Genotypic analysis of DNA isolated from fine needle aspiration biopsies

DNA was isolated from 20 fine needle aspiration (FNA) biopsies from lymphomas, hyperplastic lymph nodes and nonlymphoid malignant tumors. Small aliquots (0.2 microgram to 2.0 micrograms) of DNA from each sample were digested to completion with restriction endonuclease Eco RI and/or Bam HI and electrophoresed in 0.8% agarose minigels. DNA was transferred to a nylon filter after brief treatment in HCl and subsequent denaturation and neutralization. Filters were hybridized to radiolabeled JH, C kappa, TCR beta or bcl-2 probes to determine if these genes were in germline or rearranged configurations in each of the samples. It was possible to demonstrate rearrangement of at least one immunoglobulin gene in each of the samples diagnosed as lymphoma, while all samples derived from hyperplastic lymph nodes and nonlymphoid malignant tumors exhibited a germline pattern for each probe tested. Thus, FNA biopsies can provide suitable and sufficient DNA for genotypic analysis using molecular probes that detect gene rearrangement.     

Immunoglobulin and T cell receptor gene rearrangements in lymphoproliferative disorders

Thirty-one samples representing Hodgkin's and non-Hodgkin's lymphomas, angioimmunoblastic lymphadenopathy (AILD), and benign follicular hyperplasia in HIV infections were examined for rearrangements of the immunoglobulin (Ig) and T cell receptor (TcR) beta-chain gene loci. In 11 of 12 non-Hodgkin's lymphomas (classified as Burkitt lymphoma (2), centrocytic lymphoma (1), centrocytic-centroblastic lymphoma (5), centroblastic lymphoma (3], only rearranged Ig genes could be detected. The exceptional case was an unclassified high-grade lymphoma, which represented a rearrangement of the TcR beta-chain. We also examined DNA from lymphoid neoplasms in which the lineage of the malignant cell was still controversial. Rearrangement of the TcR could exclusively be demonstrated in all 3 cases of AILD. One Ig gene rearrangement and 4 TcR beta-chain rearrangements were found in 13 samples of Hodgkin's lymphomas (11 lymph nodes, 1 pleura effusion and 1 bone biopsy with proven infiltration). Examination of 3 cases of benign follicular hyperplasia in HIV infection represented one Ig rearrangement.     

Molecular genetic analysis in the diagnosis of lymphoma in fine needle aspiration biopsies. I. Lymphomas versus benign lymphoproliferative disorders

The configurations of immunoglobulin genes, T-cell receptor (TCR) beta chain genes and bcl-2 genes were analyzed by Southern blotting in DNAs derived from 35 fine needle aspiration biopsies from various lymphoproliferative disorders. Only 1 of 16 benign lymphoproliferative disorders showed clonality: the lymph node of a patient with Wiskott-Aldrich immunodeficiency syndrome, in which clonal rearrangement of the TCR beta chain gene was detected. Clonality was demonstrated in all 14 non-Hodgkin's lymphomas (NHLs), 2 of 3 cases of Hodgkin's disease (HD) and 2 cases diagnosed as NHL or angioimmunoblastic lymphadenopathy (AILD). None of the aspirates exhibited rearrangement of the bcl-2 gene. The studies of diagnostically difficult cases proved that molecular genetic analysis of DNA, when appropriately combined with clinical data and light microscopic analysis of the lesions, can be helpful in distinguishing between: (1) a hyperplastic lymph node and NHL or AILD; (2) NHL and well-differentiated lymphocytes; and (3) a hyperplastic lymph node and HD.     

Secondary malignant neoplasms in patients with non-Hodgkin's lymphoma

In 1979-1987, 570 patients with non-Hodgkin's lymphomas (226 female and 344 male patients) were treated at the Department of Hematology of the Pomeranian Medical Academy and hematological outpatient clinic. The second malignant tumors were diagnosed in 25 (4.4%) patients. Two patients suffered from three malignant tumors. The most frequent combination of 2 tumors were: non-Hodgkin lymphoma and cancer of the lungs in 8 patients, non-Hodgkin lymphoma and cancer of the skin in 6 patients, non-Hodgkin lymphoma and cancer of the larynx in 4 patients, non-Hodgkin lymphoma combined with cancer of the stomach in 2 patients, and non-Hodgkin lymphoma together with cancer of the bladder in 2 patients. Moreover, non-Hodgkin lymphoma coexisted with cancer of the colon, cervix and prostate (one case of each). The authors stress the possibility of other malignant tumors in patients with non-Hodgkin lymphomas and occurrence of the subsequent neoplasms without preceding chemo- or radiotherapy.     

Cytomorphology and immunocytochemistry of fine needle aspirates from blastic non-Hodgkin's lymphomas

Fine needle aspirates from 54 consecutive patients with primary or recurrent blastic (high-grade malignant) non-Hodgkin's lymphomas (NHLs) were analyzed by cytomorphology and immunocytochemistry. The cytologic diagnoses induced follicular center-cell-derived (centroblastic or anaplastic centrocytic) lymphoma (31 cases), immunoblastic lymphoma (11 cases), lymphoblastic lymphoma (9 cases) and histiocytic lymphoma (3 cases). Immunocytochemistry showed a B-cell phenotype of the neoplastic lymphocytes in all lymphoblastic lymphomas, 29 follicle center-cell lymphomas and 4 immunoblastic lymphomas. Four of the immunoblastic lymphomas were of T-cell origin while one case was not evaluable due to necrosis. A histiocytic origin was confirmed in two of the three cases that had a cytologic diagnosis of histiocytic lymphoma; the third case was shown by immunocytochemistry to be a true Ki-1-positive large cell lymphoma. Histologic and immunohistochemical analysis were performed on surgical biopsies from 18 patients. The results were in agreement with those on the fine needle aspiration (FNA) material in 14 cases. Three lymphomas could be phenotyped on aspirated material while marker studies on excised material were inconclusive. One lymph node aspirate contained mostly necrotic cells, which were unsatisfactory for adequate immunocytochemistry. However, sections from a removed tonsil from the same patient could be used for conclusive histology and phenotyping. In conclusion, the high diagnostic accuracy of combined cytomorphologic and immunocytochemical assessment of FNA samples validates the use of the technique in the diagnostic work-up of blastic (high-grade malignant) NHLs. In fact, the diagnostic accuracy seems so high that the technique can safely be used in the final diagnosis of blastic NHLs.     

Pleural effusions in non-Hodgkin's lymphoma. A cytomorphologic, cytochemical and immunologic study

Review of the records of 243 cases of cytologically diagnosed non-Hodgkin's lymphomas (NHL) revealed pleural effusions in 21 (8.6%). Cytologic examination of pleural fluid was done in 17 cases, of which 16 were reported as positive. Cytologic examination was supplemented with cytochemical staining (acid phosphatase, alpha naphthyl acetate esterase and periodic-acid-Schiff reactions) and E-rosetting studies in 12 cases. Of the 16 positive cases, 11 were malignant lymphomas consisting of convoluted lymphocytes. Acute lymphatic leukemia of the prothymocytic type (T-ALL) and chronic lymphocytic leukemia of the T-cell type (T-CLL) comprised one case each, and there were three cases of follicular center cell lymphomas, two of the cleaved-cell type and one of the Burkitt-type. Comparison of the cytomorphology of the tumor cells in the pleural effusion with those in fine needle aspiration smears from the solid tumors in 14 cases showed an identical appearance in 13 cases; in one, the Burkitt-type lymphoma, the cells were larger and more pleomorphic in the pleural effusion. This study indicates that the cytologic diagnosis and categorization of NHL of the convoluted-cell type is greatly enhanced by the study of neoplastic lymphocytes in a pleural effusion.     

Leukocyte-common antigen and vimentin are reliable adjuncts in the diagnosis of non-Hodgkin's lymphoma in fine needle aspirates

Alcohol-fixed fine needle aspirates of 82 non-Hodgkin's malignant lymphomas (NHLs) were tested for the presence of vimentin and leukocyte-common antigen (LCA) by means of monoclonal antibodies (MAbs) and indirect immunofluorescence. All NHLs stained positively for vimentin; the staining was strong in all except three cases. Of the 69 NHLs tested for LCA, 1 (a large cell T-cell lymphoma) was negative while the staining was weak in 6. Thus, vimentin and LCA MAbs are sensitive, specific and reliable complementary diagnostic adjuncts that are useful in the definitive diagnosis of NHLs in alcohol-fixed fine needle aspirates. Their presence in the aspirate confirmed a cytologic diagnosis of NHL in 47 cases, helped to diagnose NHL in 31 cases in which a cytologic differential diagnosis with small cell anaplastic carcinoma could not be made with confidence and helped to change the initial cytologic diagnosis of anaplastic carcinoma to NHL in 4 cases.     

DNA polymerase chain reaction using fine needle aspiration biopsy smears to evaluate non-Hodgkin's lymphoma.

OBJECTIVE: To apply polymerase chain reaction (PCR) analysis to the fine needle aspiration biopsy (FNAB) evaluation of lymphoid proliferations. STUDY DESIGN: We analyzed 37 consecutive archived FNAB malignant lymphoma specimens. Immunophenotypic data from the fine needle aspiration biopsy and excisional biopsy material was available for all specimens. PCR to identify monoclonal rearrangements of the immunoglobulin heavy chain gene, T-cell receptor and translocations involving the bcl-1 and bcl-2 genes was performed. RESULTS: Seventy-eight percent of cases were detected by at least one of these assays. Where DNA analysis was performed on excisional biopsy material, 70% of the cases had identical results; no discordant results for the immunoglobulin heavy chain gene or T-cell receptor were found. In 23% of cases, after review of all available data, a discordant result was thought to be a consequence of a false negative result in DNA analysis of excisional biopsy material. CONCLUSION: These findings indicate that PCR analysis of archived FNAB material, when necessary, provides useful information for diagnosis and staging of malignant non-Hodgkin's lymphomas.     

Cytodiagnosis of malignant non-Hodgkin's lymphomas in effusions (author's transl)

Body cavity effusions in malignant non-Hodgkin's lymphomas, particularly in the early stages of those neoplasms, are rare in comparison to the far more common effusions in other malignant diseases and in inflammatory processes. Therefore, the cytological differential diagnosis is of great importance. Of 7,000 pleural and 1,700 ascitic effusions, only 42 cases were malignant non-Hodgkin's lymphoma and in 30 lymphoma was suspected. When lymphoma is suspected, particularly low-grade lymphoma, there are great difficulties in making a differential diagnosis. Using the more or less typical cellular and nuclear criteria of the various lymphoma types, an attempt was made to classify the unequivocal lymphomas according to the Kiel classification of malignant non-Hodgkin's lymphomas. In principle these criteria are the same in cytological and histological examinations. In 31 cases the lymphoma subtype could be specified and confirmed in part by subsequent histological examination. Apart from the suspect lymphoma cases (40%), cases of a low grade of malignancy were predominantly observed (28%). Lymphomas with a high grade of malignancy were less frequently encountered (15%), a proportion similar to that of unclassifiable lymphomas (16%). Apparently the cytological and karyological criteria are not yet adequate to classify lymphomas from conventionally prepared cytological specimens with a higher degree of accuracy.     

Diagnosis of follicular lymphoma by fine needle aspiration biopsy.

This study evaluated the diagnostic accuracy of fine needle aspiration biopsy (FNAB) of follicular lymphoma (FL). Fourteen aspirates of lymph nodes in which follow-up surgical biopsy revealed FL were studied. Two aspirates were deemed unsatisfactory because of a paucity of cells. The remaining 12 cases received the following diagnoses: 4 positive for malignant lymphoma, 4 highly suspicious for malignant lymphoma and 4 false negatives. FNAB of FL can show a monomorphic or polymorphic cell population. The aspirates with a positive or suspicious diagnosis showed monomorphic cell populations. False-negative diagnoses were attributable to misleading sampling or preparation methods in most cases. We conclude that FNAB of FL is less accurate than FNAB of non-Hodgkin's malignant lymphoma (NHL) in general, but the accuracy rate is similar to that of FNAB of all low-grade NHL. The value of current approaches to the diagnosis of suspected lymphoma by FNAB is emphasized.     

Morphometric characterization of nuclei in non-Hodgkin's malignant lymphoma

In addition to the nuclear area and a form factor, four morphometric parameters of nuclear shape (ID, R1, R2 and ND), obtained by the application of the principles of mathematical morphology, were used to characterize the nuclear contours in non-Hodgkin's malignant lymphomas. The values for each parameter were determined in 58 cases of non-Hodgkin's lymphoma categorized according to the Kiel and National Cancer Institute classifications. Small-cell, mixed and large-cell lymphomas could be distinguished on the basis of the mean nuclear area. The shape parameters R1, R2 and ID were efficient discriminators of the large centrocytic (cleaved-cell) lymphomas. Neither size nor shape factors could distinguish between centroblastic and immunoblastic tumors. The good correlation between the morphometric findings and the histopathologic categories suggest that morphometry may provide a quantitative and objective method for grading lymphomas.     

The role of fine needle aspiration cytology in the diagnosis of lymphoma

The accuracy of fine needle aspiration (FNA) cytology for the diagnosis of lymphoma and other hematolymphoid malignancies was investigated by a review of 158 FNA specimens from 143 patients. Patients included in the study had either a diagnosis of a hematolymphoid malignancy by FNA cytology or a biopsy diagnosis of lymphoma that was preceded by FNA cytology. Biopsy specimens were obtained from 85% of the patients. Of the 158 needle aspirates, 118 (75%) were diagnosed as lymphoma, 13 (8%) as suspicious of lymphoma, 8 (5%) as myelomas, 3 (2%) as leukemias, 12 (8%) as positive for malignancy and 4 (2%) as negative for malignancy. Two of the 118 needle aspirates diagnosed as lymphoma were false positives while 3 of 13 diagnosed as suspicious for lymphoma were found to be benign. Overall, there were four false negatives. Morphologic subclassification of the lymphomas, originally attempted for 60 needle aspirates, was identical to the histologic subclassification in 51 cases (85%). FNA cytology provided the initial diagnosis of a hematolymphoid malignancy in 51% of the cases and allowed the documentation of recurrent disease in 49%. The results demonstrate the usefulness of FNA cytology for the diagnosis and management of patients with lymphoma.     

Fine needle aspiration of pediatric abdominal masses. Cytologic and electron microscopic diagnosis.

Fine needle aspiration (FNA) was performed under ultrasound guidance on 17 abdominal masses in 16 pediatric patients at Baragwanath Hospital. The aspirated cellular material was assessed by conventional cytomorphology and by electron microscopy (EM). A diagnosis of malignancy was rendered for all 15 tumors that were adequately sampled (88.2%); the remaining 2 masses yielded insufficient material for either light microscopy or EM. Cytologic cell typing (including the use of EM) was successful in 12 of the 15 tumors (80%) as compared with the histologic diagnosis. EM was in agreement with the initial cytologic diagnosis in eight tumors, but corrected the initial impression in four tumors. The tumors with adequate aspirates included nine nephroblastomas and single examples of neuroblastoma, hepatoblastoma, non-Hodgkin's lymphoma, rhabdomyosarcoma, renal carcinoma and malignant rhabdoid tumor. The last three were not accurately typed by cytology plus EM. These preliminary results suggest that FNA cytology with adjunctive EM could become a useful technique in the preoperative assessment of pediatric abdominal tumors.     

Cytodiagnosis of lymphoid proliferations by fine needle aspiration biopsy. Adjunctive value of flow cytometry

OBJECTIVE: To determine the accuracy of fine needle aspiration biopsy (FNAB) complemented by flow cytometry (FC) for the diagnosis of reactive and neoplastic lymphoid proliferations and subclassification of malignant lymphomas. STUDY DESIGN: Forty-one FNABs of lymphoid lesions on which FC had been performed were evaluated retrospectively. All cases were correlated with histology or clinical follow-up. RESULTS: Twelve FNABs were diagnosed as reactive. Eleven of the 12 were confirmed as reactive on follow-up. One was a case of posttransplant lymphoproliferative disorder. Twenty-five FNABs diagnosed as lymphoma were confirmed by histology. In 22 of these 25 cases, there was 100% correlation between the subclassification given on FNAB with FC and that given on histology. Two of the remaining cases, which were correctly called follicular center cell lymphoma, showed discrepancies in grading. One case called Hodgkin's disease on FNAB was T-cell lymphoma on histology. Of four FNABs given an inconclusive diagnosis, two were lymphoma on follow-up, and two were reactive. CONCLUSION: FNAB examination, when it includes immunophenotyping by FC, is a useful technique for distinguishing reactive lymphoid proliferations from malignant lymphomas and for the subclassification of lymphomas.     

Morphologic and immunocytochemical evaluation of 220 fine needle aspirates of malignant lymphoma and lymphoid hyperplasia

A total of 220 fine needle aspiration (FNA) specimens from 212 patients with clinically suspected or previously histologically confirmed lymphoma were evaluated by cytology in conjunction with immunophenotyping analysis of the aspirate; the results were compared with the histologic diagnosis made on previous or current accessions of lymph node or extranodal tissue. Smears of the aspirates were stained with the Diff-Quik and Papanicolaou stains while immunoperoxidase staining using antibodies against kappa and lambda immunoglobulin light chains and Leu-4 was routinely performed on Cytospin preparations. Where indicated, additional marker studies (including T-200, Leu-1, Leu-2a, Leu-3a + 3b, Leu-M1, B1, Leu-12, IgM, CALLA and TdT) were performed. For the non-Hodgkin's lymphomas, specimens were classified by the cytologic characteristics of the neoplastic cells according to the International Working Formulation scheme. The combination of cytologic smears and immunoperoxidase studies resulted in a diagnosis of lymphoma in 173 cases (79%). The remaining aspirates were interpreted as suspicious for lymphoma (7%), benign (10%) or inadequate for diagnosis (4%). Of the 15 suspicious aspirates, 5 proved to be Hodgkin's disease and 2 to be T-cell lymphoma by subsequent biopsy. The cause of failure in the nine inadequate aspirates were necrosis (3 cases), sclerosis (2 cases) and faulty technique (4 cases). In the cases that had concurrent tissue biopsies, no false-positive diagnoses were rendered. These results indicate that FNA used in association with immunocytochemistry is a reliable tool for establishing the diagnosis and classification of the majority of cases of lymphoma. Optimal immunoglobulin light-chain ratios for defining monoclonality in FNA specimens of B-cell lymphomas are proposed.     

Cytomorphologic characteristics of non-Hodgkin's lymphoma

The cytologic samples of 84 non-Hodgkin's lymphomas, classified according to the Rappaport system, were reviewed, with particular attention to the cell pattern, the size of the cells and other morphologic characteristics. The analysis revealed that: (1) the subgroups of malignant lymphoma in the Rappaport classification display a heterogeneous cytologic picture; (2) cytology cannot make the differentiation between nodular and diffuse non-Hodgkin's malignant lymphomas; and (3) reliable cytologic classification is possible only in certain cases of well-differentiated lymphocytic and diffuse histiocytic lymphomas. Well-differentiated lymphocytic lymphoma is characterized by a uniform cell picture consisting of mature lymphocytes, prolymphocytes or centrocytes up to 12 micron in size, by the presence of paraimmunoblasts and by the absence of reticulum cells. The diffuse histiocytic lymphoma contains over 48% centroblasts or over 8% immunoblasts or multinucleated giant blast cells.     

Preoperative cytologic diagnosis of primary gastrointestinal malignant lymphoma

This report is based on the review and study of primary gastrointestinal malignant lymphomas as seen in cytologic brushing and washing specimens. During a period of 12 years (1970 to 1981), a total of 2,675 patients with malignant lymphoma involving the gastrointestinal tract were seen at Memorial Sloan-Kettering Cancer Center. Of these patients, 73 were diagnosed as having primary malignant lymphoma of the gastrointestinal tract. A total of 49 preoperative cytologic specimens obtained from 29 patients with histologically confirmed primary gastrointestinal malignant lymphoma were examined and are the basis for this study. Twenty-four patients had gastric primaries; three tumors were in the colon and two were small intestinal lymphomas. Thirty-three cytologic specimens taken from 25 patients were considered diagnostic for malignant lymphoma. A positive cytologic brushing was the only diagnostic preoperative specimen for 9 of the 29 patients. Combined cytologic and biopsy specimens provided a diagnosis of malignant lymphoma for 16 patients. Cytologic washings did not add to the diagnostic accuracy. The 29 cases of malignant lymphoma reviewed here were histologically subclassified as 23 large-cell, poorly differentiated and six small-cell, well-differentiated lesions. The cytomorphologic features of malignant lymphoma as observed in gastrointestinal specimens are outlined, and differential diagnoses are discussed. Clinicopathologic implications of the cytologic findings are considered.     

Analysis of proliferating cell fraction determined by monoclonal antibody to M1-subunit ribonucleotide reductase and Ki-67 in relation to p53 protein expression in fine-needle aspirates from non-Hodgkin's lymphomas

The purpose of this study was to analyse the proliferative fraction with the monoclonal antibody M1-R-R to M1-subunit ribonucleotide reductase and with MIB-1 to Ki-67 antigen in relation to p53 protein expression in fine needle aspirates from B-cell non-Hodgkin's lymphomas. One hundred and thirty-seven cases, previously diagnosed and sub-typed according to the Kiel classification and characterized by immunophenotyping, were included in the study. The M-1 subunit ribonucleotide reductase (M1-R-R), Ki-67 and p53 antigens were detected using monoclonal antibodies on stored cytospin preparations. There was a good correlation (r = 0.72) between Ki-67 and M1-R-R positive cell fraction in both high and low grade lymphomas. High-grade lymphomas had a median percentage of M1-R-R/MIB-1 positive cells of 53.0/73.0 for lymphoblastic, 61.0/52.0 for immunoblastic and 33.5/41.0 for centroblastic lymphomas, respectively. In low grade lymphomas figures of median percentage of M1-R-R/MIB-1 were 9.0/15.0 for centroblastic/centrocytic, 11.0/9.5 for chronic lymphocytic leukaemia, 16.0/27.0 for centrocytic and 12.0/9.0 for immunocytomas, respectively. The median percentages of M1-R-R/MIB-1 for high and low grade lymphomas were 37.0/50.5 and 11.0/12.0, respectively. In the p53 positive cases the proliferation rate as measured by staining for M1-R-R and MIB-1 was higher than in p53 negative cases, but the difference was not statistically significant. The results show that cytospin material obtained by fine needle aspiration and stored at -70 degrees C for years can be used reliably for both peroxidase-avidin-biotin and three-step alkaline phosphatase immunocytochemical staining. In addition, proliferation fraction determined by M1-R-R monoclonal antibody staining correlates well with that measured by an established marker for cell proliferation, the Ki-67 antibody. However, the proliferation fraction as measured by the two antibodies differs in the various subtypes of non-Hodgkin's lymphoma which indicates that they may contribute different prognostic information.     

Fine needle aspiration cytology diagnosis of lymphoproliferative disease of the breast

OBJECTIVE: To evaluate the role of fine needle aspiration cytology (FNAC) in the diagnosis of lymphoproliferative disease (LPD) of the breast. STUDY DESIGN: Over a period of 20 years (January 1982-December 2001), 13 diagnosed and/or suspected cases of LPD of the breast on FNAC were retrieved and reviewed from the files of the Cytology Laboratory, Department of Pathology, All India Institute of Medical Sciences. For each case, both May-Grünwald-Giemsa- and Papanicolaou-stained smears were reviewed along with hematoxylin and eosin-stained tissue sections and immunohistochemistry, when available. RESULTS: Of the 13 cases, 1 aspirate was from a male breast and the rest were from female. Only 12 cases with documented histology were included in the study. Five of the 12 cases were diagnosed on FNAC as high grade lymphoma, 2 as low grade lymphoma, 2 as poorly differentiated malignant tumor/lymphoma, and 1 each as Hodgkin's lymphoma, acute myeloid leukemia (AML) deposit and immature lymphoid cells, ?leukemia/lymphoma deposit. The tumors manifested mostly as an unilateral mass (10 cases), with 2 cases presenting with bilateral breast lumps. The lymph nodes were involved in 8 cases. Histologically, 2 of the 12 cases were poorly differentiated malignant tumors. Of the remaining 10 cases, 8 were documented as non-Hodgkin's lymphoma and 1 each as Hodgkin's lymphoma, mixed cellularity and AML. CONCLUSION: FNAC is an inexpensive but highly useful diagnostic tool to distinguish between primary lymphoma and carcinoma of the breast. This helps with clinical management in avoiding unnecessary surgical procedures.     

Value of aspiration cytology of the thyroid in metastatic disease

Metastases may simulate primary malignant tumors of the thyroid, causing problems in the diagnosis and management of patients with a history of cancer. In the seven-year period of July 1978 through June 1985, 8 of 549 needle aspirates of the thyroid contained metastatic tumor, 6 of which were subsequently confirmed by histologic study. The primary sites of origin were the breast, kidney, colon and stomach as well as lymphoma. The cytologic features observed in the aspiration biopsy material from the six cases were characteristic of each of the primary tumors. Three of the patients had had prior resections of carcinomas (breast, colon and stomach) while in three patients the cytologic diagnosis of the thyroid aspirates led to the discovery of the primary tumor (kidney and two lymphomas). One case of lymphoma/leukemia and one case of previously biopsied lung carcinoma were confirmed on clinical grounds. It is of critical importance that primary thyroid neoplasms occurring in patients known to have primary tumors elsewhere be distinguished from disseminated tumors involving the thyroid. Our experience suggests that fine needle aspiration is of considerable value in this differential diagnosis. Needle aspirates of the thyroid are also of value in leading to the diagnosis of unsuspected nonthyroidal primary cancer.