Progressive Transformation Of Germinal Centers Research Articles

Increased IgG4+ plasma cells are common in excised lymph nodes from children and adolescents without IgG4-related disease.

Lymphadenopathy is a common finding in patients with IgG4-related disease (IgG4-RD) and often associated with increased IgG4+ plasma cells in this setting. The histologic features of so-called IgG4-related lymphadenopathy (IgG4-LAD) have seldom been investigated in children and adolescents, and step-wise progression to extranodal IgG4-RD has not been described. This study was performed to further evaluate the frequency, pathologic features, and clinical significance of IgG4-LAD-like histologic changes in the pediatric setting. We analyzed 37 benign lymph nodes collected semi-consecutively from children aged 0-18 years at our institution for both absolute and relative IgG4+ plasma cell abundance and recurrent histomorphologic patterns associated with IgG4-LAD. The combination of IgG4+/IgG+ plasma cell ratio >40% and IgG4+ plasma cell count ≥50 were considered as IgG4-LAD-like per expert consensus guidelines. Seven cases (19%) met both diagnostic criteria. The dominant histomorphologic patterns were follicular hyperplasia (n = 6), interfollicular expansion (n = 3), and progressive transformation of germinal centers (n = 3). Extranodal manifestations of IgG4-RD were not identified in this cohort (38 months average follow-up). Instead, clinical and laboratory findings indicated that lymph node enlargement in most patients could likely be attributed to alternative processes including antecedent dentistry, concurrent infection, and incipient Crohn's disease. Our findings suggest that the histologic features of IgG4-LAD are likely much more common in children and adolescents than previously recognized, often existing in complex with common reactive lymphadenopathies. The diagnostic value of routine immunohistochemical assessment for IgG4+ plasma cells in benign lymph nodes from pediatric patients without established extranodal IgG4-RD and/or other supportive clinical and laboratory data is therefore uncertain.

A single‐center retrospective review of pediatric cases of progressive transformation of germinal centers

Progressive transformation of germinal centers (PTGC) is a rare diagnosis characterized by asymptomatic lymph node enlargement. It has previously been associated with lymphoma, autoimmune conditions, and lymphoproliferative diseases in small pediatric case series. We conducted a single-center retrospective review of pediatric cases of PTGC diagnosed at our institution by hematopathologists from 2000 to 2020. We identified 57 primary cases and three recurrent cases of PTGC. Laboratory and imaging evaluations were obtained inconsistently. Nine patients (16%) saw a pediatric hematology/oncology (PHO) specialist prior to diagnosis, and 21 (37%) had follow-up with PHO after diagnosis. Patients with PTGC had similar age and involved lymph node sites to those from previous case series. Fewer patients underwent recurrent lymph node biopsy than previously described. PTGC has been linked to certain types of lymphoma, although never definitively associated with lymphoma. Follow-up with a PHO provider is indicated to ensure that close surveillance is performed.

Progressive transformation of germinal centers or nodular lymphocyte-predominant Hodgkin lymphoma? Issues of differential diagnosis: a clinical case

Progressive transformation of germinal centers (PTGC) is a benign reactive lymphadenopathy, which can be an independent disease or occur in association with other lymphomas, the most common variant of which is nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). To date, it has not been definitively clarified how PTGC and NLPHL are interconnected, despite the abundance of works presented on this topic. PTGC may precede NLPHL, occur synchronously with it, or develop after a course of therapy in patients with NLPHL. Despite similar clinical and morphological features, the approach to the treatment and management of patients is different. In the case of NLPHL, one of the therapeutic options is chemotherapy, which is not used in patients with PTGC. This article presents a clinical case of partial lymph node lesion of NLPHL associated with PTGC, on the example of which the main issues of differential diagnosis of PTGC and NLHLP will be considered. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

Neinfektivna unilateralna cervikalna limfadenopatija u djece - prikaz pacijenata

Cervical lymphadenopathy in children is often the reason to seek medical attention. According to the literature, 90% of children aged 4-9 years has cervical lymphadenopathy, mainly caused by acute infections, that is treated in the out-of-hospital setting. In a small, but significant number of cases, cervical lymphadenopathy is caused by malignancy and wide range of other clinical entities, that require more detailed clinical approach. Three patients with non-infectous unilateral cervical lymphadenopathy are presented; adolescent boy with unicentric Castleman disease, young adult with progressive transformation of germinal centers, and an infant with viral parotitis mistaken for cervical lymphadenopathy. Unicentric Castleman disease was diagnosed by pathohistological assesment of excised lymph node to a 14-year-old boy after 7 months of persistent cervical lymphadenopathy, and close follow-up was suggested as no disease progression was verified by PETCT. Histopathological-clinical diagnosis of progressive transformation of germinal centers was established in an adolescent with 3-month history of lymphadenopathy, after extensive radiological and infectious assesment. Chronic reccurent course of the disease was once again confirmed, as this patient awaits his third extirpation in the last year. Viral parotitis is one of the conditions that can mimic cervical lymphadenopathy as showed with the third presented patient – a 6-month-old male infant with the submandibular swelling lasting for three days. This article emphasises the importance of a detailed history taking and clinical assesment, but is also a reminder of a less often, noninfectious causes of lymphadenopathy in children, where systematic approach is the key to a correct diagnosis and treatment.

Progressive Transformation of Germinal Centers Simulating Malignant Axillary Lymphadenopathy in a Breast Cancer Patient on FDG PET/CT.

A 64-year-old woman with breast cancer underwent FDG PET/CT for follow-up. The study revealed highly increased FDG uptake in newly diagnosed enlarged axillary lymph nodes, which were worrisome for malignancy. Histopathology revealed a rarely diagnosed benign disease of progressive transformation of germinal centers mimicking malignant lymphadenopathy. As imaging findings of this entity, which usually involves the axillary and cervical areas, have been reported in very few studies, nuclear medicine physicians should be familiar with this potential "false-positive" FDG uptake representing an interpretative pitfall, especially during evaluation of breast cancer patients.

Pediatric-Type Indolent B-Cell Lymphomas With Overlapping Clinical, Pathologic, and Genetic Features.

Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric-type indolent B-cell lymphomas (PedIBCL) that differ clinicopathologically from their adult counterparts. Accurate diagnosis is important to avoid overtreatment but is often challenging. The mutational landscape of PTFL is known and may aid diagnosis, but the genetic features of PNMZL are not well understood. We analyzed 21 cases of PedIBCL according to their clinicopathologic findings and classified them into PTFL (n=11), PNMZL (n=2), and “mixed type” tumors (n=8) showing ambiguous histology. We also analyzed 2 cases of adult B-cell lymphomas showing features of PedIBCL. Targeted sequencing of 121 lymphoma-related genes was performed. The median age of PedIBCL patients was 16 years (range: 3 to 47), and all but 1 PTFL patient were male. All patients presented with limited-stage disease, and only 1 relapsed. There were no significant differences in clinical features among the 3 PedIBCL groups. The most frequently mutated genes were MAP2K1, TNFRSF14, KMT2C, IRF8, and NOTCH2. The genetic features of all groups were similar to the established mutational landscape of PTFL. The 2 adult B-cell lymphomas cases also had MAP2K1, TNFRSF14, and IRF8 mutations, but the clinical features were not typical of PedIBCL. In summary, this study demonstrated that PTFL and PNMZL are similar diseases with overlapping clinical, pathologic, and genetic features; mixed type tumors can also occur. Atypical adult cases with similar histologic features were also observed. Therefore, the disease spectrum of PedIBCL may be much broader than is currently believed.

Ultrasensitive RNA In Situ Hybridization for Kappa and Lambda Light Chains Assists in the Differential Diagnosis of Nodular Lymphocyte-predominant Hodgkin Lymphoma.

Establishing a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is often challenging as the differential diagnosis is broad, including classic Hodgkin lymphoma (cHL), progressive transformation of germinal centers (PTGC), and other lymphoproliferative disorders. In this study, we investigate the utility of a recently described ultrasensitive in situ hybridization assay for kappa and lambda immunoglobulin light chains in distinguishing nLPHL, cHL, and PTGC. A total of 72 cases were examined (21 nLPHL, 33 cHL, and 18 PTGC). In nLPHL, the large neoplastic cells were light chain restricted in 21/21 (100%) cases (16 kappa, 5 lambda). In contrast, Reed-Sternberg cells of cHL were negative for kappa and lambda in all cases (0/33, 0%; P <0.001). In PTGC, polytypic B cells were noted in mantle zones and germinal centers in all cases, with 1 case (5%) also showing focal collections of light chain restricted large B cells. Background monotypic small B cells were identified in 3 cases, including 1 nLPHL and 2 cHL (1 of which arose in chronic lymphocytic leukemia). Ultrasensitive in situ hybridization for kappa and lambda is a useful addition to a standard immunophenotyping panel for the evaluation of suspected nLPHL.

Chronic Generalized Lymphadenopathy in a Child-Progressive Transformation of Germinal Centers (PTGC).

Background: Enlarged lymph nodes are a common complaint in a Pediatrician’s office. Diagnosis of reactive lymphadenopathy secondary to infectious, inflammatory, immune dysregulation calls for clinical investigation, including a thorough history, physical exam, imaging, and less often, a biopsy of the lymph node. Here we discuss a rare presentation of extensive generalized, chronic, waxing, and waning lymphadenopathy diagnosed as Progressive Transformation of Germinal Centers (PTGC) and the course of illness over eight years follow up period. Discussion: Progressive Transformation of Germinal Centers (PTGC) is considered a benign condition, but extensive recurrent generalized lymphadenopathy in a very young child has not been reported before. This case demonstrates the importance of long-term follow-up and tailoring the diagnostic work-up and management based on new signs and symptoms. Here we focus on the clinical considerations and management of complex presentation of a common clinical finding.

In-situ follicular neoplasia: a clinicopathological spectrum.

In-situ follicular neoplasia (ISFN) occurs in approximately 2-3% of reactive lymph nodes, and is currently set apart from 'partial involvement by follicular lymphoma' (PFL). ISFN can progress to overt lymphoma, but precise parameters with which to assess this risk and its association with related diseases remain incompletely understood. The aim of this study was to explore these parameters. We reviewed 11 cases of ISFN and one of PFL between 2003 and 2018. Ten patients had ISFN in the lymph nodes, and one had ISFN in the spleen. Haematoxylin and eosin and immunohistochemical stains were reviewed. Involvement of follicles by ISFN was scored with a three-tier scheme. Of five patients with low ISFN scores, one had chronic myelomonocytic leukaemia, one had mycosis fungoides, and three were free of haematopoietic disease. Among them, four are alive and one was lost to follow-up. Of the six ISFN patients with high scores, two had concurrent marginal zone lymphomas, one had concurrent diffuse large B-cell lymphoma (DLBCL), one had Castleman-like disease, one had progressive transformation of germinal centres with IgG4-related disease, and one had no haematopoietic disease; all are alive except for one who died of concurrent DLBCL. The patient with PFL developed DLBCL 7 years after diagnosis. On the basis of this limited series, we conclude that only cases with high scores are associated with an overt lymphoma or an abnormal lymphoid process, and that scoring may be a useful parameter with which to assess the risk of associated lymphoma, and deserves further study. We also performed a comprehensive review of the literature.

Flow Cytometry Analysis of Recurrent or Persistent Lymphadenopathy in Patients with Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Objectives: We recently examined the utility of flow cytometric analysis in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by examining reactive T-cell features. This study aims to compare these features in sequential biopsies of persistent or recurrent lymphadenopathy in patients with NLPHL. Methods: We reanalysed the histopathology and flow cytometry findings of 9 patients with multiple biopsies for persistent or recurrent lymphadenopathy and either initial or recurrent NLPHL. A flow cytometry signature was considered suggestive of NLPHL if ≥12% of T-cells expressed CD57 or ≥3% of T-cells co-expressed CD4 and CD8. Results: A flow cytometry signature considered suggestive of NLPHL was seen in 18 of 20 specimens. Based on histopathology, 11 were diagnosed as NLPHL, 3 were initially underdiagnosed as atypical lymphoid proliferation, and 4 were initially incorrectly diagnosed as negative or progressive transformation of germinal centers. Flow cytometry showed similar expression patterns of CD57 and CD4/CD8 in T-cells between initial and subsequent biopsies. The remaining 2 specimens lacked the flow cytometry signature suggestive of NLPHL and were histopathologically diagnosed as reactive hyperplasia. Conclusion: Flow cytometry analysis based on our criteria is highly sensitive in detecting NLPHL. Correlation with the cytospin cytology may increase the diagnostic specificity. A negative flow essentially ruled out the possibility of NHLPHL.

FDG-PET Utilizing Deauville Scoring Is Superior to Conventional Imaging for Staging and Response Assessment in Pediatric and Adult Patients with Nodular Lymphocyte Predominant Hodgkin's Lymphoma

Introduction:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Data are limited regarding FDG-PET-CT scan (PET-CT) use in NLPHL. We are reporting our experience with PET-CT utility in staging and response assessment of patients with NLPHL and compare this with conventional contrast enhanced CT scan (CT).Methods:Using prospectively collected lymphoma data base and Hospital Tumor Registry, all pediatrics and adult patients with NLPHL seen at our institution from 2003 to 2016 were captured. Patients who underwent pre-treatment CT and PET-CT, during the course of chemotherapy, at the end of planned treatment or for relapsed /refractory disease prior to have new treatment were included in this study. PET-CT response was assessed using both visual assessment method (mediastinal blood pool activity was used as a reference for normal uptake) and Deauville criteria. Both methods were compared (5-point Deauville Criteria; a score of 1-3 as negative-disease and 4-5 as positive-disease).ResultsWe identified 67 NLPHL who met the inclusion criteria. Median age at diagnosis was 27 years (6-56 years) and median follow-up was 30.7 months (5.95-157.4) with a male: female ratio of 4.1:1. Median SUV-max was 8.8 (2.0 to 18.8). In 30 pediatrics patients (age <21 years), median SUV-max was 8.7 (4.0 to 18.8).In the per-scan analysis, the sensitivity, specificity and positive predictive value of pre-treatment PET-CT was 100 %, 99% and 98% respectively. Among the total of 79 pre-therapeutic PET-CT, 948 sites were analyzed, 238 sites were true-positive (1 bone/3 bone marrow involvement, 4 parotids, 4 nasopharynx, 3 liver, 2 lungs, and 221 nodal involvement), 5 were false positive (4 were progressive transformation of germinal center and 1 was reactive lymph node) and 705 sites were true negative. In 5 patients, PET-CT revealed extra nodal disease that was subsequently confirmed on follow-up, but was not picked by CT. There was an agreement between the CT and the PET-CT staging in 68 scans (86%). The staging was changed in 11 (14%) patients; 8 (10%) were upstaged (7 nodal and 1 bone marrow) and 3 (4%) were down staged by PET-CT.A total of 33 bone marrow biopsies (BMBx) were performed and PET-CT confirmed all BMBx results (32 BMBx negative and PET-CT negative, 1 patient BMBx positive and PET-CT positive) showing 100% concordance and suggesting a positive PET-CT for bone or bone marrow is adequate to designate advanced stage. In 2 patients, pre-therapeutic PET-CT revealed bone marrow involvement that was unsuspected before the PET-CT examination.A total of 83 end of treatment PET-CT were carried out, 72 scans were negative (score 1-3) and 11 scans were positive (score 4-5). Treatment consisted of local treatment in the form of surgery/radiation in 7 patients, 2-4 cycles of ABVD +/- radiotherapy in 43 patients, and 6-8 cycles of ABVD +/- radiotherapy in 17 patients. Of the 238 previously involved sites, 204 became true negative, 31 remained true positive, and 3 sites had false negative results with no false positives, showing the negative predictive value of 98.6% with specificity of 100%. Deauville criteria correlated very well with visual assessment criteria. 83 post treatment CT scans showed that out of 238 previously involved sites, 180 became true negative, 24 sites were false positive with specificity of 88%. Two year progression free survival of the entire cohort was 83%.Twenty one patients with stage II, III and IV patients whom were planned to receive 6-8 cycles of chemotherapy underwent mid-treatment PET-CT that were assessed based on Deauville Criteria. 13 patients had negative-disease with none failed primary treatment. 8 had positive-disease; out of which 4 failed primary treatment (numbers are too small for statistics) (Table1).Conclusion:Our data suggest that baseline PET scan is far superior to CT staging. A negative pre-therapy PET-CT for bone/bone marrow is sufficient to omit BMBx. Mid-treatment PET-CT response may have a prognostic role. The validity of the Deauville Score for interpretation of the end of treatment response assessment scans in adult and pediatric patients has been confirmed by the present study. PET-CT has much better specificity for response assessment than CT. Deauville criteria are in concordance with visual assessment criteria and can be applied in real practice. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pitfalls in the Diagnosis of Nodular Lymphocyte Predominant Hodgkin Lymphoma: Variant Patterns, Borderlines and Mimics.

Simple SummaryNodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma containing infrequent tumor cells (LP cells) in a background of non-neoplastic cells. Some cases of NLPHL can recur or progress to a more aggressive lymphoma, such as diffuse large B-cell lymphoma. Awareness of the different appearances of NLPHL and its overlap with other lymphomas are important for the appropriate diagnosis, classification and research. This article discusses the conceptual framework and guidelines for the diagnosis of NLPHL, and how NLPHL can be best separated from its mimics. Emerging data in the field point to genetic changes in LP cells that are shaped by immune mechanisms. In addition, non-neoplastic cells in the background of LP cells also appear to play an important role. Further investigation is necessary to fully understand the biology of NLPHL and personalize cancer care for patients affected by this lymphoma.Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of Hodgkin lymphoma and typically affects children and young adults. Although the overall prognosis is favorable, variant growth patterns in NLPHL correlate with disease recurrence and progression to T-cell/histiocyte-rich large B-cell lymphoma or frank diffuse large B-cell lymphoma (DLBCL). The diagnostic boundary between NLPHL and DLBCL can be difficult to discern, especially in the presence of variant histologies. Both diagnoses are established using morphology and immunophenotype and share similarities, including the infrequent large tumor B-cells and the lymphocyte and histiocyte-rich microenvironment. NLPHL also shows overlap with other lymphomas, particularly, classic Hodgkin lymphoma and T-cell lymphomas. Similarly, there is overlap with non-neoplastic conditions, such as the progressive transformation of germinal centers. Given the significant clinical differences among these entities, it is imperative that NLPHL and its variants are carefully separated from other lymphomas and their mimics. In this article, the characteristic features of NLPHL and its diagnostic boundaries and pitfalls are discussed. The current understanding of genetic features and immune microenvironment will be addressed, such that a framework to better understand biological behavior and customize patient care is provided.

Markers of Follicular Helper T Cells Are Occasionally Expressed in T-Cell or Histiocyte-Rich Large B-Cell Lymphoma, Classic Hodgkin Lymphoma, and Atypical Paracortical HyperplasiaA Diagnostic Pitfall For T-Cell Lymphomas of T Follicular Helper Origin.

Follicular helper T cell (TFH) markers are expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma of the TFH phenotype (PTCL-TFH). However, differential expression and coexpression of these markers in benign and other malignant lymphoid proliferations have not been well studied. We performed programmed death-1 (PD-1), C-X-C motif chemokine ligand 13 (CXCL13), inducible costimulator (ICOS), CD10, and B-cell lymphoma 6 protein (BCL-6) immunohistochemistry on AITL, PTCL not otherwise specified (PTCL-NOS), PTCL-TFH, T-cell or histiocyte-rich large B-cell lymphoma (THRLBCL), classic Hodgkin lymphoma (CHL), atypical paracortical hyperplasia (PCH), progressive transformation of germinal centers (PTGC), and reactive follicular hyperplasia (RFH). CXCL13 and ICOS were more sensitive but less specific for AITL than PD-1, CD10, and BCL-6. Moreover, 74% of AITL (none of PTCL-NOS or PTCL-TFH) coexpressed more than 2 TFH markers. In background T cells of THRLBCL, 70% of cases coexpressed more than 1 marker. The background T cells of CHL expressed all TFH markers except CD10 in all cases. In addition, 13% of PCH cases coexpressed more than 1 marker. In RFH and PTGC, all markers were expressed mainly in germinal centers with rare extrafollicular staining. AITL, PTCL-NOS, and PTCL-TFH show differential expression of TFH markers. AITL frequently coexpresses more than 2 TFH markers. TFH markers can be expressed in PCH and in background T cells of THRLBCL and CHL. Consequently, caution should be used before a diagnosis of AITL is established, particularly with limited samples.

Progressive Transformation of Germinal Centers in Axillary Lymph Nodes Mimicking Metastatic Lymphadenopathy after Breast Cancer Surgery: A Case Report

Progressive transformation of germinal centers (PTGC) is a rarely diagnosed, benign disease of the lymph nodes that commonly manifests as chronic lymphadenopathy. PTGC may be characterized by single or multiple non-tender lymph nodes, and it commonly involves the cervical, axillary, and inguinal areas. Although PTGC is identified with concurrent lymphoma in some patients, it is not considered as a premalignant entity. Histopathologic diagnosis of PTGC is rarely made, and imaging findings have been reported in very few studies. We present a case of PTGC that occurred at the contralateral axillary lymph nodes and mimicked metastatic lymphadenopathy after breast cancer surgery. We also discuss its imaging findings.

A rare face of follicular lymphoma: reverse variant of follicular lymphoma

BackgroundReverse Variant of Follicular Lymphoma (RVFL) is one of the rare morphological variants of FL, characterized by dark staining small centrocytes in the center and pale staining large centroblasts at the periphery of the neoplastic follicles. Only rare cases of RVFL have been described to date. The histological appearance of this little known variant of FL may be misinterpreted if pathologists are unaware of its existence. The main purpose of this study is to draw pathologists’ attention to such an uncommon growth pattern of FL so that this variant can be correctly recognized and the clinical significance further studied in the future.MethodsFour cases of FL with unusual morphologic features were evaluated for the expression pattern of CD20, CD10, BCL6, BCL2, CD21, CD23, CD3, CD5, Cyclin D1, IgD and Ki67 by immunohistochemistry. Fluorescence in situ hybridization (FISH) with break-apart probes was performed to detect BCL2 gene rearrangement.ResultsAll four cases showed distinctive morphologic pattern of RVFL; in addition, each also exemplified unique morphological features. Immunohistochemical stains confirmed the cells in both the central areas and the peripheral cuffs had the same immunophenotypic profiles, contrasting to the FL with marginal zone differentiation in which only the center of the nodules showed expression of CD10. FISH demonstrated BCL2 gene rearrangement in all cases.ConclusionThe growth pattern of this rare FL variant may mimic FL with marginal-zone differentiation and other entities including but not limited to marginal zone lymphoma (MZL), progressive transformation of germinal centers (PTGC) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Pathologists should be familiar with this unusual morphological variant to avoid diagnostic pitfalls.

Progressive Formation of Germinal Centers with Multiple Nodule in The Lung

Enlarged lymph nodes in the head, neck, and axillary region are a common cause for patients to contact doctors. The most common cause of lymphadenopathy is infection and usually regresses with treatment. In the differential diagnosis of chronic lymphadenopathies, infection, lymphoproliferative diseases and progressive transformation of germinal centers should be considered. In this article, we aimed to discuss the patient with bilateral widespread nodular appearance in the cervical, supraclavicular, axillary, mediastinal lymph node and lungs. A 43-year-old female patient was referred for her mass in the neck and bilateral axillary region. Biopsy from the cervical region in the outer center was evaluated as an infection. In radiological imaging, lymph nodes were observed in the left cervical 15*11 mm, right supraclavicular 24*11 mm, left supraclavicular 18*11 mm, right axillary 11*21 mm, left axillary 27*18 mm, mediastinum 24*15 mm. In addition, extensive nodular lesion, the largest of which was 15 mm, was observed in both lungs. Excisional biopsy was performed from the left axillary region. Pathologically, progressive transformation of germinal centers was diagnosed. In the presence of lymphadenopathies that do not pass with medical treatment, an excisional biopsy should be performed and the diagnosis should be clarified for a definitive diagnosis.

Utility of Flow Cytometry in the Diagnostic Evaluation of Recurrent or Persistent Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Abstract Objectives We previously reported that lymph nodes involved by nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) had unique flow cytometric features. To further validate their diagnostic utility, we have examined the flow cytometry features in cases of persistent lymphadenopathy (LAD) prior to the diagnosis of NLPHL or recurrent LAD following diagnosis and treatment for NLPHL. Methods We retrospectively identified nine patients (2-3 specimens per patient for a total of 20 specimens) with persistent or recurrent lymphadenopathy before or after they were diagnosed with NLPHL between the ages of 13 and 76 years. Their histopathology diagnoses were reviewed and flow cytometry data were reanalyzed. Results Based on our published criteria (Am J Clin Pathol 2016;145:107-115), positive flow cytometry findings (at least 12% of T cells expressing CD57 or at least 3% of T cells coexpressing CD4 and CD8) were seen in 18 specimens. Based on histopathology, 11 of them were correctly diagnosed as NLPHL, 3 of them initially underdiagnosed as atypical lymphoid proliferation, and 4 of them initially incorrectly diagnosed as negative or progressive transformation of germinal centers (PTGCs). The flow cytometry studies showed similar expression patterns of CD57, CD4, and CD8 in T cells and very similar high percentages of CD57+ T cells and CD4+CD8+ T cells between initial biopsies and subsequent biopsies in these patients. Negative flow cytometry findings were seen in two specimens pathologically confirmed as negative for NLPHL in two patients after treatment. Their initial diagnostic specimens showed positive flow cytometry findings, different from that seen in the subsequent specimens posttreatment. Conclusion Flow cytometry appears to be a useful adjunct in detecting early or relapsed NLPHL, especially in atypical lesions. The presence of positive flow cytometry features is very sensitive in detecting recurrent or persistent NLPHL, while absence of positive flow cytometry features helps rule out NLPHL.

Spectrum of histopathological diagnosis of lymph node biopsies and utility of immunohistochemistry in diagnosis of lymphoma: A 5 year retrospective study from a tertiary care Centre in South India

Spectrum of histopathological diagnosis of lymph node biopsies and utility of immunohistochemistry in diagnosis of lymphoma: A 5 year retrospective study from a tertiary care Centre in South India - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.083, Indian Journal of

Rare mature B‐cell lymphomas in children and adolescents

Pediatric-type follicular lymphoma (PTFL), pediatric nodal marginal zone lymphoma (pnMZL), and large B-cell lymphoma (LBCL) with IRF4 rearrangement have been introduced into the current World Health Organization (WHO) classification. They account for 5% to 10% of mature B-cell lymphomas in children and adolescents. Both PTFL and pnMZL predominantly affect male adolescents and usually present with localized lymphadenopathy in the head and neck region. The cells within the follicles of PTFL typically show high-grade cytology, IGH monoclonality and lack the t(14;18) chromosomal alteration. In contrast, pnMZL is characterized by progressive transformation of germinal center (PTGC)-like features and interfollicular proliferation of the cells with expansion of the marginal zones with diffuse areas. Watch and wait after complete resection seems an adequate therapy with chemotherapy restricted to incompletely resected disease. All children with PTFL and pnMZL reported, so far, survived. B-cell lymphomas presenting in the Waldeyer's ring are characterized by the expression of IRF4/MUM1 and often associated with IRF4 rearrangements. Because of the frequent diffuse component, treatment often follows current protocols for mature B-NHL. The prognosis is excellent.

Progressive Transformation of Germinal CentersA Mimicker of Lymphoma

Progressive transformation of germinal centers (PTGC) is an uncommon variant of non-specific reactive follicular hyperplasia. PTGC is a clinically asymptomatic condition characterised by persistent lymphadenopathy. PTGC may occur before, concurrently with or after the onset of nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL). It may also be confused for follicular lymphoma and mantle zone lymphoma. We report an interesting case of PTGC in a 23 year female with swelling in the left side of neck of one year duration. Histology revealed PTGC, which was confirmed by immunohistochemistry which showed CD3+, CD20+ in appropriate B and T cell region and negative for CD15, CD30 and bcl-2. As PTGC mimics lymphoma, it should be followed up carefully.