Head and neck follicular lymphoma with marginal zone differentiation and BCL2 translocation t(14;18) in both nodular and extranodular sites: a case report with mini-review.

OBJECTIVE: Head and neck follicular lymphoma (FL) with marginal zone (MZ) differentiation is a rare high-risk B-cell composite variant that has been reported in nodular but not extranodular sites in the parotid glands. Here we summarize the literature on FL with MZ differentiation in head and neck nodular sites and describe a rare case of extranodular FL with MZ differentiation in the parotid gland. STUDY DESIGN: We examined both the germinal center and MZ components of the parotid and bone-marrow biopsies of a 65-year-old female histologically, immunohistochemically, and molecularly to identify B-cell, germinal center, and follicular dendritic cell markers. RESULTS: The immunohistochemical and molecular analysis provided evidence that the FL and the MZ components derived from the same B-cell clone with a similar BCL2/IGH t(14;18) translocation site. The differentiated cells in the MZ did not express germinal center markers BCL6 and CD10. Both the parotid and bone-marrow proliferative B cells showed BCL6, CD2O, and CD79a positivity. CONCLUSIONS: Head and neck FL with MZ differentiation can develop in both nodular and extranodular sites and is characterized by BCL2 translocation t(14;18). Although the mechanism of MZ differentiation is unclear, the characterization of this rare histopathologic phenomenon might be clinically important.

Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma.

MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1-2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance.

Single-cell analysis can define distinct evolution of tumor sites in follicular lymphoma.

Tumor heterogeneity complicates biomarker development and fosters drug resistance in solid malignancies. In lymphoma, our knowledge of site-to-site heterogeneity and its clinical implications is still limited. Here, we profiled 2 nodal, synchronously acquired tumor samples from 10 patients with follicular lymphoma (FL) using single-cell RNA, B-cell receptor (BCR) and T-cell receptor sequencing, and flow cytometry. By following the rapidly mutating tumor immunoglobulin genes, we discovered that BCR subclones were shared between the 2 tumor sites in some patients, but in many patients, the disease had evolved separately with limited tumor cell migration between the sites. Patients exhibiting divergent BCR evolution also exhibited divergent tumor gene-expression and cell-surface protein profiles. While the overall composition of the tumor microenvironment did not differ significantly between sites, we did detect a specific correlation between site-to-site tumor heterogeneity and T follicular helper (Tfh) cell abundance. We further observed enrichment of particular ligand-receptor pairs between tumor and Tfh cells, including CD40 and CD40LG, and a significant correlation between tumor CD40 expression and Tfh proliferation. Our study may explain discordant responses to systemic therapies, underscores the difficulty of capturing a patient's disease with a single biopsy, and furthers our understanding of tumor-immune networks in FL.

The diagnostic and therapeutic challenges of Grade 3B follicular lymphoma.

Grade 3B follicular lymphoma (G3B FL) is rare, accounting for only 5-10% of FLs. Not only has it been routinely excluded from clinical trials, but data published on diagnosis, outcomes, choice of therapies and role of imaging are conflicting. With the advent of increasingly diverse treatment options for low-grade (G1-3A) FL, and the molecular subcategorisation of high-grade B-cell lymphomas, characterisation and treatment of G3B FL is ever more important as extrapolation of data becomes more difficult. New data have emerged exploring unique genetic characteristics, specific features on positron emission tomography imaging, choice of therapy, and outcomes of G3B FL in the current era. The present review will summarise and appraise these new data, and offer recommendations based on current evidence.

Orbital soft tissue composite lymphoma presenting as recurrence of a nodal lymphoma with mantle and follicular cell components: A case report, literature review and guideline for the treatment of patients.

Composite lymphoma with mantle and follicular cell components is a challenging diagnosis. Flow cytometry, immunohistochemistry and molecular genetics are required to distinguish the two components, as often the more aggressive one is predominant and masks the other. A 58-year-old man with history of nodal composite lymphoma presented with right exophthalmos and diplopia. A head CT scan showed an orbital tumor. A biopsy of the tumor revealed a mantle cell lymphoma predominating over a follicular lymphoma. Immunoglobulin heavy chain and light chain rearrangements analysis by PCR proved that both components of the orbital tumor were recurrences of the same nodal composite lymphoma diagnosed two years earlier. The nodal lymphoma was composed of a follicular lymphoma and an in situ mantle cell neoplasia. Consensus view is that dominant lymphoma should be treated when needed but taking into account if the mantle cell lymphoma is an in situ neoplasia and if it expresses CD5 and SOX11.

[Clinicopathological features of follicular lymphoma in children].

Objective: To investigate the clinicopathologic features of follicular lymphoma (FL) in children. Methods: One female and one male patients with FL diagnosed in the First College of Clinical Medical Science, China Three Gorges University and Beijing Friendship Hospital of the Capital University of Medical Science in February 2016 and June 2015 were studied by HE immunohistochemistry, EBER in situ hybridization, IgH and IgK gene rearrangement analysis and IRF4 fusion gene detection. Results: The two patients' age were 6.3 and 12 years, respectively. The lesions involved head and neck lymph nodes with duration of more than 2 months. Histopathologically, the lesions consisted of nodular proliferation of lymphoid follicles with diffuse distribution of large cells. Starry sky phenomenon was seen in one of the two cases. Immunohistochemistry showed that one case was positive for bcl-2 and MUM1, but negative for bcl-6 and CD10. Ki-67 index was>50% and oligoclonal IgK rearrangement was observed. The second case showed positivity for bcl-6, and CD10 but negative for bcl-2. Ki-67 index was>50% and clonal IgH FR1-JH and IgH FR2-JH rearrangements were detected. Both cases showed no evidence of IRF4 gene fusion. Conclusions: Childhood FL is a rare B-cell lymphoma with characteristic features and high-grade histomorphology. However, its immunophenotype and molecular genetic characteristics are divergent.

Analysis of GNA13 Protein in Follicular Lymphoma and its Association With Poor Prognosis.

GNA13 is a G protein involved in modulating tumor proliferative capacity, infiltration, metastasis, and migration. Genomic alteration of GNA13 was frequently observed in follicular lymphoma (FL). In this study, we examined 167 cases of FL by immunostaining of GNA13 using tissue microarray to evaluate the clinical significance. There were 26 GNA13-positive cases (15.6%) and 141 GNA13-negative cases (84.4%). GNA13-positive cases had a higher incidence of early progression of disease for which disease progression was recognized within 2 years compared with GNA13-negative cases (P=0.03). There were no significant differences in other clinicopathologic factors including histological grade, BCL2-IGH translocation, immunohistochemical phenotype, and Follicular Lymphoma International Prognostic Index. In addition, overall survival and progression-free survival were poorer in GNA13-positive cases than in GNA13-negative cases (P=0.009 and 0.005, respectively). In multivariate analysis, GNA13 positivity was found to be a poor prognostic factor for overall survival and progression-free survival. Thus, GNA13 protein expression was an independent prognostic factor and may affect disease progression in FL.

[Cut-off value of Ki-67 labeling index in the pathologic grading of follicular lymphoma].

Objective: To determine the cut-off values of Ki-67 labeling index (LI) in the histological grading of follicular lymphoma (FL). Methods: Clinicopathological data of 350 FL patients diagnosed at Beijing Friendship Hospital from June 2014 to January 2016 were analyzed retrospectively by quantitative evaluation and statistical analysis of Ki-67 LI. Results: Of the 350 patients with FL, the male and female ratio was 1.1 and the average age was (50.2±14.0) years with a median age of 51 years (range 4 to 82 years). The tumors were graded as grade Ⅰ-Ⅱ in 215 cases (61.4%), grade Ⅲ A in 105 cases (30.0%), and grade Ⅲ B in 30 cases (8.6%). The average Ki-67 values were (22.8%±8.3%) for the FL low (grade Ⅰ-Ⅱ) and (50.4%±10.7%) for high grade (Ⅲ A and Ⅲ B) and were statistically significant by Mann Whitney U test (P<0.01). Receiver operated characteristic curve analysis showed that the best diagnostic cut-off value of low grade FL was 35% (sensitivity of 96.3% and specificity of 93.3%) with the largest area under curve (AUC=0.990, P<0.01, 95%CI for 0.982-0.998). According to the analysis of four lattice diagnostic tests, Ki-67 LI >40% was an important factor (χ2=230.733, P<0.01) in predicting high grade FL. When the cut-off value of Ki-67 LI was set at 40%, high grade LF could be diagnosed with the greatest sensitivity (98.1%) and specificity (87.7%). Moreover, a significant correlation between the Ki-67 LI and the pathological grade of FL (r=0.836, P<0.01) was observed. Conclusions: Ki-67 LI of below a cut-off value of 35% is a reliable indicator of low grade FL.Ki-67 over 40% is consistent with high grade FL. These Ki-67 cut-off values may serveas an important auxiliary indicator in the grading of FL.

Concomitant 1p36 deletion and TNFRSF14 mutations in primary cutaneous follicle center lymphoma frequently expressing high levels of EZH2 protein.

Primary cutaneous follicle center lymphoma (PCFCL) is an indolent variant of follicular lymphoma (FL) with limited information available on the genetic background of the disease. The genetic hallmark of nodal FL, the t(14;18) translocation, affecting the BCL2 gene, is rare in PCFCL. Loss of 1p36, the most common secondary chromosomal abnormality in nodal FL, has been recently reported in 16.7% of PCFCL cases. In order to further characterize PCFCL, 21 cases were analyzed using interphase fluorescence in situ hybridization with BCL2 break apart and 1p36/1q25 dual color probes. Sanger sequencing was used to investigate TNFRSF14 and EZH2 mutations and immunohistochemistry to assess BCL2, EZH2 protein expressions.1p36 deletion occurred in 22% (5/21), BCL2 gene break in 10% (2/20) of the PCFCL cases. Mutations of the candidate tumor suppressor gene of the 1p36 region, TNFRSF14 mutations were detected in 4/17 (23.5%) cases with 2 cases presenting with concurrent 1p36 deletion. EZH2 hotspot mutations at Y641, A682, and A692 were not found. High EZH2 protein expression associated with a BCL2 negative phenotype was observed in 43% (9/21) of the cases. BCL2 gene break or 1p36 deletion did not impact the prognosis; however, they showed association with advanced stages at diagnosis (p = 0.016) and a tendency with shorter event free survival (p = 0.052).In conclusion, 1p36 deletion co-occurs with acquired TNFRSF14 mutations, suggesting a role of this tumor suppressor gene in the development of a subgroup of PCFCL. High EZH2 protein expression associated with BCL2 negative phenotype is common and might represent an ideal therapeutic target.

Follicular lymphoma with hyaline-vascular Castleman-like features: analysis of 6 cases and review of the literature.

Follicular lymphoma (FL) with features reminiscent of hyaline-vascular Castleman disease (CD) is an unusual morphologic variant that may create diagnostic difficulties. To our knowledge, only 5 cases of this variant have been reported. We describe the clinicopathologic features of 6 cases including 2 men and 4 women with a median age of 63 years (range, 41-77). Morphologically, all lymph node biopsy specimens showed at least a focal area of conventional FL; 4 cases showed neoplastic follicles with hyalinized blood vessels penetrating into germinal centers (lollipop-like lesions); 4 cases had interfollicular areas with increased vascular stroma; 2 cases showed small neoplastic follicles with prominent, onionskin-like mantle zones; and 1 case showed 2 or more germinal centers within follicles (twinning). The small neoplastic follicles were more cellular than lymphocyte-depleted follicles of true hyaline-vascular CD, and the interface between germinal centers and mantle zones was ill defined. No cases showed dysplastic follicular dendritic cells. Immunohistochemistry for BCL-2 was positive in all 6 cases. Flow cytometry immunophenotypic analysis showed a monotypic B-cell population in 2 of 3 cases assessed. Conventional cytogenetic or fluorescence in situ hybridization studies performed in 3 cases showed t(14;18)(q32;q21) or IGH-BCL2, supporting the diagnosis of FL. The cases presented here add clinicopathologic data to the few cases of FL with hyaline-vascular CD-like features reported previously in the literature. Distinguishing this variant of FL from hyaline-vascular CD is important given the differences in treatment and prognosis of patients with each disease.

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas.

Comparison of clinicopathologic characteristics of gastric follicular lymphomas and duodenal follicular lymphomas.

We compared the incidence, esophagogastroduodenoscopy (EGD) findings, and histopathologic characteristics of gastric and duodenal follicular lymphomas (FL). Of 626 FL cases, primary gastric FL and secondary gastric involvement of FL were observed in 1% and 5% of the cases, respectively, which were lower incidences than duodenal FL (10% and 9%, respectively). Gastric FL usually appeared as submucosal tumors (primary, 71%; secondary, 79%), whereas duodenal FL, as granular lesions (primary, 92%: secondary, 87%). In the granular duodenal lesions, the neoplastic follicles were located sparsely on the muscularis mucosa and could be found between villi, whereas in the stomach, similar lesions were hidden within the lamina propria, and only larger lesions such as submucosal tumors could be detected on the mucosal surface. The differences in the incidences and EGD findings were considered to be associated with structural differences of the lamina propria. Typical FL features: grades 1-2 histology, follicularity, and CD10+ and/or BCL6+ and BCL2+ were usually observed in all primary and secondary gastric and duodenal FL. Gastroduodenal and bone marrow involvement were found in 12% and 33% of the cases, respectively, and there was no significant correlation between them (P=.095). Twenty-nine cases (5%) were up-staged by gastroduodenal-positive results. In conclusion, the histopathology of gastric FL was similar to that of duodenal and nodal FL; the differences in the incidence and EGD findings between gastric and duodenal FL were considered to be associated with structural difference of the lamina propria, and EGD was useful as a staging procedure.

Lymphoblastic lymphoma with a triple-hit profile: a rare but distinct and relevant entity.

Follicular lymphoma with progression to a high-grade lymphoma bears a poor prognosis. We describe a case of a 60-year-old man who presented in 2012 with an epidural mass, diagnosed as a diffuse large B-cell lymphoma (DLBCL) with concurrent low-grade follicular lymphoma. Three years later, the patient presented with a cervical mass, diagnosed as a lymphoblastic lymphoma (LBL). Both the DLBCL and LBL contained a "triple hit" with BCL2, BCL6, and cMYC translocations demonstrated by fluorescence in situ hybridization analysis and a complex karyotype by single-nucleotide polymorphism array analysis. Furthermore, the 2 lymphomas were shown to be clonally related by clonality analysis and single-nucleotide polymorphism array analysis. This case report presents a highly unusual case of an LBL with a triple hit, originating from a DLBCL, which has rarely been described in the literature and deserves further exploration.

Double-hit follicular lymphoma with MYC and BCL2 translocations: a study of 7 cases with a review of literature.

Follicular lymphoma with MYC and BCL2 translocations, so-called double-hit follicular lymphoma (DH-FL), is rare. Here, we report the clinicopathological features of 7 cases of DH-FL. All neoplasms had a follicular pattern (1 partially diffuse). Five cases were predominantly low grade, 4 of which had focal (≤20%) grade 3A areas, and 2 cases were of grade 3. All cases were positive for pan-B-cell antigens, CD10, and BCL6; 6 cases were positive for BCL2. Ki-67 was less than or equal to 50% in 6 cases and 90% in 1 grade 3 case. Three patients presented with stage IV disease and 3 had a Follicular Lymphoma International Prognostic Index score of greater than 2. Six patients received immunochemotherapy, and 1 is still under induction therapy with rituximab, ibrutinib, and lenalidomide. Four achieved complete remission and two had a partial response with persistent or refractory disease. The median follow-up time was 25 months (range, 8.5-53.7 months). Two patients treated with standard regimen for follicular lymphoma had relapsed or refractory disease, and 1 died from complications of allogeneic stem cell transplant administered for relapse. In contrast, all 4 patients treated with more intensive regimen for double-hit lymphoma achieved complete remission. In summary, despite predominantly low-grade histology, cases of DH-FL in this study were aggressive and responded better to more intensive than standard treatment regimens, suggesting DH-FL is part of the spectrum of double-hit high-grade lymphoma.

Two cases of histiocytic sarcoma with BCL2 translocations and occult or subsequent follicular lymphoma.

Histiocytic sarcoma is rare and difficult to distinguish from histologic mimics such as myeloid sarcoma due to its relatively nonspecific immunoprofile. A subset of histiocytic sarcomas are clonally related to synchronous or metachronous follicular lymphomas. Interestingly, the histiocytic tumor component has been shown to harbor BCL2 gene translocations that are identical to those found in the lymphoma. We present one case of histiocytic sarcoma and initially occult follicular lymphoma in which detection of a BCL2 gene translocation helped support the diagnosis. We also provide follow-up regarding a previously published case of histiocytic sarcoma with IGH/BCL2 fusion gene in which the patient subsequently developed follicular lymphoma and, later, diffuse large B-cell lymphoma. Our findings suggest that BCL2 gene translocations are a recurrent feature of a distinct subset of histiocytic sarcomas that are associated with follicular lymphoma; the follicular lymphoma component may be clinically occult at the time of diagnosis. Testing for an IGH/BCL2 translocation should be considered in the diagnostic workup of difficult-to-characterize neoplasms with histiocytic/monocytic morphology and immunoprofile.

Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations.

A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2 translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al. Along with pertinent clinical information, we detail their histopathology, IGH/BCL2 translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well- to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situ hybridization analysis, the vast majority lacked IGH/BCL2 translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14 mutations were identified in three, highlighting the strong association of 1p36/TNFRSF14 abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6 mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6 mutations is higher than recently reported in conventional follicular lymphoma (11%). These findings lend support for a clinicopathologic variant of t(14;18) negative nodal follicular lymphoma and suggests importance of the interleukin (IL)-4/JAK/STAT6 pathway in this variant.

Partial lack of BCL2 in follicular lymphoma: An unusual immunohistochemical staining pattern explained by ongoing BCL2 mutation.

Follicular lymphomas are characterized by overexpression of BCL2 which, in the large majority of cases, is due to a t(14;18) translocation which juxtaposes the BCL2 locus to the immunoglobulin heavy chain locus (IGH). Here, we report partial absence of BCL2 immunohistochemical staining in a case of FL, due to a mutation in the part of BCL2 that encodes the epitope for the most frequently used antibody against BCL2. This finding shows that mutations in BCL2 occur in an ongoing process in follicular which can give rise to unusual immunohistochemical staining patterns.

Primary Cutaneous Follicle Center Lymphomas Expressing BCL2 Protein Frequently Harbor BCL2 Gene Break and May Present 1p36 Deletion: A Study of 20 Cases.

The classification of cutaneous follicular lymphoma (CFL) into primary cutaneous follicle center lymphoma (PCFCL) or secondary cutaneous follicular lymphoma (SCFL) is challenging. SCFL is suspected when tumor cells express BCL2 protein, reflecting a BCL2 translocation. However, BCL2 expression is difficult to assess in CFLs because of numerous BCL2+ reactive T cells. To investigate these issues and to further characterize PCFCL, we studied a series of 25 CFLs without any extracutaneous disease at diagnosis, selected on the basis of BCL2 protein expression using 2 BCL2 antibodies (clones 124 and E17) and BOB1/BCL2 double immunostaining. All cases were studied using interphase fluorescence in situ hybridization with BCL2, BCL6, IGH, IGK, IGL breakapart, IGH-BCL2 fusion, and 1p36/1q25 dual-color probes. Nineteen CFLs were BCL2 positive, and 6 were negative. After a medium follow-up of 24 (6 to 96) months, 5 cases were reclassified as SCFL and were excluded from a part of our analyses. Among BCL2+ PCFCLs, 60% (9/15) demonstrated a BCL2 break. BCL2-break-positive cases had a tendency to occur in the head and neck and showed the classical phenotype of nodal follicular lymphoma (CD10+, BCL6+, BCL2+, STMN+) compared with BCL2-break-negative PCFCLs. Del 1p36 was observed in 1 PCFCL. No significant clinical differences were observed between BCL2+ or BCL2- PCFCL. In conclusion, we show that a subset of PCFCLs harbor similar genetic alterations, as observed in nodal follicular lymphomas, including BCL2 breaks and 1p36 deletion. As BCL2 protein expression is usually associated with the presence of a BCL2 translocation, fluorescence in situ hybridization should be performed to confirm this hypothesis.

Utility of immunohistochemistry with an antibody against MYC at the initial diagnosis of follicular lymphoma, grade 3A, for predicting a more aggressive clinical course: a case report and review of the literature.

Follicular lymphoma (FL) is the most common indolent lymphoma, and associated with the chromosomal translocation t(14;18)(q32;q21). While, FL harboring both BCL2 and MYC translocation at diagnosis is very rare. The evaluation of MYC expression in typical FL at presentation using southern blot, G-banded karyotyping or fluorescence in situ hybridization (FISH) analyses has been described so far. However, there are no reports about the use of immunohistochemistry (IHC) to evaluate MYC protein expression in FL at presentation. Here, we present a FL patient who transformed to a B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma, accompanied by concurrent BCL2, BCL6, and MYC translocations; i.e., triple-hit lymphoma. Paraffin-embedded tissue section-FISH analysis demonstrated that the FL was negative for MYC, but MYC protein expression was subsequently detected in the lymph node specimen obtained at the initial diagnosis using IHC. This case revealed aggressive clinical course and central nervous system involvement. In the literature concerning MYC positive FL five out of 8 patients were dead within 24 months. The detection of MYC protein expression in FL using IHC might be useful to predict more aggressive clinical course.

PET/CT Assessment of Follicular Lymphoma and High Grade B Cell Lymphoma - Good Correlation with Clinical and Histological Features at Diagnosis.

BACKGROUND: Follicular lymphoma is a common type of non-Hodgkin's lymphoma observed in Western countries. The diagnosis of this disease is based primarily on morphological and immunohistochemical assessment. The proliferative index Ki67 correlates with histological grading and clinical aggressiveness. Currently, positron emission tomography/computed tomography scanning are not applied for standard staging at diagnosis of follicular lymphoma and its use is limited to those patients for whom the identification of residual disease is crucial for therapeutic decisions and only when transformation to a high-grade lymphoma is suspected. OBJECTIVES: Our aim was to assess whether a correlation exists between the maximal standardized uptake value (SUVmax) at the biopsy site as detected via positron emission tomography/computed tomography and pathological (Ki67 and FL histological grade) and clinico-biological features (e.g. LDH, beta-2-microglobulin, Ann Arbor stage and FL International Prognostic Index--FLIPI) at diagnosis. MATERIAL AND METHODS: We retrospectively identified 16 patients during the previous 3.5 years in whom node biopsies were guided, taking into account the SUVmax as detected upon PET/CT scan at diagnosis. The results of these biopsies were diagnostic of follicular lymphoma. We also included 6 patients with high grade B cell lymphoma: 5 diffuse large B cell lymphoma (DLBCL) and 1 FL 3b histological grade. A 2-tailed non-parametric Spearman's correlation analysis of the SUVmax with Ki67, histological grade, LDH and b-2-microglobuline was performed. RESULTS: The Ki67 (r=0.73) and follicular lymphoma histological grade (r=0.75) at the biopsy displayed a significant correlation with the SUVmax at diagnosis (p<0.01). CONCLUSIONS: Our results suggest that SUV detected by positron emission tomography/computed tomography correlates with histological grade in follicular lymphoma/high grade B cell lymphoma, Ki67 and LDH. Positron emission tomography/computed tomography should be considered for guiding lymph node biopsy when transformation to a high-grade B cell lymphoma is suspected.