results: The cannibalistic cells were more common in effusions with disseminated malignancy (nine out of 50 cases i.e. 18%) compared with cases of contiguous, local spread (two out of 50 cases i.e. 4%). Chi square test showed this difference to be statistically significant (x2 5.005, P=0.025). The majority of the cases were of carcinoma lung (6/11). Cytomorphologically, histiocytes displaying phagocytosis can simulate tumor cells and need to be distinguished.
Conclusions: Presence of cell cannibalism in malignant effusions is more often an indicator of disseminated malignancy with secondaries and higher tumor stage. Furthermore, cannibalism may provide a reliable predictor of progression of tumor from primary to the metastatic site.

Keywords: Cannibalism, cytology, malignant effusion

How to cite this article:
Bansal C, Tiwari V, Singh U S, Srivastava A N, Misra J S. Cell Cannibalism: A cytological study in effusion samples. J Cytol 2011;28:57-60

How to cite this URL:
Bansal C, Tiwari V, Singh U S, Srivastava A N, Misra J S. Cell Cannibalism: A cytological study in effusion samples. J Cytol [serial online] 2011 [cited 2020 Sep 19];28:57-60. Available from: http://www.jcytol.org/text.asp?2011/28/2/57/80736



   Introduction Top


Effusion fluid examination on cytology is a relatively easy and quick method for the diagnosis of primary or secondary malignancy. The features of malignancy in effusion fluids are subtle and include ball-like three-dimensional clusters, pleomorphism, nuclear hyperchromasia, nuclear membrane irregularities, and prominence of nucleoli. [1],[2] Cell cannibalism is defined as the ability of a cell to phagocytose another cell. Cannibalism was first described by Leyden [3] in 1904, who called them "bird's-eye cells". In cytological preparation it is seen as a cell that is contained within another bigger cell that has a crescent-shaped nucleus. Studies suggest that this peculiar property gives tumor cells a survival advantage in adverse conditions like low nutrient supply. [4] However, only few studies have mentioned this phenomenon in fluid cytology. [5],[6],[7] We present a series of 11 cases that demonstrated tumor cell cannibalism in malignant effusion samples.


   Materials and Methods Top


The present study was a retrospective review of 100 malignant effusion cases over a time period of three years. We had Group "A" of consecutive 50 cases of contiguous, local spread to pleural/ascitic fluid. In these cases, there was no apparent secondary nodal/organ parenchymal involvement present clinically or radiologically. Group "B" constituted the remaining 50 cases which were of disseminated malignancy with secondaries in nodes/organ parenchyma in addition to the presence of pleural or ascitic fluid collection. In the period specified for inclusion of the cases, we did not have any case of mesothelioma or primary peritoneal serous carcinoma. Effusions due to hematolymphoid malignancy and urine cytology samples were not included.

All the 100 cases included were diagnosed cytologically on May-Grünwald-Giemsa and hematoxylin and eosin smears stained by standard methods. None of the preparations were cell blocks or liquid-based preparations. Samples were reported either positive for adenocarcinoma or carcinoma. Smears from all 100 cases were examined for tumor cells showing presence of another tumor cell in the cytoplasm. Phagocytosis of non-self cells (leucocytes, erythrocytes) was excluded. Eleven cases showed feature of cannibalism. The number of cannibalistic cells/100 tumor cells was counted in 30 random fields at ×10 magnification and confirmed by ×40 magnification. Two observers counted the cannibalistic cells independently (C.B. and A.N.). We also wanted to include the count of cannibalistic cells in the primary tumor site, but unfortunately we had smears from the primary site in only six out of 11 cases. The number was not sufficient for a valid comparative study, so we did not compare the observations from the primary site cytology.

Details of the 11 cases demonstrating feature of cannibalism along with number of cannibalistic cells are tabulated [Table 1]. Statistical analysis was done by SPSS Version 13. Chi-square test and Student's t-test were applied for interpretation of the data.
Table 1: Details of 11 cases with presence of cell cannibalism in effusion samples

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   Results Top


Fifty cases of Group "A" comprised 32 pleural effusion and 18 ascitic fluid samples. Fifty cases of Group "B" comprised 27 pleural effusion and 23 ascitic fluid samples.

Out of total 100 cases of malignant effusion, smears from 11 cases (11%) showed the feature of cannibalism with engulfment of another cell with round to oval faded nucleus [Figure 1]. These 11 cases included six males and five females, with an age range of 43 to 74 years. Out of 11 cases featuring the phenomenon of cannibalism, six cases (54%) were of lung carcinoma, two cases (18%) were of gall bladder carcinoma and one case (9%) each was of liver, gastric and breast carcinoma. [Table 1] presents the individual case details including effusion site, primary site, secondary site involved and mean number of cannibalistic cells/100 tumor cells. The mean number of cannibalistic cells/100 tumor cells found in Group "B" (0.94±2.14) was significantly higher than in Group "A" (0.08±0.39) {Student t-test, P=0.006} [Table 2].
Figure 1: Photomicrograph showing a tumor cell with another tumor cell engulfed in the cytoplasm (H and E, ×400)

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Table 2: Distribution of cannibalistic cell count/100 tumor cells in Group A and B

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In all the cases exhibiting the phenomenon of cell cannibalism, smears showed malignant cells with high-grade cytological features, poor differentiation with presence of tumor giant cells [Figure 2].
Figure 2: Photomicrograph showing malignant cells with high-grade cytological features, poor differentiation with a tumor giant cell in the field (H and E, ×400)

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The cannibalistic cells were more common in Group "B" effusions with disseminated malignancy (nine out of 50 cases i.e. 18%) compared with cases of Group "A" (two out of 50 cases i.e. 4%). On applying the Chi square test this difference was found to be statistically significant (x2 5.005, P=0.025).


   Discussion Top


Cannibal tumor cells have been given different names uch as "bird's-eye cells" or "signet-ring cells". [8] The studies related to the presence and significance of cannibalism in serous effusions are very limited. [5],[6],[7] Not much attention has been paid to this cytological aspect of a tumor which actually can be of relevance in terms of staging the tumor and its aggressiveness. During evaluation of cytological smears for cannibalism, the cancer cells have to be distinguished from macrophages. Macrophages with ingested cellular debris may be present in malignant effusions as well as in inflammatory conditions, where they ingest inflammatory cells. The macrophages typically have a small vesicular nucleus with abundant pale vacuolated cytoplasm. In all our tabulated cases in the present series, tumor cells were highly anaplastic with large hyperchromatic nuclei which were easy to distinguish from that of macrophages. In difficult cases immunostaining with CD 68 antibody can be done to exclude macrophages. [9] One should also exclude binucleated tumor cells on morphology-these cells do not show indentation in nuclei which is due to phagocytosis of the nucleus placed in its vicinity [Figure 3]. Moreover, both the nuclei in a binucleated cell show the same intensity of hyperchromatism unlike the faded appearance of phagocytosed nuclei.
Figure 3: Photomicrograph showing binucleated tumor cell with same intensity of hyperchromasia in both the nuclei (H and E, ×400)

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Search for cannibalism should be done in that part of the slide where the smear is thin and cells are evenly dispersed. Areas with overlapping of cell clusters give a false positive impression of "cell within a cell" morphology.

A study has quoted that the mechanism of phagocytosis by tumor cells is different from that of the macrophages and that tumor cells eat everything without distinguishing between the feeding materials. [4] We too observed in the present series, that wherever the background had rich inflammatory component, the tumor cell had also phagocytosed the inflammatory cells in its vicinity [Figure 4].
Figure 4: Photomicrograph showing tumor cell with phagocytosed inflammatory cell in its vicinity (H and E, ×400)

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A few studies [10],[11],[12] in the past have described the feature of xeno-cannibalism, which is phagocytosis of non-self cells and a study has shown that the non-self cell most often phagocytosed is a leukocyte. In 2008, Malorni et al., [10] explained xeno-cannibalism as an exacerbation of self-cannibalism and a possible fruitful survival strategy for cancer cells. Metastatic cells cannibalize their siblings as well as cells from the immune system, which represents a formidable opportunity for metastatic cells to survive in adverse conditions.

Cannibalism has been shown in breast carcinoma, [13] giant cell carcinoma of lung, [14] gall bladder carcinoma, [15] malignant melanoma, [4] endometrial stromal sarcoma, [6] etc. In our study, cases with disseminated malignancy exhibited cannibalism more frequently. A study by Lugini et al., [16] showed that melanoma cell lines derived from metastatic lesions exhibit phagocytosis whereas primary tumors did not show this phenomenon. Chandrasoma P [11] hypothesized that the ability for phagocytosis could be used as a marker for the metastatic potential of the tumor cells. Studies have shown that metastatic tumor cells use cannibalism to feed in conditions of low nutrient supply and phagocytic properties offer them a survival advantage. [4] In our series, phagocytic tumor cells were present more often in effusion samples of disseminated malignancy with secondary site involvement and all the cases displayed more prominent anaplastic cell morphology [Table 1].


   Conclusions Top


Cytological studies on cell cannibalism in effusion samples are very few. Tumor cell cannibalism is more often a feature of an aggressive tumor with anaplastic morphology and relates to its ability to metastasize.

 
   References Top

1.Koss LG. Diagnostic cytology and its histopathologic bases. 4 th . Philadelphia: JB Lippincott; 1992.   Back to cited text no. 1
    
2.Gaur DS, Chauhan N, Kusum A, Harsh M, Talekar M, Kishore S, Pathak VP. Pleural fluid analysis - role in diagnosing pleural malignancy. J Cytol 2007;24:183-8.  Back to cited text no. 2
  Medknow Journal  
3.Bauchwitz MA. The bird's eye cell: cannibalism or abnormal division of tumor cells. Acta Cytol 1981;25:92.  Back to cited text no. 3
    
4.Fais S. Cannibalism: a way to feed on metastatic tumors. Cancer Lett 2007;258:155-64.   Back to cited text no. 4
    
5.Gupta K, Dey P. Cell cannibalism: diagnostic marker of malignancy. Diagn Cytopathol 2003;28:86-7.  Back to cited text no. 5
    
6.Kojima S, Sekine H, Fukui I, Ohshima H. Clinical significance of "cannibalism" in urine cytology of bladder cancer. Acta Cytol 1998;42:1365-9.  Back to cited text no. 6
    
7.Hong JS. The exfoliative cytology of endometrial stromal sarcoma in peritoneal fluid. Acta Cytol 1981;25:277-81.   Back to cited text no. 7
    
8.Breier F, Feldmann R, Fellenz C, Neuhold N, Gschnait F. Primary invasive signet-ring cell melanoma. J Cutan Pathol 1999;10:533-6.  Back to cited text no. 8
    
9.Gupta RK, Wakefield SJ. Needle aspiration cytology, immunocytochemistry, and electron microscopic study of unusual pancreatic carcinoma with pleomorphic giant cells. Diagn Cytopathol 1992;8:522-7.  Back to cited text no. 9
    
10.Matarrese P, Ciarlo L, Tinari A, Piacentini M, Malorni W. Xeno-cannibalism as an exacerbation of self-cannibalism: a possible fruitful survival strategy for cancer cells. Curr Pharm Des 2008;14:245-52.   Back to cited text no. 10
    
11.Chandrasoma P. Polymorph phagocytosis by cancer cells in an endometrial adenoacanthoma. Cancer 1980;45:2348-51.  Back to cited text no. 11
    
12.Caruso RA, Muda AO, Bersiga A, Rigoli L, Inferrera C. Morphological evidence of neutrophil-tumor cell phagocytosis (cannibalism) in human gastric adenocarcinomas. Ultrastruct Pathol 2002;26:315-21.   Back to cited text no. 12
    
13.Uei Y, Watanabe Y, Hirota T, Yamamoto H, Watanabe H. Cytologic diagnosis of breast carcinoma with nipple discharge: special significance of the spherical cell cluster. Acta Cytol 1980;24:522-8.   Back to cited text no. 13
    
14.Craig ID, Desrosiers P, Lefcoe MS. Giant-cell carcinoma of lung. A cytological study. Acta Cytol 1983;27:293-8.   Back to cited text no. 14
    
15.Guo KJ, Yamguchi K, Ejoji M. Undifferentiated carcinoma of the gall bladder. A clinicopathological, histochemical and immunohistochemical study of 21 patients with a poor prognosis. Cancer 1988;61:1872-9.  Back to cited text no. 15
    
16.Lugini L, Matarrese P, Tinari A, Lozupone F, Federici C, Iessi E, et al. Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Cancer Res 2006;66:3629-38.  Back to cited text no. 16
    

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Correspondence Address:
Cherry Bansal
Department of Pathology, Eras Medical College and Hospital, Lucknow
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.80736

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    Figures

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    Tables

  [Table 1], [Table 2]

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