Epidermodysplasia Verruciformis and Vδ2 γδ T-cell Expansion in STK4 Deficiency.

The clinical penetrance of infectious diseases varies considerably among patients with inborn errors of immunity (IEI), even for identical genetic defects. This variability is influenced by pathogen exposure, healthcare access and host-environment interactions. We describe here a patient in his thirties who presented with epidermodysplasia verruciformis (EV) due to infection with a weakly virulent beta-papillomavirus (HPV38) and CD4+ T-cell lymphopenia. The patient was born to consanguineous parents living in the United States. Exome sequencing identified a previously unknown biallelic STK4 stop-gain mutation (p.Trp425X). The patient had no relevant history of infectious disease during childhood other than mild wart-like lesion on the skin, but he developed diffuse large B-cell lymphoma (DLBCL) and EBV viremia with a low viral load in his thirties. Despite his low CD4+ T-cell count, the patient had normal counts of CD3+ cells, predominantly double-negative T cells (67.4%), which turned out to be Vδ2+ γδ T cells. γδ T-cell expansion has frequently been observed in the 33 reported cases with STK4 deficiency. The Vδ2 γδ T cells of this STK4-deficient patient are mostly CD45RA-CD27+CCR7+ central memory γδT cells, and their ability to proliferate in response to T-cell activation was impaired, as was that of CD4+ T cells. In conclusion, γδ T-cell expansion may act as a compensatory mechanism to combat viral infection, providing immune protection in immunocompromised individuals.

Clinical characteristics and outcome of early-stage diffuse large B cell lymphoma of female genital track: A retrospective study of the Hellenic cooperative lymphoma group.

Involvement of female genital track (FGT) by diffuse large B cell lymphoma (DLBCL) represents an extremely rare diagnosis. Especially data regarding early-stage disease (i.e., IE, IIE) is very limited. Importantly, previous studies showed controversial results about the risk of central nervous system (CNS) relapse in this entity. Herein, we describe one of the largest reported real-world series of patients with early-stage FGT DLBCL aiming to investigate the clinicopathological characteristics, response to therapy and survival outcomes in the era of immunochemotherapy. We analyzed 21 consecutive patients with biopsy proven DLBCL from uterus or ovary classified as stage IE or IIE out of 1905 newly diagnosed DLBCL patients (1.1%). Uterine and ovarian localization was observed in 14 and seven patients, respectively. Median age was 66 years (range 33-96); 9/21 (43%) were <55 years. Regarding Cell of Origin DLBCL subtype, Germinal Center B-cell subtype was found in seven patients, non-GCB in 10 and non-classified in 4 patients. Median follow-up was 57 months and 5-year overall survival, lymphoma specific survival and Freedom from Progression were 78%, 89% and 90%, respectively. There was no correlation of patients' characteristics with survival parameters. Interestingly, none of the patients experienced CNS relapse. Our results indicate that localized FGT DLBCL exhibits a good prognosis and may not increase the risk for secondary CNS involvement.

Fluid Overload-Associated Large B-Cell Lymphoma with Light Chain Restriction Type Plasma Cell Infiltration: A Case Report.

BACKGROUND Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a recently described malignant lymphoma that presents with serous effusions in the pleura, peritoneum, and/or pericardium but without an identifiable lymphoma mass. This report describes the case of an 80-year-old man who presented with a pleural effusion and describes the approach to diagnosis and management of FO-LBCL. CASE REPORT We present a case of an 80-year-old man who presented with right pleural effusion and shortness of breath at work. Initial radiological assessment suggested a pleural effusion on the right side, without an identifiable mass, given the patient's symptoms and imaging characteristics. Subsequently, he underwent a pleural fluid puncture and biopsy. Based on the initial pathological assessment, malignant lymphoma, a non-epithelial tumor, was considered likely, but differentiation from reactive proliferative cells was difficult, given the patient's symptoms and cytologic characteristics. Postoperatively, histopathological examination and immunohistochemistry confirmed a diagnosis of FO-LBCL. After 1 year of follow-up, the condition had progressed and the patient died due to recurrence. CONCLUSIONS This report has presented a case of FO-LBCL in an elderly man with pleural effusion and described how this rare and recently described lymphoma was diagnosed and managed.

Enhanced prognostic evaluation of diffuse large B-cell lymphoma: A comprehensive surveillance study incorporating Epstein-Barr virus infection status and immunohistochemical markers.

Emerging biologic subsets and new prognostic markers are significantly important for aggressive diffuse large B-cell lymphoma (DLBCL). Nevertheless, the high cost of testing limits the availability of these tests in most hospitals, thus making prognostic judgment based on basic immunohistochemical testing, whole blood Epstein-Barr virus DNA (WBEBV) surveillance and clinical features advantageous for hospitals and patients with poor medical conditions. We included 647 DLBCL patients treated in our hospital from January 2009 to March 2023. Non-germinal center B-cell like, Ki-67, and International Prognostic Index (IPI) scores were related to cMYC/B-cell lymphoma 2 (Bcl-2)-double expression. Age, Epstein-Barr virus-encoded small RNA (EBER) positivity, and IPI scores were associated with mortality. The cutoffs for differential overall survival (OS) of age, WBEBV, Bcl-2, and cMYC were 57 years, 1514 copies/mL (baseline), 5.89 × 104 copies/mL (treatment), 40%, and 55%, respectively. EBER positivity was significantly associated with a worse OS. Patients with newly defined DE (Bcl-2 ≥ 40 and cMYC > 55) had a worse prognosis than controls (p = 0.04). We found that cMYC with an optimal cutoff of 47.5 could effectively predict high-grade DLBCL with an area under the curve of 0.912, and the specificity and sensitivity were 70.7% and 100%, respectively. Our study provides valuable insights into the prognostic factors and biomarker cutoffs that influence OS in DLBCL patients, which may guide clinicians in tailoring treatment strategies and improving patient outcomes.

[Chinese expert consensus on the diagnosis and management of elderly patients with diffuse large B-cell lymphoma (2024)].

The general population in China is aging, and thus the number of older patients with diffuse large B-cell lymphoma (DLBCL) will continue to increase. Individualized treatment is required to maximize therapeutic potential while minimizing the risk of toxicity. To improve the diagnosis and treatment of DLBCL in older people in China, the Lymphocyte Disease Group of the Hematology Division of the Chinese Medical Association and Lymphoma Expert Commitee of Chinese Society of Clinical Oncology (CSCO) have organized relevant experts to formulate this consensus.

Dermatomyositis Associated With High-Grade B-Lymphoproliferative Disorders: A Case Report and Literature Review.

Dermatomyositis (DM) and polymyositis are idiopathic inflammatory myopathies (IIMs), most associated with solid organ malignancies, and less commonly hematological malignancies. We discuss a case of DM associated with diffuse large B-cell lymphoma, followed by a review of literature on the pathogenesis, clinical course, treatment, and prognosis. Various challenges with the diagnosis and management of underlying lymphoproliferative disorders (LPDs) in patients with IIM are discussed. The case demonstrates the importance of being vigilant of the association between IIM and LPD. Cancer screening in patients with IIM is discussed, including the recently published International Guideline for IIM-Associated Cancer Screening. More research is required to address knowledge gaps in cancer screening in IIM.

[Primary laryngeal lymphoma: a case report]. / Lymphome primitif laryngé: à propos d'un cas.

Primary laryngeal lymphoma is rare, accounting for less than 1% of all laryngeal cancers. Treatment depends on the stage and severity of the disease. We here report the exceptional case of a 64-year-old woman, non-smoker, suffering from dysphagia for solids and a foreign body sensation. Laryngoscopy and biopsies revealed polyploid tumor of the left epiglottic fold. The diagnosis of diffuse large B-cell lymphoma was made. The patient underwent chemotherapy followed by radiotherapy, with significant improvement at 2-year follow-up, with no local recurrence. Due to the rarity of this disease and the variety of symptoms, the optimal management strategy for this type of cancer is controversial, requiring a specific diagnostic and therapeutic approach.

Prognostic value of lactate dehydrogenase to absolute lymphocyte count ratio and albumin to fibrinogen ratio in diffuse large B-cell lymphoma.

With the continuous improvement of treatment strategy, the prognostic value of international prognostic index (IPI) alone is limited for diffuse large B-cell lymphoma (DLBCL). Our study aims to explore the effect of lactate dehydrogenase (LDH)to absolute lymphocyte count (ALC) ratio (LAR) and albumin to fibrinogen ratio (AFR) on the prognosis of patients with DLBCL. The venous blood LDH, ALC, albumin and fibrinogen within 1 week before the first chemotherapy in 74 DLBCL patients were collected to calculate the LAR and AFR values. The impact of LAR and AFR on the progression-free survival (PFS) of patients with DLBCL was studied by the survival analysis. The area under the receiver operating characteristic curve (AUC) and concordance index (C-index) were used to analyze the predictive efficiency of each model for the PFS of DLBCL patients. Cox univariate analysis suggested that elevated LAR (P < .001) and decreased AFR (P < .001) were risk factors for PFS in DLBCL patients. Multivariate analysis revealed that LAR (P < .001) and AFR (P = .004) were 2 independent prognostic parameters. The AUC values of IPI, AFR + IPI, LAR + IPI and AFR + LAR + IPI to predict the PFS of DLBCL patients were 0.806 (95%CI 0.707-0.905, P < .001), 0.839 (95%CI 0.747-0.932, P < .001), 0.851 (95%CI 0.764-0.938, P < .001), and 0.869 (95%CI 0.787-0.952, P < .001), respectively. The C-index values of above 4 models were 0.802 (95%CI 0.629-0.975, P < .001), 0.842 (95% CI 0.735-0.949, P < .001), 0.846 (95%CI 0.716-0.976, P < .001), and 0.864 (95%CI 0.781-0.941, P < .001), respectively. The results suggest that both LAR and AFR are independent prognostic factors for PFS in DLBCL patients. Furthermore, their combination with IPI has better predictive efficiency for the prognosis of DLBCL patients.

Primary diffuse large B-cell lymphoma of the central nervous system identified with CSF biomarkers.

BACKGROUND: Diagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy. CASE PRESENTATIONS: The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3. CONCLUSIONS: Taken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.

Plasma circulating tumour DNA is a better source for diagnosis and mutational analysis of IVLBCL than tissue DNA.

Diagnosis of intravascular large B-cell lymphoma (IVLBCL) is a challenge due to its heterogeneous clinical presentation and lack of specific markers. This retrospective study investigated the utility of circulating tumour DNA (ctDNA) sequencing for diagnosing IVLBCL and analysing its mutation landscape. A cohort of 34 IVLBCL patients enrolled and underwent plasma ctDNA targeted sequencing. The median plasma ctDNA concentration was 135.0 ng/mL, significantly higher than that in diffuse large B-cell lymphoma (DLBCL) controls. Correlations were found between ctDNA concentration and disease severity indicators, LDH and SF. Mutation analysis revealed frequent mutations in B-cell receptor and NF-κB signalling pathways, including MYD88 (56%), CD79B (44%), TNFAIP3 (38%) and IRF4 (29%). CNS involvement was significantly related with BCL6 and CD58 mutation. Patients with complicated hemophagocytic lymphohistiocytosis had significantly higher mutation rates in B2M. Comparison with DLBCL subtypes showed distinctive mutation profiles in IVLBCL. Moreover, plasma ctDNA detected more mutations with higher variant allele fraction than tissue DNA, suggesting its superiority in sensitivity and accessibility. Dynamic monitoring of ctDNA during treatment correlated with therapeutic responses. This study revealed the role of ctDNA in IVLBCL diagnosis, mutation analysis, and treatment monitoring, offering a promising avenue for improving patient diagnosis in this rare lymphoma subtype.

Bilateral Lacrimal Gland Lymphoma - Case Presentation.

Lacrimal gland lymphomas are rare orbital tumors, constituting a minor fraction of all orbital and ocular adnexal malignancies. This case study presents an 83-year-old male with bilateral lacrimal gland tumors, more prominent in the left orbit, causing decreased visual acuity, red eye, excessive tearing, and diplopia. Initial ophthalmological evaluations and imaging suggested bilateral lacrimal gland lymphoma, confirmed by histopathology as diffuse large B-cell non-Hodgkin lymphoma of the MALT type. Due to the significant tumor size and risk of visual function loss, surgical intervention was performed, followed by corticosteroid therapy. Postoperatively, a marked improvement in symptoms and a reduction in tumor size were observed. This case underscores the importance of comprehensive diagnostic approaches, including clinical, imaging, and histopathological evaluations, highlighting the need for a multidisciplinary approach in managing rare orbital tumors like lacrimal gland lymphoma. The patient's postoperative and follow-up care included oncological management to monitor and ensure long-term disease control and patient well-being. Abbreviations: RE = right eye, LE = left eye, CT = Computer tomography, MRI = Magnetic Resonance Imaging, TOD = intraocular pressure of right eye, TOS = intraocular pressure of left eye, US = ultrasound.

Intravascular large B-cell lymphoma as a covert trigger for hemophagocytic lymphohistiocytosis complicated with capillary leak syndrome: a case report and literature review.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed.

Diffuse large B-cell lymphoma in the uterus with unexpected manifestations: a case report.

BACKGROUND: Lymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract. CASE PRESENTATION: A 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor). CONCLUSION: Primary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment.

[Clinical characteristics and prognostic analysis of 34 patients with primary thyroid lymphoma].

Objective: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) . Methods: A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors. Results: All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis (P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion: PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

Extranodal diffuse large B-cell lymphoma involving the uterine cervix.

This is a case of primary diffuse large B-cell lymphoma involving the uterine cervix which presented with irregular vaginal bleeding. The diagnosis was confirmed following multiple cervical biopsies. Treatment with a combination of immunotherapy, chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)) and radiotherapy produced a good response.

[A Case of Small Lymphocytic Lymphoma with -X Transformed Into Diffuse Large B-Cell Lymphoma].

An 80-year-old woman had developed a slight fever and loss of appetite since October 20XX. In November of the same year, the patient visited our hospital. Peripheral blood tests revealed the presence of atypical lymphocytes and a significant increase in sIL-2R. Tests of bone marrow aspiration samples showed the infiltration of small lymphocytes positive for CD19, CD20, CD23, and lambda. Therefore, a diagnosis of small lymphocytic lymphoma(SLL)was made. A complex karyotype including -X and del(13q)was observed in 19/20. Additionally, an enlarged spleen and retroperitoneal tumors were observed. As a result of 3 courses of fludarabine plus rituximab therapy, atypical lymphocytes were no longer observed in the peripheral blood and the enlarged spleen decreased in size. However, the retroperitoneal tumors could not be reduced. Consequently, a needle biopsy from the same area was performed in February 20XX+1, and a diagnosis of diffuse large B-cell lymphoma(DLBCL)was made. Because massive infiltration of CD23-negative lymphocytes was observed in the bone marrow, it was suggested that chronic lymphocytic leukemia(CLL)had transformed into DLBCL. Following 4 courses of CHOP therapy, the retroperitoneal tumors were reduced. In cases where -X is a microclone, the mutation is often age-related. However, in cases of advanced chronogenesis, as occurred in this patient, a correlation with hematopoietic tumors is arguable. Moreover, cases of CLL with -X have been reported to be related to de(l 13q). Our results strongly suggest that -X with del(13q)may be a clonal expansion in CLL/SLL.

Expression and Clinical Significance of Ki-67, CD10, BCL6, MUM1, c-MYC, and EBV in Diffuse Large B Cell Lymphoma Patients.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. Although studies regarding the association between the expression of Ki-67, CD10, BCL6, and MUM1 proteins, as well as c-MYC amplification and EBV status with clinicopathologic characteristics have rapidly progressed, their co-expression and prognostic role remain unsatisfactory. Therefore, this study aimed to investigate the association between the expression of all markers and clinicopathologic features and their prognostic value in DLBCL. Also, the co-expression of markers was investigated. METHODS: The protein expression levels and prognostic significance of Ki-67, CD10, BCL6, and MUM1 were investigated with clinical follow-up in a total of 53 DLBCL specimens (including germinal center B [GCB] and activated B cell [ABC] subtypes) as well as adjacent normal samples using immunohistochemistry (IHC). Besides, the clinical significance and prognostic value of c-MYC and EBV status were also evaluated through chromogenic in situ hybridization (CISH), and their correlation with other markers was also assessed. RESULTS: The results demonstrated a positive correlation between CD10 and BCL6 expression, with both markers being associated with the GCB subtype ( P< 0.001 and P =0.001, respectively). Besides, we observe a statistically significant association between MUM1 protein expression and clinicopathologic type ( P< 0.005) as well as a positive association between c-MYC and recurrence ( P =0.028). Our survival analysis showed that patients who had responded to R-CHOP treatment had better overall survival (OS) and progression-free survival (PFS) than those who did not. CONCLUSION: Collectively, this study's results add these markers' value to the existing clinical understanding of DLBCL. However, further investigations are needed to explore markers' prognostic and biological roles in DLBCL patients.

Molecular characterization of a rare case of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 rearrangements.

Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass. Computed tomography showed a 1.9-cm mass in left the tonsil with bulky cervical lymphadenopathy. The presence of all four chromosomal rearrangements can reportedly occur with disease progression in both diffuse large B-cell lymphomas and mantle cell lymphomas. Further characterization of the tumor by next-generation sequencing may be of benefit to delineate between these two possibilities. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing were used to confirm and classify the diagnosis. Histologic sections of the cervical lymph node demonstrated an atypical lymphoid infiltrate with large and pleomorphic cells, which were positive for CD20, CD10, BCL1 (Cyclin D1), BCL2, BCL6, and cMYC and negative for CD5 and SOX11 on immunohistochemistry with a Ki-67 proliferative index of 70%. FISH demonstrated MYC, BCL2, BCL6, and CCND1 rearrangements and the diagnosis of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 was rendered. Our patient was treated with dose adjusted etoposide, doxorubicin, cyclophosphamide, prednisone, and rituximab chemotherapy and has been in remission for 20 months.