Diagnosis Of Classical Hodgkin Lymphoma Research Articles

T-Cell-Rich Hodgkin Lymphoma With Features of Classic Hodgkin Lymphoma and Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Borderline Category With Overlapping Morphologic and Immunophenotypic Features.

It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies. To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation. The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated. These 3 cases harbored lymphocyte-predominant-like and Hodgkin and Reed-Sternberg-like cells that partially expressed B-cell and CHL markers and were negative for Epstein-Barr virus-encoded small RNA, in a T-cell-rich background with residual follicular dendritic cell meshworks; 1 case had frequent and the other 2 cases scant/absent eosinophils and plasma cells. Two patients with advanced-stage (III or IV) disease presented with axillary and supraclavicular lymphadenopathy, respectively, and without B symptoms. These patients underwent NLPHL-like therapeutic management with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone) chemotherapy; both are in complete remission 7 years posttherapy. One patient presented with stage I disease involving an internal mammary lymph node without B-symptoms and was treated with surgical excision alone; this patient is also in complete remission 1 year later. These cases illustrate overlapping features of T-cell-rich NLPHL and CHL with neoplastic cells expressing both B-cell program and CHL markers. This underrecognized overlap has not been fully illustrated in the literature, although it portrays a therapeutic challenge. These neoplasms may deserve in-depth investigation in the future that may bring up diagnostic or theragnostic implications.

Diagnostic Utility of CD200 Immunohistochemistry in Distinguishing EBV-Positive Large B-Cell Lymphoma From Classic Hodgkin Lymphoma.

Epstein-Barr virus-positive large B-cell lymphoma (EBV+ LBCL) is a heterogeneous group of diseases that may resemble classic Hodgkin lymphoma (CHL) both morphologically and immunophenotypically. However, these diseases are treated with different therapies and carry distinct prognoses. We examined CD200 expression by immunohistochemistry in EBV+ LBCL and evaluated its diagnostic utility in the differential diagnosis with CHL. CD200 immunohistochemistry was performed on archival material from 20 cases of CHL (11 EBV+, 9 EBV-), 11 cases of EBV+ LBCL, and 10 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS). Staining pattern and intensity (0-3+ scale) were recorded. CD200 positivity was seen in Reed-Sternberg cells in 19 (95%) of 20 cases of CHL, predominantly in a strong (3+, 15/19) and diffuse (>50% of cells, 17/19) pattern. In contrast, CD200 was negative in 8 (73%) of 11 cases of EBV+ LBCL; the 3 positive cases showed 1 to 2+ staining in less than 50% of lesional cells. All cases of DLBCL NOS were negative for CD200. CD200 may be a useful immunophenotypic marker in differentiating EBV+ LBCL from CHL, with negative to partial/weak staining favoring a diagnosis of EBV+ LBCL and strong diffuse staining favoring a diagnosis of CHL.

CD30 expression is frequently decreased in relapsed classic Hodgkin lymphoma after anti-CD30 CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cells anti-CD30 is an innovative therapeutic option that has been used to treat cases of refractory/relapsed (R/R) classic Hodgkin lymphoma (CHL). Limited data are available regarding the CD30 expression status of patients who relapsed after this therapy. This is the first study to show decreased CD30 expression in R/R CHL in patients (n = 5) who underwent CAR T-cell therapy in our institution between 2018 and 2022. Although conventional immunohistochemical assays showed decreased CD30 expression in neoplastic cells in all cases (8/8) the tyramide amplification assay and RNAScope in situ hybridisation detected CD30 expression at different levels in 100% (n = 8/8) and 75% (n = 3/4), respectively. Hence, our findings document that certain levels of CD30 expression are retained by the neoplastic cells. This is not only of biological interest but also diagnostically important, as detection of CD30 is an essential factor in establishing a diagnosis of CHL.

Methotrexate-related lymphoproliferative disease showing different histological findings at recurrence

A 55-year old female patient was treated with methotrexate (MTX) and infliximab (IFX) for rheumatoid arthritis (RA). She experienced unknown fever, generalized lymphadenopathy, and liver tumors. Histological examination of the inguinal lymph node and a liver tumor resulted in the pathological diagnosis of classic Hodgkin lymphoma, with many Reed-Sternberg cells with the positivity of Epstein-Barr virus (EBV). She was diagnosed with MTX-related lymphoproliferative disorders (MTX-LPDs). She received chemotherapy after the cessation of MTX and IFX and achieved complete remission. RA showed recurrence after a while, and she was treated with steroids or other drugs. Six years after the chemotherapy, she experienced low-grade fever and anorexia. Whole computed tomography images showed an appendix tumor and enlargement of the surrounding lymph nodes. Appendectomy with the radical lymph nodes dissection was performed. The pathological diagnosis was diffuse large B-cell lymphoma, resulting in the clinical diagnosis of the relapse of MTX-LPD. EBV was negative at this point. The pathological findings of MTX-LPD may change at relapse; thus, biopsy should be considered when the relapse of MTX-LPD is suggested.

Aorto-enteric fistula: a case report

A case report focused on imaging aspects of an aorto-enteric fistula (AEF) in a 39-year-old patient with a recent diagnosis of classic Hodgkin Lymphoma with multiple enlarged retroperitoneal lymph nodes. AEF is a pathologic communication between the aortic lumen and any portion of the gastrointestinal tract. Without prompt intervention, the associated mortality approaches 100%. Early clinical suspicion is essential for a successful outcome and the role of imaging is fundamental to diagnose it. Owing to its widespread availability, short acquisition time, and high resolution, CT with intravenous contrast has become the first-line modality for imaging evaluation of suspected aorto-enteric fistula.

The Grey Zones of Classic Hodgkin Lymphoma

Simple SummaryClassic Hodgkin lymphoma (CHL) is a well-defined lymphoid neoplasm with a minority of characteristic neoplastic cells of B cell origin, namely Hodgkin and Reed–Sternberg cells immersed in a rich reactive inflammatory infiltrate in the background. Although CHL has always been set apart from non-Hodgkin lymphomas, cases with morphological and phenotypic features intermediate between CHL and other lymphomas have been described. Whereas some of these lymphomas only represent morphological mimics, others exhibit mutational and gene expression profiles which overlap with CHL, indicating that these cases, frequently termed grey zone lymphomas, reside on the biological boundary between CHL and large B-cell lymphomas. In the present review, we aim to describe the current knowledge of these rare lymphomas, address diagnostic issues and summarize today’s concepts on the classification of grey zone lymphomas and related tumors.Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed–Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore are set apart from other B cell lymphomas in the current WHO classification. However, cases with morphological and phenotypic features overlapping with CHL have been recognized, and the category of B cell lymphoma—unclassifiable—with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL, also termed grey zone lymphoma, was first introduced into the WHO classification in 2008 as provisional entity. These cases, as well as others raising a differential diagnosis of CHL can present diagnostic problems, as well as therapeutic challenges. Whereas some of these lymphomas only represent biologically unrelated morphological mimics, others, especially mediastinal grey zone lymphoma, exhibit genetic and gene expression profiles which overlap with CHL, indicating a true biological relationship. In this review, we address areas of diagnostic difficulties between CHL and other lymphoma subtypes, discuss the biological basis of true grey zone lymphoma based on recent molecular studies and delineate current concepts for the classification of these rare tumors.

Patients with Classical Hodgkin Lymphoma with Less Than 10.5 CD20-Positive Reed-Sternberg Cells in 10 High-Power Fields Have Better Prognosis.

The CD20 immunoexpression in classical Hodgkin lymphoma (CHL) is variable and it may represent an intersection between the pathophysiology of CHL and the clinical prognosis of patients. Retrospective study with 174 patients with pathological diagnosis of CHL. Clinical data were reviewed from medical records. Immunophenotypic study with CD20 were performed in two ways: hotspot count and in 10 high-power fields (HPF). The data were tabulated and the p value less than 0.05 was considered significant. The CD20-positive phenotype was found in 45 (25.9%) of the total of 174 patients with available material. Patients with CD20 positivity on neoplastic cells tend to heal earlier, particularly those with less than 10.5 cells/10 HPF (p = 0.037). Patients with CHL with less than 10.5 CD20-positive Reed-Sternberg cells in 10 HPF have better prognosis.

Poster: HL-325: A Case Report of Classic Hodgkin Lymphoma with Unusually Abundant Tumor Cell Expression of B-Cell Markers: A Diagnostic Dilemma and Treatment Challenge

Context The diagnosis of classic Hodgkin Lymphoma (cHL) appears quite straightforward, as it is built upon extended histological and immunophenotypic assessment. Hodgkin and Reed-Sternberg cells reflect monoclonal cell proliferation, presumably originating from germinal center B-cells. In general, these cells lose the B-cell phenotype, yet one-third of cHL cases express at least one B-cell marker, which in some instances leads to diagnostic difficulties in distinguishing cHL from B-Cell Lymphomas (BCL). Objective We present a diagnostically complex case of cHL CD30+/CD15+ in a 21-year-old male. Immunohistochemistry demonstrated unusual, strong expression of markers of B-cell differentiation and positivity for Epstein-Barr Virus (EBV), which brought out serious constraints in the differential diagnosis of an EBV-positive Diffuse Large BCL. Patient Case Report A previously healthy 21-year-old male presented at our institution with neck lymphadenopathy. He experienced no B-symptoms. Except for a slightly elevated sedimentation rate, blood analyses were within normal ranges. Initial PET-CT scan identified stage II disease involving supradiaphragmatic lymph nodes. Fine needle aspiration of the lymph node was suggestive of HL. However, histological examination of the surgically extirpated lymph node was puzzling. The atypical lymphoid cells expressed classical Hodgkin phenotype CD30+/CD15+, but they showed strong CD20+ co-expression. The tumor cells were strongly positive for EBV, and a diagnosis of EBV-associated BCL was assumed. In addition, high EBV loads in blood were confirmed. PCR studies for B- and T-cell gene rearrangements were negative. The tumor tissue was sent for consultative opinion in three centers independently. Immunostains were consistent; lymphoma cells were strongly positive for CD30, CD15, EBV, and EBV receptor CD21, as well as the B-cell markers CD20, Bcl-6, and MUM1. Finally, next-generation sequencing for B-cell rearrangement was negative. In absence of sufficient diagnostic criteria for EBV-positive BCL and all things considered, the diagnosis of classic HL was concluded. Conclusions In consensus with reported literature, treatment was initiated with R-ABVD regimen. Complete regression of tumor masses became evident after the first cycle. An interim PET scan is planned for further evaluation.

Development and validation of a prediction model for 1-year mortality among older adults with Hodgkin Lymphoma who receive dose-intense chemotherapy

BackgroundOlder adults with Hodgkin Lymphoma (HL) have poorer outcomes than younger patients. There are little data about which baseline patient and disease factors inform prognosis among older patients. We sought to create a prediction model for 1-year mortality among older patients with new HL who received dose-intense chemotherapy. MethodsWe included adults ≥65 years old with a new diagnosis of classical HL between 2000–2013 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset who received full-regimen chemotherapy. Through a non-random 2:1 split, we created development and validation cohorts. Multiple imputation was used for missing data. Using stepwise selection and logistic regression, we identified predictive variables for 1-year mortality. The model was applied to the validation cohort. A final model was then fit in the full cohort. ResultsWe included 1315 patients. In the development cohort (n = 813), we identified significant predictors of 1-year mortality including age, Charlson comorbidity index (CCI), B symptoms at diagnosis, and advanced stage at diagnosis. The c-statistic was 0.70. When this model was applied to the validation cohort (n = 502), the c-statistic was 0.65. Predictors of 1-year mortality in the final model were CCI (OR = 1.41), B symptoms (OR = 1.54), advanced stage (OR = 1.44), and older age at diagnosis (OR = 1.33). ConclusionWe present a prediction model for use among older adults with HL who receive intensive chemotherapy. We identify risk factors for death within 1 year of diagnosis. Future work will build upon prognostication and shared decision-making after diagnosis for this population.

Role of Flow Cytometric Immunophenotyping for Classic Hodgkin Lymphoma in Small Biopsy and Cytology Specimens.

The diagnosis of classic Hodgkin lymphoma (CHL) traditionally requires surgical tissue biopsy because of the paucity of diagnostic Hodgkin and Reed-Sternberg cells. Diagnosis can be challenging in small core needle and cytologic biopsies, which are increasingly used because of reduced costs and minimal invasiveness. Flow cytometric (FC) identification of Hodgkin and Reed-Sternberg cells is possible, but FC test efficacy is not well studied outside of validation settings, especially in small specimens. To assess the testing efficacy of FC performed on small biopsy and cytology specimens for the diagnosis of CHL. We reviewed 131 patients with CHL and 459 patients without CHL during a 3-year period who underwent a small biopsy procedure, including core biopsy and/or cytology evaluation, with concurrent routine clinical FC testing for CHL, assessing performance of FC in small specimens. Evaluating testing efficacy, sensitivity was 95.4% and specificity was 98.2%, whereas positive and negative predictive values were 92.2% and 99.0%, respectively. Although there were more false-positive results than compared with published validation studies, expert review identified distinct diagnostic pitfalls; awareness of these may improve testing efficacy. Although FC diagnosis of CHL was historically considered unfeasible, our findings in a real-world clinical setting suggest that FC adds diagnostic value to small biopsy evaluation, reducing time to treatment, costs, and invasive excisional procedures.

Classic Hodgkin Lymphoma - Old Disease, New Directions: An Update on Pathology, Molecular Features and Biological Prognostic Markers.

The aim of this paper is to review morphologic, immunophenotypic, and molecular features of classic Hodgkin lymphoma, as well as different prognostic markers in this neoplasm. Classic Hodgkin lymphoma (CHL) accounts for 15-25% of all lymphomas in the Western world. The hallmark of this disease is the neoplastic Hodgkin/Reed-Sternberg (HRS) cell, which is favored to be derived from germinal center B-cells but has lost many of the B-cell markers. HRS cells are scattered within a dense inflammatory infiltrate, and through a network of cytokines and chemokines they shape their microenvironment, evade immune response, survive, and grow. In the last two decades multiple prognostic markers related to HRS cells, the microenvironment or both, have been evaluated in patients with CHL. They include clinical, immunohistochemical, cytogenetic, and molecular markers that can predict survival and identify high-risk patients who will likely relapse after therapy. More recently, circulating tumor DNA analysis by next-generation sequencing has opened new avenues for diagnosis and disease monitoring after therapy. The increased understanding of molecular mechanisms underlying CHL pathogenesis has led to successful implementation of novel therapies, such as anti-PD-1 antibodies, which are becoming a mainstay of treatment in relapsed/refractory patients. CONCLUSION: Currently, pathologic prognostic markers are not routinely assessed at initial diagnosis of CHL. However, as more therapies become available, it will be important to identify patients with high-risk disease who may benefit from more intense or targeted therapy upfront.

Is classical Hodgkin lymphoma a different disease in the elderly? A single-center retrospective cohort study.

Although the clinical features and treatment results of Hodgkin lymphoma (HL) in young adults are well known, it is thought that the disease may have different characteristics in elderly patients with HL, which constitutes almost 25% of the group. In this study, our aim is to evaluate the clinicopathological features, treatment outcomes, and survival of elderly classical Hodgkin lymphoma (CHL) patients. Patients aged 60 and over who were treated with a diagnosis of CHL were included in our retrospective cohort study. Patients under the age of 60, those with a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) were excluded from the study. The median age of 51 patients in the study was 66 (60-76). Forty (78.4%) patients had at least one comorbid disease. The most common histological subtype was mixed cellular HL (n = 23, 45%) and 23 (45%) patients had B-symptoms. Thirty-two (62.8%) patients were in the advanced stage. The most preferred regimen in first-line treatment was doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) combination chemotherapy (n: 45; 88.2%). Forty-three (84.3%) patients were able to complete the initially planned treatment. Complete response was achieved in 34 (66.7%) patients. During the median follow-up period of 45.2 months, 23 (42.6%) patients had died. The 5-year OS was 57.4%. In conclusion, it was observed that the distribution of histological subtypes was different in elderly patients with CHL, B-symptoms were more common in elderly patients, and OS decreased with increasing age.

Primary infradiafragmatic bony classical Hodgkin lymphoma

Infradiaphragmatic Hodgkin’s lymphoma (IDHL) is a scarce neoplasm and primary pelvic bone exhibition is limited to case reports. Recognition and management of likewise a rare disease are challenging. Here the authors present a peculiar case of classic Hodgkin lymphoma (CHL) of pelvic bone. A 31year-old man was admitted to our hospital with chief complaint of left hip pain. Imaging showed a lytic lesion in the left iliac bone with sclerotic margin and extension to soft tissue. Open biopsy confirmed the diagnosis of CHL. CHL at first introducing as pelvic bone involvement is really uncommon. The diagnosis of primary bone CHL should be made by tough histological and clinical expression.

PD-1 and PD-L1 Immunohistochemistry as a Diagnostic Tool for Classic Hodgkin Lymphoma in Small-volume Biopsies.

It is becoming increasingly important to obtain detailed diagnostic information on small-volume tissue biopsies, such as core needle biopsies. This is particularly crucial in the workup and diagnosis of classic Hodgkin lymphoma (CHL) and other morphologically similar lymphomas such as T-cell/histiocyte-rich large B-cell lymphoma (THRLBL), where small-volume lymph node biopsies often represent the frontline tissue source, and the differential diagnosis includes a reactive process. Immunohistochemical markers could be helpful to differentiate CHL from reactive lymph node changes (RLN) in this setting. The use of programmed cell death-1 (PD-1) and its ligand (PD-L1) immunohistochemistry has historically focused on prognostic and therapeutic value when evaluating CHL. However, the present study seeks to determine the diagnostic utility of these markers in core needle biopsies of CHL (25), THRLBL (3), and RLN (31). The cases of CHL and THRLBL were previously diagnosed and confirmed with standard immunohistochemistry, allowing the utility of PD-1 and PD-L1 to be tested in this setting. Different PD-1 and PD-L1 expression patterns were observed between the reactive process of RLN and the malignant lymphomas (CHL and THRLBL). CHL cases overall showed the greatest expression of PD-L1 within the malignant Reed-Sternberg cell population, with 40% of CHL cases exhibiting >50% PD-L1 expression. This degree of PD-L1 expression was not seen in the lymphocytic cell population of any RLN (P<0.001). Conversely, CHL cases showed an overall lower expression of PD-1, as 96% of CHLs had <5% PD-1 expression in Reed-Sternberg cells compared with only 10% expression within the lymphocytic population of RLN (P<0.001). THRLBL cases followed a similar trend to CHL. These results demonstrate that upfront PD-1 and PD-L1 immunohistochemistry can aid in the diagnosis of CHL in small-volume tissue biopsies.

Primary Extranodal Classical Hodgkin Lymphoma of the Sphenoid Sinus: A Case Report and Brief Review of the Literature

Abstract Primary sinonasal lymphoma is a relatively rare disease, particularly in Western societies, and the vast majority of these are non-Hodgkin lymphoma. Classical Hodgkin lymphoma (CHL) characteristically originates in lymph nodes; primary extranodal CHL of the sinonasal tract is extremely rare. We report a case of a 63-year-old woman with primary CHL of the sphenoid sinus. The patient presented to the emergency department with complaints of “flashing light” in both eyes. Magnetic resonance imaging studies revealed a 4.2-cm enhancing mass in the sphenoid sinus. Histologic examination of the sphenoid mass revealed a diffuse mixed inflammatory infiltrate, within which were scattered large atypical cells with enlarged nuclei with irregular nuclear contours and prominent eosinophilic nucleoli, consistent with Hodgkin/Reed-Sternberg cells. Immunohistochemical studies showed the large atypical cells to be positive for CD15 and CD30 and negative for CD20 and CD45. In situ hybridization staining for small Epstein-Barr virus–encoded RNA was also positive in the atypical cells. These findings supported the diagnosis of CHL.

Classic Hodgkin lymphoma and Castleman disease: an entity appears to be emerging.

Hodgkin lymphoma is a B cell neoplasm characterized by Hodgkin and Reed-Sternberg (HRS) cells in an inflammatory background. Classic Hodgkin lymphoma (CHL) accounts for approximately 90% of all cases of HL and four types are recognized in the World Health Organization (WHO) classification: lymphocyte-rich, nodular sclerosis, mixed cellularity, and lymphocyte depleted. Castleman disease (CD) is a designation used for a heterogeneous group of diseases that involve lymph nodes. Histologically, there are hyaline vascular and plasma cell variants, the latter including human herpes virus 8 (HHV8)-positive and HHV8-negative subsets. In this study, we describe three men, 45-57years of age, one HIV-positive, who had coexistent CHL and CD. All patients had the interfollicular variant of CHL and HHV8-negative plasma cell variant CD. Immunohistochemical analysis supported the diagnosis of CHL; the HRS cells were positive for CD15, CD30, and PAX-5 (dim). In two cases, the HRS cells and the plasma cells of CD expressed interleukin-6 (IL-6). Our review of the literature identified 34 cases of coexistent CHL and CD reported previously. In aggregate, about two-thirds of all cases of CHL have been the interfollicular variant and around 90% of CD cases were plasma cell variant, HHV8-negative in the subset of cases tested. We suggest that interfollicular variant CHL and plasma cell variant CD may be a distinct entity with a common pathogenesis, possibly related to IL-6 dysregulation. The few cases in the literature describing other forms of CHL and hyaline vascular variant CD are different from the entity reported here, with a different pathogenesis, likely similar to focal Castleman-like changes that have been described in association with various types of non-Hodgkin lymphoma.

Hodgkin lymphoma detection and survival: findings from the Haematological Malignancy Research Network.

BackgroundHodgkin lymphoma is usually detected in primary care with early signs and symptoms, and is highly treatable with standardised chemotherapy. However, late presentation is associated with poorer outcomes.AimTo investigate the relationship between markers of advanced disease, emergency admission, and survival following a diagnosis of classical Hodgkin lymphoma (CHL).Design & settingThe study was set within a sociodemographically representative UK population-based patient cohort of ~4 million, within which all patients were tracked through their care pathways, and linked to national data obtained from Hospital Episode Statistics (HES) and deaths.MethodAll 971 patients with CHL newly diagnosed between 1 September 2004–31 August 2015 were followed until 18th December 2018.ResultsThe median diagnostic age was 41.5 years (range 0–96 years), 55.2% of the patients were male, 31.2% had stage IV disease, 43.0% had a moderate–high or high risk prognostic score, and 18.7% were admitted via the emergency route prior to diagnosis. The relationship between age and emergency admission was U-shaped: more likely in patients aged <25 years and ≥70 years. Compared to patients admitted via other routes, those presenting as an emergency had more advanced disease and poorer 3-year survival (relative survival 68.4% [95% confidence interval {CI} = 60.3 to 75.2] versus 89.8% [95% CI = 87.0 to 92.0], respectively [P<0.01]). However, after adjusting for clinically important prognostic factors, no difference in survival remained.ConclusionThese findings suggest that CHL survival as a whole could be increased by around 4% if the cancer in patients who presented as an emergency had been detected at the same point as in other patients.

Comparative pathologic analysis of mediastinal B-cell lymphomas: selective expression of p63 but no GATA3 optimally differentiates primary mediastinal large B-cell lymphoma from classic Hodgkin lymphoma

BackgroundInterpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions.MethodsSearch for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above.ResultsMost clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL.ConclusionsP63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL.

Outcome of Autologous Stem Cell Transplantation Following PD-(L)1 Based Salvage Therapy for Multiply Relapsed Patients with Classic Hodgkin Lymphoma

Outcome of Autologous Stem Cell Transplantation Following PD-(L)1 Based Salvage Therapy for Multiply Relapsed Patients with Classic Hodgkin Lymphoma

'NOT SO CLASSICAL': A STUDY OF THE IMMUNOPROFILE IN CLASSICAL HODGKIN LYMPHOMA, AN EXPERIENCE FROM A REFERRAL CENTER

Introduction: According to WHO classification, Classical Hodgkin Lymphoma (CHL) expresses CD15 and CD30 antigens in majority of cases, and CD20 in a small subset of cases. Expression of CD20 may affect the patients' prognosis, relapse, and refractoriness to the therapy. We come across a subset of cases of CHL in our lymphoma consultation cases that exhibit a lack of the ‘positive’ diagnostic marker CD15 and express CD20 in the Hodgkin and Reed-Sternberg (HRS) cells. This observation has important prognostic implication, based on the western studies from the more developed world, and furthermore prompted us for a systematic evaluation of the immunoprofile of South-East Asian CHL patients and to compare those with the Western data. Methods: In this retrospective analysis, 111 cases of CHL diagnosed over a period of six months were studied. Demographics, clinical details, histopathological (including unusual morphologic patterns), and immunohistochemical (IHC) parameters were recorded. The diagnoses were made according to the 2016 WHO classification of lymphoid neoplasms. The cases were further subtyped. The IHC panel included CD45, CD15, CD30, CD3, CD20, PAX5, ALK1, and EBV (LMP-1) in all cases and MUM1, CD21, EMA, PD1, OCT2, BOB.1, and BCL6, in a subset of cases, wherever necessary. A case was designated CD20+, if >10% of HRS cells were strongly positive. Results: The cases of CHL fit into 'textbook phenotype' (WHO 2016 update) of CD15+, CD30+, CD20- in 54% cases. HRS cells were positive for CD30 in all, CD15 in 56%, PAX5 in 96%, CD20 in 18% cases and EBV (LMP1) in 58.3% cases. In majority of instances, morphology and an initial panel of CD3, CD20, CD15, CD30, CD45, and PAX5 were sufficient for diagnosis. When IHC pattern discordance was noted or mimics of CHL were in the differential diagnostic consideration, additional markers supported the diagnosis of CHL. Conclusions: 1. Our study results broaden the understanding of the demographic, histopathologic, and IHC characteristics of CHL cases. 2. The second peak of bimodal distribution occurs two decades earlier as compared to those of the western population in majority cases in our cohort. 3. 56% of our cases expressed CD15 that is lower than the reported positivity rates (75% to 85%). 4. Significant CD20 positivity in HRS cells as seen in our cohort can create diagnostic dilemma. However, CD45 negativity in the presence of weak to barely perceptible PAX5 and moderate to strong expression for EBV aid in arriving at a diagnosis of CHL. 5. Future directions: The management of CHL is essentially based on radiotherapy and chemotherapy, due to lack of information about the clinical outcomes with anti-CD20 antibody therapy or combined drug therapy using a classic regimen. The prognostic impact of lack of CD15 and positive CD20 expression in the cases of CHL requires further research and clinical follow-up studies in a larger cohort of patient to assess the role of CD20 in the pathophysiology and progression of CHL. Keywords: CD20; classical Hodgkin lymphoma (cHL); immunohistochemistry (IHC).