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.     

Contribution of flow cytometric immunophenotyping to the evaluation of tissues with suspected lymphoma?

BACKGROUND: A critical analysis of the contribution of flow cytometric immunophenotyping (FCI) to the evaluation of lymph nodes and extranodal tissues with suspected lymphoma by a large, retrospective approach has not been reported previously and represents the purpose of this study. METHODS: A total of 278 lymph nodes and 95 extranodal tissue specimens submitted over a 2-year period with complete histologic, FCI, and immunohistochemical (IH) data formed the basis of the study. RESULTS: The FCI data contributed significantly to or was consistent with the final tissue diagnosis in the majority (94%) of the tissue samples. There is no well-described utility of flow cytometry markers for Hodgkin's lymphoma (HL) due to the usual scarcity of tumor cells in the final cell suspensions obtained from these tumors. However, the FCI data excluded non-Hodgkin's lymphoma (NHL) and suggested the possible usefulness of CD15 and CD30 by FCI in HL. In addition, immunophenotypic data by FCI in combination with touch imprint cytomorphology was useful in excluding a diagnosis of NHL in cases of nonhematopoietic malignancies and was particularly useful in defining the following hematopoietic tumors and malignancies: thymoma, T-cell lymphoblastic lymphoma, leukemia cutis, and plasma cell dyscrasia. Thus, IH was not essential for the diagnosis in these latter cases and was performed in only two cases (one thymoma and one plasma cell dyscrasia). Of interest, FCI supported the diagnosis in 3 cases of Ewing's sarcoma/primitive neuroectodermal tumor by detection of CD56 on the surface of the malignant cell. Only 11% of NHL were "negative" by FCI (i.e., an aberrant T-cell or monoclonal B-cell population was not identified). Reasons for these discrepancies included partial tissue involvement by the NHL with sampling differences, T-cell rich or lymphohistiocytic-rich variants with a small population of monoclonal B cells, marked tumoral sclerosis, poor tumor preservation, and T-cell NHL without an aberrant immunophenotype. Only 60% of CD30+ anaplastic large cell lymphomas (ALCL) were CD30+ by FCI. CONCLUSIONS: FCI data should always be correlated with light microscopy if no FCI abnormalities are detected; IH may need to be performed in selected cases. It is less necessary to perform microscopic examination of tissues when the FCI data are positive and indisputable. However, in selected cases in which FCI data is diagnostic, microscopic observations may provide additional information due to sampling.     

Nodal presentation of nasal-type NK/T-cell lymphoma. Report of two cases with fine needle aspiration cytology findings

BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoma typically occurs in extranodal sites, such as nasal cavity, nasopharynx, gastrointestinal tract, skin, testis and salivary gland. Secondary lymph node involvement is rarely encountered until late in the disease course. The fine needle aspiration cytology of NK/T-cell lymphoma with a nodal presentation has not been described before. CASES: Two cases of nasal-type (extranasal) NK/T-cell lymphoma with a nodal presentation were seen at Pamela Youde Nethersole Eastern Hospital, Hong Kong. Both patients presented with submandibular lymph node enlargement but unremarkable peripheral blood and bone marrow findings. Fine needle aspiration cytology was available in both cases, showing a heterogeneous population of small to medium-sized lymphoid cells, follicular center cells, plasma cells, eosinophils and some histiocytes. The medium-sized lymphoid cells showed readily discernible nuclear atypia with an irregular nuclear outline. Cell block sections revealed occasional lymphoid cells with pleomorphic nuclei. Immunocytochemical study confirmed the presence of CD56-positive lymphoma cells. In situ hybridization for EBV-encoded RNA also revealed positive nuclear signals. Histologic examination of the surgical biopsies showed interfollicular expansion by malignant lymphoid cells. Immunoglobulin heavy chain gene and T-cell receptor gene rearrangement studies demonstrated a germline pattern, confirming the putative NK (natural killer cell), non-B and non-T lineage of the lymphoma cells. CONCLUSION: Nodal presentation of NK/T-cell lymphoma, though rare, is diagnosable on the basis of fine needle aspiration biopsy alone, especially in view of its distinctive immunophenotype and EBV association. Recognition of the subtle but definite cytologic atypia of malignant lymphoid cells and presence of an appropriate background (including more eosinophils than usual), together with proper application of ancillary techniques, is crucial to arriving at a correct diagnosis.     

Primary non-Hodgkin's lymphoma of the breast: a case report

Extranodal non-Hodgkin's lymphoma (NHL) of the breast is a rare entity. It represents 0.04-1.1% of malignant tumors of the breast. 1.7-2.2% of extranodal lymphomas and 0.7% of all NHL. However, primary NHL (PNHL) is the most frequent hematopojetic tumor of the breast. CASE: A 23-year-old woman presented with a mass in the left breast for 3 months followed by enlarged left axillary lymph nodes. Mammography showed a diffuse increase in the density of the left breast. Other investigations were unremarkable. Both fine needle aspiration cytology (FNAC) and histopathology were diagnostic of NHL. Immunohistochemistry was confirmatory of NHL, diffuse large cell type, of B-cell lineage. CONCLUSION: Primary and secondary lymphomas of the breast, though rare, should be considered in the differential diagnosis of breast malignancies. PNHL of the breast is usually right sided, but this patient had left breast involvement. Diagnosis by FNAC was successful as the cytologic picture is similar to that of any other lymphoid or extranodal NHL. When histopathology and immunohistopathology are conclusive, FNAC, supplemented by immunocytochemistry, can be applied as a simple, reliable and cost-effective tool in the early diagnosis of breast lymphomas.     

Fine needle aspiration cytology of primary non-Hodgkin's lymphoma of the tongue. A case report.

BACKGROUND: Fine needle aspiration cytology (FNAC) of extranodal non-Hodgkin's lymphoma of the tongue has rarely been described. CASE: A 47-year-old male was referred to the cytology laboratory for FNAC of a 3-cm-diameter swelling on the dorsum of the tongue, with a primary clinical diagnosis of soft tissue tumor. FNAC smears showed discrete, monomorphic, round to oval cells with scanty, deep blue cytoplasm. The nuclear margin was regular, with occasional prominent nucleoli and fine nuclear chromatin. The background showed many lymphoglandular bodies. The cells were strongly positive for leukocyte common antigen. A cytologic diagnosis of high grade non-Hodgkin's (NHL) was offered and subsequently confirmed by histopathology. CONCLUSION: Primary NHL of the tongue is relatively rare. As there are no characteristic clinical features of extranodal NHL of the tongue, FNAC may be useful for rapid diagnosis and management of such cases.     

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.     

Cytologic features of NK/T-cell lymphoma

OBJECTIVE: To describe the diagnostic cytologic features of NK/T-cell lymphoma. STUDY DESIGN: The cytologic features of 3 cases of natural killer cell (NK)/T-cell lymphoma were studied and correlated with histology. Immunohistochemistry for CD56, T-cell intracellular antigen (TIA-1) and EBV-encoded small nuclear RNAs (EBER) in situ hybridization was reviewed. RESULTS: The lymphomas have mixed-sized cells with eccentric, round to ovoid nuclei; 1 or 2 prominent nucleoli; and abundant, clear to pale, eosinophilic cytoplasm. Mitotic figures, necrotic debris and tingible body macrophages are common accompaniments. In fluid, the lymphoma cells appear more shrunken. A clot section of 1 case was positive for CD56, TIA-1 and EBER. CONCLUSION: Helpful cytologic features for the diagnosis of NK/T-cell lymphoma are described. Immunohistochemistry for CD56, TIA-1 and EBER in situ hybridization are very helpful adjuncts for the diagnosis.     

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.     

Primary cardiac lymphoma initially diagnosed by routine cytology. Case report and literature review

A case of primary cardiac lymphoma initially diagnosed by routine cytologic examination of pericardial fluid is presented. In a 64-year-old woman woman who originally presented with chest pain and heart block, the initial clinical impression was ischemic heart disease. However, coronary angiography failed to reveal significant disease. An echocardiogram demonstrated pericardial fluid, which was drained. A small amount was sent for cytologic examination, and the diagnosis of malignant lymphoma, large cell type, was made. Subsequent radiologic examinations revealed an intracardiac mass involving the atrioventricular canal; surgical biopsy confirmed the diagnosis of a large cell lymphoma. While primary malignant lymphoma of the heart is rare, this case highlights the efficacy of routine cytologic examination of an effusion fluid (often drained therapeutically) in establishing the correct diagnosis.     

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.     

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.     

Fine needle aspiration diagnosis of malignant lymphoma with confirmation by immunoperoxidase staining

Cytospin preparations of fine needle aspirates in 14 cases of suspected lymphoma were studied by immunoperoxidase techniques. The combination of cytologic smears and immunoperoxidase studies resulted in a working diagnosis in 13 of the 14 cases. The immunologic markers in conjunction with the cytologic appearance of the aspirates were reliable and consistent in differentiating between malignant and benign lymphoproliferative lesions and in determining the B-cell or T-cell nature of the process.     

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.     

Fine needle aspiration cytology of Hodgkin's lymphoma: A cytohistologic correlation study from a cancer center in Kuwait

OBJECTIVE: To assess the diagnostic accuracy offine needle aspiration cytology (FNAC) in the diagnosis of Hodgkin's lymphoma (HL). STUDY DESIGN: We selected all the cases in which a cytologic diagnosis of HL, suggestive of or suspicious for HL, or HL as the prime differential diagnosis was offered on FNAC. These cases were correlated with histopathologic follow-up. Cases of primary HL diagnosed on cytology but without histopathology were excluded from the study. RESULTS: Histopathologic follow-up was available in 46 cases. Of these, 42 were correctly diagnosed as HL, and there was a discorrelation in 4 cases, comprising 3 cases of non-HL (T-cell-rich B-cell lymphoma [TCRBCL]-2, anaplastic large cell lymphoma-1) and 1 case of metastatic carcinoma. Overall accuracy was 91.3%. In 14 cases, the cytologic features were diagnostic ofrecurrence; hence, no histopathologic examination was done. No follow-up was available for the remaining 19 cases, which were excluded from the study. CONCLUSION: FNAC is very useful for rapid and accurate approach to the diagnosis of recurrent and most cases of primary HL. Because of morphologic similarities, it is difficult to differentiate HL from anaplastic large cell lymphoma and TCRBCL on FNAC. It is advisable to request a histopathologic examination in all cases of primary HL.     

Anaplastic large cell lymphoma presenting as a pleural effusion and mimicking primary effusion lymphoma. A report of 2 cases

BACKGROUND: Systemic anaplastic large cell lymphoma (ALCL) is predominantly a nodal disease, but extranodal involvement can occur during the disease course or as the primary presentation. We report two rare cases of ALCL presenting with a pleural effusion, mimicking primary effusion lymphoma (PEL). CASES: Two patients, a 47-year-old woman and an 81-year-old man, presented with a pleural effusion for investigation. The pleural fluid contained abundant, large, lymphoid cells with marked nuclear atypia. These neoplastic cells strongly expressed CD30 and EMA and showed a T-cell phenotype (CD3+CD45RO+ for case 1 and CD4+ for case 2). Case 1, in addition, showed ALK1 expression. The tumor cells in both cases were negative for human herpes virus type 8 (HHV8) and Epstein-Barr virus (EBV). ALCL shows overlapping cytologic features with PEL, but the T-cell phenotype, ALK1 expression in case 1, lack of association with HHV8 and EBV, HIV seronegativity and subsequent discovery of nodal disease in case 2 were all in favor of ALCL over PEL. CONCLUSION: In rare cases a pleural effusion is the presenting feature of ALCL, and distinction from PEL depends on correlation with clinical findings, detailed immunophenotyping and study of the status of HHV8 and EBV.     

Immunocytochemical study of malignant lymphoma in serous effusions

OBJECTIVE: To cytologically evaluate a large series of serous effusions associated with malignant lymphoma (ML), identify the immunoreaction patterns of the cells from selected positive cases and to investigate the correlation of cytomorphology with tissue section diagnosis. STUDY DESIGN: From 1966 to 1990, a review of the files of the Department of Anatomic Pathology, A. C. Camargo Hospital, disclosed 4,297 cases of serous effusions, 256 of which were associated with ML. Cytopathologically positive cases were selected for immunocytochemical study. All paraffin sections stained with hematoxylin and eosin were reviewed to confirm the malignancy of the cases. Immunostaining was performed on both cytocentrifuge slides previously stained with Papanicolaou stain and new sections of the biopsy samples using the immunoperoxidase method and avidin-biotin complex with monoclonal mouse antihuman B-cell marker L-26 and monoclonal (mouse) antihuman T-cell marker UCHL-1. RESULTS: Immunocytochemical reactions were performed in 54 cases: 22 were pan-B positive and 10 pan-T positive; 24 cases showed no reactivity for either monoclonal antibody. Immunohistochemical reactions were performed in 24 available cases: 15 were pan-B positive and pan-T positive; 3 cases showed no reactivity for either monoclonal antibody. Cytohistoimmunoreactions were similar in 11 pan-B positive cases and 2 pan-T positive cases. Three cases were negative for both markers, 4 cases were pan-T positive in tissue samples and negative in cytocentrifuge smears, 3 cases were pan-B positive in tissue and negative on cytology and 3 cases were negative for both markers in both tissue and cytologic specimens. CONCLUSION: Cytology is an effective method of evaluating serous effusions associated with malignant lymphoma: no false positive diagnosis was observed in this series. Immunophenotyping of lymphoid cells is useful to classify and confirm the cytologic diagnosis.     

Intraocular lymphoma. Cytologic diagnosis and the role of immunologic markers

We retrospectively reviewed the cytology and immunohistochemistry of vitreous cells from 14 patients with benign or malignant intraocular diseases. Nine patients had intraocular lymphoma and five had benign forms of diffuse uveitis. The most useful cytologic criteria for lymphoma included an irregular nuclear outline, a coarse chromatin pattern and prominent nucleoli. In several cases, it was necessary to obtain more than one specimen to establish the diagnosis of lymphoma. When vitreous fluid was mixed with a balanced salt solution prior to processing, a resulting artifact interfered with interpretation of the specimen. A diagnosis of lymphoma was established by cytology in all nine patients; immunohistochemical techniques were less sensitive than was cytology.     

Peripheral T-cell lymphoma or Hodgkin's disease in a HIV seropositive patient: a histopathological study

Malignant lymphomas occurring in patients with AIDS are usually derived from the B-cell lineage while T-cell malignant lymphomas are very rare in these patients. We report a HIV seropositive 29-year-old homosexual man in whom cervical lymph node biopsy showed an atypical lymphoproliferative process. On morphological and paraffin section immunohistochemical grounds the possibility of Hodgkin's disease (HD) mixed cellularity was initially suggested, but frozen section immunohistochemical studies revealed that the cellular infiltrate exhibited an aberrant pan T immunophenotype and consequently the diagnosis of peripheral T-malignant lymphomas (T-ML) was made. However, genotypic studies would be required to definitely confirm this diagnosis, in such cases. In our case, varying numbers of small and medium-sized cells were positive for both Leu 3/CD4 and Leu 2/CD8 whereas some large cells reacted only with Leu 3/CD4 antibody. Some medium-sized, large and giant cells showed cytoplasmic positivity for Leu M1/CD15. Furthermore, the positivity of many large and giant cells with the activation markers BerH2/CD30, Ki-1/CD30, Tac/CD25 and HLA-DR suggested an activation state for these cells. Our findings emphasize the usefulness of frozen section immunohistochemical methods in order to investigate the spectrum of lymphoid malignancies occurring in HIV seropositive patients, and confirm results of previous studies which stressed the diagnostic difficulties that may appear in distinguishing HD from peripheral T-ML.     

The role of cytology in the detection of malignant lymphoma of the uterine cervix.

The success of cytologic examination in the diagnosis of malignant lymphoma of the cervix is at present limited. The generally accepted cytologic criteria for the identification of malignant lymphoma may have to be applied with caution when examining material obtained by abrasive technique; the diagnosis should not be entirely excluded, even in the presence of cell aggregates.