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Fine Needle Aspiration Cytology Diagnosis of Malignant Lymphoma

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Fine Needle Aspiration Cytology Diagnosis of Malignant Lymphoma J Clin Pathol 1998;51:197–203 197 Fine needle aspiration cytology diagnosis of J Clin Pathol: first published as 10.1136/jcp.51.3.197 on 1 March 1998. Downloaded from malignant lymphoma and reactive lymphoid hyperplasia C J R Stewart, J A Duncan, M Farquharson, J Richmond Abstract and, therefore, helps to guide appropriate spe- Aims—To assess the diagnostic accuracy cialist referral and further investigation.1 of lymph node fine needle aspiration FNA cytology is highly reliable in the identi- (FNA) cytology to distinguish reactive fication of metastatic carcinoma and melanoma lymphoid hyperplasia from malignant in lymph nodes, limiting the requirement for lymphoma, and to evaluate the contribu- diagnostic excision biopsy in many patients. tion of ancillary techniques applied to However, the role of aspiration cytology in the cytological material. assessment of primary lymphoproliferative dis- Methods—Two hundred and seventy seven orders has been less certain.2 Both clinicians consecutive lymph node FNA specimens and pathologists have doubted whether an reported to be consistent with reactive accurate cytological diagnosis of lymphoma is lymphoid hyperplasia (n = 213) or possible, and early reports suggested that FNA suggestive/diagnostic of malignant lymph- produced high false negative rates in patients oma (n = 64) were reviewed. Follow up data with Hodgkin’s disease and low grade non- were obtained by case record review or by Hodgkin’s lymphoma. In addition, the com- histological correlation. The value of im- plexity of lymphoma classifications and the munocytochemistry, in situ hybridisation prognostic importance of architectural assess- for immunoglobulin light chain mRNA, ment in some lymphoid tumours limits the and polymerase chain reaction (PCR) extent of cytological correlation with histology. towards the final clinicopathological diag- However, recent studies have indicated that an nosis was assessed in 92, 61, and 45 cases, accurate diagnosis of lymphoma can be respectively. achieved by FNA in 85–90% of cases, particu- Results—Sixty one of 67 lymphomas and larly when morphological assessment is com- 207 of 209 reactive lymph nodes were accu- plemented by the use of immunocytochemical rately diagnosed by FNA cytology. There techniques.2–4 Furthermore, genotypic analysis were six false negative aspirates including including Southern blot and polymerase chain http://jcp.bmj.com/ three cases of follicular lymphoma, two reaction (PCR) to detect immunoglobulin and cases of Hodgkin’s disease, and one T cell receptor gene rearrangements, and in situ chronic lymphocytic leukaemia. Two FNA hybridisation (ISH) to detect immunoglobulin specimens considered suspicious of light chain mRNA expression may be applied lymphoma proved reactive on histology or successfully to FNA specimens.5–9 Skoog and clinical follow up. One metastatic small Tani have suggested that lymph node aspiration cell carcinoma was wrongly diagnosed as cytology supplemented by appropriate ancillary lymphoma. Ancillary studies contributed investigations oVers similar diagnostic accuracy on September 29, 2021 by guest. Protected copyright. to the correct diagnosis in most cases to excision biopsy.10 although occasional misleading results Previously, we described the use of immuno- were obtained, particularly with PCR. cytochemistry, ISH, and PCR in the assess- Conclusions—FNA cytology accurately ment of small series of lymphoid aspirates distinguished reactive lymphoid hyper- derived from both lymph nodes and extranodal plasia from malignant lymphoma in 97% sites.89 In this report, we studied the value of of cases. However, occasional wrong diag- these techniques in routine practice, and noses occurred owing to sampling error or examined the diagnostic accuracy of FNA in Department of misinterpretation. Ancillary studies can distinguishing malignant lymphoma from reac- Pathology, The Royal be applied to cytological samples and con- tive lymphoid hyperplasia in a series of 277 Infirmary, Castle tribute to the diagnosis in most cases. consecutive lymph node aspirates performed in Street, Glasgow ( 1998; :197–203) G4 0SF, UK J Clin Pathol 51 Glasgow Royal Infirmary. C J R Stewart M Farquharson Keywords: fine needle aspiration; cytology; lymphoma; J Richmond lymph node Methods DIAGNOSTIC CASES Department of All fine needle aspiration performed on pa- Medical Oncology, The Royal Infirmary Fine needle aspiration (FNA) cytology is being tients with palpable lymph node enlargement J A Duncan used increasingly in the assessment of patients in Glasgow Royal Infirmary between January with lymph node enlargement. The technique 1993 and May 1997 were reviewed. The aspi- Correspondence to: is safe and simple and can be used to sample rates were performed by cytology staV using 23 Dr Stewart. multiple sites. The use of rapid staining or 25 G needles. In most cases, needles were Accepted for publication techniques often allows a provisional diagnosis attached to 10 ml syringes with a syringe 9 December 1997 to be made at the patient’s initial presentation holder (Cameco, London, UK), but a few 198 Stewart, Duncan, Farquharson, et al Table 1 Correlation of FNA diagnosis and final (Dako) was performed in those cases in which clinicopathological diagnosis in 277 lymphoid aspirates metastatic carcinoma or melanoma were in- J Clin Pathol: first published as 10.1136/jcp.51.3.197 on 1 March 1998. Downloaded from cluded in the diVerential diagnosis. In situ Final clinicopathological diagnosis hybridisation and PCR were used in cases of FNA diagnosis Reactive NHL HD Met CA suspected B cell lymphoma, mainly in the latter Reactive lymphoid half of the study period. hyperplasia (n = 213) 207 4 2 – In each case, an attempt was made to catego- Diagnostic of NHL (n = 40) – 39 – 1 Suggestive of NHL (n = 8) 1 7 – – rise the value of the special techniques in reach- Diagnostic of HD (n = 13) – – 13 – ing the final clinicopathological diagnosis. The Suggestive of HD (n = 3) 1 – 2 – technique was considered helpful if it supported NHL, non-Hodgkin’s lymphoma; HD, Hodgkin’s disease; Met or confirmed the correct diagnosis, unhelpful if CA, metastatic carcinoma. it was essentially non-contributory, and mis- leading if it suggested either a false negative specimens were obtained using the non- (reactive pattern in proven lymphoma) or a false aspiration technique. Routinely, two aspirates positive (monoclonal pattern in proven reactive were performed and direct smears were lymph node) diagnosis. prepared for staining with DiV-Quick (Dade, Abingdon, UK), May-Grunwald-Geimsa, Results and/or Papanicolaou methods. Thereafter, the CLINICOPATHOLOGICAL CORRELATION needles were rinsed in 10 ml normal saline. In The 277 lymphoid aspirates were obtained selected cases, cytospin preparations from the from 260 patients. Fifteen patients underwent saline washes were used for special techniques, FNA on two occasions and one patient had and the washes were submitted for culture in three aspirates. those cases where infection was suspected. The correlation between the cytological In total, 549 lymph node aspirates were diagnoses and the final clinicopathological performed during the study period of which 235 assessment is summarised in table 1. (42.8%) showed metastatic carcinoma or Sixty four aspirates were considered diagnos- melanoma. Thirty seven (6.7%) FNA speci- tic (n = 53) or suspicious (n = 11) of mens were inadequate for diagnosis. The lymphoma and, of these, 47 represented the remaining 277 aspirates showed a lymphoid primary diagnosis of a lymphoproliferative dis- pattern that was considered reactive in 213 cases order while 17 represented recurrent disease (38.8%) and diagnostic or suggestive of malig- after treatment. Forty eight specimens were nant lymphoma in 64 cases (11.7%); these lym- considered to be derived from non-Hodgkin’s phoid aspirates form the basis of this study. lymphoma, of which 46 were reported as B cell The diagnostic accuracy of FNA cytology lymphomas on the basis of cytomorphology and was assessed by histological correlation or by ancillary investigations; two non-Hodgkin’s clinical follow up. Clinical data were obtained lymphomas were not otherwise specified cyto- by review of case records or by correspondence logically. Sixteen cases were reported as sugges- http://jcp.bmj.com/ with referring physicians and general practi- tive or diagnostic of Hodgkin’s disease. In gen- tioners. The follow up period for those eral, no attempt was made to subclassify specimens diagnosed as reactive lymphoid lymphomas further on FNA cytology. hyperplasia averaged 13 months. Of those cases considered diagnostic of lymphoma cytologically, clinicopathological SPECIAL TECHNIQUES correlation confirmed the FNA diagnosis in 39 Additional studies were performed on selected of 40 non-Hodgkin’s lymphomas and in all 13 aspirates to aid distinction between reactive cases of Hodgkin’s disease. However, one aspi- on September 29, 2021 by guest. Protected copyright. and neoplastic lymphoid proliferations and, in rate considered diagnostic of non-Hodgkin’s a few cases, to distinguish lymphoid from non- lymphoma was shown to be metastatic small lymphoid neoplasms. cell carcinoma on excision biopsy. Lymph node Immunocytochemistry, ISH to detect immu- biopsy was confirmatory in eight of 11 aspirates noglobulin light chain mRNA, and PCR for reported as suspicious of lymphoma, while one immunoglobulin heavy chain gene rearrange- further case (not biopsied) was clinically ment were used, as described previously.89 consistent with
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