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

BACKGROUND: 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. PROCEDURES: We conducted a single-center retrospective review of pediatric cases of PTGC diagnosed at our institution by hematopathologists from 2000 to 2020. RESULTS: 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. CONCLUSIONS: 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.

[Resolution of dasatinib-associated lymphadenopathy following discontinuation of dasatinib in patients with chronic myeloid leukemia].

This study reports two cases of dasatinib-associated lymphadenopathy (DAL). Case 1 involved a 58-year-old man diagnosed with chronic myelogenous leukemia (CML). After 13 months of starting on dasatinib treatment, a molecular response (MR) 4.5 was achieved. Due to the loss of MMR, dasatinib was discontinued at 39 months but restarted at 42 months. Right cervical lymphadenopathy appeared 51 months after starting the treatment. DAL was diagnosed based on the findings of a cervical lymph node biopsy. After dasatinib was switched to ponatinib, the lymphadenopathy disappeared without recurrence. In case 2, a 54-year-old man was diagnosed with CML. He was started on dasatinib and MR 4.5 was achieved after 6 months. Left cervical lymph node adenopathy appeared 21 months later, and a diagnosis of DAL was made based on the findings of a cervical lymph node biopsy. After discontinuation of dasatinib, cervical lymph node adenopathy disappeared without recurrence. The possibility of DAL should be considered if lymphadenopathy is observed during dasatinib treatment.

Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation.

Chronic/recurrent behaviour may be encountered in some distinct atypical or malignant lymphoproliferations, while recurrences are not generally observed in reactive/benign lymphadenopathies. We retrospectively analysed a consecutive series of 486 human immunodeficiency virus-negative adults, who underwent lymphadenectomy. Neoplastic and benign/reactive histopathological pictures were documented in 299 (61·5%) and 187 (38·5%) cases, respectively. Of note, seven of the 111 (6·3%) patients with benign lymphadenopathy without well-defined aetiology, showed chronic/recurrent behaviour, without constitutional symptoms. Enlarged lymph nodes were round in shape and hypoechoic, mimicking lymphoma. Reactive follicular hyperplasia and paracortical expansion were observed. Human herpesvirus (HHV)-6B positive staining in follicular dendritic cells (FDCs) was documented in all seven patients. Serological, molecular and immunological examinations suggested HHV-6B reactivation. Among the remaining 104 cases with reactive lymphoid hyperplasia in the absence of well-known aetiology and without recurrences, positivity for HHV-6B on FDCs was found in three cases, whereas in seven further patients, a scanty positivity was documented in rare, scattered cells in inter-follicular regions. Immunohistochemistry for HHV-6A and HHV-6B was invariably negative on 134 lymph nodes, with either benign pictures with known aetiology or malignant lymphoproliferative disorders, tested as further controls. Future studies are warranted to investigate a potential association between HHV-6B reactivation and chronic/recurrent benign lymphadenopathy.

Follicular tissue fragments in fine-needle aspiration cytology of lymph nodes: A useful clue in differential diagnosis of follicular lymphoma and reactive follicular hyperplasia.

BACKGROUND: In Fine-needle aspiration cytology (FNAC) of lymph nodes, tissue fragments derived from follicular structures may be observed in specimens. We defined such tissue fragments as follicular tissue fragments (FTF), and investigated differences in cytological findings for FTFs of each histological type. METHOD: A total of 41 cases with FNAC of lymph nodes were examined. In these cases, the histopathological diagnoses were reactive lymphoid hyperplasia (RLH) (n = 17), follicular lymphoma (FL) (n = 13), diffuse large B-cell lymphoma (DLBCL) (n = 18), and Burkitt lymphoma (n = 1). Specimens were analyzed for the presence of FTFs, and for tingible-body macrophages (TBMs) and monomorphism of lymphocytes in FTFs. FTFs with a maximum diameter of >500 µm were defined as large-FTFs. RESULTS: FTFs were identified in RLH (14/17, 82.4%), FL (13/13, 100%), and DLBCL (3/18, 16.7%). In the RLH subtypes, FTFs were present only in follicular hyperplasia (FH) (14/15, 93.3%) and not in paracortical hyperplasia (0/2). The number of cases with large FTFs among those with FTFs were as follows: RLH (10/14, 71.4%), FL (11/13, 84.6%), and DLBCL (0/3). Similarly, those with TBMs in FTFs were as follows: RLH (13/14, 92.9%), FL (0/13) and DLBCL (2/3, 66.7%). Monomorphism was observed in RLH (1/14, 7.1%) and FL (11/13, 84.6%), but not in DLBCL (0/3). CONCLUSIONS: Distinction between FL and FH is possible by identifying large-FTFs. In FL, TBMs are absent in FTFs and lymphocytes often show monomorphism. Therefore, recognizing FTFs and observing details inside the FTFs are useful for identification and differential diagnosis of FL and FH in FNAC of lymph nodes.

Dysregulated expressions of PTEN, NF-κB, WWP2, p53 and c-Myc in different subtypes of B cell lymphoma and reactive follicular hyperplasia.

This study aimed to investigate the value of PTEN, NF-κB, WWP2, p53 and c-Myc expressions in distinguishing B cell lymphomas from reactive follicular hyperplasia (RFH), and their abilities to discriminate different B cell lymphoma subtypes. Lymphoma tissue samples were obtained from 30 follicular lymphoma (FL) patients, 30 germinal center B-cell like (GCB) diffuse large B cell lymphoma (DLBCL) patients, 30 non-GCB DLBCL patients and 30 Burkitt's lymphoma (BL) patients. And hyperplasia tissue samples were obtained from and 30 RFH patients. Immunohistochemistry was used to quantify the expressions of PTEN, NF-κB, WWP2, P53 and c-Myc. PTEN expression was elevated in GCB DLBCL and BL compared with RFH, and in GCB DLBCL, non-GCB DLBCL and BL than that in FL; WWP2 expression was higher in FL, GCB DLBCL, non-GCB DLBCL and BL compared with RFH; p53 expression increased in non-GCB DLBCL compared with RFH, and in BL compared with RFH, FL or GCB DLBCL; c-Myc expression was higher in GCB DLBCL, non-GCB DLBCL and BL compared with RFH; c-Myc expression was elevated in GCB DLBCL, non-GCB DLBCL and BL compared with FL. Additionally, PTEN negatively correlated with p53 expression in FL and CGB DLBCL, whereas NF-κB negatively correlated with WWP2 in GCB DLBCL, but positively associated with PTEN in RFH and c-Myc in BL. PTEN, WWP2, p53 and c-Myc expressions might be served as biomarkers for identification of B cell lymphomas from RFH as well as distinguishing different B cell lymphoma subtypes.

CD38 expression on paraffin sections distinguishes follicular lymphoma from reactive follicular hyperplasia.

This study explored the utility of CD38 immunodetection in paraffin-embedded tissue sections for differentiating follicular lymphoma (FL) from reactive follicular hyperplasia (RFH) by examining RFH (n = 47) and FL (n = 178). In RFH specimens, uniform weak-to-moderate CD38 immunostaining was observed in centrocytes and centroblasts across germinal centers (GCs). Moreover, these specimens contained a subset of strongly CD38-positive cells predominantly located in the light zone, which may represent antigen-selected surviving centrocytes that are committed to differentiate into plasma cells, i.e., centrocytoid plasma cells (CPCs). In FL specimens, CD38 staining yielded two patterns. In pattern I (146 specimens), weak-to-moderate CD38 staining was observed in tumor cells within neoplastic follicles. Neoplastic follicles in 126 of the 146 specimens did not contain strongly CD38-positive CPCs. Furthermore, individual neoplastic follicles in the remaining 20 FL specimens contained very few strongly CD38-positive cells (which may represent normal residual CPCs). In pattern II (32 cases), neoplastic follicles exhibited loss of CD38 expression accompanied by disappearance of CPCs. In conclusion, compared with RFH, the decrease of strongly CD38-positive CPCs in neoplastic follicles was a striking alteration, reflecting blocks in the lymphoid differentiation pathway. Moreover, loss of CD38 expression in neoplastic GC B-cells in some FL specimens can serve as an immunophenotypic characteristic of FL.

High frequency of Bob1lo T follicular helper cells in florid reactive follicular hyperplasia.

Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH. When we analyzed tonsils of OSA and recurrent tonsillitis (RT) as a control, tonsils of OSA were found to harbor Tfh cells with a nearly 3-fold higher ratio in total CD4+ T cells than that in tonsils of RT. Further analysis showed that, in comparison to Tfh cells of RT tonsils, Tfh cells of OSA tonsils were relatively tolerant to CD3-mediated activation-induced cell death (AICD) and also expressed lower levels of a Bob1 transcription coactivator and IL-4, which fosters the development of GC-B cells. Given that Bob1 controls the proliferative activity in response to CD3 stimulation and has been suggested to have a role in the production of IL-4 in Tfh cells, the unique structure of FRFH is possibly associated with the function of Bob1lo Tfh cells.

IgM expression in paraffin sections distinguishes follicular lymphoma from reactive follicular hyperplasia.

The trapping of IgM-containing immune complexes (ICs) by follicular dendritic cells (FDCs) serves as an important step in promoting germinal center (GC) formation. Thus, the deposition of IgM-containing ICs on FDCs can be detected by antibodies recognizing IgM. The present investigation provides the first comprehensive report on the IgM staining pattern in follicular lymphoma (FL, n = 60), with comparisons to reactive follicular hyperplasias (RFH, n = 25), demonstrating that immunohistochemical staining for IgM in paraffin-embedded sections seems to be an additional tool for differentiating between FL and RFH. In RFH, IgM highlighted processes of FDCs, with stronger and more compact staining in light than in dark zones, with occasional very dim staining of GC B cells. In FL, IgM expression patterns were of three types. Pattern I (38 cases) stained tumor cells within neoplastic follicles, with no staining of FDCs. Pattern II (15 cases) stained neither tumor cells nor FDCs. Pattern III (7 cases) stained tumor cells with (3 cases) or without (4 cases) IgM expression; however, variable and attenuated IgM expression was observed on FDCs in each case. Interestingly, significant numbers of IgD+ mantle cells were preserved around the neoplastic follicles in these 7 cases. The data suggested that a complete or considerable loss of IgM expression in FDCs, reflecting the loss of IgM-containing ICs in FDCs, is a typical feature of FL. Increased IgM expression by GC B cells can also serve as an indicator of immunophenotypic abnormality in FL.