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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 2  |  Issue : 3  |  Page : 51-54

Significance of mast cells in diagnosis and grading of non-Hodgkin's lymphomas on fine-needle aspiration cytology


1 Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry; Department of Pathology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Web Publication21-Sep-2018

Correspondence Address:
Prita Pradhan
Department of Pathology, Kalinga Institute of Medical Sciences, Kushabhadra Campus, Bhubaneswar-751024, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/oji.oji_21_18

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  Abstract 


Background: Information regarding the diagnostic role of mast cells in non-Hodgkin's lymphomas (NHLs) on fine-needle aspiration cytology (FNAC) is negligible. Aim of the Study: To assess the role of mast cells in diagnosing and distinguishing reactive lymphoid hyperplasia (RLH) versus low-grade NHL and low- versus high-grade NHLs on FNAC. Materials and Methods: Fine-needle aspirates from 50 reactive lymph nodes and 51 NHLs were studied. Cytologic smears of NHL cases and reactive controls were evaluated in a blinded manner. A standardized mast cell count (MCC) was performed on May–Grünwald–Giemsa smears of both “NHL” and “RLH” cases. MCC was compared between RLH and NHL groups and between low- and high-grade NHLs. Mann–Whitney U-test and Wilcoxon W-test were done for statistical analysis, takingP> 0.05 as statistically significant. A receptor operator characteristic curve was plotted to calculate the cutoffs for MCC. Results: Various morphologic types of NHL were encountered with 25 high-grade and 26 low-grade NHLs. The standardized MCC in RLH ranged from 0/25 hpf to 14/25 hpf (a mean MCC of 1.54/25 hpf), while for NHL group, it ranged from 0/25 hpf to 30/25 hpf (a mean MCC of 2.39/25 hpf). The difference in the median MCC between the two groups was statistically not significant (P > 0.05). Conclusion: Performing an MCC on cytologic smears may not be of significant practical value in distinguishing RLH versus low-grade NHL, and low/intermediate grade versus high-grade NHLs. Further larger studies are required to refute or support the cytodiagnostic role of mast cells in some specific subtypes of NHL.

Keywords: Fine-needle aspiration, high grade, low grade, mast cell count, non-Hodgkin's lymphoma, reactive lymphoid hyperplasia


How to cite this article:
Praveen J, Siddaraju N, Pradhan P. Significance of mast cells in diagnosis and grading of non-Hodgkin's lymphomas on fine-needle aspiration cytology. Oncol J India 2018;2:51-4

How to cite this URL:
Praveen J, Siddaraju N, Pradhan P. Significance of mast cells in diagnosis and grading of non-Hodgkin's lymphomas on fine-needle aspiration cytology. Oncol J India [serial online] 2018 [cited 2018 Nov 19];2:51-4. Available from: http://www.ojionline.org/text.asp?2018/2/3/51/241838




  Introduction Top


Mast cells are critical for a number of pathologic conditions, including acute and chronic inflammation and tumor angiogenesis.[1] Their increased presence has been documented on histologic sections of bone marrow[2] and lymph node biopsies from non-Hodgkin's lymphoma (NHL) cases, especially in follicular lymphomas.[1] Some of the authors have observed an increase in mast cell number in cases of fibrosing lymphoid malignancies inclusive of Hodgkin's lymphoma and NHLs.[3] Although debatable and diagnostically challenging, the fine-needle aspiration cytologic (FNAC) aspects of various NHL cases have been dealt in detail, in various standard text books, discussing also their limitations.[4],[5],[6] There have been rare, but significant studies assessing the role of mast cells in different morphologic subtypes of lymphomas on histology.[7],[8] However, surprisingly, except for two studies dealing with a very small number of cases, not much information is available with respect to their importance in fine-needle aspirates of lymphoma cases.[9],[10]

The present study has made an attempt to evaluate the significance of an increased mast cell count (MCC) in distinguishing a reactive node versus non-Hodgkin's lymphoma in the fine-needle aspirates and also to assess the varied proportions of mast cells in distinguishing a low-grade versus high-grade NHL by performing a standardized MCC on May–Grünwald–Giemsa (MGG)-stained smears.


  Materials and Methods Top


Fine-needle aspirates from 50 cytologically and clinically reactive lymph nodes and 51 cytologically diagnosed and biopsy-proven cases of NHL constituted the study material. The cytologic smears of the cases that were histologically diagnosed as NHL were reevaluated by two cytopathologists, who were totally blinded to the histopathologic diagnosis. All cases included were the histologically and immunohistochemically proven NHLs. A good-quality MGG-stained smear was selected from each case, in which a portion of the smear with uniformly distributed and well preserved lymphoid cells was chosen (after a careful screening of the entire smear), and the number of mast cells was counted for 75 high-power fields (hpf) and an average was calculated for a minimum of 25 high-power fields (×40). Similarly, MCC was performed on smears from reactive nodes. The median MCC was compared between the reactive lymphoid hyperplasia (RLH) and NHL groups, as well as between low- and high-grade NHLs. IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY: IBM Corp.) software was used for statistical analysis. As the sample size was large and whether the distribution of MCC was normal or not was unknown, Mann–Whitney U-test (930.500) and Wilcoxon W-test (2205.500) were performed to compare the median MCC between lymphomas and reactive groups, taking P < 0.05 as statistically significant. A receptor operator characteristic (ROC) curve was attempted to assess the area under the curve and thereby calculate the cutoffs for MCC for distinguishing lymphomas from reactive lymph nodes.


  Results Top


Age of the reactive/lymphoma patients ranged between 2 months and 78 years with a median of 55 years. There were 58 males and 43 females. Clinical diagnoses in these cases included 31 (30.69%) lymphomas, 15 (14.85%) suspected metastases, 10 (9.90%) suspected tuberculosis, and others (5.94%). Thirty-nine (38.61%) cases had no provisional clinical diagnosis. The sites of aspiration included 51 (50.50%) cervical nodes, 17 (16.83%) axillary nodes, 10 (9.90%) inguinal nodes, and others such as mediastinal, thyroid, and deep-seated node aspirates (22.77%). The nature of aspirates in these cases ranged from blood-mixed to particulate material. Morphologically, all 50 reactive nodes showed either follicular or parafollicular hyperplasia, while the lymphoma group had a diagnosis of either low- or high-grade NHL. A monotonous population of atypical large lymphoid cells or a polymorphous population of pleomorphic lymphoid cells lacking classic reactive spectrum were seen in cases of NHL. Increased mitoses and tingible body macrophages admixed with a strikingly atypical lymphoid population of cells, apoptotic bodies, or necrotic debris in the smear background were some of the important features in cases of high-grade NHL. Histologic subtypes of 51 NHLs included diffuse large B-cell lymphomas (DLBCLs) (17); Burkitt lymphoma (4); peripheral T-cell lymphoma (PTCL) (4); anaplastic large cell lymphoma (ALCL) (3); marginal zone lymphoma (MZL) (3) [Figure 1]; small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) (3) [Figure 2]; mantle cell lymphoma (MCL) (2); extranodal NHL (1), plasmablastic lymphoma (1); low-grade follicular lymphoma (1), mucosa-associated lymphoid tissue (1), and grade-3 follicular NHL (1). Ten NHLs were not subtyped. As for the grading, there were 25 high-grade and 26 low-grade NHLs. The MCC in 50 reactive nodes ranged from 0/25 hpf to 14/25 hpf with a mean of 1.54/25 hpf. Majority of the reactive nodes (28) had an MCC of “0/25 hpf.” Eleven cases had an MCC of “1/25 hpf:” two had “2/25 hpf,” three had “3/25 hpf,” and one case each had 4, 6, 7, 10, 12, and 14 mast cells/25 hpf, respectively. The MCC in NHL group ranged between 0/25 hpf and 30/25 hpf with a mean of 2.39/25 hpf. [Table 1] shows the subsets of lymphomas encountered in our study with the range of mast cells observed in them. Mann–Whitney U-test and Wilcoxon W-test which were done to compare the median MCC between lymphomas and reactive groups showed no statistically significant difference with the asymptotic significance P = 0.117. Furthermore, there was no statistically significant difference between the median MCC between low- and high-grade NHLs (P = 0.808). A ROC curve was attempted to calculate the cutoffs for MCC for diagnosing lymphomas and differentiate them from reactive lymphomas. However, as the area under the curve showed an asymptotic significance (P) of = 0.147, which was statistically insignificant, the “cutoffs” to distinguish between reactive and lymphoma could not be established.
Figure 1: A case of ENMZL which showed prominent mast cells (May–Grünwald–Giemsa, ×400)

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Figure 2: A case of chronic lymphocytic leukemia showing a striking increase in the number of mast cells (May–Grünwald–Giemsa, ×400)

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Table1: The subtypes of lymphomas with the range and average number of mast cells encountered in them

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  Discussion Top


Tissue infiltration of mast cells is well known in a variety of inflammatory and neoplastic lesions. Among the neoplastic lesions, apart from the hematopoietic neoplasms, it is also described in epithelial malignancies such as hepatocellular carcinoma and cholangiocarcinomas,[11] as well as mesenchymal malignancies such as synovial sarcoma.[12] Although there are a decent number of studies on the possible functional role of mast cells in neoplastic and nonneoplastic lesions,[13],[14],[15],[16],[17],[18],[19] the literature with regard to the diagnostic role of mast cells in lymphoid lesions on FNAC is sparse.[9],[10] The hematolymphoid malignancies associated with mast cell infiltration include Hodgkin's lymphoma and a variety of T- and B-cell NHLs such as PTCL, DLBCL, lymphoplasmacytic lymphoma (LPL), and SLL/CLL.[7],[8],[10],[17] In most of these lymphoid neoplasms, mast cell infiltration has been shown to be associated with angiogenesis and tumor progression.[14],[15] In a quantitative study of mast cells in a series of T- and B-cell NHLs, Crocker and Smith[7] found T-cell NHLs to contain more number of mast cells than B-cell NHLs; however, they also noted that, similar to T-cell NHLs, some of the B-cell NHLs such as LPL contained as many mast cells as T-cell NHL. Another observation in their study was that some of their cases of reactive follicular hyperplasia also had more number of mast cells (like T-cell NHL) than the B-cell NHL. The same study showed that the mast cells in reactive follicular hyperplasia were confined to the T cell predominant paracortical areas and were absent in the B follicular zone. However, in cases of lymphoma, this topographic distribution pattern of mast cells was lost.[7]

In the present study, based on one of our previous observations,[10] we made an attempt to know the significance of mast cells in the diagnosis and grading of NHLs on FNAC, and also in differentiating NHLs from RLH by performing a standardized MCC on MGG-stained smears. Although some individual cases of NHLs such as MZL [Figure 1], DLBCL, and extranodal NHL showed a striking increase in mast cells, it was an inconsistent finding. As highlighted before, we were expecting a significant increase in MCC in cases of SLL/CLL and low/intermediate-grade follicular lymphomas. Only one of the three cases of SLL/CLL showed a considerable increase in mast cells [Figure 2]. Both the cases of follicular NHL, irrespective of grade, showed an MCC of 0/25 hpf. Although there are no studies regarding the diagnostic role of mast cells on FNAC in cases of DLBCL, apparently, there have been rare publications highlighting the increased presence of mast cells in the histologic sections of DLBCL.[8] In the present study, DLBCL constituted a major bulk of NHLs with a wide range of MCC (0 to 18/25 hpf); three of these cases had an MCC of 7/25 hpf, 8/25 hpf, and 18/25 hpf, while the majority of them had an MCC ranging between 0/25 hpf and 4/25 hpf. Of the three MZLs, a considerable MCC of 6/25 hpf and 22/25 hpf was encountered in two cases, while the third case had a low MCC of 3/25 hpf. The other NHLs including ALCL, plasmablastic lymphoma, and PTCL had an MCC of 0–3/25 hpf only. All four cases of Burkitt lymphoma had an MCC of 0/25 hpf. The cases of NHL which were not subtyped on histology showed an MCC ranging from 0 to 6/25 hpf, with only two cases revealing an MCC of 5/25 hpf and 6/25 hpf.

Thus, on the whole, our findings did not favor a definitive diagnostic role of MCC in diagnosing and grading lymphomas, which was confirmed by the Mann–Whitney and Wilcoxon tests. An increase or decrease in mast cells was an inconsistent finding in the reactive lymph nodes as well with an MCC range of 0–14/25 hpf and a mean of 1.5/25 hpf. However, one cannot ignore the fact that two of our morphologically and clinically reactive nodes with a high MCC of 12/25 hpf and 14/25 hpf had no histopathologic correlation to be sure of a diagnosis of RLH, although morphologic features were consistent with RLH. Nonetheless, as noted by Crocker and Smith,[7] reactive nodes can have increased mast cells confined to the T cell predominant paracortical areas, which is appreciable only on histologic sections.

In our study, we had hypothesized that the varying proportions of increased mast cell number may prove to be “a useful parameter” or serve as a clue in distinguishing a “reactive lymph node versus low-grade NHL” and a “low-grade NHL versus high-grade NHL. Considering the simplicity of the FNA procedure and its ability to provide quicker results, had our hypothesis been substantiated, it would have been very useful in the patient management. However, the present study did not support our hypothesis.

One of the merits of the study is that although the hypothesis was disproven, the study touched upon the “debatable” diagnostic role of mast cells in the diagnosis and grading of NHLs on FNAC, paving the way for further studies in this direction. One of the further innovations that can be attempted is a similar count on paraffin-embedded tissue sections with special stains and immunohistochemistry specific for mast cells. The primary limitations of our study are that, despite being the largest study so far in evaluating the significance of mast cells in NHLs on FNAC, considering the vast number of the subtypes of NHL, our sample size is too low in individual categories. This precludes any generalization, warranting that larger studies with larger sample size in each subcategory of lymphoma are required for the testing of the hypothesis.


  Conclusion Top


Although the sample size is inadequate for a definitive conclusion, our study indicates that the mast cell number may not be of significant practical value in distinguishing RLH versus low-grade NHL and low/intermediate-grade versus high-grade NHLs. However, considering some of our selective cases of lymphoma subtypes such as MZL and DLBCL showing increased MCC and also the previous studies highlighting the increased mast cells in lymphoma subtypes such as DLBCL, further studies with larger numbers of lymphoma cases need to be carried out to refute or support the cytodiagnostic role of mast cells, at least in some specific subtypes of NHL.

Financial support and sponsorship

This study was funded by the Indian Council of Medical Research under the short-term studentship. (STS Reference ID: 2014]00704).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Crivellato E, Nico B, Vacca A, Ribatti D. Ultrastructural analysis of mast cell recovery after secretion by piecemeal degranulation in B-cell non-Hodgkin's lymphoma. Leuk Lymphoma 2003;44:517-21.  Back to cited text no. 1
    
2.
Wilkins BS, Buchan SL, Webster J, Jones DB. Tryptase-positive mast cells accompany lymphocytic as well as lymphoplasmacytic lymphoma infiltrates in bone marrow trephine biopsies. Histopathology 2001;39:150-5.  Back to cited text no. 2
    
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Tataroglu C, Sarioglu S, Kargi A, Ozkal S, Aydin O. Fibrosis in Hodgkin and non-Hodgkin lymphomas. Pathol Res Pract 2007;203:725-30.  Back to cited text no. 3
    
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Orell SR, Sterret GF, Walters MN, Whitaker D, Heerde PV. Lymph nodes. In: Orell SR, Sterret GF, Walters MN, Whitaker D, editors. Manual and Atlas of Fine Needle Aspiration Cytology. 3rd ed. London: Churchill-Livingstone; 1999. p. 74-108.  Back to cited text no. 4
    
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Young NA, Al-Saleem T. Lymph nodes: Cytomorphology and flow cytometry. In: Bibbo M, Wilbur DC, editors. Comprehensive cytopathology. 3rd ed. China: Saunders Elsevier; 1997. p. 671-711.  Back to cited text no. 5
    
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Inamdar KV, Kini SR. Reactive and malignant lymphadenopathies. In: Kini SR, editor. Colour Atlas of Differential Diagnosis in Exfoliative and Aspiration Cytopathology. 2nd ed. Philadelphia, United States: Lippincott Williams and Wilkins; 2011. p. 543-70.  Back to cited text no. 6
    
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Crocker J, Smith PJ. Mast cells in non-Hodgkin's lymphomas: A quantitative study. J Clin Pathol 1987;40:470.  Back to cited text no. 7
    
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Fukushima H, Ohsawa M, Ikura Y, Naruko T, Sugama Y, Suekane T, et al. Mast cells in diffuse large B-cell lymphoma; their role in fibrosis. Histopathology 2006;49:498-505.  Back to cited text no. 8
    
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Saikia UN, Dey P, Saikia B, Das A. Fine-needle aspiration biopsy in diagnosis of follicular lymphoma: Cytomorphologic and immunohistochemical analysis. Diagn Cytopathol 2002;26:251-6.  Back to cited text no. 9
    
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Subramanian R, Solo S, Mishra MM, Murugan P, Siddaraju N, Basu D, et al. Fine needle aspiration cytology of primary lymphoid lesions of the orbit: Report of four cases. Acta Cytol 2007;51:417-20.  Back to cited text no. 10
    
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Terada T, Matsunaga Y. Increased mast cells in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Hepatol 2000;33:961-6.  Back to cited text no. 11
    
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Srinivasan R, Gautam U, Gupta R, Rajwanshi A, Vasistha RK. Synovial sarcoma: Diagnosis on fine-needle aspiration by morphology and molecular analysis. Cancer 2009;117:128-36.  Back to cited text no. 12
    
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Chen Y, Pappu BP, Zeng H, Xue L, Morris SW, Lin X, et al. B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6 production in mast cells. J Immunol 2007;178:49-57.  Back to cited text no. 13
    
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Iamaroon A, Pongsiriwet S, Jittidecharaks S, Pattanaporn K, Prapayasatok S, Wanachantararak S. Increase of mast cells and tumor angiogenesis in oral squamous cell carcinoma. J Oral Pathol Med 2003;32:195-9.  Back to cited text no. 14
    
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Fukushima N, Satoh T, Sano M, Tokunaga O. Angiogenesis and mast cells in non-hodgkin's lymphoma: A strong correlation in angioimmunoblastic T-cell lymphoma. Leuk Lymphoma 2001;42:709-20.  Back to cited text no. 16
    
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Tripodo C, Gri G, Piccaluga PP, Frossi B, Guarnotta C, Piconese S, et al. Mast cells and th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma. Am J Pathol 2010;177:792-802.  Back to cited text no. 17
    
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Tournilhac O, Santos DD, Xu L, Kutok J, Tai YT, Le Gouill S, et al. Mast cells in Waldenstrom's macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling. Ann Oncol 2006;17:1275-82.  Back to cited text no. 19
    


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