Atypical Lymphoid Hyperplasia Research Articles

Progressively transformed germinal center-like follicular T-cell lymphoma:a clinicopathological analysis of 14 cases

Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.

Orbital Lymphoproliferative Disorders (OLPDs) in a 3-year-old Child: Case Report and Review of Literature

Background: Orbital lymphoproliferative disorders (OLPDs) consist of a spectrum of diseases ranging from benign to malignant lesions including reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma. OLPDs rarely present as an orbital mass lesion in children. Accurate discrimination of OLPDs is crucial for treatment planning. We report a case to investigate the clinical and pathological features of OLPDs in children. Case presentation: A 3-year-old female with orbital mass was admitted to the hospital and proceeded to have a CT orbit which showed an orbital mass. The orbital mass was removed after operation and pathologic diagnosis was identified. Pathological diagnosis with histopathological features and immunohistochemical markers was lymphoproliferative lesion in the left orbit. The diagnosis was consistent with OLPDs. There was no recurrence after one-year follow-up. Conclusions: OLPDs are rare in children. The clinical manifestations and imaging have no specificity; pathological diagnosis with histopathological features and immunohistochemical markers is the main basis for the diagnosis and treatment.

Atypical Cutaneous Lymphoid Hyperplasia of Nose: A Pathological Puzzle.

Atypical cutaneous lymphoid hyperplasia is a rare tumour of the head and neck which represents a lymphoproliferative continuum andmimics cutaneous lymphoma. Hereby reporting the case of a 40-year-old gentleman who presented with a swelling over dorsum of nose. On evaluation, Fine needle aspiration cytology was inconclusive with only inflammatory cells. Contrast Enhanced CT Nose and PNS suggested a possibility of a haemangioma. Patient underwent laser assisted excision of mass and frozen section showed sheets of basaloid cells suggestive of basal cell carcinoma. Wide local excision and primary paramedian forehead flap closure was done. Histopathology was suggestive of CD30 + atypical cutaneous lymphoid hyperplasia which has potential for malignant transformation into overt lymphoma. Patient underwent pedicle division of flap and is on regular follow up. In this case, aspiration cytology and frozen section reports were discordant with the histopathology, and thereby enlightens us of a rare differential diagnosis for head and neck tumours.

COVID-19 post-vaccination lymphadenopathy: A review of the use of fine needle aspiration cytology.

COVID-19 vaccine-associated clinical lymphadenopathy (C19-LAP) and subclinical lymphadenopathy (SLDI), which are mainly detected by 18F-FDG PET-CT, have been observed after the introduction of RNA-based vaccines during the pandemic. Lymph node (LN) fine needle aspiration cytology (FNAC) has been used to diagnose single cases or small series of SLDI and C19-LAP. In this review, clinical and LN-FNAC features of SLDI and C19-LAP are reported and compared to non-Covid (NC)-LAP. A search for studies on C19-LAP and SLDI histopathology and cytopathology was performed on PubMed and Google Scholar, on 11 January 2023. Reports on LN-FNAC of C19-LAP were retrieved. A total of 14 reports, plus one unpublished case of C19-LAP observed in our institution, diagnosed by LN-FNAC were included in a pooled analysis and compared to the corresponding histopathological reports. In total, 26 cases were included in this review, with a mean age of 50.5 years. Twenty-one lymphadenopathies assessed by LN-FNAC were diagnosed as benign, and three cases as atypical lymphoid hyperplasia; the latter were subsequently confirmed as benign (one by repetition of LN-FNAC, two by histological control). One case of mediastinal lymphadenopathy in a patient suffering from melanoma was reported as reactive granulomatous inflammation, while one unsuspected case was diagnosed as metastasis from melanoma. In all cases, the cytological diagnoses were confirmed by follow-up or excisional biopsy. The high diagnostic value of LN-FNAC in excluding malignant processes was extremely useful in this context and may be particularly valuable when CNB or histological excisions are difficult to perform, as was the case during Covid lockdowns.

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.

Clinicopathological Manifestations and Immune Phenotypes in Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibodies.

Anti-interferon (IFN)-γ autoantibodies (anti-IFN-γ Abs) is an emerging adult-onset immunodeficiency syndrome. Immune dysfunction in this distinct disorder remains to be clarified. We prospectively collected blood samples of 20 patients with anti-IFN-γ Abs and 40 healthy normal subjects. The percentages of lymphocyte subpopulations, most relevant to T, B, and NK cells, and the percentages of stimulated lymphocytes with cytokine production were assessed using eight-color flow cytometry. The results were adjusted to age and absolute lymphocyte counts. Most (85%) patients presented nontuberculous mycobacterial infection. Skin lesions were predominantly manifested by neutrophilic dermatoses. The involved lymph nodes had granulomatous inflammation, except 22.2% showing atypical lymphoid hyperplasia without granuloma formation. The percentages of CD4 + T cells and nonactivated subpopulations (recent thymic emigrants and naïve subtypes) decreased significantly with increased expression of activation markers and polarization to differentiated cells. The percentage of NK cells increased, but that of two major NK subpopulations, CD161 + CD56bright and CD161 + CD56 + CD16 + subsets, decreased. Increased CD161dim, CD161 + CD56 - CD16 + , and CD57 + NK cell subsets coupled with the decreased expression of NKp30 and NKp46 indicate reconfiguration of the NK cell population and acquisition of adaptive features. Intracellular cytokine production of the lymphocyte subpopulations was significantly low in the patients compared with the control group. We conclude that the immune system in patients with anti-IFN-γ Abs could be exhausted in T cells and be adaptive in NK cells, contributing to the distinct clinicopathologic features.

The imaging signs and significances of the enlargement of the infraorbital nerve and the frontal nerve in orbital lymphoproliferative diseases

Objective: To describe imaging signs of infraorbital nerve enlargement (IONE) and frontal nerve enlargement (FNE) in orbital lymphoproliferative diseases (LPDs), and to explore the diagnostic value and differential diagnostic role of the signs. Methods: A retrospective case series study. The data of 222 cases (262 eyes) of LPDs and 95 cases (134 eyes) of inflammatory pseudotumors (IPs) pathologically confirmed by the Peking University People's Hospital and the Third Medical Center of the Chinese PLA General Hospital from January 2013 to December 2018 were analyzed. The LPDs were lymphoma (including atypical lymphoid hyperplasia) in 91 cases (110 eyes) and reactive lymphoid hyperplasia (RLH) in 131 cases (152 eyes). The patients with LPD included 101 males and 121 females, aged (58±17) years, and the patients with IP included 44 males and 51 females, aged (49±21) years. All patients underwent orbital CT or MRI with T1 weighted imaging, T2 weighted imaging and enhanced T1 weighted imaging scanning. Slice thickness was 3 mm. In the coronal CT or MRI, the criterion for determining IONE was the inferior orbital nerve diameter greater than the optic nerve, and the criterion for determining FNE was the forehead nerve diameter equal to or greater than the optic nerve. The pathological types and imaging features of nerve enlargement were recorded. The incidence rates of different pathological types were compared using chi-square test. Results: The enlarged nerves showed homogeneous soft tissue density on CT images, accompanied with enlarged bony infraorbital nerve grooves (foramina). MRI showed moderate signals of T1 and T2 weighted imaging, with clear boundaries and obvious enhancement, which could spread to the pterygopalatine fossa and the cranial cavity. The accompanying images included the enlargement of lacrimal glands or extraocular muscles, intraorbital mass or sinuses opacity. The IONE and/or FNE were found in 12 patients with LPD, but were not found in any patients with IP. The difference was statistically significant (12/222 vs. 0/95, χ²=5.337, P=0.021). Among the cases with nerve enlargement, there were 2 cases of diffuse large B cell lymphoma and 10 cases of RLH (2/91 vs. 10/131, χ²=3.103, P=0.078), as well as 7 cases of IgG4-related ophthalmic disease (IgG4-ROD) and 3 cases of non-IgG4-ROD (7/28 vs. 3/103, χ2=15.232, P=0.000). Conclusions: Lymphoma and RLH can express IONE and/or FNE, in which the IgG4-ROD is the most common and specific type. CT and MRI scans can show enlarged nerves and accompanying signs. Neural thickening can also be applied as a discrimination marker of LPDs and IPs. (Chin J Ophthalmol, 2020, 56: 832-838).

Histopathologic Analysis of Conjunctival Lymphoproliferative Disease After Topical Brimonidine Use.

Purpose: To describe of histopathological findings of conjunctival lymphoproliferative disease (CLD) after topical brimonidine use. Methods: This is a retrospective medical record review study, including histopathologic description. We reviewed the medical records of 208 patients (415 eyes) who were diagnosed with glaucoma and who were treated with topical brimonidine only for a minimum of 6 months. Of these, the medical records of 19 patients with suspected CLD clinical features were reviewed in detail. When CLD was suspected due to administration of brimonidine, histopathological analysis was performed by biopsy of these lesions. In addition, immunohistochemical staining was performed to analyze lymphocyte markers in some pathological tissues. Results: Nineteen patients had suspected CLD without definite irritative symptoms. Diffuse elevated (11 patients) or follicular lesion (8 patients) of salmon pink appearance was observed in inferior palpebral conjunctiva. Among these patients, 5 patients who agreed to conjunctival biopsy had histopathological findings of CLD such as reactive lymphoid hyperplasia (LH) (2 cases) or atypical LH (2 cases). The mean duration of brimonidine use was 29.00 ± 20.25 months (6-76 months). And follow-up period after discontinuation of brimonidine was 27.93 ± 11.87 months (12-58 months). At the last visit, complete resolution of the lesion was seen in 13 patients, and partial improvement was observed in 6 patients. Conclusions: We found 4 cases of CLD following long-term administration of brimonidine. However, large-scale additional studies should be performed to establish causality, to determine whether these novel side effects were caused by long-term brimonidine treatment.

Misdiagnosis as diffuse large B-cell lymphoma: clinicopathological analyses of 431 patients

Objective To analyze the cases that are easily misdiagnosed as diffuse large B-cell lymphoma (DLBCL), and to explore the diagnosis, differential diagnosis and clinicopathological features of DLBCL. Methods The clinicopathological data of 431 cases preliminarily diagnosed as DLBCL in the Department of Pathology, School of Basic Medical Science, Peking University from October 2016 to December 2017 were retrospectively analyzed. Further immunohistochemical staining and molecular biological tests were performed if necessary. Results The diagnostic accuracy rate of DLBCL was 88.86% (383/431). Misdiagnosis mainly occurred in follicular lymphoma (36 cases, 8.35%), high-grade B-cell lymphoma (HGBL) with gene rearrangement of c-myc and bcl-2 or bcl-6 (4 cases, 0.93%), atypical lymphoid tissue hyperplasia (3 cases, 0.70%), mantle cell lymphoma (3 cases, 0.70%), classic Hodgkin lymphoma (CHL) (1 case, 0.23%) and composite lymphoma (DLBCL and CHL) (1 case, 0.23%). Except the poor quality of sections, the lack of immunohistochemical markers, the poor knowledge of the diagnosis of DLBCL and high-grade FL as well as HGBL were the main reasons of misdiagnosis. Conclusions The diagnosis and differential diagnosis of DLBCL is based on morphology, and it needs to combine with the corresponding immunohistological markers and molecular biological detection when necessary. The recognition of clinical and pathological features of various types of misdiagnosed lymphomas should be strengthened. Key words: Lymphoma, large B-cell, diffuse; Lymphoma, follicular; High-grade B-cell lymphoma; Misdiagnosis; Differential diagnosis

Prevalence and clinical challenges among adults with primary immunodeficiency and recombination-activating gene deficiency

Prevalence and clinical challenges among adults with primary immunodeficiency and recombination-activating gene deficiency

Diagnostic significance of lymph node core needle biopsy for lymphoproliferative disease: a clinicopathologic study of 1 013 cases

Objective: To study the clinicopathologic features of lymphoproliferative disease by lymph node core needle biopsy(CNB)and to evaluate the diagnostic significance of CNB for lymphoproliferative disease. Methods: The annual distribution, entity constitute, clinical finding, gross feature, morphologic change, affiliate study and repeat biopsy diagnosis of 1 013 cases of lymph node CNB diagnosed at West China Hospital of Sichuan University from January 2009 to December 2015 were investigated. Results: (1) Proportion of lymph node CNB in total amount of biopsy specimens increased from 0.2% in 2009 to 0.8% in 2015.(2) The study cohort included 471 lymphomas, 12 atypical lymphoid hyperplasia (ALH), 136 suspected lymphomas, 372 benign lesions, and 22 cases of descriptive diagnoses. The most common types were diffuse large B cell lymphoma and T-lymphoblastic lymphoma. (3) Majority of patients were adolescents and children younger than 20 years or the elderly older than 60 years. 53.1% CNB tumor specimen consisted of ≥4 tissue cores and 40.5% were >2 cm in length. (4) 104 CNB cases with previous history of excision biopsy was included 45 carcinomas(no metastatic carcinoma was found), 32 lymphomas for treatment observation.1/14 suspicious lymphomas, 1/1 ALH and 3/22 cases benign lesions were diagnosed as lymphoma by repeat biopsy respectively. (5) 217 CNB cases were diagnosed as lymphoma by subsequent CNB (70), or subsequent excision biopsy (147) including 78.5%(73/93) suspected lymphomas, 5/7 ALH and 32.3%(20/62)benign lesions. Conclusions: Lymph node CNB has certain clinical indications, although limited for the diagnosis of lymphoproliferative disorders. Suspected lymphomas and ALH diagnosed by CNB should be followed by repeat tissue biopsy. For the benign lesions by CNB it does not rule out additional biopsy to further investigate the lesion.

Effects of ICOS+ T cell depletion via afucosylated monoclonal antibody MEDI-570 on pregnant cynomolgus monkeys and the developing offspring

MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did not cause any abortifacient effects. Changes in hematology and peripheral blood T lymphocyte subsets in maternal animals and infants and the attenuated infant IgG immune response to keyhole limpet hemocyanin (KLH) were attributed to MEDI-570 pharmacology. Adverse findings included aggressive fibromatosis in one dam and two infant losses in the high dose group with anatomic pathology findings suggestive of atypical lymphoid hyperplasia. The margin of safety relative to the no observed adverse effect level (NOAEL) for the highest planned clinical dose in the Phase 1a study was 7. This study suggests that women of child bearing potential employ effective methods of contraception while being treated with MEDI-570.

Morbidity and mortality in infant mountain gorillas (Gorilla beringei beringei): A 46‐year retrospective review

Long-term studies of morbidity and mortality in free-ranging primates are scarce, but may have important implications for the conservation of extant populations. Infants comprise a particularly important age group, as variation in survival rates may have a strong influence on population dynamics. Since 1968, the Mountain Gorilla Veterinary Project (MGVP, Inc.) and government partners have conducted a comprehensive health monitoring and disease investigation program on mountain gorillas (Gorilla beringei beringei) in Rwanda, Uganda, and the Democratic Republic of the Congo. In an effort to better understand diseases in this species, we reviewed reliable field reports (n = 37), gross post-mortem (n = 66), and histopathology (n = 53) reports for 103 infants (less than 3.5 years) mountain gorillas in the Virunga Massif. Our aim was to conduct the first comprehensive analysis of causes of infant mortality and to correlate histological evidence with antemortem morbidity in infant mountain gorillas. Causes of morbidity and mortality were described, and compared by age, sex, and over time. Trauma was the most common cause of death in infants (56%), followed by respiratory infections and aspiration (13%). Gastrointestinal parasitism (33%), atypical lymphoid hyperplasia (suggestive of infectious disease) (31%), and hepatic capillariasis (25%) were the most significant causes of antemortem morbidity identified post-mortem. Identifying the causes of mortality and morbidity in infants of this critically endangered species will help to inform policy aimed at their protection and guide ante- and post-mortem health monitoring and clinical decision-making in the future.

Establishment of a combination scoring method for diagnosis of ocular adnexal lymphoproliferative disease

Lymphoproliferative diseases (LPDs) of the ocular adnexa encompass the majority of orbital diseases and include reactive follicular hyperplasia (RFH), atypical lymphoid hyperplasia (ALH), and mucosa-associated lymphoid tissue lymphoma (MALToma). Lymphoid follicles (LFs) are usually observed during the histological examination of LPDs. Currently, because there is a lack of specific clinical signs and diagnostic immunohistochemical biomarkers, it is difficult for pathologists to distinguish MALToma from ocular RFH and ALH, which makes the clinical management of these conditions difficult. Here, we analyzed the clinical features of patients with ocular adnexal LPDs (n = 125) and investigated the structure of LFs in paraffin-embedded tissue samples using anti-CD23 and anti-IgD immunochemistry. We found that some clinical features including age, sex, and laterality were different among RFH, LFH, and MALToma. Additionally, immunohistochemistry revealed that the expression of IgD and CD23 was higher in RFH patients and decreased in patients with ALH and MALToma. Moreover, LFs in RFH were intact, whereas the structures of most LFs were disrupted in ALH. In MALToma specimens, few intact LFs were observed. In a further investigation, we combined the results for CD23/IgD immunohistochemistry and the structure of LFs to establish a scoring method for the differential diagnosis of LPDs. According to the BIOMED-2 protocol, we further detected IgH gene monoclonal rearrangement in 73 cases (35 RFH, 17 ALH, and 21 MALToma cases). The sensitivity of our scoring method, based on a comparison with the results of IgH gene monoclonal rearrangement detection, was 85.7% (18/21) for MALToma and 35.3% (6/17) for ALH. Our study provides a method that may be useful for the differential diagnosis of RFH, ALH, and MALToma.

Human immunodeficiency virus-associated cystic lymphoid hyperplasia: An immunohistochemical description.

Cystic lymphoid hyperplasia (CLH) describes benign salivary lymphoepithelial cysts with a strong link to human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The pathogenesis is related to ductal dilatation of entrapped salivary elements due to intranodal HIV-associated atypical lymphoid hyperplasia. Very little is known about the immunophenotypic profile of this entity. This study aims to describe the immunopathological features of a series of CLH cases in HIV-positive patients to clarify the etiopathogenesis. Paraffin-embedded tissue from 25 cases of parotid CLH in HIV seropositive patients was immunohistochemically analyzed with CD3, CD20, CD4, CD8, and p24 using standard procedures. The data are mostly descriptive and were analyzed using EpiInfo (3.5.1) (CDC, Atlanta, USA); significant differences were analyzed using the Student's t-test and the Chi-square test with a statistical significance level of P < 0.05 being used. Immunostaining showed a CD8:CD4 of ~1:1 except in selected cases with decreased CD4 and increased CD8 expression in the interfollicular (IF) areas. p24 staining revealed 100% specificity in HIV-associated CLH. The immunohistochemical description of CD20, CD3, CD4, and CD8 provides an understanding of CLH pathogenesis. CLH of parotid lymph nodes in confirmed HIV-positive patients with 100% specificity with HIV p24 antibody validates the strong association of CLH with HIV and AIDS. The CD4:CD8 ratio was ~1:1; however, increased CD8 expression within IF areas may indicate possible HIV-related CLH as compared to other cystic parotid lesions.

Clinical, Biological Characteristics and Outcome of Pediatric Follicular Lymphoma at Children's Cancer Hospital - Egypt: A Single Center Experience

Background: Pediatric follicular lymphoma is a rare entity that had been provisionally included in the WHO classification of hematologic malignancies. Unlike adults, pediatric follicular lymphoma patients usually presents with localized nodal disease, are translocation (14; 18) and BCL2 negative. It shows different clinical behavior and thus distinct outcome. We analyzed the three pediatric follicular lymphoma cases presented to Children's Cancer Hospital- Egypt (CCH-E) during the period from July 2007 to December 2014.Results: All patients presented with localized stage II disease, responded well to R-CHOP chemotherapy (Rituximab target therapy with conventional CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). One of them received involved field radiotherapy in addition. All patients are in continuous complete remission. The first case: A male patient 7 years old who presented with left upper deep cervical lymph node with B symptoms (fever and night sweets). Biopsy was taken, partial effacement of the nodal structure and obliteration of the sub-capsular sinus by confluent follicles, intermediate and large cells were seen microscopically. Immunohistochemical staining showed positivity to CD20 and BCL6 and negative reaction to CD3 and BCL2. MIB-1 index was high (80%). The diagnosis of diffuse large cell B-cell lymphoma in 40% of cells and pediatric follicular lymphoma grade 3a in the remaining 60% was made. The patient received 8 cycles of R-CHOP and placed under follow up from July 2011 till now.He is in complete remission. The second case: A male patient 8 years old who presented in March 2013 with recurrent right pre-auricular lymph node. Repeated biopsies were done, all revealed atypical lymphoid hyperplasia. The patient was placed under follow up till April 2014 when he presented with large right parotid mass from which another biopsy was taken. Microscopic examination revealed effaced nodal architecture by evenly distributed large uniform, crowded follicles & nodules, populated by centroblasts intermixed with centrocytes consistent with grade 3a follicular lymphoma. Some foci displayed diffuse pattern with evident extra nodal extension. Immunohstochemical staining showed positive reaction to CD20 and BCL6 while negative reaction to BCL2 and low expression of Ki-67. The diagnosis of pediatric follicular NHL, predominantly grade 3a was made. He received 6 cycles of R-CHOP, evaluation post 3rd cycle was in complete remission by CT and PET scan He completed 6 courses of R-CHOP followed by involved field radiotherapy. He is under follow up since April 2015 till now ; alive and in complete remission. The third case is also for a male patient 12 years old who presented with left parotid and bilateral cervical lymph node enlargement. Initial PET-CT was negative. Cervical lymph node biopsy showed partial effacement of lymph node architecture with observed vague follicular pattern as well as diffuse infiltrate dominantly composed of centroblastic neoplastic lymphoid cells admixed with centrocytes . Immunohostochemical staining revealed positive reaction to CD20 in the neoplastic large cells. BCL2 highlighted mainly the neoplastic cells mainly of diffuse pattern. BCL6 and CD10 highlighted the deformity of neoplastic follicles by growth of neoplastic cells. CD21 stained admixed follicular dendritic cells. Ki-67 labeling index was high (60%). The diagnosis of follicular NHL, mixed follicular and diffuse, grade 3 a was made. He received 6 cycles of R-CHOP, was in complete remission post the third cycle by CT evaluation and is currently under follow up since March 2015.In conclusion, pediatric follicular lymphoma patients presented to our center had localized disease, responded well to R-CHOP chemotherapy and had durable complete remission. DisclosuresNo relevant conflicts of interest to declare.

Clinical features and prognosis of conjunctival lymphoid hyperplasia

Background Primary conjunctival lymphoid hyperplasia exhibit atypical clinical symptoms and easy to cause misdiagnosis and mistreatment.Understanding the clinical characteristics of primary conjunctival lymphoid hyperplasia is of an important clinical significance. Objective This study was to analyze the clinical characteristics and therapeutic outcome of patients with primary conjunctival lymphoid hyperplasia. Methods The medical records of 20 patients with primary conjunctival lymphoid hyperplasia who was treated in Beijing Tongren Hospital from January 2012 to December 2014 were retrospectively analyed.The age, symptoms, therapy, prognosis, histopathological features and immonochemistry results were reviewed, and the treating approach targeting to different types of conjunctival lymphoid hyperplasia was evaluated.The fellow-up duration was 1-2 years. Results Age of the patients ranged from 27 to 83 years old.The lesions were classified as benign lymphocytic hyperplasia, atypical lymphoid hyperplasia and lymphoma.Majority of lesions located in fornix conjunctiva tissue (90%). Follicle-like appearance was seen in the benign lymphocytic hyperplasia, and pink elavation was exhibited at the bulbar conjunctiva in the atypical lymphoid hyperplasia.A diffuse salmon fish like appearance in conjunctiva was the primary feature of conjunctival lymphoma.Histopathological examination showed that conjunctival benign lymphocytic hyperplasia had follicle-like tissue in lesions, atypical lymphoid hyperplasia exhibited diffuse lymphocyte filtration, and conjunctival lymphoma appeared monocyte filtration.The 3 tpyes of lesions also could be differentiated by immunochemistry.The medicine was applied in the eyes with benign lymphocytic hyperplasia, and the combination of resection of lesions with conjunctival tissue or amniotic membrane transplantation was used for the atypical lymphoid hyperplasia or lymphoma eyes.No recurrence of the lesions was found during fellow-up duration. Conclusions The clinical manifestations of conjunctival lymphoid hyperplasia lesions are varied, and it is easy to be confused with chronic ocular surface diseases.Pathology and immunochemistry are helpful for the differential diagnosis.The treating regimen is dependent on the lesion type.Most patients have a favorable prognosis with treatment. Key words: Conjunctival diseases/pathology; Conjunctival neoplasms/diagnosis & therapy; Hyperplasia; Lymphoid tissue/pathology; Lymphoma/pathology; Retrospective studies; Humans

Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia.

Indolent lymphomas in the pediatric population were discussed during the 2014 European Association for Haematopathology/Society of Hematopathology workshop in Istanbul, Turkey. This session was focused on pediatric-type follicular lymphoma (FL), and its differential diagnosis with the newly recognized entity of IRF4/MUM1+ lymphomas mainly involving Waldeyer's ring. The differential diagnosis between t(14;18) negative FL grade 1/2 and pediatric-type FL in adults was highlighted. The overlapping pathological and clinical features between FL and nodal marginal zone lymphoma (NMZL) in children and young adults were recognized and morphologic and immunophenotypical criteria helpful for the differential diagnosis were presented. Both pediatric-type FL and NMZL are indolent processes that should be distinguished from atypical lymphoid hyperplasia of the tonsils and lymph nodes. The demonstration of a B cell monoclonal population by molecular studies is strongly recommended for the diagnosis. Recognition of these indolent variants to avoid overtreatment was emphasized. Whereas most indolent lymphomas in the pediatric population show characteristic clinical, pathologic, and genetic features that differ from the adult counterpart, other rare indolent lymphoid tumors such as chronic lymphocytic leukemia (CLL) have similar characteristics. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be discussed.

Immunoglobulin heavy chain gene rearrangement study in difficult cases of B-cell lymphoproliferative disorder

To evaluate the ancillary diagnostic value of IgH gene rearrangements in those B-cell lymphoproliferative disorder cases whom are difficult in making a final diagnosis. IgH gene clonal rearrangements were retrospectively analyzed in a total of 77 diagnostically difficult B-cell lympho-proliferative patients. Standardized BIOMED-2 system IgH gene clonality assay kit targeting FR1, FR2, FR3 was used, followed by heteroduplex-polyacrylamide gel electrophoresis (PAGE) and silver nitrate staining. The final diagnoses of the 77 cases were: 12 cases of reactive lymphoid hyperplasia, 20 cases of atypical lymphoid hyperplasia or suspicious lymphoma, and 45 cases of B-cell lymphoma. Detection rates of at least one positive reaction were 2/12, 11/20 (55%), 36/45 (80%) in the three groups, respectively. In B-cell lymphomas, the clonality detection rate of FR1, FR2 and FR3 was 60% (27/45), 60% (27/45) and 56% (25/45), respectively. The type distribution were: 20 marginal zone lymphomas, including 18 extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, 7 diffuse large B-cell lymphomas, 7 follicular lymphomas, 1 mantle-cell lymphoma, 1 Burkitt's lymphoma, 4 plasma cell neoplasms and 5 unclassified B-cell lymphomas. Rearrangements of FR1, FR2 or FR3 were not detected in 9 (20%) of the B cell lymphoma cases, nevertheless, one of them had developed liver lesion later, and was confirmed finally to be B cell lymphoma. Fourteen patients of reactive lymphoid hyperplasia with positive IgH gene clonal rearrangements, and atypical lymphoid hyperplasia had follow-up history available. Four of them were diagnosed as lymphoid malignancies upon further biopsy, and in three of them, clonal IgH gene rearrangements were detected. B-cell lymphoproliferative disorder requiring a detection of clonal IgH gene rearrangement for making a final diagnosis. Combined detections of three IgH FR1, FR2 and FR3 rearrangements provide important ancillary diagnostic value in confirming suspected B-cell lympho-proliferative disorders. It is important to take an additional biopsy or to follow-up those patients who that have a detectable IgH gene clonal rearrangement but without apparent morphological evidence of lymphoma. For cases with a negative IgH gene rearrangements, it might be necessary to perform clonality analysis for other forms of gene rearrangements including IgH or IgK and IgL in order to further improve the detection sensitivity.

Recent advances in intestinal lymphomas

A large variety of lymphoma types may develop as primary intestinal neoplasms in the small intestines or, less often, in the colorectum. Among these are a few entities such as enteropathy-associated T-cell lymphoma or immunoproliferative small intestinal disease that, essentially, do not arise elsewhere than in the gastrointestinal tract. In most instances the primary intestinal lymphomas belong to entities that also occur in lymph nodes or other mucosal sites, and may show some peculiar features. In the case of follicular lymphoma, important differences exist between the classical nodal cases and the intestinal cases, considered as a variant of the disease. It is likely that the local intestinal mucosal microenvironment is a determinant in influencing the pathobiological features of the disease. In this review we will present an update on the clinical, pathological and molecular features of the lymphoid neoplasms that most commonly involve the intestines, incorporating recent developments with respect to their pathobiology and classification. We will emphasize and discuss the major differential diagnostic problems encountered in practice, including the benign reactive or atypical lymphoid hyperplasias, indolent lymphoproliferative disorders of T or natural killer (NK) cells, and Epstein-Barr virus (EBV)-related lymphoproliferations.