Cytogenetics of Malignant Lymphoma

Abstract

The identification of specific chromosomal abnormalities in the malignant lymphomas has both clinical and biological significance. Translocations t(14;18) and t(8;14) (with variant translocations t(2;8) and t(8;22)) in particular are associated with follicular disease and Burkitt's lymphoma, respectively.

Rearrangements of the immunoglobulin and T cell receptor genes in B and T cell disorders, respectively shown by cytogenetic analysis to be frequently involved in nonrandom translocations, provide useful diagnostic information.

Despite these advances, there is no clear consensus of clinical significance of most chromosome abnormalities because of the heterogenous nature of lymphomas. Further cytogenetic studies are needed of tumors with atypical presentations and patterns of behavior to advance knowledge of lymphoma etiology and to achieve better modes of diagnosis and treatment. (The J Histotechnol 15:253-261, 1992)     

Hodgkin's lymphoma: Diagnostic difficulties in fine‐needle aspiration cytology

It is commonly believed that cytodiagnosis of Hodgkin's lymphoma (HL) is much easier than that of non‐Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed‐Sternberg (R‐S)‐like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine‐needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty‐one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin‐like cells and typical R‐S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnois of HL. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Lymphoma phenotyping in formalin-fixed and paraffin wax-embedded tissues: II. Profiles of reactivity in the various tumour types

Recently, monoclonal antibodies capable of phenotyping malignant lymphomas in routinely fixed and processed tissue have become available. Some of these reagents identify lineage-restricted variants of the leucocyte common molecule, whereas others identify unique fixation-resistant epitopes on lymphoid cells, some of which are shared by non-lymphoid tissues. A new generation of antibodies recognizing 'classical' leucocyte antigens such as CD3 are also emerging. Refinements in antigen detection systems, especially for immunoglobulin recognition, combined with these new reagents promise to improve the accuracy of lymphoma diagnosis in routine histopathology. These new antibodies are reviewed, and their limitations, cross reactivities and profiles of staining in lymphoreticular disease are discussed. A strategy for their optimal use is proposed.     

The application of the metalophil method for the demonstration of histiocytes

The metalophil method has been performed on 250 sections of a wide variety of inflammatory and neoplastic lesions in which different types of histiocytes might be encountered. In lymph nodes, dendritic histiocytes related to the B-lymphocyte system were consistently metalophil. They appeared as small cells with slender extensions in lymph nodes with follicular hyperplasia and/or sinus histiocytosis and in some cases of Hodgkin's lymphomas or as larger pleomorphic cells in primary or secondary malignancies of lymph nodes. Small, rounded cells were seen in some cases of marked paracortical reaction, in dermatopathic lymphadenitis and in some cases of mycosis fungoides. These cells most probably represented Langerhans cells and interdigitating reticulum cells, which are related to the T-lymphocyte system. Interdigitating cells become metalophil when they are activated or proliferating. Epithelioid cells in different benign and malignant lesions were metalophil like the sinus histiocytes of the lymph nodes, the Kupffer cells of the liver and the alveolar histiocytes in the lung. Foreign-body giant cells in lymph nodes after lymphography were also metalophil. The sinus lining cells lymph nodes were also well-delineated. Histiocytes of malignant histiocytic proliferations were sometimes metalophil as were the so-called histiocytes in malignant fibrous histiocytomas. Epithelial cells, particularly the basal cells of squamous epithelium often take up the silver. Carcinoma cells were sometimes metalophil and the method appeared not to be of value in the differentiation between metastatic carcinomas and lymphomas. The most promising application seems to be the study of the distribution of dendritic histiocytes in malignant proliferations of B-lymphocytes.     

Lymphoma phenotyping in formalin-fixed and paraffin wax-embedded tissues. I. Range of antibodies and staining patterns

Recently, monoclonal antibodies capable of phenotyping malignant lymphomas in routinely fixed and processed tissue have become available. Some of these reagents identify lineage-restricted variants of the leucocyte common molecule, whereas others identify unique fixation-resistant epitopes on lymphoid cells, some of which are shared by non-lymphoid tissues. A new generation of antibodies recognizing 'classical' leucocyte antigens such as CD3 are also emerging. Refinements in antigen detection systems, especially for immunoglobulin recognition, combined with these new reagents promise to improve the accuracy of lymphoma diagnosis in routine histopathology. These new antibodies are reviewed, and their limitations, cross reactivities and profiles of staining in lymphoreticular disease are discussed. A strategy for their optimal use is proposed.     

Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with 'malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer-Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.     

Lymphocyte-depleted Hodgkin's disease: Diagnostic challenges by fine-needle aspiration

The diagnosis of Hodgkin's disease by fine-needle aspiration (FNA) can be problematic. A case of Hodgkin's disease, lymphocyte depleted subtype, sampled by FNA biopsy is presented. We describe the cytomorphologic features present in this unusual subtype of Hodgkin's disease and discuss the differential diagnosis. Immunohistochemical and morphologic findings of a subsequent biopsy specimen supported the diagnosis. Although FNA is an increasingly used diagnostic modality to evaluate tumors including malignant lymphomas, Hodgkin's disease remains, as in this case, a difficult diagnosis by FNA. Diagn. Cytopathol. 1998;19:66–69. © 1998 Wiley-Liss, Inc.     

Cytotoxic molecule expression is predictive of prognosis in Hodgkin's-like anaplastic large cell lymphoma

AIMS: The Revised European American Lymphoma classification uses the term Hodgkin's-like anaplastic large cell lymphoma (HD-like ALCL) for borderline cases with features of both anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL). The aim of this study was to clarify the association between cytotoxic molecule (CM) expression and clinical outcome in HD-like ALCL. METHODS AND RESULTS: Subjects were 59 patients with HD-like ALCL, defined by nodal presentation without mediastinal bulky lesions, T- or null-cell phenotype, CD30+ anaplastic lymphoma kinase (ALK)- phenotype and by confluent sheets or nodules of large cells mimicking classic Hodgkin and Reed-Sternberg cells. We evaluated the presenting features and prognosis of subjects on categorization into two defined groups, namely CM (TIA1 and/or granzyme B)-positive (n = 21) and CM-negative (n = 38). The series consisted of 18 women and 41 men ranging from 16 to 88 years of age (median 59 years). The CM+ group had poorer disease-specific survival than the CM- group (P = 0.02) despite the absence of differences in other clinical characteristics. Multivariate analysis confirmed that CM expression was an independent prognostic factor, in contrast to phenotypic categorization (T-cell vs. null-cell group), which had no prognostic impact on disease-specific survival. CONCLUSION: CM expression is predictive of prognosis in HD-like ALCL.     

Interdigitating dendritic reticulum cell sarcoma: cytologic, histologic and immunocytochemical features

Tumors of dendritic reticulum cells are rare neoplasms that exhibit significant morphologic overlap with other malignancies. Fine-needle aspiration cytologic appearances of this neoplasm are not well understood. A 33-yr-old woman presented with a rapidly growing nodular mass in the right upper cervical region and right-sided ptosis. Fine-needle aspiration cytology of the mass showed dissociated as well as clustered, large, polygonal cells that showed high nuclear-cytoplasmic ratio. Nuclei were round, oval, or irregular in shape. Large and small blastoid forms with prominent nucleoli and chromatin clumping as well as binucleated cells and cells with lobulated nuclei were seen. Numerous mitoses were observed. The tumor cells expressed focal immunocytochemical reactivity to CD45 and CD68, but were negative for CD2, CD3, CD4, CD8, CD20, CD30, CD45RO, epithelial membrane antigen (EMA), cytokeratin, and HMB45. Histologic sections of the biopsy from the growth showed nodal tissue effaced by a tumor composed of large, pleomorphic neoplastic cells with some binucleate and multinucleate forms resembling Reed-Sternberg cells. The intervening stroma contained numerous small lymphocytes. Tumor cells expressed vimentin, S-100 protein, CD68, and MAC387, but were negative for LCA, CD1a, CD3, CD15, CD20, CD21, CD23, CD30, CD35, carcino-embryonic antigen, HMB45, cytokeratin AE1/3, EMA, myeloperoxidase, lysozyme, smooth-muscle actin, and desmin. The combined histologic and immunohistologic features suggested a histiocytic/dendritic reticulum cell neoplasm and a diagnosis of interdigitating dendritic reticulum cell sarcoma was made.     

Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed-Sternberg cells in Hodgkin's disease

Vascular endothelial growth factor (VEGF) is involved in tumour angiogenesis, an important process for the growth and metastatic potential of solid tumours. Numerous studies have demonstrated up-regulation of VEGF at both mRNA and protein level in various tumours and a correlation with advanced stage and prognosis has been demonstrated in some cases. Limited information exists about its role in lymphoid malignancies and in particular, Hodgkin's disease. The present study examined the immunohistochemical expression of VEGF using the monoclonal antibody VG1 in a series of 61 cases of Hodgkin's disease, including both classical Hodgkin's disease and the nodular lymphocyte predominance variant, and correlated these results with microvessel density, using an anti-CD31 monoclonal antibody. In 41 cases (70.6%) of classical Hodgkin's disease and one of the three cases of nodular lymphocyte predominance Hodgkin's disease, the neoplastic Reed-Sternberg and Hodgkin cells expressed VEGF. The staining observed was cytoplasmic, either diffuse or with a focal paranuclear distribution. Macrophages were always positive, while reactive lymphocytes showed occasional positivity. A variable amount of strong extracellular staining was also observed in the tissue stroma and intravascular plasma staining was prominent. There was no statistically significant relationship between VEGF expression and the subtype of Hodgkin's disease or microvessel density. In vitro studies using the Reed-Sternberg cell lines L428 and KM-H2 were also performed in both normoxia and hypoxia and VEGF protein production was assessed by flow cytometry (FACS), immunoassay of cell culture supernatant, and RT-PCR. Analysis by FACS demonstrated a subset of cells in both cell lines reacting with VG1 and analysis of secreted VEGF (pg/ml per 1x10(6) cells) in cell culture supernatant confirmed the normoxic production in both cell lines and significant hypoxic induction (p<0.005). Additionally, both cell lines expressed VEGF mRNA, as demonstrated using the RT-PCR method. In conclusion, neoplastic cells express VEGF in Hodgkin's disease, as is the case in solid tumours, and this expression may be induced by hypoxia. The presence of VEGF in reactive macrophages and in the extracellular matrix might facilitate tumour progression.     

Primary Gastric Malignant Lymphoma: A Morphological and Immunohistochemical Study of 38 Cases

Thirty eight cases of primary gastric malignant lymphoma were studied morphologically and immunohistochemically. The Working Formulation was used for classification of non-Hodgkin's lymphoma (1). The results indicated that 37 cases were non-Hodgkin's lymphoma while the remaining case was Hodgkin's disease. Thirty-three cases (89%) of non Hodgkin's lymphoma were considered to be of B cell origin and 2 cases (5%) of histiocytic origin. No case was considered to be of T cell origin. We suggest that the majority of primary gastric malignant lymphomas are derived from follicular center cells, and that gastric plas-macytoma is not as rare as previously described. Acta Pathol Jpn 39: 229–234, 1989.     

Diagnostic fine needle core biopsy of deep lymph nodes for the diagnosis of lymphoma in patients unfit for surgery

The use of a technique for safe percutaneous fine needle biopsy of inaccessible lymph nodes is described. In a prospective study of 24 patients, including five cases positive for the human immunodeficiency virus (HIV), this technique was used to provide diagnostic material. A firm diagnosis was made in 21 cases; four cases of Hodgkin's disease, 14 non-Hodgkin's lymphomas, one case of Kaposi's sarcoma, one case of mycobacterial infection, and one which showed the features of persistent generalized lymphadenopathy (PGL). In the cases of lymphoma, available serial sections allowed characterization of the tumour with immunocytochemistry. In three cases, no diagnosis could be made, with one of these requiring a subsequent open biopsy. Percutaneous fine needle biospy is ideal for patients unfit or unsuitable for general anaesthesia or surgery. The biopsy obtained gives the pathologist sufficient tissue for an accurate diagnosis in the majority of cases. The preservation of architecture and multiple sections available are advantages over fine needle aspiration.     

Exfoliative respiratory cytology in the diagnosis of leukemias and lymphomas in the lung

Leukemias and lymphomas involving the lung were diagnosed by means of exfoliative cytology in 31 specimens from 20 patients. Initial diagnostic categorizations included 29 specimens “positive for malignancy,” including two thought to represent “carcinoma vs. lymphoma,” and two considered suspicious for lymphoma. Previous diagnoses of lymphoma (13 patients) and acute myelogenous leukemia (AML) (2 patients) were available. In 5 additional patients, exfoliative respiratory cytology yielded the first diagnosis of hematopoietic malignancy. Cytologic diagnosis included nine large-cell and six small-cell non-Hodgkin's lymphomas (NHL), three Hodgkin's lymphomas (HD), and two AML. Key cytologic features included markedly pleomorphic and monomorphic cell populations in HD and NHL, respectively, as well as lack of tumor cell cohesion and necrosis in all cases. Cytologically, acute leukemia may be difficult to differentiate from large-cell NHL, and small-cell NHL from reactive/benign small lymphocytes. Blood, scant cellularity, crush artifacts, and apparent molding may affect diagnostic accuracy. Immunocytochemistry in cell block sections of sputa and washings is useful in the diagnostic workup in selected cases. Although involvement of the respiratory system by leukemias and lymphomas is uncommon and not always preceded by a history of malignancy, cytologic diagnosis is usually prompt, reliable, and accurate. Diagn Cytopathol 1996;14:108–113. © 1996 Wiley-Liss, Inc.     

Syncytial variant of nodular sclerosing Hodgkin's disease: Fine-needle aspiration findings in two cases

The syncytial variant is a recently described, uncommon form of nodular sclerosing Hodgkin's disease that was previously termed “sarcomatoid.” In addition to foci of typical sclerosis, it is characterized histologically by sheets or clusters of mononuclear Reed-Sternberg variants. These may be arranged around areas of necrosis with variable numbers of neutrophils. In excised material, differential diagnostic considerations include non-Hodgkin's malignant lymphoma, granulocytic sarcoma, malignant melanoma, metastatic carcinoma, thymoma, and metastatic germ cell tumor. We describe the fine-needle aspiration cytologic finding in two examples of this entity. Cohesive clusters and sheets of malignant cells with clear cytoplasm, vesicular nuclei, and prominent nucleoli are easily mistaken for metastatic carcinoma or germ cell tumor. Ancillary tests useful in this differential diagnosis are discussed. Diagn. Cytopathol. 1997;17:477–479. © 1997 Wiley-Liss, Inc.     

Cytologic diagnosis and monitoring of Hodgkin's disease in cerebrospinal fluid: a case report

Central nervous system (CNS) involvement in Hodgkin's disease is rare, but when the tumor extends into the CNS the route of tumor spread is similar to that seen in non-Hodgkin's lymphoma. Reed-Sternberg cells were identified in the cerebrospinal fluid (CSF) of a patient with Hodgkin's disease involving the CNS. Sequential cytologic examination of the CSF proved valuable in evaluating the efficacy of therapy. The ability to identify Reed-Sternberg cells in the CSF makes CSF cytology a useful adjunct in the management of patients with established or suspected CNS involvement of Hodgkin's disease.     

Bendamustine Combined with Donor Lymphocytes Infusion in Hodgkin's Lymphoma Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation

The management of Hodgkin's lymphoma (HL) recurring after allogeneic stem cell transplantation is challenging. We retrospectively describe 18 adults treated with bendamustine followed by escalated donor lymphocyte infusion. Hematological toxicity was manageable (39% grade III to IV neutropenia and 28% grade III to IV thrombocytopenia). The overall response rate was 55%, with 3 complete and 7 partial responses. Median overall and progression-free survival were 11 (range, 1 to 52) and 6 (range, 1 to 28) months, respectively. One-year overall survival of responders (complete or partial) was 70% (95% confidence interval, 42% to 98%), although it was only 16% for nonresponders (n = 8). Our data show that bendamustine followed by donor lymphocyte infusion is feasible and can be efficacious as salvage treatment in HL relapsing after an allograft.     

Fine-needle aspiration biopsy for the diagnosis of lymphoma: A perspective

Fine-needle aspiration (FNA) has become a widely used diagnostic tool and it remains one of the most rapid and cost-effective methods of assessing a variety of pathologic conditions. However, FNA as a method of evaluation of enlarged lymph nodes has been approached with a greater degree of caution and reservation, largely because Hodgkin's disease and the non-Hodgkin's lymphomas represent a diverse group of neoplasms, which is mirrored by a large range of histopathologic and cytologic appearances. For these reasons, adjunctive techniques such as immunohistochemical staining, cytogenetics, and molecular techniques have been introduced to improve the diagnostic accuracy. While such procedures have made significant contributions to the identification and typing of lymphomas, there is still a requirement for a simple and rapid diagnostic procedure for the patient who presents with persistent lymphadenopathy. Light microscopic examination of FNA smears fulfills this role, provided its limitations and pitfalls are recognised. Diagn Cytopathol 1996;15:352–357. © 1996 Wiley-Liss, Inc.     

Serous effusions in malignant lymphomas: a review

Serous effusions are a common complication of lymphomas. Although the frequency of pleural effusion is 20-30% in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD), the involvement of peritoneal and pericardial cavities is uncommon. Among lymphoma subtypes, T-cell neoplasms, especially the lymphoblastic lymphomas, more frequently involve the serous fluids. The thoracic duct obstruction and impaired lymphatic drainage appear to be the primary mechanism for pathogenesis of pleural effusion in HD and direct pleural infiltration is the predominant cause in NHL. There is wide variation in rate of positive cytologic findings of NHL in pleural effusion (22.2-94.1%). Cytologic features of specific lymphoma subtypes such as lymphoblastic lymphoma, follicular center cell lymphoma, including Burkitt-type lymphoma, marginal zone lymphoma, MALT lymphoma, and anaplastic large-cell lymphoma, etc., have been described in the literature. The differential diagnostic problems of lymphomas in serous effusions include reactive lymphocytoses, early involvement by lymphomatous process, small round-cell tumors (SRCT), and presence of look-alike of Reed-Sternberg cells. To overcome these difficulties, various ancillary studies, including immunocytochemistry (ICC), morphometry, flow cytometry (FCM), and cytogenetics/molecular genetics (PCR, in-situ hybridization, and Southern blotting), have been performed on effusion specimens. ICC not only distinguishes lymphomas from reactive lymphocytoses and SRCTs, it significantly modifies the morphologic diagnosis to achieve a better classification of lymphomas. Combined morphology and immunophenotyping by FCM, has a sensitivity as well as specificity of 100%. Morphometry also distinguishes reactive lymphocytoses from malignant lymphoma with a high degree of sensitivity (>85%) and specificity (>95%). Limitations of individual ancillary techniques can be overcome by using multiple parameters. Although lymphomas rarely present as serous effusions without the involvement of other thoracic and extrathoracic sites, a small group of lymphomas called primary effusion lymphomas (PEL) exhibit exclusive or dominant involvement of serous cavities, without a detectable solid tumor mass. This body cavity based lymphoma (BCBL) is a distinct clinicopathologic entity and is found predominantly in AIDS patients with preexisting Kaposi sarcoma. In the absence of obstructive or infiltrative tumor mass, its pathogenesis has been attributed to stimulation by vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), leading to vascular leakage. Cytomorphologically, PEL is usually a large-cell lymphoma, which appears to bridge features of large-cell immunoblastic and anaplastic large-cell lymphoma (ALCL). Most of these cases comprise a unique subgroup of B-cell lymphoma, with features of both high-grade anaplastic and B-immunoblastic lymphoma, but T-cell and/or natural killer cell immunophenotypes are described. Its association with various viral DNAs has been studied in detail by molecular techniques. Pleural effusion due to lymphomas, either primary or otherwise, is considered as one of the factors adversely influencing overall survival. The presence of pleural effusion at the time of presentation is not only associated with extremely poor outcome of lymphomas, it is also a predictor of disease relapse after chemotherapy and decreased survival. When the patients of lymphomatous pleural effusions with and without mediastinal mass present in respiratory distress, thoracocentesis is the initial diagnostic and therapeutic choice in these patients. In such situations, cytology along with ancillary studies not only gives a quick diagnosis of lymphoma, but also offers prognostically significant information such as classification of lymphomas, its grade and immunophenotype, and presence/absence of viral DNAs and tumor lysis syndrome.