Journal of Cytology
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 25  |  Issue : 1  |  Page : 10-12
Fine needle aspiration cytology in the diagnosis of Hodgkin lymphoma: Hits and misses

Department of Pathology, St. John's Medical College, Bangalore - 560 034, India

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Background: Fine needle aspiration (FNA) is said to have greater diagnostic accuracy in Hodgkin lymphoma (HL) as compared to non-Hodgkin lymphoma (NHL). In spite of this, HL accounts for most of the false negative cytodiagnoses among lymphomas.
Aims: To evaluate the accuracy of FNA in HL and to identify the diagnostic pitfalls.
Materials and Methods: A retrospective study of 18 biopsy-proven cases of HL that had a preceding FNA from the same lymph node.
Results: Nine out of eighteen cases were labeled HL, which were diagnosed on the basis of atypical mononuclear cells in preference to classic Reed-Sternberg (RS) cells. Three cases were termed lymphoproliferative, which showed the presence of only atypical mononuclear cells with eosinophilic nucleoli. Six cases were false negative cases. Four of these were hypocellular with biopsy in two cases displaying marked fibrosis. The remaining two cases were labeled reactive and review also showed no additional findings.
Conclusions: Presence of atypical mononuclear cells in cytology should prompt a cautious search as classic RS cells may not be a prominent feature in aspirates of HL. Focal involvement and abundance of reactive lymphoid cells may lead to false negative diagnoses. Hypocellularity of aspirates disproportionate to lymph node size warrant caution. Overall, FNA is useful in the diagnosis of HL, provided one is aware of the pitfalls. It is particularly valuable in screening cases that will require biopsy.

Keywords: Fine needle aspiration cytology; Hodgkin lymphoma.

How to cite this article:
Rashmi Kumari T R, Rajalakshmi T. Fine needle aspiration cytology in the diagnosis of Hodgkin lymphoma: Hits and misses. J Cytol 2008;25:10-2

How to cite this URL:
Rashmi Kumari T R, Rajalakshmi T. Fine needle aspiration cytology in the diagnosis of Hodgkin lymphoma: Hits and misses. J Cytol [serial online] 2008 [cited 2023 Jan 31];25:10-2. Available from:

   Introduction Top

Fine needle aspiration cytology (FNAC) is said to have a higher diagnostic accuracy in Hodgkin lymphoma (HL) (91.8%) as compared to non-Hodgkin lymphoma (NHL) (67.5-86%). [1],[2] In spite of this, HL accounts for one-third of all false negative FNA diagnoses among lymphomas. [3]

This prompted us to undertake this study to assess the diagnostic utility of FNAC in cases of HL and also to analyze the reasons for a false negative diagnosis.

   Materials and Methods Top

Eighteen consecutive cases of biopsy-proven HL with a preoperative FNA from the same lymph node, diagnosed in a teaching hospital over a period of six years from 2000 to 2005, were included in the study. Two observers independently reviewed both the FNA smears and biopsies of all the cases.

Results were recorded as: (a) Reactive/negative for HL; (b) Diagnostic of/suspicious for HL; (c) Lymphoproliferative disorder, unclassified (LPD) and (d) Nondiagnostic/hypocellular.

The features assessed in cytology smears included cellularity of the smear; presence of classic Reed-Sternberg (RS) cells and atypical mononuclear/Hodgkin cells, granulomas, and the composition of the background infiltrate including eosinophils.

A careful review of false negative smears was done later to identify any subtle clues that might have been missed.

   Results Top

A summary of the cytodiagnosis offered on FNAC is shown in [Table - 1] with the corresponding histopathological diagnosis.

All nine cases diagnosed as HL on FNAC showed the presence of classic RS cells along with atypical mononuclear cells. However, the latter component was more prominent and more numerous as compared to the former. In addition, all these cases also had a mixed population of lymphoid cells in the background, comprising of lymphocytes, plasma cells, and macrophages, with prominent eosinophils in only one case. Four cases were associated with non-necrotizing granulomas consisting of epithelioid cells and macrophages.

The three cases classified under LPD had a polymorphous lymphoid background without any classic RS cells. All three cases showed the presence of only atypical mononuclear cells with prominent eosinophilic nucleoli while one case had epithelioid granulomas with an occasional multinucleated giant cell.

Two cases categorized as reactive hyperplasia on FNAC were diagnosed as Hodgkin lymphoma-lymphocyte predominant (HL-LP) on histopathology. The only significant feature on cytology in these cases was the presence of eosinophils in significant numbers.

Of the remaining four aspirates reported as hypocellular smears, biopsy was reported as Hodgkin lymphoma-mixed cellularity (HL-MC) in two cases Hodgkin lymphoma-nodular sclerosis (HL-NS) in one and Hodgkin lymphoma-lymphocyte-depleted (HL-LD) in the remaining case.

   Discussion Top

FNAC is a popular technique used in the evaluation of lymph nodes for the diagnosis of lymphomas. In conjunction with immunophenotyping and molecular studies, it has gained acceptance in many centers as an initial diagnostic tool. [4]

The cornerstone of cytodiagnosis of HL is the finding of classic Reed-Sternberg/Hodgkin cells in an appropriate polymorphous cellular background. [5] The wide spectrum of cytologic features seen in HL reflects not only the histological diversity of the disease but also overlaps considerably with other reactive and malignant lesions, leading to problems in diagnosis. In the present study, although classic RS cells were found in all cases categorized as HL, atypical mononuclear cells with prominent nucleoli apparently outnumbered them and proved to be a better indicator in cytological evaluation. In the cases termed LPD, it was these atypical mononuclear cells, which appeared more prominent and were diagnostic.

Furthermore, when present, RS cells need to be differentiated from immunoblasts, which typically are not only smaller than RS cells but also lack prominent nucleoli and may have a plasmacytoid appearance. [4]

Another noteworthy problem is that of separating HL from peripheral T-cell lymphoma (PTCL) that may contain cells, which are notorious for mimicking RS cells. Although this problem has been well addressed in a study by Mathur et al. [6] and criteria have been proposed to delineate the two, practical difficulties do persist.

Another confounding factor is the presence of an exuberant granulomatous response in association with HL, which may distract the observer from the underlying pathology. [7] In our study, we observed five cases that had well-formed granulomas. Along with a meticulous search for atypical cells that stand out in a reactive background, clinical suspicion may resolve the issue in these cases to some extent.

A total of six false negatives were encountered. Two of these were signed out as reactive smears, which even upon careful review did not show any features to substantiate a diagnosis of HL or even LPD. These were possibly due to focal involvement of the lymph node by the disease in one case and a preponderance of reactive lymphoid cells in the other, which were inadequately sampled on FNAC.

Of the four hypocellular aspirates, biopsy showed marked fibrosis in two cases, one each of nodular sclerosis and lymphocyte depletion. Fibrosis has been reported as a major confounding factor even in other studies. [4],[8] Disparity between the size of the lymph node and cellularity should alert one to this possibility and a repeat FNA/biopsy is recommended. The cause for discrepancy in the remaining two cases could be attributed to possible sampling error, due to the small size (less than 1 cm) in one while it remained unexplained in the other.

   Conclusions Top

FNA is a useful tool in the initial diagnosis of HL, but one has to always be aware of its pitfalls. Classic RS cells are not always abundant. Instead, the presence of atypical mononuclear cells and granulomas together should raise a high index of suspicion for further evaluation. One has to make a careful search for these features in a reactive background, which is a difficult task. Hypocellular aspirates from clinically significant/large lymph nodes should also alert the pathologist to the possibility of fibrosis obscuring the primary pathology. Biopsy is mandatory in such cases.

In the end, even if one is unable to make a definitive diagnosis of HL with FNAC, it certainly identifies patients who need a biopsy especially in cases with strong clinical suspicion and hence, is a good screening tool.

   References Top

1.Das DK, Gupta SK, Datta BN, Sharma SC. Fine needle aspiration ­cytodiagnosis of Hodgkin's disease and its subtypes: scope and ­limitations. Acta Cytol 1990;34:329-36.  Back to cited text no. 1    
2.Das DK. Value and limitation of fine-needle aspiration cytology in diagnosis and classification of lymphomas: a review. Diagn Cytopathol 1999;21:240- 9.  Back to cited text no. 2    
3.Steel BL, Scwartz MR, Ramzy I. Fine needle aspiration biopsy in the diagnosis of lymphadenopathy in 1,103 patients: role, limitations and analysis of diagnostic pitfalls. Acta Cytol 1995;39:76-81.  Back to cited text no. 3    
4.Chhieng DC, Cangiarella JF, Symmans WF, Cohen JM. Fine needle aspiration cytology of Hodgkin disease: a study of 89 cases with emphasis on the false-negative cases. Cancer Cytopathol 2001;93:52-9.  Back to cited text no. 4    
5.Demay RM. The art and science of cytopathology. Vol II. ASCP: ­Chicago, IL; 1996. p. 779-846.  Back to cited text no. 5    
6.Mathur S, Verma K. Peripheral T-cell lymphoma not otherwise specified vs. Hodgkin's lymphoma on fine needle aspiration cytology. Acta Cytol 2005;49:373-7.  Back to cited text no. 6    
7.Khurana KK, Stanley MW, Powers CN, Pitman MB. Aspiration cytology of malignant neoplasms associated with granulomas and granuloma-like features: diagnostic dilemmas. Cancer 1998;84:84-91.  Back to cited text no. 7    
8.Jogai S, Dey P, Al Jassar A, Amanguno HG, Adesina AO. Role of fine needle aspiration cytology in nodular sclerosis variant of Hodgkin's lymphoma. Acta Cytol 2006;50:507-12.  Back to cited text no. 8    

Correspondence Address:
T Rajalakshmi
Department of Pathology, St. John's Medical College, Bangalore - 560 034
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.40651

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