Subclassification Of Lymphomas Research Articles

Non-Hodgkin lymphomas – T cell type: Histomorphology and immunohistochemistry

Introduction: Non-Hodgkin lymphomas (NHL) comprise a wide variety of neoplasms and are subdivided into two main categories of low grade and high grade lymphomas. The major subtypes among T cell lymphomas are Peripheral T cell lymphomas – Not otherwise specified, Anaplastic Large cell lymphoma, ALK positive, Angioimmunoblastic T-cell lymphoma, T lymphoblastic leukemia/lymphoma and Extranodal NK/T cell lymphoma, nasal type. In this study, the histomorphological diagnostic features and the adjunct immunohistochemical expression of various markers are studied in a tertiary care centre in South India. Materials and Methods: Patients with lymphadenopathy over a period of two years were included in the study. Lymph nodes excised from these patients were routinely processed and examined. After initial examination with H&E stain, appropriate special stains like Reticulin stain, Periodic Acid Schiff stain and Ziehl-Neelsen stains are performed along with the specific Immunohistochemical markers. Results: A total of 30 cases were classified as Non-Hodgkin Lymphoma, high grade, T cell type. Peripheral T cell lymphomas-NOS is found to be the most common tumors accounting for 40% of all high grade T cell NHLs. The next common tumor was Anaplastic Large Cell Lymphoma, ALK positive with 36% of cases. T lymphoblastic leukemia/lymphoma accounted for 10% of cases and the rest of the cases were reported as Angioimmunoblastic T-cell lymphoma (7%) and Extranodal NK/T cell lymphoma, nasal type (7%). Conclusion: Appropriate use of immunohistochemistry aids in the sub-classification of lymphomas according to the recommendations of WHO 2008. But, further molecular studies should be performed for confirmation of the subtyping done by immunohistochemistry. Keywords: High grade lymphoma, Anaplastic large cell lymphoma, Peripheral T cell lymphoma.

Image-guided core needle biopsy as the first-line diagnostic approach in lymphoproliferative disorders-A review of the current literature.

The World Health Organization (WHO) and numerous expert guidelines for lymphoma diagnosis and subclassification advocate the use of histology from surgical nodal excision biopsy (SEB) over core needle biopsy (CNB) due to perceived higher diagnostic yield. CNB is associated with lower morbidity and is more cost-effective compared to SEB. Furthermore, current practice increasingly demonstrates material obtained from CNB can rapidly diagnose individuals with a clinical suspicion of lymphoma and allow initiation of treatment in the majority of patients. We performed a literature review to assess the suitability of CNB in lymphoma diagnosis given recent advances in radiological and histopathological techniques in obtaining and processing tissue. Additionally, expert international guidelines in lymphoma diagnosis were compared. We found that CNB demonstrated a diagnostic efficacy between 79% and 97% (median 91%) where the diagnostic outcome was conclusive with full lymphoma subclassification. Studies demonstrate that there is a high diagnostic reproducibility amongst haematopathologists (87%-93%) in lymphoma diagnoses with full subtyping from material obtained via CNB. Furthermore, CNB is a safe, rapid and reliable method of obtaining tissue from lymph nodes for histopathological analysis. These procedures are minimally invasive, well-tolerated and should be considered the first-line diagnostic approach in clinical practice in patients with suspected lymphoproliferative disorders.

Letter to the Editor—subtype-specific orbital lymphomas

Through the last decades, our knowledge about ocular adnexal lymphoma (OAL) including orbital lymphoma has increased markedly due to the focus on lymphoma subclassification and the focus on improved staging of OAL. Our retrospective study of 797 patients with orbital lymphoma (1), discussed in the Editorial by Stagner and Zukerberg (2), provides additional insight into this relatively rare disease.

Stereotyped B Cell Receptor Immunoglobulins in B Cell Lymphomas.

Comprehensive analysis of the clonotypic B cell receptor immunoglobulin (BcR IG) gene rearrangement sequences in patients with mature B cell neoplasms has led to the identification of significant repertoire restrictions, culminating in the discovery of subsets of patients expressing highly similar, stereotyped BcR IG. This finding strongly supports selection by common epitopes or classes of structurally similar epitopes in the ontogeny of these tumors. BcR IG stereotypy was initially described in chronic lymphocytic leukemia (CLL), where the stereotyped fraction of the disease accounts for a remarkable one-third of patients. However, subsequent studies showed that stereotyped BcR IG are also present in other neoplasms of mature B cells, including mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL). Subsequent cross-entity comparisons led to the conclusion that stereotyped IG are mostly "disease-specific," implicating distinct immunopathogenetic processes. Interestingly, mounting evidence suggests that a molecular subclassification of lymphomas based on BcR IG stereotypy is biologically and clinically relevant. Indeed, particularly in CLL, patients assigned to the same subset due to expressing a particular stereotyped BcR IG display remarkably consistent biological background and clinical course, at least for major and well-studied subsets. Thus, the robust assignment to stereotyped subsets may assist in the identification of mechanisms underlying disease onset and progression, while also refining risk stratification. In this book chapter, we provide an overview of the recent BcR IG stereotypy studies in mature B cell malignancies and outline previous and current methodological approaches used for the identification of stereotyped IG.

Endoscopic Ultrasound Fine Needle Aspiration and Biopsy Provide High Yields for Lymphoma Subclassification

Endoscopic Ultrasound Fine Needle Aspiration and Biopsy Provide High Yields for Lymphoma Subclassification

Image-guided fine-needle aspiration cytology and flow cytometry phenotyping of neck lymphadenopathy for the diagnosis of recurrent lymphoma.

In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography (US), US-guided fine-needle aspiration cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of recurrent lymphoma and (ii) whether these tools were independent predictors of correct results. Retrospective cohort study with stepwise forward logistic regression analysis of results. Tertiary referral centre. A total of 151 patients with a history of lymphoma who developed a cervical mass during follow-up. On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results (P = 0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.986). This minimally invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded.

Impact of Flow Cytometry in Liver Cytopathology

Background: Fine needle aspiration (FNA) is commonly used as a diagnostic tool for the evaluation of lymphoproliferative diseases. Cytomorphology alone is often insufficient for the diagnosis and subclassification of lymphoma; therefore, flow cytometry (FC) plays an important role in the characterization of lymphoproliferative disorders. This study reviews our experience with FC on liver FNA at the Johns Hopkins Hospital. Methods: 2,424 liver FNAs performed over a 21-year period were reviewed for clinical FC data (n = 74) or a subsequent diagnosis of lymphoma in the liver without FC data (n = 40). Results: In our study, 114 cases (4.7%) were included out of the 2,424 liver FNAs performed during the study period. Lymphoma was diagnosed 79 times. Cytomorphology alone was diagnostic of lymphoma in 45 cases, and in 33 cases both the cytomorphology and the FC were consistent with a diagnosis of lymphoma. Neither FC nor cytomorphology were diagnostic of lymphoma on 1 specimen. In 39 cases, FC had negative results on a lesion suspicious for lymphoma based on cytomorphology. In several nonlymphoma cases, FC provided information that allowed further subclassification of the neoplasm. Conclusion: FC is a useful adjuvant diagnostic test for liver FNAs performed on patients with lymphoproliferative disorders.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy for Diagnosis of Intra-Abdominal Lymphoma without Accessible Peripheral Lymphadenopathy

Introduction: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) is considered the procedure of choice for the diagnosis and staging of intra-abdominal non-Hodgkin’s lymphoma (NHL) without accessible peripheral lymphadenopathy. However, diagnosis and subclassification lymphoma by FNAB is often challenging due to variable cellularity and lack of architecture. Recent advances of ancillary techniques such as immunohistochemical staining, flowcytometry (FCM), fluorescence in situ hybridization (FISH) analysis and molecular analysis allowed classify lymphoma more precisely, although sufficient information can be obtained through this procedure remained undetermined. The present study was performed to evaluate the yield of EUS-FNAB using a standard 19 or 22-gauge needle for diagnosis and subclassification of lymphoma, assessing the feasibility of immunohistological, FCM, molecular and cytogenetic assessments.Methods: Between April 2008 and July 2014, 90 patients with malignant lymphoma who had an intra-abdominal mass without accessible peripheral lymphadenopathy underwent EUS-guided fine needle aspiration biopsy at our hospital. All patients received positron emission tomography/computed tomography and had 2-deoxy-2-(18F)fluoro-D-glucose-avid lesions in abdomen before examination. The aspirated materials were processed for flowcytometry (FCM), molecular analysis of immunoglobulin heavy (IgH) and T-cell receptor (TCR) gene rearrangement, cytogenetic analysis by conventional G banding, and FISH analysis, in addition to standard histopathological studies. Patients’ baseline data, including age, sex, laboratory examinations, imaging studies, and final diagnosis of lymphoma, were collected and examined to determine the feasibility and sensitivity for diagnosis and subclassification of lymphoma.Results: The mean of the diameter of mass was 37mm (9.7-149mm). Among the 90 patients, conventional G banding, FCM analysis, standard cytogenetic analysis, and FISH were successfully performed in 67 (74%), 78 (87%), 44 (49%), and 58 (64%) cases, respectively. G banding analysis were successful in 45 patients (67%) that showed normal karyotype in 5 cases (7%), t(14;18)(q32;q21) in 7 cases (10%), t(8;14)(q24;q32) in one case, and complex abnormality in 32 cases (48%), respectively. FCM analysis showed immunoglobulin light chain restriction in 48 cases (62%) and were diagnosed as B-cell lymphoma. FCM could not determine the T-cell clonality. Molecular analyses for TCR and/or IgH receptor rearrangements were successful in 35 patients (83%), 31 rearranged in IgH and 4 rearranged in TCR, respectively. There were 32 cases with IgH/Bcl2 fusions by FISH analysis, 26 cases in follicular lymphoma (FL) and 6 cases in diffuse large B-cell lymphoma (DLBCL), respectively. IgH/Bcl6 fusion was seen in 2 case of DLBCL and IgH/C-myc fusion was seen in 1 case of Burkitt lymphoma (BL). Finally, our cohort included 82 B-cell lymphomas (91%) and 8 T-cell lymphomas (9%). Subclassification of lymphoma in accordance with WHO system included 40 cases of FL, 39 cases of DLBCL, one case of BL, 2 cases of lymphoblastic lymphoma, 7 cases of peripheral T cell lymphoma not specified, and one case of angioimmunoblastic lymphoma. Although all of the outpatients were hospitalized until the day after biopsy, there were no serious complications related to this procedure like bleeding, perforation, ileus, and infection.Conclusions: EUS-FNAB using a standard 19 or 22-gauge needle is safe and feasible and has high diagnostic value for subclassification of intra-abdominal lymphoma without accessible peripheral lymphadenopathy. With the use of simultaneous immunophenotyping, molecular, and cytogenetic studies, lymphoma subclassification was possible in most of the cases. DisclosuresNo relevant conflicts of interest to declare.

IgG4-related disease in the head and neck

Lymphoid infiltrates are relatively common in the ocular adnexa and the salivary glands. They are of a variety of types and include both reactive processes and lymphomas. Within the ocular adnexa in years past, lymphoid proliferations were classified as inflammatory pseudotumor, reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma. With improvements in diagnostic techniques and with advances in lymphoma subclassification, it became clear that many of the dense lymphoid infiltrates, including cases classified as lymphoma and likely some classified as atypical lymphoid hyperplasia, represented low-grade B-cell lymphomas, the most common of which by far were extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas. Ocular adnexal inflammatory pseudotumor, reactive lymphoid hyperplasia, and chronic sclerosing sialadenitis were recognized, but the focus in diagnosis had been on avoiding misdiagnosis as a neoplastic process and in planning appropriate therapy. Recently, it has become clear that many cases of these reactive processes fall into the spectrum of immunoglobulin G4 (IgG4)-related disease, offering new insight into the pathogenesis of inflammatory lesions occurring in the ocular adnexa and the salivary glands. The majority of entities previously classified as chronic sclerosing sialadenitis, Mikulicz disease, orbital pseudolymphoma, and eosinophilic angiocentric fibrosis are now considered a part of the IgG4-related disease spectrum. In this review, we discuss the histologic and immunohistochemical features of IgG4-related disease of the head and neck and provide guidance for distinguishing this disease from its many mimics.

Role of endoscopic ultrasonography with and without fine needle aspiration cytology in the diagnosis and staging of lymphoma

Diagnosis of lymphoma is frequently challenging. The complexity of the sub-classification of lymphomas along with the necessity of a high quality sample leads to costly and invasive procedures in order to achieve the correct diagnosis. Endoscopic ultrasound is a valuable tool for the diagnosis and staging of gastrointestinal neoplasms as well as those that involve structures in the vicinity of the digestive tract. Whereas most gastrointestinal lymphomas are diagnosed and sub-classified using endoscopic biopsies, those involving deep-seated organs or lymph nodes might be targeted by minimal invasive procedures as endoscopic ultrasound-guided fine needle aspiration cytology. Endoscopic ultrasound is also an accurate tool for the local staging of gastrointestinal lymphomas and prediction of the response to Helicobacter pylori eradication. This review summarizes the indications and evidence of endoscopic ultrasonography with or without fine needle aspiration cytology in the diagnosis and staging of lymphoma.

28. Trends in lymphoma diagnosis

Accurate diagnosis and subclassification of lymphoma is essential as it directly dictates therapy and underpins translational research. We audited all cases of lymphoma diagnosed histologically at Royal North Shore Hospital during the calendar year 2010. 191 cases were definitively diagnostic of lymphoma and 28 cases were reported as non-diagnostic but lymphoid or atypical lymphoid proliferations. There were 67 (35%) diffuse large B-cell lymphoma, 40 (21%) follicular centre cell lymphoma, 21 (11%) marginal, seven (4%) T-cell and five (3%) mantle. There were 27 (14%) cases of Hodgkin's lymphoma. One hundred and five lymphomas were diagnosed in nodal tissue with the most common site being the neck nodes (29%). We encountered 11 cases of CNS lymphoma representing 6% of all lymphoma diagnoses. Core biopsy was performed in only 92 (43%) of cases but was definitively diagnostic of lymphoma in 82 (89%). This high rate of positive core biopsy confirms its role in diagnosis.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy for Diagnosis of Lymphoproliferative Disorders: Feasibility of Immunohistological, Flow Cytometric, and Cytogenetic Assessments

In addition to morphology, immunophenotype and genetic abnormalities should be assessed during diagnosis and subclassification of lymphoproliferative disorders. The objective of this study was to evaluate the yield of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) using a standard 19-gauge needle for diagnosis and subclassification of lymphoma, assessing the feasibility of immunohistological, flow cytometric, and cytogenetic assessments. Two hundred forty patients with suspected lymphoma were referred for EUS-FNAB to our quaternary EUS center between June 2005 and December 2010. EUS-FNAB using a conventional 19-gauge needle was attempted for all patients, followed by histological assessments including immunohistological staining, flow cytometry, and cytogenetic analysis (G-band karyotyping). Among the patients, 152 were ultimately diagnosed with lymphoma. The primary outcome measure of this study was the sensitivity of histological assessment, including immunohistological staining, flow cytometry, and G-band karyotyping, for diagnosis and subclassification of lymphoma. Among the 152 patients ultimately diagnosed with lymphoma, 147 patients (96.7%) were diagnosed by EUS-FNAB, and classification in accordance with the WHO (World Health Organization) system was also possible for 135 patients (88.8%) on the basis of histological findings, including immunohistological staining. Flow cytometry showed abnormal or unusual cell populations in 121 (79.6%) of the 152 patients diagnosed with lymphoma, and in 114 (90.5%) of the 126 patients diagnosed with B-cell lymphoma. Specific cytogenetic abnormalities were detected in 21 (13.8%) of the lymphoma patients. EUS-FNAB using a standard 19-gauge needle has high diagnostic value for lymphoma. Immunophenotyping is usually possible, while cytogenetic abnormalities can be identified in a relatively limited number of patients.

Diagnosis and subclassification of lymphomas and non‐neoplastic lesions involving mediastinal lymph nodes using endobronchial ultrasound‐guided transbronchial needle aspiration

The value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been established for staging mediastinal lymph nodes in lung carcinoma patients with radiologically enlarged lymph nodes, but its utility for evaluation of primary lymph node disorders is not well defined. The objective of this study was to evaluate the usefulness of EBUS-TBNA with on-site assessment and triage of sample for multiple ancillary techniques, for the diagnosis and subclassification of lymphomas and non-neoplastic lesions involving mediastinal lymph nodes. One hundred and twenty consecutive patients who underwent EBUS-TBNA between January 2008 and August 2009 were reviewed. The final cytological diagnosis was based on air-dried Romanowsky and alcohol-fixed Papanicolaou stained direct smears, immunohistochemistry, immunophenotyping, and fluorescence in situ hybridization (FISH). A total of 38 cases were included in this study consisting of eight reactive lymphoid hyperplasia, 20 granulomatous lymphadenitis (17 non-necrotizing and 3 necrotizing granulomatous inflammations), 3 Hodgkin lymphomas and 7 non-Hodgkin lymphomas (1 small lymphocytic lymphoma (SLL), 1 SLL with scattered Reed-Sternberg cells, 1 marginal zone lymphoma, and 4 large B cell lymphomas). Cultures performed in 13 cases were negative for AFB and fungi. Immunophenotyping and immunohistochemistry for MIB1 in six cases, and FISH in five cases provided necessary information for subclassification. EBUS-TBNA is a minimally invasive procedure which provides sufficient sample for definitive primary diagnosis and classification of malignant lymphoma and granulomatous inflammation in patients with mediastinal lymphadenopathy. Rapid on-site specimen assessment is invaluable for appropriate assignment of sample to ancillary studies.

Combined Core Needle Biopsy and Fine-Needle Aspiration With Ancillary Studies Correlate Highly With Traditional Techniques in the Diagnosis of Nodal-Based Lymphoma

Core needle biopsy (CNB) and fine-needle aspiration (FNA) are increasingly replacing excisional lymph node biopsy in the diagnosis of lymphomas. However, evaluation of CNB and FNA remains challenging owing to limited architectural information and the more detailed subclassification of lymphomas required by the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Our study is the largest study to assess diagnostic accuracy of CNB and FNA in conjunction with ancillary studies. We analyzed 263 cases and a diagnosis was established in 237, of which 193 were completely subclassified. In cases in which excisional biopsy was available as a reference for comparison, CNB and FNA had a sensitivity of 96.5%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 90%. CNB and FNA with ancillary studies represent a viable alternative in the diagnosis of lymphoma, as long as the number and size of cores for morphologic studies are not compromised.

Ultrasound-Guided Core Needle Biopsy of Cervical Lymphadenopathy in Patients with Lymphoma: The Clinical Efficacy and Factors Associated with Unsuccessful Diagnosis

This study attempts to identify factors that influence the success or failure of subclassifying 154 cases of neck lymphoma by ultrasound-guided core needle biopsy (UGCNB). Variables including age, gender, nodal size, cutting needle bore, number of core tissues obtained, presence of nodal necrosis or infarct, fragmentation of the specimens and subclassification of lymphoma were reviewed and statistically analyzed to check if they were related to the success of UGCNB. UGCNB was successful in subclassifying lymphoma in 138 (89.7%) cases, in diagnosing lymphoma in 11 (7.1%) and unsuccessful in diagnosing lymphoma in five (3.2%) cases. No complications were encountered. The factors leading to failure in subclassification included the presence of composite lymphoma ( p = 0.001), nodal necrosis or infarct ( p = 0.001) and insufficiency or fragmentation of the specimens ( p < 0.001). UGCNB is a safe and efficient procedure in subclassifying lymphoma. It may obviate surgical biopsy in 89.7% of cases. (E-mail: ylw0518@adm.cgmh.org.tw )

EUS-guided biopsy for the diagnosis and classification of lymphoma

EUS-guided FNA and Tru-cut biopsy (TCB) is highly accurate in the diagnosis of lymphoma. Subclassification, however, may be difficult in low-grade non-Hodgkin lymphoma and Hodgkin lymphoma. To determine the yield of EUS-guided biopsy to classify lymphoma based on the World Health Organization classification of tumors of hematopoietic lymphoid tissues. Retrospective study. Tertiary referral center. A total of 24 patients referred for EUS-guided biopsy who had a final diagnosis of lymphoma or "highly suspicious for lymphoma." EUS-guided FNA and TCB combined with flow cytometry (FC) analysis. MAIN OUTCOMES MEASUREMENT: Lymphoma subclassification accuracy of EUS guided biopsy. Twenty-four patients were included in this study. Twenty-three patients underwent EUS-FNA, and 1 patient had only TCB. Twenty-two underwent EUS-TCB combined with FNA. EUS correctly diagnosed lymphoma in 19 out of 24 patients (79%), and subclassification was determined in 16 patients (66.6%). Flow cytometry correctly identified B-cell monoclonality in 95% (18 out of 19). In 1 patient diagnosed as having marginal-zone lymphoma by EUS-FNA/FC only, the diagnosis was changed to hairy cell leukemia after a bone marrow biopsy was obtained. EUS had a lower yield in nonlarge B-cell lymphoma (only 9 out of 15 cases [60%]) compared with large B-cell lymphoma (78%; P = .3 [Fisher exact test]). Retrospective, small number of patients. EUS-guided biopsy has a lower yield to correctly classify Hodgkin lymphoma and low-grade lymphoma compared with high-grade diffuse large B-cell lymphoma.

Metallothionein as a useful marker in Hodgkin lymphoma subclassification

Metallothionein (MT) expression is considered to be a prognostic factor that promotes tumor resistance to apoptosis. In non-Hodgkin lymphomas, MT is differentially expressed and constitutes a risk factor. We have characterised MT in lymph nodes of Hodgkin lymphoma (HL) [patients with nodular sclerosis (NSHL), mixed cellularity (MCHL), lymphocyte-rich classical HL (LRCHL) and nodular lymphocyte predominant HL (NLPHL)] and in controls. MT expression is significantly and differentially altered in the HL subtypes. NSHL and MCHL show highly increased MT throughout the lymph node. In contrast, MT is barely increased in LRCHL relative to controls. NLPHL shows a distinct pattern of heterogeneous MT with increased MT in nodular areas surrounded by MT-negative tissue. The cellular MT sources are reactive, infiltrating (non-neoplastic) cells, whereas neoplastic cells are devoid of MT. We show for the first time that MT is differentially expressed in subclassified HL.

Arachidonic Acid Metabolism-Related Molecules as Candidate Markers in Subclassification of Lymphoma

Arachidonic acid metabolites, like prostaglandins and leukotrienes, have been suggested to play an important role not only in inflammation but also in carcinogenesis. We have recently reported that the cysteinyl leukotriene receptor 1 (CysLT1) and 15-lipoxygenase-1 (15-LO-1), a sister enzyme to 5-LO (which is essential for leukotriene synthesis), are expressed by the malignant Hodgkin Reed-Sternberg cells of Hodgkin lymphoma (HL) and certain HL-derived cell lines, and that these cells convert arachidonic acid to the novel pro-inflammatory eoxins (Int J Cancer, 2008; FEBS J, 2008; PNAS, 2008). Given the pleiotropic effects of the CysLT1 receptor and 15-LO-1 and the fact that their expression is strictly regulated in a cell-type and tissue-specific manner, it was of interest to elucidate whether these proteins are exclusively expressed by the tumor cells of the classical HL entities. Therefore, the expression of these molecules was investigated by immunohistochemistry in a broad range of lymphomas (lymphocyte predominance (LP) HL, MALT lymphoma, T cell-derived anaplastic large cell lymphomas (ALCL), immunocytoma, mantle cell lymphoma, B-CLL, Burkitt lymphoma, follicular lymphoma, DLBCL, PTCL, primary mediastinal B cell lymphoma (PMBCL), T cell-rich B cell lymphoma; n=58). The tumor cells in one of four T cell-derived ALCLs, in contrast to all other studied non-Hodgkin lymphomas (NHLs) and LP HL tumors, strongly expressed 15-LO-1. PMBCL was the only NHL entity showing tumor cells positive for the CysLT1 receptor (9 of 10 tumors), and the PMBCL cell line Med-B1 expressed functional CysLT1 receptors, responding with a robust calcium signal upon cysteinyl leukotriene challenge. These findings further corroborate the pathologic overlap between PMBCL and classical HL. Although most cases of PMBCL are identified by routine diagnostics, the distinction between PMBCL and DLBCL may be challenging. After future careful validation in extended patient series, the CysLT1 receptor may be a potential additional marker to phenotypically distinguish these two lymphoma entities.

頸部リンパ節の腫脹をきたす疾患の鑑別（口腔病理から）

Diagnosis of malignant lymphoma should be made basically morphological observation with HE specimen as well as data by multimeric analyses. Otherwise there are some cases that cannot obtain a precise diagnosis. In addition, pathologists must understand the characteristics of many subclassification of lymphoma enough, and based on the knowledge, it becomes often necessary to add various kinds of analysises.

Diagnostic Uses of Pax5 Immunohistochemistry

Pax5, or B-cell-specific activator protein, is a nuclear protein in the paired-box containing (PAX) family of transcription factors involved in control of organ development and tissue differentiation. Pax5 is mostly expressed in B lymphocytes and B-cell lymphomas, although recent data have shown expression in the developing central nervous system, some neuroendocrine tumors, and occasional myeloid leukemias. Pax5 immunohistochemistry shows robust nuclear staining, and has become a valuable tool in the diagnosis and subclassification of lymphomas. Pax5 staining is positive in most Hodgkin and B-cell non-Hodgkin lymphomas, and also precursor B-cell lymphoblastic neoplasms. Plasma cell neoplasms, multiple myeloma, and plasmablastic lymphomas typically are negative. T-cell lymphomas are, to date, consistently negative. Recently, Pax5 expression has been described in the majority of small cell carcinomas and Merkel cell carcinomas. Rare cases of Pax5 expression in other carcinomas have been reported. With these exceptions, Pax5 immunohistochemistry is fairly specific for B-cell lineage and is a valuable addition to the armamentarium of markers available for lymphoma subtyping.