Indolent B-cell non-Hodgkin lymphomas in children: high association with inborn errors of immunity.

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively.

Pediatric-type follicular lymphoma in a Crohn's disease patient receiving anti-α4ß7-integrin therapy: A case report.

BACKGROUND: Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas (NHL). Vedolizumab (anti-α4ß7-integrin antibody), a treatment-of-choice for Crohn's disease (CD), reduces inflammatory lymphocyte trafficking into the intestinal mucosa. This effect is believed to be confined to the colon. CASE SUMMARY: We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma. Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens. Rituximab, cyclophosphamide, vincristine, and prednisone chemo-immunotherapy resulted in durable lymphoma remission, and vedolizumab treatment was continued. While the patient's T-lymphocyte population and immunoglobulin production recovered, the T-lymphocyte mitogen response remained suppressed. CONCLUSION: This patient's NHL may be linked to receiving anti-α4ß7 therapy. Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.

Case report: Clinicopathological and molecular characteristics of pediatric-type follicular lymphoma.

Pediatric-type follicular lymphoma (PTFL) is a rare pediatric-type indolent B-cell lymphoma that clinicopathologically differs from adult lymphoma. Accurate diagnosis of PTFL, which is often challenging, is essential to avoid missed diagnosis, misdiagnosis, and overtreatment. To improve our understanding of PTFL, clinicopathological features, differential diagnosis, and molecular mutation characteristics of four patients of PTFL were analyzed using hematoxylin and eosin staining, immunohistochemistry, polymerase chain reaction, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). A relevant literature review was also performed. All four PTFL patients were male, with ages of 6, 18, 13, and 15 years, and had St. Jude stage I or III. Microscopic results showed that the structure of the lymph nodes was destroyed; the tumor follicles were enlarged and irregular; medium-large blastoid cells with a consistent shape were visible in tumor follicles, and the nucleus was round or oval; and the "starry sky" pattern was easily observed. Tumor cells expressed CD20, PAX-5, BCL6, and CD10. None of the tumor cells expressed BCL2, CD3, CD5, MUM1, and CyclinD1. CD21 showed dilated growth of a follicular dendritic cell network in tumor follicles. EBER genes were negative in all cases. FISH testing also showed negative BCL2 gene breaks and IRF4 gene breaks in all cases. NGS detected 12 related mutant genes, including KMT2D, CD79B, GNA13, MYD88, PCLO, TCF3, IRF8, MAP2K1, FOXO1, POLE, INPP5D, and FAT4. Two of the four patients had an IRF8 gene mutation, and one patient had a dual mutation of the MAP2K1 gene. Our study revealed the unique clinicopathological features and molecular mutational characteristics of PTFL, consolidated our understanding of PTFL, and identified other rare mutant genes, which may further contribute to the study of the molecular mechanism and differential diagnosis of PTFL.

Comparison of histological and molecular features of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma.

Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma are pediatric B cell lymphomas with similar clinical characteristics but distinct histological features. We investigated the differences between pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma by comparing their histological and molecular characteristics. A total of 5 pediatric-type follicular lymphoma and 11 pediatric nodal marginal zone lymphoma patients were included in the study. In the histological review, 5 of the 16 cases showed overlapping morphological features of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma; hence, they were reclassified as "mixed type." In molecular analysis, using panel-based massively parallel sequencing, MAP2K1, TNFRSF14, and IRF8 mutations were found in 6, 3, and 2 of the 11 pediatric nodal marginal zone lymphoma patients, respectively, and IRF8 mutation was found in one of the five pediatric-type follicular lymphoma patients. There were no significant differences in genetic alterations established from the histologically reclassified diagnosis as well as the initial diagnosis. Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma showed morphological overlap in some cases, and no difference between the two was found upon molecular analysis. These findings suggest the possibility that pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma are single entity pediatric B-cell lymphoma with broad morphological spectrum.

Cytomorphologic features of pediatric-type follicular lymphoma on fine needle aspiration biopsy: case series and a review of the literature.

INTRODUCTION: Pediatric-type follicular lymphoma (PTFL) is a rare and recently recognized subtype of nodal follicular B-cell lymphoma. While significant recent progress has been made in understanding the morphologic, immunophenotypic, and molecular findings, there are only rare case reports describing the cytomorphologic features of PTFL. MATERIALS AND METHODS: Four cases of PTFL initially evaluated on fine needle aspiration (FNA) biopsy were retrieved from our institutions' databases. The cytologic and subsequent surgical excision specimens were compared in terms of cytology, histology, immunophenotype, and molecular findings. RESULTS: A constellation of cytologic features for PTFL are able to distinguish it from other cytomorphologic entities in the differential including: 1) the presence of large blastoid cells with fine chromatin and irregular nuclear membranes, 2) small/intermediate-sized lymphocytes with subtle nuclear membrane irregularities, 3) near complete absence of cytoplasmic vacuoles in lymphoid cells, 4) tingible body macrophages, 5) mitotic figures, 6) absence of a diffuse large cell component, 7) and no significant plasma cell population. CONCLUSIONS: We present four cases of PTFL initially evaluated on FNA biopsy and define the cytomorphologic features of PTFL. FNA biopsy is presented as a practical tool for initial evaluation of this rare entity as part of a multimodal diagnostic approach, for which increased awareness among cytopathologists can ensure the appropriate triage of specimen studies necessary for the diagnosis. Additionally, we comprehensively review the current literature on PTFL and discuss the differential diagnosis on cytology, including potential pitfalls.

Conjunctival Pediatric-Type Follicular Lymphoma in a Young Male: A Case Report and Literature Review.

Pediatric-type follicular lymphoma is a disease that affects the lymph nodes of the head and neck in the adult and pediatric patient groups. Ocular involvement is exceedingly rare, especially in the pediatrics age group; therefore, keeping a high clinical suspicion is warranted. Here, we report a rare conjunctival pediatric-type follicular lymphoma in a 15-year-old boy presenting with progressive swelling over the medial aspect of the left bulbar conjunctiva for two months. On examination, the mass was firm, mobile, well encapsulated, wide-based, and had a negative transillumination. An excisional biopsy was performed, and histopathological examination and immunohistochemistry studies revealed lymphoid tissue that was positive for CD20, CD79a, BCL6, and CD10; and negative for BCL2 and MUM1. The CD21 and CD23 positivity highlighted the presence of an expanded follicular dendritic cell meshwork. The patient was diagnosed with conjunctival pediatric-type follicular lymphoma and referred to an oncology center for further examination and treatment. This lymphoma is rare, requiring high clinical suspicion, and thus, reporting the case detail is important and valuable for ophthalmologists and general pediatrics practitioners alike.

Clinical observation of pediatric-type follicular lymphomas in adult: Two case reports.

BACKGROUND: Pediatric-type follicular lymphoma (PTFL) is a unique pathological type in the 4th edition of hematopoiesis and lymphoid tissue tumor classification revised by World Health Organization. It is unique in clinical practice and seldom seen in adult. PTFL mainly occurs in the head and neck lymph nodes. Most of the cases are short of fever, night sweat, weight loss, and other B symptoms which substitute for lymphadenopathy as the main symptom. PTFL can be disposed of surgical resection and it can achieve long-term tumor-free survival, and it has an excellent outcome. CASE SUMMARY: Two cases of PTFL were reported and their clinicopathological features, differential diagnosis, therapy and prognosis were discussed. PTFL showed gray-brown tough texture in general performance. The histological manifestations of PTFL were similar to that of adult-follicular lymphoma (FL). Under low power microscope, the structure of lymph nodes was destroyed in different degree, the follicles were closely arranged, expanded and irregular, and the mantle zone became thin or disappeared. In addition, the "starry sky phenomenon" could be seen. At high magnification, the follicles were mainly composed of single medium-sized central cells, and some of them mainly consisted of centroblastic cells to characterize scattered chromatin and inconspicuous nucleoli. Immunohistochemical showed the tumor cells expressed CD20, PAX5, CD79a and CD10, BCL6, FOXP-1, which were limited in germinal center; Ki-67 was highly expressed in germinal center. CD21 and CD23 showed nodular and expanded follicular dendritic cells. Immunoglobulin gene rearrangement was positive for IGH and IGK. The two patients underwent surgical resection with no complications. After discharge, the two patients with a close review for 18 mo and 5 mo respectively and showed no evidence of recurrence. CONCLUSION: PTFL in adult is generally supposed to be extremely rare. PTFL displayed characteristic morphological, immunophenotypic, and molecular biological changes which are a kind of neoplasm with satisfactory prognosis after surgical excision.

Fine needle biopsy of pediatric-type follicular lymphoma-Cytology, flow cytometry and FISH pattern: A case report.

Pediatric-type follicular lymphomas are rare lymphomas, affecting mostly children and young adults. These are characterized by an excellent prognosis, despite their conservative therapeutic approach. Recognized as an entity in the most recent 2016 WHO classification of tumors of hematopoietic and lymphoid tissues, its diagnosis is based on the recognition of an exclusively nodular architecture, thus conditioning the possibility of a cytological diagnosis. It is thus not odd, the scant literature found on the cytological approach to these lesions. Herein we describe a case of a pediatric-type follicular lymphoma, first approached through fine needle biopsy. The case is thoroughly discussed from a cytologic, immunophenotypic, and molecular point of view. Differential diagnoses are discussed. The final diagnosis was performed on histology.

Pediatric Lymphoid and Histiocytic Lesions in the Head and Neck.

Lymphoid and histiocytic lesions of the head and neck in pediatric patients is a fascinating topic as most of these lesions are benign, but that the neoplastic cases are essential to diagnose accurately for appropriate treatment. It is thought that 90% of children will have palpable lymph nodes between the ages of 4 to 8; most, but not all, are non-malignant and some resolve spontaneously without treatment. This paper will look at many of the benign and malignant lesions of both lymphocytic and histiocytic origin that present in the head and neck of children focusing on their diagnostic criteria. There is a very pertinent discussion of nonmalignant lymphoid proliferations, as infections and other reactive conditions dominate the pathology of pediatric lymphohistiocytic head and neck lesions. Discussion of those lymphomas which arise more frequently in the head and neck focuses on those seen in children and young adults such as classic Hodgkin lymphoma and Burkitt lymphoma, as well as new more controversial entities such as pediatric-type follicular lymphoma. Histiocytic lesions, both benign and malignant, are described and may be challenging to diagnose.

Novel markers in pediatric-type follicular lymphoma.

The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)-associated markers stathmin and LLT-1 were positive in most of the cases (12/13 and 12/13, respectively). Interestingly, FOXP-1 was uniformly positive in PTFL (12/13 cases) in contrast to reactive GCs in FH, where only a few isolated positive cells were observed. FISH revealed no evidence of BCL2, BCL6, or MYC rearrangements in the examined cases. By PCR, clonal immunoglobulin gene rearrangements were detected in 100% of the tested PTFL cases. Our study confirmed the unique morphological and immunophenotypic features of PTFL and suggests that FOXP-1 can represent a novel useful diagnostic marker in the differential diagnosis between PTFL and FH.

[Clinical observation of five pediatric-type follicular lymphoma in adult].

Objective: To investigate the characteristics in pathological diagnosis, clinical features, treatment and prognosis of adult patients with pediatric-type follicular lymphoma (PTFL) . Methods: The clinical and pathological features, laboratory examination, diagnosis and treatment, follow-up results of 5 adult PTFL patients admitted in Jiangsu Province Hospital were retrospectively analyzed, and literature review was conducted in combination with related reports. Results: All 5 patients developed PTFL in their adulthood with a median age of 22 years old (15-33 years) . The initial inanifestation of the disease was local painless lymphadenopathy with no fever, night sweats, emaciation or other systemic B symptoms. Pathological characteristics including typical large follicular structures and high proliferation index were found. Meanwhile, additional clonal rearrangement of immunoglobulin heavy chain gene was observed. However, there was no BCL-2 expression in histochemistry as well as BCL-2 gene abnormality in fluorescence in situ hybridization among these PTFL patients. These adult PTFL patients were all in stage Ⅰ-Ⅱ of the disease. For treatment, they were only treated with local surgical excision after diagnosis while didn't receive subsequent local radiotherapy or systemic immunochemotherapy. During a median follow-up of 27 months, the 5 cases of PTFL kept in a state of sustained complete remission. Conclusion: Adult-onset PTFL is characterized by high pathological proliferation index, while no BCL-2 expression or BCL-2 gene abnormality. Besides, PTFL is clinically manifested as a localized disease that can achieve a quite good prognosis through local surgical intervention. The aforementioned attributes of PTFL are distinctly different from classic adult follicular lymphoma.

Clinical observation of five pediatric-type follicular lymphoma in adult / 中华血液学杂志

Objective: To investigate the characteristics in pathological diagnosis, clinical features, treatment and prognosis of adult patients with pediatric-type follicular lymphoma (PTFL) . Methods: The clinical and pathological features, laboratory examination, diagnosis and treatment, follow-up results of 5 adult PTFL patients admitted in Jiangsu Province Hospital were retrospectively analyzed, and literature review was conducted in combination with related reports. Results: All 5 patients developed PTFL in their adulthood with a median age of 22 years old (15-33 years) . The initial inanifestation of the disease was local painless lymphadenopathy with no fever, night sweats, emaciation or other systemic B symptoms. Pathological characteristics including typical large follicular structures and high proliferation index were found. Meanwhile, additional clonal rearrangement of immunoglobulin heavy chain gene was observed. However, there was no BCL-2 expression in histochemistry as well as BCL-2 gene abnormality in fluorescence in situ hybridization among these PTFL patients. These adult PTFL patients were all in stage Ⅰ-Ⅱ of the disease. For treatment, they were only treated with local surgical excision after diagnosis while didn't receive subsequent local radiotherapy or systemic immunochemotherapy. During a median follow-up of 27 months, the 5 cases of PTFL kept in a state of sustained complete remission. Conclusion: Adult-onset PTFL is characterized by high pathological proliferation index, while no BCL-2 expression or BCL-2 gene abnormality. Besides, PTFL is clinically manifested as a localized disease that can achieve a quite good prognosis through local surgical intervention. The aforementioned attributes of PTFL are distinctly different from classic adult follicular lymphoma.

Clinical observation of five pediatric-type follicular lymphoma in adult / 中华血液学杂志

Objective@#To investigate the characteristics in pathological diagnosis, clinical features, treatment and prognosis of adult patients with pediatric-type follicular lymphoma (PTFL) .@*Methods@#The clinical and pathological features, laboratory examination, diagnosis and treatment, follow-up results of 5 adult PTFL patients admitted in Jiangsu Province Hospital were retrospectively analyzed, and literature review was conducted in combination with related reports.@*Results@#All 5 patients developed PTFL in their adulthood with a median age of 22 years old (15-33 years) . The initial inanifestation of the disease was local painless lymphadenopathy with no fever, night sweats, emaciation or other systemic B symptoms. Pathological characteristics including typical large follicular structures and high proliferation index were found. Meanwhile, additional clonal rearrangement of immunoglobulin heavy chain gene was observed. However, there was no BCL-2 expression in histochemistry as well as BCL-2 gene abnormality in fluorescence in situ hybridization among these PTFL patients. These adult PTFL patients were all in stage Ⅰ-Ⅱ of the disease. For treatment, they were only treated with local surgical excision after diagnosis while didn’t receive subsequent local radiotherapy or systemic immunochemotherapy. During a median follow-up of 27 months, the 5 cases of PTFL kept in a state of sustained complete remission.@*Conclusion@#Adult-onset PTFL is characterized by high pathological proliferation index, while no BCL-2 expression or BCL-2 gene abnormality. Besides, PTFL is clinically manifested as a localized disease that can achieve a quite good prognosis through local surgical intervention. The aforementioned attributes of PTFL are distinctly different from classic adult follicular lymphoma.

Pediatric-Type Follicular Lymphoma in the Dura: A Case Report and Literature Review.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a relatively common tumor of the central nervous system. Although PCNSLs generally arise from the parenchyma, lymphomas arising primarily from the dura are termed dural lymphomas (DLs). Mucosa-associated lymphoid tissue is the most unique histological feature of DLs. Because of its rarity, the clinical characteristics of and treatments for DL have not been fully elucidated to date. CASE DESCRIPTION: A 31-year-old man with no past medical history presented with numbness in his left upper limb. Magnetic resonance imaging revealed a dural-based tumoral lesion and cervical lymphadenopathies. The lesion was diagnosed radiologically as a meningioma, and tumor resection was planned. However, an intraoperative pathological diagnosis showed neoplastic lymphocytes, and the planned total tumor resection was halted. Histologically, the tumor was characterized by areas of poorly defined follicular architecture consisting of medium and large centroblasts. These tumor cells were immunohistologically positive for CD10 and CD20 and negative for B-cell lymphoma (BCL) 2 and BCL6. Fluorescence in situ hybridization did not show evidence of an Immunoglobulin H/BCL2 fusion. The lesion was subsequently diagnosed as a pediatric-type follicular lymphoma (PTFL). Six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) plus 2 cycles of rituximab were administered. The patient showed no evidence of relapse at 12 months after diagnosis, and follow-up was ongoing at the time of this report. CONCLUSIONS: This very rare case of DL was originally diagnosed as a PTFL. The tumor could be treated by immunochemotherapy alone.

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.