Reed‐sternberg cells in breast FNA of a patient with left breast mass

Hodgkin's lymphoma is a potentially curable malignancy of the lymphatic system characterized by a variable number of scattered and large mononucleated and multinucleated tumor cells, the Hodgkin and Reed‐Sternberg cells residing in an abundant heterogeneous admixture of non‐neoplastic inflammatory cells. It represents approximately 30% of all lymphomas according to the World Health Organization (WHO). Patients with Hodgkin's lymphoma typically present with painless peripheral adenopathy, fever, night sweats, and weight loss. We report a rare case of Hodgkin's lymphoma presented as a breast mass in a 23‐year‐old woman diagnosed on fine needle aspiration (FNA). At presentation, she had no B symptoms, or palpable lymphadenopathy. Diagn. Cytopathol. 2010;38:663–668. © 2010 Wiley‐Liss, Inc.     

Morphological and immunohistochemical investigation of non-Hodgkin's lymphoma combined with Hodgkin's disease

Twenty cases with a morphological picture highly suspicious for a combination of non-Hodgkin's lymphoma and Hodgkin's disease were investigated. The infiltrates of Hodgkin's disease differed from those of non-Hodgkin's lymphoma in their cellular component of Hodgkin and Sternberg-Reed cells and the irregularity in the fibre pattern. Based upon histological and immunohistochemical criteria the 20 cases were divided into three groups. Group 1 (n = 10) contained seven chronic lymphocytic leukaemias of B type, one lymphoplasmacytoid immunocytoma, and two centroblastic/centrocytic lymphomas. The non-Hodgkin's lymphoma components showed a monotypic immunoglobulin distribution pattern and/or leukaemic blood picture. Adjacent to the non-Hodgkin's lymphoma was typical Hodgkin's disease in which Hodgkin and Sternberg-Reed cells were positive for both immunoglobulin light chains and IgG and reacted with anti-CD15. Group 2 (n = 5) consisted exclusively of centroblastic/centrocytic lymphoma in combination with Hodgkin's disease in which the few Hodgkin and Sternberg-Reed cells were negative with anti-CD15 monoclonal antibody. Group 3 (n = 5) consisted of four chronic lymphocytic leukaemias of B type and one lymphoplasmacytoid immunocytoma. In these cases no combination with Hodgkin's disease could be diagnosed apart from the presence of partially CD15 positive Hodgkin and Sternberg-Reed cells. The following conclusions were drawn: anti-CD15 (LeuM1 and 3C4/C3D-1) can neither confirm nor exclude Hodgkin's disease since, while they do not detect Hodgkin and Sternberg-Reed cells in all cases of Hodgkin's disease, they do recognize Hodgkin and Sternberg-Reed cells in some B-cell lymphomas; anti-CD30 (Ber-H2) reacted with Hodgkin and Sternberg-Reed cells in all cases of Hodgkin's disease and also detected these cells in cases of non-Hodgkin's lymphoma.     

Waldenstrom's macroglobulinemia associated with Hodgkin's lymphoma: a case report

Waldenstrom''s macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is a low-grade B-cell non-Hodgkin''s lymphoma with an indolent clinical course. Higher-grade non-Hodgkin lymphoma (NHL) and therapy-related myelodysplasia/acute leukemia (t-MDS/AML) have been reported in patients with WM/LPL in previous studies. However, only two cases with WM/LPL were reported to develop to Hodgkin lymphoma (HL). Here, we report the first case of WM/LPL who developed classical HL simultaneously 3 years after initial nucleoside analog-based chemotherapy.     

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)     

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.     

Cytological diagnosis of bilateral primary adrenal lymphoma with cutaneous involvement

Primary adrenal lymphoma (PAL) is an extremely rare condition. We describe here, a case of bilateral adrenal lymphoma in a 62‐year‐old man. He later developed subcutaneous masses on the hand and the leg. Fine‐needle aspiration cytology from the adrenals and the soft tissue swellings led to a diagnosis of non‐Hodgkin's lymphoma (NHL). Histopathological examination from the lesion on the leg, confirmed the diagnosis to be B‐cell NHL. The case highlights the cytomorphological findings of this unusual case. Awareness of this entity is essential to differentiate it from other common causes of adrenal enlargement and formulate an appropriate treatment.     

Flow Cytometry in the Diagnosis of Non-Hodgkin's Lymphoma (NHL)

Abstract

In recent years, flow cytometry has become an important adjunct to light microscopy in the diagnosis of malignant lymphoma. Flow cytometric techniques are useful in distinguishing benign from malignant lesions and in determining the lineage and stage of differentiation of a neoplastic infiltrate. Certain immunophenotypic antigen profiles are characteristic of specific neoplasms, whereas other profiles are useful as prognostic indicators of outcome. In this review, we present details of the flow cytometric analyses that we perform on suspected lymphoid malignancies, including methods of gating, criteria that we have found useful in distinguishing benign from malignant processes, details of antibody panel selection for two color studies, and common pitfalls in the use of flow cytometry in the clinical laboratory. Highlights of new areas of investigation in the study of malignant lymphomas are presented. By utilizing flow cytometric techniques, these recent scientific advances can be rapidly integrated into routine patient care. As with any specialized diagnostic technique, flow cytometric data must always be integrated with the morphologic and clinical features of each case. (The J Histotechno 1 15:219-227, 1992)     

Expression of β-tubulin isotypes in classical Hodgkin's lymphoma

Microtubules consist of heterodimers of α- and β-tubulin. Aberrant expression of specific β-tubulin isotype is associated with resistance to chemotherapy in malignant tumors. In this study, we examined the expressions of β-tubulin isotypes in classical Hodgkin's lymphoma (cHL) by immunohistochemistry. Among the β-tubulin isotypes, class II β-tubulin (31/34, 91%) was most frequently overexpressed in the cytoplasm of almost all Hodgkin's and Reed-Sternberg (HRS) cells, followed by class I β-tubulin (18/34, 53%) and class III β-tubulin (12/34, 35%). Class IV β-tubulin was not expressed in any cHL case. Class I β-tubulin was expressed in the background lymphoid cells as well as the HRS cells. Thus, our results indicate that class II β-tubulin may be very useful for immunohistochemical diagnosis of cHL, and provide valuable information for the potential application of β-tubulin isotype-specific targeting.     

Primary refractory and early‐relapsed Hodgkin's lymphoma: strategies for therapeutic targeting based on the tumour microenvironment

Classical Hodgkin's lymphoma (cHL), a distinct disease entity with characteristic clinical and pathological features, accounts for approximately 10% of all malignant lymphomas. cHL can be considered a prototype model for how the tumour microenvironment influences cancer pathogenesis. Cellular components of the cHL microenvironment express molecules involved in cancer cell growth and survival, such as CD30L or CD40L. Moreover, several signal transduction pathways that are critical for the proliferation and survival of neoplastic Hodgkin Reed–Sternberg (HRS) cells, including NF‐κB, JAK–STAT, PI3K–AkT and ERK, are deregulated in cHL. Although most patients can be cured with modern treatment strategies, approximately a quarter experience either primary or secondary chemorefractoriness or disease relapse, thus requiring novel treatments. Preclinical and clinical evidence has elucidated a complex crosstalk between malignant HRS cells and the reactive cells of the microenvironment, which suggests that novel therapeutic approaches capable of targeting HRS cells along with reactive cells might overcome chemorefractoriness. In the near future, these novel therapies will also be tested in chemosensitive patients, to reduce the long‐term toxicity of chemo‐radiotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

PRDM1/Blimp-1 is expressed in human B-lymphocytes committed to the plasma cell lineage

PRDM1/Blimp-1 (in human and mouse, respectively) has a central role in determining and shaping the secretory arm of mature B-cell differentiation. In this study, a mouse monoclonal antibody that recognizes PRDM1 was used to detail its distribution in normal human lymphoid tissue and in lymphoid neoplasms that correspond to different stages of B-cell differentiation. PRDM1 was expressed in germinal centre blasts that co-express Pax5, CD19, CD20, and CD10, but not BCL6 or MTA-3. Pax5 was downregulated and full plasma cell morphology and phenotype were acquired by PRDM1+, nuclear cREL-, pre-plasma cells upon exit from the germinal centre. Activated extrafollicular B-cells (CD30+, Pax5+) were largely PRDM1-. PRDM1 was also absent in tissue histiocytes and the majority of resting T-cells and S-100+ antigen-presenting cells. PRDM1 and CD138 were expressed simultaneously in human lymphomas with plasma cell differentiation, but not in marginal zone lymphomas or chronic lymphocytic leukaemias. A minority of diffuse large B-cell lymphomas expressed PRDM1 and Hodgkin lymphomas were largely PRDM1-. Infiltrating T-cells in PRDM1- B-cell lymphomas expressed PRDM1. In conclusion, PRDM1 staining is a reliable and informative assay to define plasma cell commitment and differentiation in human normal and neoplastic B-cell lineages.     

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.     

Three cases of diffuse large B-cell lymphoma presenting as primary splenic lymphoma

Primary splenic lymphoma (PSL) is often defined as generalized lymphoma with splenic involvement as the dominant feature. It is a rare disease that comprises approximately 1% of all malignant lymphomas. We investigated three cases of non-Hodgkin's splenic lymphoma that had different clinical features on presentation. The patients' survival times from diagnosis ranged from 59 to 143 months, without evidence of relapse after splenectomy and chemotherapy, with or without radiotherapy. This data suggest that PSL is potentially curable. Further studies are needed to evaluate the impact that different treatment modalities without splenectomy have on patient survival.     

Lymphoplasmacytoid lymphoma: an immunohistological study

Eighteen cases of lymphoplasmacytoid lymphoma (LPL) have been immunophenotypically characterized with a panel of 26 monoclonal antibodies. All cases expressed leucocyte common antigen, class II MHC and stained with B cell markers (CD19, CD20, CD22) although a variable proportion of tumour cells were noticed to have lost some B cell marker expression. There was some phenotypic heterogeneity with variable immunostaining with KB61, CD21, and CD5. A variable proportion of cells in all cases contained cytoplasmic immunoglobulin. Surface immunoglobulin light chain restriction was demonstrated in 11 cases and heavy chain predominance in 16 cases. Few tumour cells were proliferating as indicated by Ki67 immunostaining. A wide variation in number of macrophages and T lymphocytes were present in association with the tumours. A significant association between the expression of CD5 and the presence of peripheral blood lymphocytosis was noticed (p less than 0.003) but there was no association between CD5 and co-expression of IgM and IgD. This data supports an origin from non-germinal centre cells for LPL and suggests that CD5 expression by B cells may be related to lymphocyte migration. LPL shows some immunological heterogeneity and can present diagnostic difficulties, but its poor prognosis makes it an important category of lymphoma to recognise.     

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.     

Prognostic significance of activation and differentiation antigen expression in B-cell non-Hodgkin's lymphoma

Immunophenotyping shows heterogeneity of expression of activation and differentiation antigens in B-cell non-Hodgkin's lymphoma (NHL). To investigate whether antigen expression correlates with clinical behaviour we have studied the clinical presentation and follow-up of a series of 111 B-cell lymphomas previously phenotyped for a panel of antigens including CD groups 5, 9, 10, 21, 23, 25, 30, 38, 4F2 antigen, and transferrin receptor. CD antigens 5, 10, and 23 were expressed significantly more often by low grade lymphomas whereas CD38, 4F2 antigen, and transferrin receptor were more often expressed by high grade lymphomas. There was a significant correlation with survival and age, stage at presentation, histological grade, and expression of 4F2 antigen and transferrin receptor but not with the other antigens studied. 4F2 antigen and transferrin receptor may identify a poor prognostic group of cases in low grade lymphoma but we conclude that phenotyping B-cell NHL for many of the antigens expressed at various stages of B-cell differentiation and activation does not provide clinically useful information in addition to that obtained from standard histological classifications.     

Effusion cytology in burkitt's lymphoma

The American form of Burkitt's lymphoma is a high-grade malignancy which usually involves the abdomen in children and young adults. There is only a limited literature which describes the cytologic features of Burkitt's lymphoma in serous effusions. We present three children with Burkitt's lymphoma initially diagnosed by effusion cytology. the first patient, an 11-yr-old boy, presented with bilateral pleural effusions, ascites, and abdominal masses and had diagnostic pleural fluid cytology without tissue confirmation (ultrastructural examination was performed on the effusion specimen). He died 7 months after the initial diagnosis. the second patient, a 9-yr-old boy, presented with ascites and abdominal masses and had diagnostic peritoneal fluid cytology with a subsequent confirmatory chest wall biopsy. the third patient, a 16-yr-old girl, presented with a 2-month history of irregular menses, a large pelvic mass, lymphadenopathy, and liver masses. Although an ovarian malignancy was clinically suspected, cytologic examination of her peritoneal fluid revealed Burkitt's lymphoma. Surgical exploration revealed involvement of her right ovary, cecum, and terminal ileum. the second and third patients are currently alive with no apparent disease following chemotherapy. in all three patients, effusion cytology revealed Burkitt's lymphoma, characterized by a uniform population of noncohesive lymphoid cells with noncleaved nuclei, prominent multiple nucleoli, and scanty-to-moderate basophilic cytoplasm. Cytoplasmic and/or nuclear vacuoles were also seen, more prominent in Diff-Quik—stained, air-dried smears. These cases demonstrate the importance of recognizing the cytologic features of Burkitt's lymphoma, as serous fluid may be the initial diagnostic specimen.     

Immunohistochemical determination of CD23 expression in Hodgkin's disease using paraffin sections

The leukocyte antigen CD23 is expressed during B-cell development, and functions as an IgE receptor and a lymphocyte growth factor. We studied the expression of CD23 in paraffin sections of lymphoid tissue using the monoclonal antibody BU38. Fifteen cases of Hodgkin's disease, ten reactive lymph nodes, eight B-cell, and seven T-cell non-Hodgkin's lymphomas were analysed immunohistologically. CD23 positivity was seen on follicular dendritic cells and a small number of lymphocytes in reactive nodes. Thirteen of the 15 cases of Hodgkin's disease showed CD23 expression in both neoplastic cells and reactive lymphocytic infiltrate. The antigen was demonstrated in four of the B-cell and one of the T-cell tumours. CD23 may be important in mediating the mixed cellular infiltrate characteristic of Hodgkin's lymphoma.     

Primary pulmonary Hodgkin's lymphoma: a rare pitfall in transthoracic fine needle aspiration cytology

Primary pulmonary Hodgkin's lymphoma (PPHL) is extremely rare. At an extranodal location such as the lung this lymphoma is likely to be confused with the more commonly occurring carcinomas at this site. We report the fine needle aspiration cytology (FNAC) findings of a PPHL in a 36-year-old male with a view to discuss the pitfalls and clues to the accurate cytologic diagnosis. This patient presented with a large, heterogeneously enhancing mass involving the anterior segment of right upper lobe without any evidence of nodal involvement. A CT-guided transthoracic FNAC of this mass revealed large connective tissue fragments with entrapped voluminous cells amidst a polymorphous population of eosinophils, polymorphs, and lymphocytes. The large cells showed abundant often stripped off cytoplasm, an irregular nucleus with nucleolus and were initially diagnosed as non-small cell carcinoma of the lung. In view of the locally advanced stage, patient received a carboplatin and gemcite-based chemotherapy with complete response but postchemotherapy patient refused local surgery. Two years later, the patient developed enlarged nodes which were diagnosed as Hodgkin's lymphoma, and a review of prior lung tumor confirmed the diagnosis of PPHL. Hence the rare diagnosis of PPHL should be kept in mind when a cytopathologist observes large cells embedded in collagenous tissue fragments with dominant cell dispersal amidst an inflammatory infiltrate in an aspirate from a primary lung tumor.